Antimicrobial Handbook 2012

Antimicrobial
Handbook – 2012
0173-ColorCover2011 1 1/9/12, 3:18 PM

Table of Contents
Microbiology Susceptibility Reports 2009 ............................................................................ 2
Guidelines for Interpretation of Gram Stain Resuilts ............................................................... 4
Key Characteristics of Selected Organisms ........................................................................... 5
Antibiotic Administration Considerations
Selected Prescribing Criteria for Restricted Anti-infective Agent ................................... 7
Antibiotic Cost Awareness ........................................................................................... 9
Antibiotic Dosage Guidelines ....................................................................................... 11
Antibiotic Dosing in Obesity ........................................................................................ 15
Automatic Therapeutic Interchange ............................................................................ 20
Quinolone and Enteral Nutrition Policy ....................................................................... 21
Clinical Guidelines
Aminoglycoside Antibiotics-Dosing and Monitoring Guidelines .................................. 22
Amphotericin B Deoxycholate .................................................................................... 28
Amphotericin B Lipid Complex (ABLC) ....................................................................... 31
Bacteremia, Staphylococcus aureus ............................................................................ 32
CAPD Perionitis Management .................................................................................... 33
Candidemia Treatment of ........................................................................................... 38
Cellulitis ..................................................................................................................... 39
Clindamycin Intervention Project ............................................................................... 43
Clostridium Difficile-Associated Disease (CDAD), Treatment of ................................... 44
Endocarditis, Prevention of Bacterial ........................................................................... 47
Endocarditis, Treatment of Bacterial ........................................................................... 49
Febrile Neutropenia
Febrile Neutropenia-High Risk Inpatient ................................................................ 54
Low Risk Febrile Neutropenia ................................................................................ 56
Empiric Therapy of Fungal Infections .......................................................................... 60
Immunization for Adults ............................................................................................. 64
Intra-abdominal Infections, Guidelines for Empiric Treatment ..................................... 68
Pelvic Inflammatory Disease ....................................................................................... 73
Penicillin Allergy ......................................................................................................... 74
Pentamidine-Suggested Dosing Guidelines ................................................................. 77
Pneumonia
Empiric Therapy .................................................................................................... 78
Community-Acquired ............................................................................................ 79
Hospital-Acquired .................................................................................................. 81
Ventilator-Associated Pneumonia ........................................................................... 74
Sepsis ......................................................................................................................... 86
Splenectomy Vaccination Guidelines .......................................................................... 88
Surgical Prophylaxis ................................................................................................... 93
Trimethoprim Sulfamethoxazole Desensitization ......................................................... 94
Urinary Tract Infections (UTIs)
Classification and Diagnosis ................................................................................... 104
Management of UTIs ............................................................................................. 105
Vancomycin
Usage Guidelines ................................................................................................... 107
Dosage Guidelines ................................................................................................ 108
Intravenous to Oral Step Down
Sequential Antibiotic Therapy and Therapeutic Interchange ....................................... 110
Potential Savings Intravenous-to-Oral (IV to PO) Stepdown ........................................ 111
Bioavailability of Oral Antibiotics ................................................................................ 112
Notes .............................................................................................................................. 113
Published by the Antimicrobial Agents Subcommittee, District Drugs and Therapeutics Committee © Revised 2012
This handbook has been designed to aid practitioners at Capital Health in the appropriate utilization of
antimicrobials.
Editor Dr. Kathy Slayter in conjunction with the Antimicrobial Agents Subcommittee.
Access at http://cdhaintra.cdha.nshealth.ca/departmentservices/pharmacy/rxpublications.cfm
Antimicrobial Handbook 1
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Microbiology
Susceptibility Reports May 2009
GRAM POSITIVE ISOLATES - % SUSCEPTIBLE
Gentamicin synergy
Nitrofurantoin *
Erythromycin
Ciprofloxacin
Clindamycin
Vancomycin
Tetracycline
Gentamicin
Cephalexin
Cloxacillin
TMP-SMZ
Ampicillin
Cefazolin
Staphylococcus aureus NT 81 81 76 64 81 64 98 99 97 98 100
Coagulase negative
staphylococci NT 38 38 45 38 38 40 67 98 93 57 100
Enterococcus faecalis 97 IR IR IR IR IR IR IR 99 30 IR 96 82
Enterococcus faecium 12 IR IR IR IR IR IR IR NT 60 IR 65 99
* For use in urinary tract infection only.

IR - Usually not active either because of intrinsic or acquired resistance.
NT - Not tested.
Methicillin resistant S. aureus strains are resistant to all penicillins, cephalosporins, and
carbapenems.
GRAM NEGATIVE ISOLATES - % SUSCEPTIBLE

Piperacillin/tazobactam
Amoxicillin/clavualnate
Nitrofurantoin *
Ciprofloxacin
Meropenem
Ceftazidime
Tobramycin
Norfloxacin
Gentamicin
Ceftriaxone
Cephalexin
Piperacillin
TMP-SMZ
Ampicillin
Cefazolin
Escherichia coli 81 68 93 97 97 84 92 96 99 97 92 96 71 85 96
Klebsiella pneumoniae 92 IR 93 96 96 87 96 97 99 53 95 94 90 91 97
Proteus mirabilis 93 82 94 99 100 91 97 96 99 IR 97 98 89 87 96
Enterobacter cloacae IR IR IR IR IR IR 97 99 100 40 97 IR IR 91 99
Citrobacter freundii IR IR IR 11 12 3 88 94 100 87 87 IR IR 81 97
Serratia marcescens IR IR IR 50 21 IR 95 97 100 IR 94 50 49 99 85
Klebsiella oxytoca 96 IR 51 100 100 49 98 99 100 93 99 96 95 98 99
Morganella morganii IR IR IR 90 94 IR 92 86 100 IR 93 97 88 78 96
Enterobacter aerogenes IR IR IR IR IR IR 100 100 100 15 100 IR IR 97 100
* For use in urinary tract infection only.

2 Antimicrobial Handbook
1-19 2 1/9/12, 3:05 PM

Microbiology
Susceptibility Reports 2009 (cont’d)
AFERMENTORS - % SUSCEPTIBLE
Piperacillin/tazobactam
Ticarcillin/clavulanate
Ciprofloxacin
Meropenem
Ceftazidime
Tobramycin
Gentamicin
Ceftriaxone
Piperacillin
Imipenem
TMP-SMZ
Amikacin
Pseudomonas aeruginosa 78 72 85 75 84 85 58 82 92 IR NT IR
Stenotrophomonas maltophilia 46 26 IR IR NT NT 16 14 13 0 38 98
Acinetobacter baumannii 78 91 94 NT 89 60 NT 93 98 54 NT 90
Burkholderia cepacia 22 3 IR NT NT NT IR IR IR IR IR 19

NT - Not tested.
N.B. - Specific susceptibilities should be consulted when they are available, as individual
results can be especially difficult to predict when the number is small of isolates tested.
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Guidelines1 for Interpretation of Gram Stain Results
Gram-Positive Cocci (GPC) Gram-Negative Cocci (GNC)
Pairs, chains, clusters: Diplococci
- Staphylococcus sp - Pairs:
Pairs, chains: > Neisseria meningitidis
- Streptococcus sp > Neisseria gonorrhoeae
- Enterococcus sp > Moraxella catarrhalis
Pairs, lancet-shaped: Other:
- Streptococcus pneumoniae - Acinetobacter sp
Pairs:
- Enterococcus sp Gram-Negative Bacilli (GNB)
Enterobacteriaceae:
Gram-Positive Bacilli (GPB) - Escherichia coli
Diphtheroids: - Serratia sp
- Small, pleomorphic: - Klebsiella sp
> Corynebacterium sp - Enterobacter sp
> Propionibacterium (anaerobe) - Citrobacter sp
Large, with spores: Nonfermentative:
- Clostridium sp - Pseudomonas aeruginosa
- Bacillus sp - Stenotrophomonas (Xanthomonas) maltophilia
Branching, beaded, rods: - Many others
- Nocardia sp Haemophilus influenzae
- Actinomyces sp (anaerobe) Bacteroides fragilis group (anaerobe)
Other: Fusiform (long, pointed):
- Listeria sp (blood/cerebrospinal fluid) - Fusobacterium sp (anaerobe)
- Lactobacillus sp (vaginal/blood) - Capnocytophyga sp
1Theseguidelines are not definitive but presumptive for the identification of organisms on gram stain. Treatment will depend on the quality of the
specimen and appropriate clinical evaluation.
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Key Characteristics of Selected Organisms
Gram-Positive Cocci (GPC) Gram-Negative Cocci
Catalase-positive: Neisseria meningitidis
- Staphylococcus sp Neisseria gonorrhoeae
Catalase-negative: Moraxella (Branhamella) catarrhalis
- Enterococcus sp Acinetobacter sp1
- Streptococcus sp (chains)
- Micrococcus sp (usually insignificant) Gram-Negative Bacilli (GNB)
Coagulase-positive: Lactose-positive:
- Staphylococcus aureus - Escherichia coli
Coagulase-negative: - Klebsiella pneumoniae (mucoid)
- Coagulase-negative staphylococci (CNS): - Enterobacter sp2
> Blood: Staphylococcus epidermidis or CNS - Citrobacter sp2
> Urine: Staphylococcus saprophyticus Lactose-negative/oxidase-negative:
> Staphylococcus lugdunensis4 - Proteus mirabilis: indole-negative
- Proteus vulgaris: indole-positive
Gram-Positive Bacilli (GPB) - Providencia sp
Diphtheroids: - Morganella morganii
- May be Corynebacterium sp: often blood culture - Serratia sp3
contaminants - Salmonella sp
- Corynebacterium jeikeium: resistant to many agents - Shigella sp
except vancomycin - Acinetobacter sp1
Anaerobic diphtheroids: Propionibacterium acnes - Stenotrophomonas (Xanthomonas) maltophilia
Bacillus sp: Bacillus anthracis: non-motile and non-ȕ- (nonfermenter)
hemolytic; Bacillus subtilisLHODUJH³ER[FDU´URGVZLWK Lactose-negative/oxidase-positive:
spores - Pseudomonas aeruginosa (green; ³JUDSH-RGRU´
Listeria monocytogenes: cerebrospinal fluid, blood - Aeromonas hydrophila (may be lactose-positive)
Lactobacillus sp: vaginal flora, rarely in blood - Rare:
Nocardia sp: Branching, beaded; partial acid-fast-positive > Other Pseudomonas sp
Rapid growing mycobacteria: > Moraxella sp1
- Mycobacterium fortuitum > Alcaligenes sp
- Mycobacterium chelonae/abscessus > Burkholderia sp
Gram-Negative Bacilli (GNB)

Other:
- Haemophilus influenzae (coccobacillary); requires
supplements/special media (chocolate agar plate)
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Key Characteristics of Selected Organisms (continued)
Fungi - Thermally dimorphic (yeast in tissue, mould in lab):
Moulds: > Histoplasma capsulatum (slow growing)
- Aseptate hyphae: > Blastomyces dermatitidis
> Zygomycetes, such as: > Coccidioides immitis
- Rhizopus sp Yeast:
- Mucor - Candida sp; Candida albicans if germ tube-positive
- Septate hyphae: - Cryptococcus sp (no pseudohyphae); Cryptococcus
> Brown pigment (phaeohyphomycetes), such as: neoformans if latex- or CAD-positive
- Bipolaris sp - Candida glabrata
- Exserohilum sp - Trichosporon sp
- Alternaria sp - Rhodotorula, Saccharomyces sp
- Curvularia sp
- Sporothrix schenckii ³URVH-JDUGHQHUV´ Anaerobes
> Non-brown pigmented (hyalohyphomycetes, most GNB:
common), such as: - Bacteriodes sp (Bacteriodes fragilis)
- Aspergillus sp (Aspergillus fumigatus, Aspergillus - Fusobacterium sp
flavus) GNC:
- Fusarium sp - Veillonella sp
- Penicillium sp GPC:
- Paecilomyces sp - Peptostreptococcus sp
- Dermatophytes GPB:
- Propionibacterium acnes
- Clostridium sp (spores)
- Actinomyces sp (branching, filamentous)
- Lactobacillus sp
- Eubacterium sp
- Bifidobacterium sp
1 May be either bacillary or coccoid.
2 May be lactose negative.
3 May produce red pigment and appear lactose-positive initially.
4 Clinically can act as Staphylococcus aureus; laboratory results will reflect this by using MIC interpretation for Staphylococcus aureus.
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Selected Prescribing Criteria For
Restricted Anti-infective Agents
Cefotaxime and ceftriaxone (Cefotaxime should be used in place
of ceftriaxone for patients with biliary sludging or severe diarrhea)
Treatment of nosocomial pneumonia.
EMPIRIC therapy of severely ill patients with suspected Gram
negative infection.
Documented Gram negative infection resistant to 1st and 2nd
generation cephalosporins in patients who cannot receive
aminoglycosides.
Meningitis.
Spontaneous bacterial peritonitis, community-acquired
secondary peritonitis (or hospital acquired with no previous
antimicrobial therapy), or intra-abdominal abscess.
Community acquired pneumonia in patients treated with a
fluoroquinolone in the last 3 months.
Therapy for low risk febrile neutropenic patients.
Other indications on recommendation by the Division of
Infectious Diseases.
Ceftazidime
Treatment of documented Pseudomonas infections.
Empiric therapy for presumed Pseudomonas infections in febrile
neutropenic and cystic fibrosis patients.
Ciprofloxacin IV
Patients unable to take oral ciprofloxacin and one of:
Treatment of a documented Gram-negative infection due to an
organism resistant to other antibiotics or when another
antibiotic is contraindicated.
Treatment of respiratory infections in cystic fibrosis.
Empiric therapy of ICU nosocomial pneumonia where
Pseudomonas or other resistant Gram-negative infections are
suspected.
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Therapy of high-risk febrile neutropenia for patients with a
severe B-lactam allergy.
Treatment of intra-abdominal infections in patients who cannot
receive penicillin or aminoglycoside-containing regimens.
Peritonitis protocol for peritoneal dialysis patients.
Imipenem
Treatment of resistant infections in cystic fibrosis patients.
Treatment of documented resistant infections or where
resistance to piperacillin-tazobactam or third-generation
cephalosporins is likely.
Piperacillin-tazobactam
As a single agent for the treatment of serious Gram-negative or
polymicrobial infections, including mixed aerobic and anaerobic
infections, where the use of other agents is not appropriate
because of resistance, contraindications or adverse events.
Treatment of high risk febrile neutropenia.
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Antibiotic Cost Awareness
Name Route Average Adult Dosage Regimen $ per dose $ per day
Aminoglycosides
Amikacin IV/IM 1000 mg (15 mg/kg) q24h $60.33 $60.33
Gentamicin IV/IM 400 mg (6 mg/kg) q24h $11.85 $11.85
Streptomycin IV 1000 mg q12h $8.40 $16.80
Tobramycin IV/IM 400 mg (6 mg/kg) q24h $19.43 $19.43
Antifungals
Amphotericin B IV 50 mg q24h $56.71 $56.71
ABLC* (amphotericin B lipid complex) IV 400 mg q24h $794.75 $794.75
Fluconazole po 200 mg q24h $5.24 $5.24
Fluconazole IV 200 mg q24h $14.15 $14.15
Itraconazole Oral Solution po 200 mg q24h $16.02 $16.02
Ketoconazole po 400 mg q24h $0.80 $0.80
Micafungin* IV 100 mg q24h $100.00 $100.00
Voriconazole* IV 400 mg q12h $280.00 $560.00
Voriconazole* po 200 mg q12h $47.50 $95.00
Antivirals
Acyclovir IV 350 mg (5 mg/kg) q8h $10.65 $31.95
Acyclovir po 200 mg 5 x per day $0.30 $1.50
Acyclovir po 800 mg 5 x per day $1.14 $5.70
Amantadine po 100 mg q12h $0.12 $0.25
Ganciclovir Implant 1 implant q5-8months
Oseltamavir (prophylaxis) po 75 mg q24h $3.90 $3.90
Oseltamavir po 75 mg q12h $3.90 $7.80
Valacyclovir po 500 mg q12h $3.31 $6.62
Valganciclovir po 900 mg q12h $44.82 $89.64
Cephalosporins
1st Generation
CeFAZolin IV/IM 1g q8h $2.39 $7.17
CephALEXin po 500 mg q6h $0.16 $0.64
2nd Generation
CefUROXime axetil po 500 mg q12h $0.98 $1.96
CefUROXime Na IV/IM 750 mg q8h $4.55 $13.65
3rd Generation
CefoTAXime* IV/IM 1g q8h $7.40 $22.20
CeftAZIDime* IV/IM 1g q6h $6.40 $25.76
CefTRIAXone* IV/IM 1g q24h $2.95 $2.95
CeFIXime po 400 mg q24h x 1 $3.18 $3.18
Fluoroquinolones
Ciprofloxacin* po 500 mg q12h $0.34 $0.68
Ciprofloxacin* IV 400 mg q12h $9.50 $19.00
Levofloxacin* po 500 mg q24h $2.80 $2.80
Levofloxacin* IV 500 mg q24h $34.00 $34.00
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Antibiotic Cost Awareness (cont’d)
Name Route Average Adult Dosage Regimen $ per dose $ per day
Penicillins
Amoxicillin po 500 mg q8h $0.06 $0.24
Amoxicillin/Clavulanate po 875 mg/125 mg q12h $0.61 $1.22
Ampicillin IV/IM 1g q6h $1.90 $7.60
Cloxacillin po 500 mg q6h $0.08 $0.32
Cloxacillin IV/IM 2g q6h $4.77 $19.08
Penicillin G Na IV/IM 3 MU q4h $2.64 $15.84
Penicillin VK po 300 mg q6h $0.02 $0.08
Piperacillin IV/IM 3g q6h $9.28 $37.12
Piperacillin/Tazobactam* IV 3.375 g q6h $7.64 $30.56
Ticarcillin/Clavulanate* IV 3.1 g q6h $11.25 $44.98
Tetracyclines
Doxycycline po 100 mg q12h $0.22 $0.44
Doxycycline† IV 100 mg q12h $15.15 $30.30
Tetracycline po 250 mg q6h $0.05 $0.20
Macrolides
Azithromycin po 500 mg on day one, q24h $1.89 $1.89
then 250 mg for 4 days
Azithromycin IV 500 mg q24h $23.92 $23.92
Azithromycin (MAC) po 1200 mg q weekly $15.25 N/A
Clarithromycin po 250 mg q12h $0.75 $1.50
Erythromycin po 500 mg q6h $0.16 $0.65
Miscellaneous
Chloramphenicol IV 1000 mg q6h $15.65 $62.60
Clindamycin po 300 mg q6h $0.31 $1.24
Clindamycin IV 600 mg q8h $4.27 $12.81
Dapsone po 100 mg q24h $0.41 $0.41
Daptomycin IV 6-8 mg/kg q24h $140.00 $140.00
Linezolid* po 600 mg q12h $70.64 $141.28
Linezolid* IV 600 mg q12h $95.51 $191.02
Imipenem IV 500 mg q6h $6.10 $24.40
Metronidazole IV 500 mg 12h $1.57 $3.14
Metronidazole po 500 mg q8h $0.04 $0.12
Nitrofurantoin po 50 mg q6h $0.11 $0.44
Trimethoprim/Sulfamethoxazole po 1 DS q12h $0.06 $0.12
Trimethoprim/Sulfamethoxazole IV 10 mL q12h $7.55 $30.20
(16 mg & 80 mg/5 mL)
Trimethoprim/Sulfamethoxazole IV 10 mL q6h $7.55 $30.20
(16 mg & 80 mg/5 mL) for PCP
Vancomycin IV 1g q12h $10.33 $20.66
Vancomycin* po 125 mg q6h $1.15 $4.59
Costs include additional $1.15/dose for IV minibag; Dose per kg based on a 70 kg adult
* Restricted antimicrobial
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GENERAL COMMENTS/ Usual Adult Dose1 CrCL CrCL CrCL HEMODIALYSIS2 PERITONEAL CONTINUOUS RENAL
MIC CONSIDERATIONS (CrCL >50 mL/min) 30 to 50 mL/min 10 to 30 mL/min <10 mL/min DIALYSIS RENAL REPLACMENT
PENICILLINS (CRRT)4
Amoxicillin (PO) 250 to 500 mg q8h 250 to 500 mg q8h 250 to 500 mg q12h 250 to 750 mg q24h 500 mg q24h 500 mg q12h 500 mg q12h
Amoxicillin/clavulanate (PO) 875 mg q12h 875 mg q12h 500 mg q12h 500 mg q24h 500 mg q24h 250 mg q12h 500 mg q12h
Ampicillin (IV) 1 to 2 g q4-6h 1 to 2 g q6-8h 1 to 2 g q8-12h 1 to 2 g q12h 1 to 2 g q12h 500 mg 1 g q12h 1 to 2 g q8-12h
Cloxacillin 2 g q4-6h 2 g q4-6h
Penicillin G (IV) 2 to 4 M Units q4h 2 M Units q4h 1 M Units q4h 1 M Units q4h 1 M Units q4h 1 to 2 M Units q4h
Piperacilln/tazobactam (IV) 3.375 g 3.375 g q8h 3.375 g q8h 3.375 g q12h 3.375 g q12h 3.375 g q12h 3.375 g q8h
CEPHALOSPORINS
Antimicrobial Handbook
Cefazolin (IV) 1 g q8h 1 g q8h 1 g q12h 1 g q24h 1 g q24h 500 mg q12h 1 to 2 g q12h
Cephalexin (PO) 500 mg q6h 500 mg q6h 500 mg q8-12h 500 mg q12-24h 500 mg q24h 500 mg q12-24h ND
11
Cefuroxime (VI) 750 mg q8h 750 mg q8h 750 mg q12h 750 mg q24h 750 mg q24h 750 mg q12h 750 mg q12h
Cefuroxime (PO) 250 to 500 mg q12h 250 to 500 mg q12h 250 to 500 mg q24h 250 to 500 mg q24h 250 to 500 mg q24h 250 to 500 mg q12h
Ceftriaxone (IV) Dose 2 g q12h for meningitis 1 g q24h 1 g q24h
Cefotaxime (IV) Dose 1 g q8h for pneumonia 1 to 2 g q8h 1 to 2 g q8h 1 to 2 g q12h 1 to 2 g q24h 1 to 2 g q24h 1 to 2 g q24h 1 to 2 g q12h
Dose 2 g q4h for meningitis 2 g q4h 2 g q6h 2 g q8h 2 g q12-24h 2 g q12-24h 2 g q12-24h 2 g q8h
Ceftazidime (IV) Dose 2 g q8h for meningitis 1g IV q6h 1 to 2 g q12h 1 to 2 g q24h 1 to 2 g q48h 1 to 2 g 3x/week after HD 500 mg q24h 1 to 2 g q8h
Imipenem (IV) Monitor renal function (SCr);
11
Use this dose empirically and 500 mg q6h 500 mg q8h 500 mg q12h 500 mg q24h 500 mg q24h 500 mg q24h 500 mg q6-8h
when know MIC ≤2 mg/L
QUINOLONES
Ciprofloxacin (PO) Mg+2, Ca+2, AI+3 containing 250-750 mg q12h 250-750 mg q12h 250-750 mg q24h 250-750 mg q24h 250-500 mg q24h 250-500 mg q24h 250-750 mg q12h
Ciprofloxacin (IV) antacids, iron, zinc, and 200-400 mg q12h 200-400 mg q12h 200-400 mg q24h 200-400 mg q24h 200-400 mg q24h 200-400 mg q24h 200-400 mg q12h
Levofloxacin (PO/IV) sucralfate ↓ PO quinolone 250 mg q24h 250 mg q24h 250 mg q48h 250 mg q48h 250 mg q48h 250 mg q24h
absorption >90% (separate 500 mg q24h 250 mg q24h 250 mg q48h 250 mg q48h 250 mg q48h 250 mg q24h
administration times ≥2 hours) 750 mg q24h 750 mg q48h 500 mg q48h 500 mg q48h 500 mg q48h 500 mg q24h
Antibiotic Dosage Guidelines
MACROLIDES
Azithromycin (IV) 500 mg q24h 500 mg q24h
Clarithromycin (PO) 500 mg q12h 500 mg q12h 500 mg q24h 500 mg q24h
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1-19
(CRRT)4
ANTIFUNGALS
Amphotericin B (IV) 0.5 to 1 mg/kg q24h 0.5 to 1 mg/kg q24h 0.5 to 1 mg/kg q24h
(consider 500 mL-1 L NS pre- or divided pre- and
post-infusion to ↓ risk of nephrotoxicity)
Micafungin 100 mg q24h 100 mg q24h
Lipid amphotericin B Monitor SCr, K+, Mg++, PO4; 5 mg/kg q24h 5 mg/kg q24h 5 mg/kg q24h
(IV) (Abelcet) Administer in D5W over 2 (consider 500 mL-1 L NS pre- or divided pre- and post-infusion
hours to ↓ risk of nephrotoxicity)
Fluconazole (PO/IV) Monitor LFTs; consider PO 200 mg q24h 200 mg q24h 100 mg q24h 100 mg q24h 100 mg q24h 200 mg q24h
therapy (>90% bioavailability);
higher daily dosing (at least
400 mg) recommended in
12
systemic infections
Monitor LFTs; consider PO 400 to 800 mg q24h 400 to 800 mg q24h 200 to 400 mg q24h 200 to 400 mg q24h 200 to 400 mg q24h 400 to 800 mg q24h
therapy (>90% bioavailability); (for systemic fungal
higher daily dosing (at least infections)
400 mg) recommended in
12
systemic infections
Flucytosine (PO) Monitor SCr, CBC 12.5 to 25 mg/kg q6h 12.5 to 25 mg/kg q12-24h 12.5 to 25 mg/kg 12.5 to 25 mg/kg 500 mg to 1 g 12.5 to 25 mg/kg
q24-48h q24-48h q24-48h q24-48h
3
Voriconazole (IV) IV: caution CrCL <50 mL/min 6 mg/kg q12h x 2, 6 mg/kg q12h x 2, then 4 mg/kg q12h
(cyclodextrin may accumulate) then 4 mg/kg q12h
PO dose: ≥40 kg:200 or 300
mg q12h, <40 kg:100 ot 150
mg q12h
Child-Pugh Class A or B: Reduce
maintenance dosage by 50%
ANTIVIRALS
Acyclovir (IV) Dose based on ideal or 5 to 10 mg/kg q8h 5 to 10 mg/kg q12h 5 to 10 mg/kg q24h 2.5 to 4 mg/kg q24h 2.5 to 5 mg/kg q24h 2.5 to 5 mg/kg q24h 5 to 10 mg/kg q24h
adjusted body weight.
Valacyclovir (PO) 1 g q8-12h 1 g q12h 1 g q24h 500 mg q24h 1 g 3x/week after HD 500 mg q48h 500 mg q24h
Antibiotic Dosage Guidelines (cont’d)
1/9/12, 3:05 PM
1-19
(CRRT)4
ANTIVIRALS (cont’d)
Ganciclovir (IV) Monitor, WBC 5 mg/kg q12h 2.5 mg/kg q24h 1.25 mg/kg q24h 1.25 mg/kg 3x/week 1.25 mg/kg 3x/week 1.25 mg/kg 3x/week 2.5 mg/kg q24h
(induction) after HD
5 mg/kg q24h 1.25 mg/kg q24h 0.625 mg/kg q24h 0.625 mg/kg 3x/week 0.625 mg/kg 3x/week 0.625 mg/kg 3x/week 1.25 mg/kg q24h
(maintenance) after HD
Valganciclovir (PO) 900 mg q12h 450 mg q12h 450 mg q48h ID or Transplant consult
(induction) (CrCL 40-59)
450 mg q48h
(CrCL 25-39)
13
900 mg q24h 450 mg q24h 450 mg twice weekly ID or Transplant consult
(maintenance) (CrCL 40-59)
450 mg q48h
(CrCL 25-39)
ANTITUBERCULOSIS
Ethambutol (PO) Monitor uric acid, 15 to 25 mg/kg q24h 15 to 25 mg/kg q24-36h 15 to 25 mg/kg q48h 15 to 25 mg/kg q48h 15 to 25 mg/kg q48h 15 to 25 mg/kg q24-36h
LFTs; vision test
13
Isoniazid (PO) Monitor LFTs 5 mg/kg q24h 5 mg/kg q24h
Pyrazinamide (PO) Monitor LFTs 15 to 30 mg/kg q24h 15 to 30 mg/kg q24h 15 to 30 mg/kg q24h
Rifampin (IV, PO)3 Monitor LFTs; significant 600 mg q24h 600 mg q24h
drug interaction potential
MISCELLANEOUS
Clindamycin (IV)3 600 to 900 mg q8h 600 to 900 mg q8h
Daptomycin (IV) Monitor baseline and 6 to 8 mg/kg q24h 6 to 8 mg/kg q24h 6 to 8 mg/kg q48h 6 to 8 mg/kg post HD 6 to 8 mg/kg q48h 6 to 8 mg/kg q24h
weekly CPK levels
Doxycycline (IV, PO) 100 mg q12h 100 mg q12h
Linezolid (IV, PO) Monitor CBC: consider 600 mg q12h 600 mg q12h
PO therapy
(-100% bioavailability)
Metronidazole (IV, PO)3 500 mg q8-12h 500 mg q8-12h 500 mg q12h 500 mg q8-12h
1/9/12, 3:05 PM
Antibiotic Dosage Guidelines (cont’d)
1-19
(CRRT)4
MISCELLANEOUS (cont’d)
Colistin (IV) Reduce dose when CrCL 2.5-3 mg/kg q24h 2.5 to 3 mg/kg load 2.5 to 3 mg/kg load x 1, 2.5 to 3 mg/kg load x 1, then 1 mg/kg q3-5 days
<80 mL/min; monitor SCr, (can divide dose 12h) x 1, then 1 to 1.5 then 1 to 1.5 mg/kg q2-3 days
electrolytes, neuroactivity mg/kg q24h
Tigecycline (IV)3 Severe (Child-Pugh Class C) 100 mg x 1, then 50 100 mg x 1, then 50 mg q12h
hepatic impairment: 100 mg mg q12h
x 1, then 25 mg q12h
Trimethoprim/sulfa (IV, PO) Monitor SCr, WBC, platelet 2.5 to 5 mg/kg q6-12h 2.5 to 5 mg/kg 2.5 to 5 mg/kg 2.5 to 5 mg/kg q24h 2.5 to 5 mg/kg q24h
count q6-12h (TMP) q6-12h q12-24h
1
The dosing recommendations presented here are for -70 kg adults with moderate to severe infections based on published literature and clinical experience. These recommendations should only be used as guidelines and dosing based
14
on pharmacokinetic and clinical evaluation is suggested where possible. 2 For antimicrobials dosed every 24 hours in patients on hemodialysis, doses should be administered after dialysis on dialysis days. Alternatively, all doses may be
administered once daily in the evening to ensure administration after dialysis on dialysis days. 3 Dosing adjustment may be necessary in patients with severe liver dysfunction. 4 For patients receiving continuous veno-venous
hemofiltration (CVVH) or continuous veno-venous hemodiafiltration (CVVHDF) at ≥ 1 L/h; ND = no data available.
14
Antibiotic Dosage Guidelines
1/9/12, 3:05 PM
Antibiotic Dosing in Obesity
Obesity can be defined based on the percentage above ideal
body weight (% IBW) or based on the body mass index (see
Table I). Although several equations have been formulated,
the Devine formulas (see Equations 1 and 2) are most
frequently used to calculate IBW.
Table I: Defining Obesity

Classification % IBW Body Mass Index (BMI)
Normal 80 -125% IBW 18.5 -24.9 kg/m2
Obese 126 -190% IBW 30.0 -39.9 kg/m2
Morbidly obese >190% IBW >40 kg/m2
Equation 1: IBW(male) = 50 kg + 2.3 kg x (inches over 5ft tall)

Equation 2: IBW(female) = 45.5 kg + 2.3 kg x (inches over 5ft tall)
Since obesity can impact the distribution and clearance of

drugs, changes to the volume of distribution (Vd) and total
body clearance (CL) are the key pharmacokinetic parameters
that must be considered in calculating the dose of antibiotic
necessary to achieve desired serum concentrations. The Vd is
physiologically determined by the volume of blood, the
volume of body tissues and organs, and the binding of the
drug in the tissues relative to the blood. The Vd in obese
patients, therefore, depends on the drug’s affinity for and
quantity of adipose tissue; a greater affinity for adipose tissue
affords a greater volume for drug accumulation. In addition
to physiologic determinants, the Vd of antibiotics can be
influenced by the drug’s solubility in body water relative to
adipose tissue. Most antibiotics are hydrophilic and will
distribute into body water better than into adipose tissue
(e.g., acyclovir). For these antibiotics, Vd correlates better
with lean body mass, or IBW. However, since lean body mass
tends to increase along with adipose tissue in obesity, the Vd
for some hydrophilic drugs (e.g., aminoglycosides) correlates
better with adjusted body weight (ABW). On the other hand,
lipophilic compounds (e.g., amphotericin B), may have an
1-19 15 1/9/12, 3:05 PM

Antibiotic Dosing in Obesity (cont’d)
expanded Vd in obese patients, and thus correlate better
with total body weight (TBW). Finally, it should be noted that
TBW is also recommended as the basis for dosing certain
obese patient populations with hydrophilic antibiotics when
(a) the safety of this approach has been demonstrated (e.g.,
daptomycin), or when (b) clinically significant differences in
Vd and CL have not been detected in comparative studies
(e.g., dalfopristin-quinupristin).
Calculating the Vd (see Equation 3) can help to determine an

appropriate loading dose for obese patients. For this
calculation, the Vd determined for a drug in a non-obese
population is simply multiplied by a factor that takes into
account the excess body weight and corrects for additional
distribution of the drug into adipose tissue. A generic
correction factor of 0.4 for hydrophilic drugs is an average of
factors (0.37-0.58) validated in pharmacokinetic studies of
aminoglycosides, but different correction factors are
recommended for beta-lactams (0.3) and ciprofloxacin
(0.45). Although the generic correction factor of 0.4 is
inferred from theoretical data on aminoglycosides, it provides
the best current alternative for estimating the parameter for
other hydrophilic antibiotics when clinical studies in obese
patients are lacking.
Equation 3: Vd(obese) = Vd(non-obese) x Adjusted Body Weight

Adjusted Body Weight = IBW + [(*C) x (TBW - IBW)]
*C = correction factor (see explanation in text above and
Table III below)
1-19 16 1/9/12, 3:05 PM

Antibiotic Dosing in Obesity
Literature-Based Antibacterial Dosing Recommendations for Obese Patients
Antibacterial Primary Considerations Adult, non-obese, Recommendation(s)

Agent normal renal function
Vd (L/kg) t1/2 (h)
Aminoglycosides
Amikacin -Aminoglycosides are primarily 0.26 2 -Initial doses should be based on Vd
distributed into extracellular using ABW with correction factor of
Gentamicin fluids (ECF). 0.25 1.5-4 0.4 (ABW=IBW+0.4[TBW-IBW]).
-Higher CL, but greater Vd -Final dosage adjustments should be
Tobramycin cancels out effect; alteration in 0.26 1.6-3 based on serum concentrations.
dosage interval not necessary.
β-Lactams/Penicillins
Ampicillin -Distributed in adipose tissue to 0.27-0.29 1-1.9 -No dose adjustment
some extent, but serum recommended.
concentration not reported.
Cloxacillin -Significant increase in Vd 0.57-1.55 0.5-1 -Increase non-obese dose of 2 g IV
(almost double that of q4h to 3 g IV q6h in obese
non-obese parameter). individuals.
Penicillin G -Drug absorption and serum 0.47 0.3-0.8 -No dose adjustment
levels not altered by obesity. recommended.
Piperacillin- -Not evaluated in obese patients; 0.14-0.23 0.9 -Base dose on diagnosis and CLcr.
Tazobactam* multi-center trials studied
patients with mean TBW of 73.3
kg.
-CL and Vd not affected by
changes in TBW.
Ticarcillin- -No data available. T:0.15 T: 1 -Base dose on CLcr.
Clavulanate* C: 0.29 C: 1-1.5
β-Lactams/Cephalosporins
Cefazolin -In surgical prophylaxis, lower 0.13-0.22 1.5-2.5 -Use 2 g for surgical prophylaxis. -
mean serum and adipose tissue Pories et al. suggest 1 g IV, 2h
concentrations in obese patients. before surgery and at induction of
-Higher prophylactic doses anesthesia, followed by 500 mg IV
needed to achieve serum and q6h x 8 doses.
tissue concentrations similar to
those in non-obese patients.
Cefepime* -Hydrophilic drug. 0.2-0.29 2 -No information on obesity dosing
-No data available. available.
Base dose on Vd using ABW with
correction factor for H20
composition of adipose tissue
(ABW=IBW + 0.3 [TBW-IBW]).
Cefotaxime -Hydrophilic drug, Vd and CL 0.46-0.53 0.8-1.4 -Base dose on Vd using ABW with
increased 50% and 25%, correction factor for H20
respectively in patients ranging composition of adipose tissue
from 190% to 210% of IBW. (ABW=IBW + 0.3 [TBW-IBW]).
Ceftazidime* -No data available. 0.28-9.4 1.6-2 -Base dose on CLcr.
Ceftriaxone* -No data available. 0.08-0.19 5.8-8.7 -No information on obesity dosing
available. Base dose on Vd using
ABW with correction factor for H20
composition of adipose tissue
(ABW=IBW + 0.3 [TBW-IBW]).
Cefuroxime* -No data available. 0.17-0.31 1.1-1.9 -Base dose on CLcr.
In addition to Vd, alterations in total body clearance (CL) should also be considered in determining a
maintenance dose and dosing interval necessary to achieve desired steady-state concentrations in obese
patients. The Cockcroft and Gault equation is most commonly used in clinical practice to estimate drug
clearance, but the accuracy of this method is limited to normal-weight patients. Although obesity generally
is associated with an increase in creatinine clearance (CLcr), the original Cockcroft and Gault equation
tends to overestimate the parameter, prompting several modifications to the original.
1-19 17 1/9/12, 3:05 PM


Vd (L/kg) t1/2 (h)
β-Lactams/Carbapenems
Ertapenem -AUC was significantly decreased 0.11 4 -Use standard dose of 1 g/day.
in obese and morbidly obese
patients; however, no dosing
adjustment was recommended.
Meropenem -Increased CL, Vd, and t1/2. 0.33-0.43 1 -No dose adjustment
-Percentage of time the dose was recommended.
above the MIC during an 8h
dosing interval was not
significantly different.
Imipenem- -No data available. 0.14-0.33 1 -Base dose on CLcr.
Cilastatin*
Fluoroquinolones
Ciprofloxacin -Less distributed to adipose tissue, 1.2-2.7 3-6 -Dose should be based on Vd using
Vd increased by 23%, increased ABW with correction factor of 0.45
CL, and lower C max; however, (ABW = IBW + 0.45[TBW-IBW]).
concentrations still within
recommended therapeutic range.
Levofloxacin* -Drug is lipophilic, and widely 1.25 6-8 -No information on obesity dosing
distributed into body tissues. available. Data suggest obesity
may not alter PK.
-Base dose on CLcr.
Moxifloxacin* 1.7-2.7 14.8 -Use standard dose of 400 mg
IV/PO daily.
Macrolides
Azithromycin* -No data available. 23-31 11-68 -No information on obesity dosing
available.
Erythromycin -Peak concentrations similar in 0.57 1-1.5 -Base dose on IBW.
obese and non-obese adults.
Miscellaneous
Acyclovir -Pharmacokinetics not 0.8 2.2-20 -Base dose on IBW.
significantly different in obese
and non-obese groups.
-Half-life depends on renal
function.
Amphotericin B -Drug is lipophilic. 4 360 -Use traditional dosing of 0.5-1.5
-Zucker rats with mg/kg based on TBW.
hyperlipoproteinemia: ↓Vd, ↓CL,
↑renal toxicity.
Aztreonam* -Drug is lipophilic. 0.1-0.2 1.5-3 -Use dose at upper end of range for
treating serious infections in
morbidly obese adults.
Clindamycin* -No data available. 0.6-1.2 1.5-5 -No information on obesity dosing
available.
Daptomycin -Increased Vd and CL in obese vs. 0.12 7-11 -Base dose on TBW.
non-obese subjects.
-Large molecular mass with high
polarity, low lipid solubility, and
high plasma protein binding.
-Exposure increased by 25-30%
when dose based on TBW, but
still safe and tolerated in subjects
ranging from 56-147 kg.
1-19 18 1/9/12, 3:05 PM


Vd (L/kg) t1/2 (h)
Miscellaneous (cont’d)
Doxycycline* Drug is lipophilic. 0.75 15-24 -No information on obesity
dosing available.
Fluconazole -Hydrophilic agent, eliminated 0.56-0.82 30 -A higher dose is recommended
by kidney. (e.g., 1200 mg/day for candida
fungaemia).
Linezolid -Prolonged inhibitory activity 0.57-0.86 5 -Use standard dose of 600 mg
observed despite ↓ serum IV/PO q12h.
concentrations.
Metronidazole* -No data available. 0.25-0.85 6-14 -No information on obesity
dosing available.
Sulfamethoxazole- -No data available. S: 0.360 S: 8-11 -No information on obesity
Trimethoprim* T: 2 T: 6-17 dosing available.
Tigecycline* -Study subjects weighed 39-200 7-9 42 -Use traditional dose of 100 mg
kg. IV followed by 50 mg IV q12h.
Vancomycin -Increased Vd and CL in obese 0.7 7-9 -Base dose on TBW, giving 20-30
patients correlates better with mg/kg/day.
TBW. -If necessary, shorten
administration interval to
maintain serum trough >5 mg/L.
Voriconazole (oral) -Vd and CL same in obese and -Adjustment of oral Voriconazole
non-obese. in patients with Class II obesity is
not necessary on the basis of TBW.
1-19 19 1/9/12, 3:05 PM

Automatic Therapeutic Interchange
Preparation/regimen ordered Dispensed as
Ampicillin Amoxicillin
•250 mg po q6h •250 mg q8h
•500 mg po q6h •500 mg q8h
•1000 mg po q6h •500 mg q8h
CeFAZolin ___ mg IV q6h CeFAZolin ___ mg IV q8h
CeFAZolin 500 mg po q6h Cephalexin 500 mg po q6h
Cefoxitin CeFAZolin
•1 g IV q6-8h •1 g IV q8h and metronidazole 500 mg IV q8h
•2 g IV q6-8h •2 g IV q8h and metronidazole 500 mg IV q8h
CefUROXime 1 g IV CefUROXime 750 mg IV
Cephalothin ___ mg IV q6h CeFAZolin ___ mg IV q8h
Ciprofloxacin 500 mg inj Ciprofloxacin 400 mg inj
Ciprofloxacin 400 mg tab Ciprofloxacin 500 mg tab
Clindamycin ___ mg IV q6h Clindamycin ___ mg IV q8h [total daily dosage
no more than 1800 mg (Exception: gynecology
patients being treated for PID and necrotizing
fasciitis may receive 900 mg IV q8h)]
Erythromycin IV (all regimens) Azithromycin 500 mg IV daily
Erythromycins, oral
•Ethylsuccinate/lactobionate •Erythromycin base
•Estolate •Erythromycin stearate
•Erythromycin base •Erythromycin base
(enteric/particle-coated tab) (conventional-release; equivalent regimen)
Gatifloxacin 400 mg IV/po days 1 & 2, then Levofloxacin 500 mg IV/po day 1, then 250 mg
q48h thereafter q24h thereafter
Meropenam ___ mg IV q__h Imipenem ___ mg IV q__h
Itraconazole cap Itraconazole sol (equivalent regimen)
Metronidazole ___ mg IV q6-8h Metronidazole ___ mg IV q12 h
(Exception: cefoxitin interchange q8h)
Metronidazole 250 mg IV q12h Metronidazole 500 mg IV q12h
Nitrofurantoin, macrocrystalline formulation Nitrofurantoin, conventional formulation
Macrodantin
Nitrofurantoin, sustained release Nitrofurantoin, conventional-release (equivalent
Macrobid regimen)
Penicillins
•Penicillin G 500 000 IU (300 mg), oral •Penicillin V potassium 300 mg, oral
•Penicillin G inj •Penicillin G sodium inj
•Penicillin G potassium inj •Penicillin G sodium inj
•Penicillin V potassium 250 mg (400,000 IU) •Penicillin V potassium 300 mg (500,000 IU)
•Penicillin V potassium 500 mg •Penicillin V potassium 600 mg
•Penicillin V 300 mg •Penicillin V potassium 300 mg
Vancomycin IV inj q __ h All dosing intervals less than q12h changed to
q12h with total daily dosage remaining the
same (e.g. 500 mg q6h becomes 1 g q12h)
Vancomycin cap Vancomycin inj (to be reconstituted and
administered orally at the prescribed dosage)
See Sequential Antibiotic Therapy (SAT) for information on “pharmacist initiated route of administration”
therapeutic interchange.
20-31 20 1/10/12, 10:16 AM

20-31
Do not administer NG Quinolones in critically ill* patients receiving Enteral Feeds
Summary of Available Data Evaluating the Compatibility of Ciprofloxacin Coadministered with Enteral Nutrition
Study Patient Population Study Design and Treatment Enteral Product Mean Pharmacokinetic Parameters Study Conclusion
(# patients) (contents mg/100 mL) Cmax AUC 0_∞ Bioavailability
(ug/mL) (ug.h/mL) (%)
Wright D, Pietz S, Konstantinides K. et al. Decreased In N/A Cipro 500mg tablet crushed and added to 240 Ensure N/A N/A N/A There is an immediate, and significant loss of FQ
Vitro Fluoroquinolone Concentrations After mL of each of the following; Ca 53.75 mg when mixed with Ensure (average decrease of 82.5±
Admixture With an Enteral Feeding Formulation. Water Mg 20.9 mg 1.5% for ciprofloxacin and 61.3% ± 5.2% for
JPEN 2000;24(1):42-48 Water + calcium Fe 2.25 mg levofloxacin 500 mg tab). An explanation for the loss
Water + magnesium Zn 2.82 mg remains unclear. Adequate spacing of Ensure
Water + calcium + magnesium Co 0.25 mg administration (at least 2 h before and after FQ
Ensure dosing) is recommended.
De Marie S, Vandenbergh M, Buijk S et al. Critically ill intensive Randomized, two sequence crossover study; Nutrison a)6.8 (3.9-9.8) a)19.3 (11.8-26.7) a)N/A Enteral dosing of ciprofloxacin 750 mg bid resulted in
Bioavailability of ciprofloxacin after multiple enteral care patients with (a)cipro 400 mg IV q12h Ca 50 mg b)3.2 (1.8-4.6) b)19.1(1.8-27.5) b)53.1 (43.5-62.8) adequate serum levels in tube-fed ICU patients with
and intravenous doses in ICU patients with severe GNIAI (b)cipro 750 mg tabs dissolved in saline Mg 20 mg severe GNIAI, and can therefore be used in the
21
gram negative intra-abdominal infections. Intensive (n=5) solution, added to enteral feeding and delivered Fe 1 mg treatment of such patients.
Care Med 1998; 24:343-6 via NG or nasoduodenal tube 12 h Zn 1 mg
Mimoz O, Binter V, Jacolot A et al. Stable critically ill Prospective, crossover study; Normo-Real Fibres a)4.1 (1.5-7.4) a)10.3 (3.3-34.6 44 (31-82) In tube-fed critically ill patients, a switch to NG
Pharmacokinetics and absolute bioavailability of patients (n=12) (a)cipro 100 mg IV (1hr infusion) Ca 60 mg b)2.3 (0.7-5.8) b)8.4 (3.6-53.4) ciprofloxacin after initial therapy to simplify the
ciprofloxacin administered through a nasogastric (b)cipro 750 mg tab crushed + water Mg.20 mg treatment of severe infections, is restricted to those
tube with continuous enteral feeding to critically ill Fe 0.8 mg whom serial assessments of ciprofloxacin levels are
patients. Intensive Care Med 1998; 24:1047-51 routinely available.
Healy D, Brodbeck M, Clendening C. Ciprofloxacin Stable hospitalized Randomized crossover study Jevity Sustacal oral 1.43±0.61 oral 9.44±4.74 27 - 67 Decreased absorption of ciprofloxacin may be of
21
Absorption is Impaired in Patients Given Enteral patients (n=26) 1.Oral Treatment Group Ca 137 mg Ca 104 mg g-tube2.27±0.67 g-tube 7.44±3.16 clinical importance when the enteral feeding is
Feedings Orally and via Gastrostomy and (a)cipro 500 mg Mg 46 mg Mg 41.6 mg j-tube1.45±0.48 j-tube 5.82±2.63 coadministered with cipro by the oral or jtube
Jejunostomy Tubes. Antimicrob Agents Chemother (b)cipro 500 mg + Sustacal 240 mL Fe 2.1 mg Fe 0.2 mg routes. Reductions in max levels of cipro in serum, as
1996;40(1):6-10 2. G tube or J tube Treatment Group Zn 2.6 mg Zn 0.02 mg a result of feedings given via g tube, are similar to
(c)cipro 500 mg crushed in 60 mL water via Co 2.3 mg Co 0.38 mg those following oral administration on an empty
feeding tube stomach, making a clinically important interaction by
(d)cipro 500 mg + Jevity this route less likely.
Cohn S, Sawyer M, Burns G et al. Enteric absorption Mechanically ventilated Subjects received ciprofloxacin 75 mg q12h via Pulmocare Dose 1: Dose 1: N/A GI absorption of ciprofloxacin in tube fed critically ill
of Ciprofloxacin during tube feeding in the critically patients with NG tube and serial drug concentrations were Ca 104 mg 2.29 (1.24-3.06) 9.90 (3.20-19.65) patients was decreased, but well above MIC values
ill. J Antimicrob Chemo 1996;38:871-876 pneumonia measured after the 1st and 4th dose. Mg 62 mg Dose 4: Dose 4: for many pathogenic bacteria.
(n=7) Fe 2 mg 2.23 (1.20-3.76) 10.63 (4.32-19.26)
Healthy volunteers Zn 2.4 mg
(n=13) Co 2.2 mg
Mueller B, Brierton D, Abel S et al. Effect of Enteral Healthy male Randomized crossover design with 4 treatments; Ensure c)3.79±0.72 c)15.96±3.12 c)N/A Switching from parenteral antibiotics to oral
Feeding with Ensure on Oral Bioavailabilities of (a)ofloxacin + 120 mL water Ca 53.75 mg d)1.99±0.57 d)11.66±3.70 d)72±14 ciprofloxacin in a patient receiving Ensure could
Ofloxacin and Ciprofloxacin. Antimicrob Agents (b)ofloxacin 400 mg+ 120 mL Ensure Mg 20.9 mg result in undesirably low concentrations in serum.
Chemother. 1994;38(9):2101-5 (c)cipro 750 mg + 120 mL water Fe 2.25 mg
(d)cipro 750 mg + 120 mL Ensure Zn 2.82 mg
Co 0.25 mg
Yuk J, Nightingale C, Sweeney K et al. Relative Randomized, three way crossover study; Osmolite Ciprofloxacin is well absorbed after administration via
1/10/12, 10:16 AM
a)2.80±0.94 a)13.17±4.81
Bioavailabilty in Healthy Volunteers of Ciprofloxacin (a)cipro 750 mg tab po Ca 53 mg b)2.12±0.37 b)11.46±4.51 NG tube (compared with an orally administered
Administered through a Nasogastric Tube with and (b)crushed 750 mg cipro tab suspended in 50 mL Mg 22 mg intact tablet) even in the presence of enteral feeding.
without Enteral Feeding. Antimicrob Agents of water administered through an NG tube Fe 0.9 mg Thus, enteral feeding does not have to be interrupted
Quinolone and Enteral Nutrition Policy
(c)crushed 750 mg cipro tab suspension Zn 1.2 mg when adminstering ciprofloxacin.

administered through an NG tube + Osmolite Co 0.11 mg
* Concomitant use in all other patients at clinical discretion. If used, space quinolone and feeds by 2-4 hours. Prepared by: Tasha Muise, Kathryn Slayter, Theresa Hurley, Hoan Linh Banh August, 2001
Aminoglycoside Antibiotics – Dosing
and Monitoring Guidelines
In spite of recent advances made with the introduction of extended spectrum beta-lactam
antibiotics, the aminoglycosides remain a major class of antibiotics for the treatment of
serious Gram negative infections.
1. SPECIFIC AMINOGLYCOSIDES
• Gentamicin
• Tobramycin
• Amikacin
2. ADVERSE EFFECTS
Associated toxicities are primarily those of ototoxicity (evidenced by sometimes
irreversible hearing loss in the high and low frequency range, nausea, tinnitus and vertigo)
and nephrotoxicity (generally reversible acute tubular necrosis signalled by elevations in
serum creatinine). Several factors contribute to the risk of aminoglycoside toxicity.
• Length of therapy > 10 days
• Renal insufficiency
• Elevated aminoglycoside trough serum concentrations
• Concomitant nephrotoxic and ototoxic drugs
• Recent prior exposure to nephrotoxic medications
(e.g. aminoglycosides, amphotericin B, cyclosporine, etc.)
• Pre-existing cochlear/vestibular dysfunction
• Sodium/volume depletion
• Old age
• Renal transplants
3. MONITORING
Certain baseline monitoring parameters should be obtained and followed at the
recommended time intervals whenever possible.
Baseline Parameter Follow-up
Weight, height Weekly as appropriate
Blood urea nitrogen Twice weekly
Serum creatinine Twice weekly
(Unstable renal function) (Daily)
Intake and output As required
Clinical and laboratory
parameters of infection As appropriate
(WBC, temperature)
20-31 22 1/10/12, 10:16 AM

and Monitoring Guidelines (cont’d)
In addition, audiograms are recommended for patients at risk.
• Patients with pre-existing hearing disorders.
• Concurrent ototoxic drugs (e.g. cisplatin).
• Prior exposure to a therapeutic course of an aminoglycoside (within 3 months).
• Aminoglycoside therapy anticipated to exceed 14 days.
Monitoring of serum aminoglycoside concentrations is discussed within the dosing guide-
lines.
4. ONCE-DAILY DOSING GUIDELINES

RECOMMENDATION
Upon the advice of the Antimicrobial Agents Sub- Committee and the District Drugs and
Therapeutics Committee, patients receiving aminoglycoside therapy may be prescribed a
once-daily dosing schedule. Please see Table 1 for appropriate dosing interval for patients
with a CLcr between 20 and 59 mL/min.
a) PATIENT EXCLUSION:
• Dialysis • Ascites
• Renal failure (CLcr < 20 mL/min) • Burns (> 20%)
• Single prophylactic dose before an • Low level synergy in which peaks of
operative or diagnostic procedure 3-5 mg/L are required and more
frequent dosing preferred
(i.e. enterococcus, staph, endocarditis)
b) DOSAGE
• Determine dosing weight:
For non-obese patients their actual body weight (ABW) is the dosing weight
For obese patients (i.e. 20% above ideal body weight (IBW)), calculate dosing weight as
follows: Obese dosing weight = IBW + 0.4 (ABW - IBW)
• The recommended dose of gentamicin or tobramycin is 6 mg/kg and 15 mg/kg for
amikacin in 100 mL of a compatible intravenous solution infused over 1 hour.
c) DOSING INTERVAL
Determine the patient’s creatinine clearance (CLcr) and choose the corresponding dosing
interval from Table 1.
Table 1. Dosing Interval
Creatinine Clearance (mL/min) Dosing Interval

> 60 q24h
40-59 q36h
20-39 q48h
< 20 Avoid once daily dosing
20-31 23 1/10/12, 10:16 AM

d) SERUM DRUG MONITORING
Standard peak and trough concentrations are not necessary. However, some patients
should receive a level (6 hours before the end of the dosing interval) to be obtained on the
1st dose and every 4 days thereafter; to assess for adequate clearance. The level for
gentamicin/tobramycin should be <1 mg/L and amikacin <2.5 mg/L. Levels should be
routinely monitored in the following:
• patients with CLcr between 40-59 mL/min (i.e. q36h)
• patients with CLcr between 20-39 mL/min (i.e. q48h)
• patients in the ICU
• aminoglycoside therapy > 5 days
• CLcr decrease from baseline > 25%
• infections involving highly resistant organisms
• patients on concurrent nephrotoxins
• patients > 65 years of age
Levels need not be obtained for patients with all of the following criteria:
• < 65 years old
• CLcr > 60 mL/min
• not receiving concurrent nephrotoxins
• not receiving renal contrast media
CYSTIC FIBROSIS PATIENTS

Tobramycin Dosing
Dose according to estimated CrCl
CrCl >50 mL/min = 10 mg/kg/24 h
CrCl 30-49 mL/min = 10 mg/kg/36 h
CrCl 20-29 mL/min = 10 mg/kg/48 h
CrCl <20 mL/min, ARF = 3 mg/kg x 1 CONSULT PHARMACY
Labs
At the time of writing for Once Daily Dosing, please order:
Pre level (6 hours before next dose)
Dosage Increases
If pre level (drawn 6 hours before the next dose) is undetectable, consider increasing the
tobramycin dosage to 12.5 mg/kg/day.
Repeat 6 hours pre level on new dosage.
Maximum Tobramycin Dosage

Maximum dosage is 15 mg/kg/day
When using this dosage >10 mg/kg/day, order peak levels 90 minutes after the end of the
infusion, in adition to pre levels.
Peak levels must not exceed 50 mg/L (or 50 ug/mL)
20-31 24 1/10/12, 10:16 AM

Use of Other Aminoglycosides
There are insufficient data in CF patients for guiding once daily dosing of other
aminoglycosides. If other aminoglycoside use is needed, use conventional dosing
guidelines (i.e. every 8 to 12 hours with normal renal function). Because of the rapid
clearance of aminoglycosides in CF patients, expert assistance from the pharmacokinetics
service is suggested if administration of other aminoglycosides is needed.
5. TRADITIONAL DOSING GUIDELINES

For patients falling within the exclusion criteria for once-daily dosing traditional dosing
guidelines can be used.
a) DOSING
• Determine dosing weight as in once-daily dosing guidelines. For patients with edema
or ascites the patients actual body weight should be used to account for drug
distribution into the large extravascular fluid compartments.
• The recommended loading dose for gentamicin or tobramycin is 1.5 - 2.0 mg/kg
followed by 1.5 mg/kg every eight hours for patients with normal renal function.
• The recommended dose for amikacin is 7.5 mg/kg given every 12 hours for patients
with normal renal function.
b) DOSING IN RENAL INSUFFICIENCY
The initial (loading) dose is the same as for adults with normal renal function. However,
the maintenance dosage regimen is adjusted based upon the degree of renal insufficiency.
See Table 2 for appropriate interval and percentage of loading dose to be used as
maintenance dose.
20-31 25 1/10/12, 10:16 AM

c) SERUM DRUG MONITORING
The purpose of measuring the serum drug concentration at steady state is to confirm that
therapeutic concentrations have been achieved and drug accumulation has not taken
place. When treatment is anticipated to be >72 hours, pre (trough) and post (peak) pairs
should be obtained after steady state conditions are achieved (with 4th or 5th dose).
Table 2. Maintenance Dose Nomogram for Aminoglycoside Antibiotics (Adults)
Determine the recommended Dosing Interval using the Estimated Creatinine

Clearance (CLcr)
Calculate Maintenance Dose as a percentage of the Loading Dose
___________________________________________________________________________
CLcr Estimated Half-life Dosing Interval
mL/min mL/sec (h) 8h 12 h 24 h
___________________________________________________________________________
90 1.5 3.1 84% - -
80 1.33 3.4 80 91% -
70 1.17 3.9 76 88 -
60 1.0 4.5 71 84 -
50 0.83 5.3 65 79 -
___________________________________________________________________________
40 0.67 6.5 - 72% 92%
30 0.50 8.4 - 63 86
25 0.42 9.9 - 57 81
20 0.33 11.9 - 50 75
17 0.28 13.6 - 46 70
15 0.25 15.1 - 42 67
___________________________________________________________________________
12 0.20 17.9 - - 61%
___________________________________________________________________________
Modified from Sarubbi FA Jr, Hull JH. Ann Int Med 1978;89: 612-18.
Table 3. Target Serum Aminoglycoside Concentrations

Gentamicin Amikacin
Tobramycin
Desired Post* (peak) mg/L mg/L
Urinary tract infections 4-6 16-20

Serious infections 6-8 20-25
Synergy for gram positive infections only 3-5 -
(e.g. enterococcus)
Desired Pre (trough) <2 <8

* Target post serum concentrations may need to be in excess of 8 mg/L (> 25 mg/L for amikacin) for
patients with severe gram-negative infections (e.g. sepsis, pneumonia, endocarditis).
20-31 26 1/10/12, 10:16 AM

Serum Sampling Technique
• Pre (trough) - Immediately before a dose (within 30 minutes)
• Post (peak) - 30 minutes after a 1/2-1 hour infusion, or
- 1 hour following an IM injection
• Specimen should be taken from opposite limb to the site of drug infusion.
• The timing of drug administration and sample collection must be carefully
documented.
Additional serum drug sampling should be carried out twice weekly for most patients. For
patients with stable renal and hydration status showing good clinical response and lack of
toxicity once weekly serum drug sampling is sufficient.
Patient Information Sheet - Aminoglycoside Treatment

You have been prescribed an antibiotic which is called an aminoglycoside.
Aminoglycoside antibiotics include drugs such as gentamicin, tobramycin and amikacin.
Aminoglycosides have been available for the treatment of bacterial infections for over 30
years and are highly effective agents. Your doctor has prescribed an aminoglycoside for you
because they consider it to be the best option to treat the infection you have, at this time.
Unfortunately, like most medications, there are potential side effects that may occur when
aminoglycosides are used. Aminoglycosides may cause reversible kidney damage in 5-10%
of patients receiving more than 5 days of treatment with the aminoglycoside, and may
cause irreversible hearing loss or imbalance and dizziness in less than 1% of patients
receiving more than 10-14 days of therapy.
• To minimize the risk of kidney damage, your care-givers are monitoring your kidney
function weekly, with the use of blood tests.
• To minimize the risk of hearing loss, you should report any symptoms of ringing in the
ears, feeling of fullness in the ears, earache, or hearing loss to your care-givers
immediately, so that your aminoglycoside therapy can be re-evaluated.
• To minimize the risk of problems with your balance, you should report any symptoms
of dizziness, unsteady walking, and loss of balance to your care-givers immediately, so
that your aminoglycoside therapy can be re-evaluated.
• If it is necessary to treat your infection for more than 14 days, you will undergo a
hearing function test. The first test will be done right away and then about 2 weeks after
aminoglycoside therapy begins. Additional testing will also be done at any time that
you report symptoms of hearing or balance problems.
If you have any additional questions about your aminoglycoside therapy, please speak
with your doctors or the ward pharmacist. Your nurse can arrange for either your
pharmacist or physician to come and speak with you about your aminoglycoside therapy.
20-31 27 1/10/12, 10:16 AM

Amphotericin B Deoxycholate Guidelines
for Intravenous Administration
Amphotericin B (AMB) is indicated for the treatment of systemic fungal infections and for
empiric therapy in febrile neutropenic patients.
ADMINISTRATION
• Reconstitute 50 mg vial with 10 mL of sterile water for injection without preservative.
The reconstituted vial is stable for 24 hours at room temperature or if refrigerated.
• Further dilute reconstituted vial in D5W to a maximum concentration of 0.1 mg/mL.
If amphotericin B is to be administered via a central line, a concentration of up to 0.25
mg/mL may be administered. (Not compatible with NaCl solutions).
• Infuse over 4-6 hours, however the drug may be given over 2 hours if cardiac and renal
status permit.
DOSAGE
• There is no need to administer a test dose as there is no evidence to suggest that a test
dose is predictive of a systemic reaction to AMB and may result in a delay of therapy,
especially in life threatening situations.
• Begin therapy with 0.25 mg/kg - 0.5 mg/kg depending on the infection and acuity of
the problem.
• Monitor pulse, temperature and blood pressure every 15 minutes during the first
infusion for one hour.
• On the next day the dose may be increased to 1.0 mg/kg depending on tolerance and
the type of infection being treated.
• A dose of 1.0 mg/kg/day should not be exceeded without consulting Infectious Disease.
• It is recommended never to exceed a maximum daily dose of 1.5 mg/kg.
SIDE EFFECTS MANAGEMENT/PREVENTION MEASURES

For prevention of adverse 25-50 mg hydrocortisone IV, 650 mg oral
systemic effects acetaminophen and 25-50 mg oral diphen-
(i.e. fever, chills, myalgias, hydramine may be administered 30 minutes
nausea, vomiting) prior to am photericin B. (There is no need to
premedicate patients not manifesting these
adverse reactions).
Severe chills, rigors 50 mg meperidine IV in 10 mL NS over 5 minutes.
(refractory to hydrocortisone)
Phlebitis Rotate the infusion sites and/or double the
daily dose on alternate days and/or administer
over 4-6 hours. Administer via central line.
Hypokalemia Serum potassium daily. Potassium supplements
as required, consider amiloride.
Hypomagnesemia Serum magnesium 2 times weekly. Magnesium
supplements as required.
Renal toxicity Serum creatinine three times weekly. Maintain
adequate hydration. If deemed appropriate,
500 mL NS may be infused before each dose of
amphotericin B.
20-31 28 1/10/12, 10:16 AM

for Intravenous Administration (cont’d)
Management of Adult Patients on Amphotericin B
Fungal infection suspected/documented - Amphotericin B indicated?
➝
Yes
Amphotericin B (See over for Administration and Monitoring)
Indication Dose
Empiric Therapy for
Febrile Neutropenia 0.6 mg/kg IV dose
Invasive Candidiasis 0.5-1 mg/kg IV daily x minimum of 14 days after last (+) blood culture
Invasive Aspergillosis 1-1.5 mg/kg IV daily
C. lusitaniae and C. guilliermondi usually resistant to Amphotericin B
➝ ➝ ➝ ➝ ➝
Assess fluid status
➝ ➝
Overloaded Normal Depleted
Assess Na status
High (>146 mmol/L)

➝ Normal (133-146 mmol/L) ➝ Low (<133 mmol/L)
➝
Investigate cause Consider 0.45% NaCl Recommend 0.9% NaCl EXCEPTIONS

of hypernatremia 1L IV before ± after 500 mL IV before ± after ➝ Patients who cannot
each Amphotericin B each Amphotericin B ➝tolerate additional Na
dose dose to prevent Na and and/or fluid, e.g. fluid
intravascular volume overloaded, CHF,
➝
depletion and pulmonary edema,

nephrotoxicity renal failure
➝
➝ ➝
➝ ➝
Assess K and Mg status

➝
High Normal Low

(K > 5.0 mmol/L) (K 3.5-5.0 mmol/L) (K <3.5 mmol/L)
(Mg >1.00 mmol/L) (Mg 0.70-1.00 mmol/L) (Mg <0.70 mmol/L)
➝
No High-Risk for Hypokalemia/Hypomagnesemia or consequences of same?:

Consider
Amiloride
➝ •• Atrial
Acute leukemia
fibrillation
• CHF
• T1DM
5-10 mg PO bid1 • Moderate-severe hepatic insufficiency
➝➝
Receiving loop/thiazide diuretics, long-term steroids, laxatives

Yes
➝
CAUTION IN:
elderly, diabetics, patients with renal or Recommend
adrenal insufficiency, hyperkalemia, ➝ ➝ Amiloride
hypermagnesemia, concomitant 5-10 mg PO bid1
administration with ACE inhibitors,
NSAIDs 1. Monitor K+ closely. May still need to
give additional K+ supplementation.
20-31 29 1/10/12, 10:16 AM

for Intravenous Administration (cont’d)
Administration of Amphotericin B
Infusion
Peripheral line - infuse dose over 4-6 hours
- maximum concentration 0.1 mg/mL
Central line - infuse dose over 2-4 hours
- maximum concentration 0.25 mg/mL*
* (concentrations up to 1.4 mg/mL are soluble in D5W and may be considered
in fluid restricted patients)
Premedication
Routine premedication NOT recommended.
May be given if infusion-related reaction occurs and then as pre-treatment with subsequent doses.
Fever /chills/rigors Meperidine 25-50 mg IV
Fever Acetaminophen 650 mg PO (max 4 g/day)
Nausea/vomiting Diphenhydramine 25-50 mg PO/IV, Metoclopramide 10 mg IV
Give premedication 30 minutes prior to Amphotericin B
AVOID OTHER NEPHROTOXIN (e.g. NSAIDS, aminoglycosides, vancomycin, etc.)
Routine Monitoring of Amphotericin B Therapy1

Renal deterioration? 1. Ensure sodium supplemented appropriately
Yes
e.g. doubling of serum creatinine
from baseline while receiving
➝ 2.AND
Suggest twice the dose (1-1.5 mg/kg,
Amphotericin B therapy max 1.5 mg/kg) every other day (q48h)
➝
➝
No
Continue current therapy No
Further/continued renal deterioration?
and monitoring1 ➝ e.g. tripling of serum creatinine from baseline
OR serum creatinine ≥ 250 mmol/L
➝
Yes
1
Routine Monitoring Options:
• Cardiovascular status (HR, BP) 1. Lipid-complex Amphotericin B (ABLC)
• Respiratory status (RR <20/min dependent (Must be prescribed by Infectious Diseases or
upon baseline and underlying illness) Hematology) OR
• Body weight (assess fluid status) 2. Continuous infusion2 of Amphotericin B
• Fluid intake and output (Ins/Outs) (same daily dose infused over 24 hours) OR
• CBC with differential 3. Micafungin (Must be prescribed by
• Serum K/Na/Ca/Mg Infectious Diseases or Hematology)
• Renal Function (i.e. Scr/BUN)
• Liver function tests
2
Continuous Infusion - NOT Routinely Recommended.
20-31 30 1/10/12, 10:16 AM

Amphotericin B Lipid Complex (ABLC)
Guidelines for Intravenous Administration
Lipid complex formulations of amphotericin B allow for higher doses to be administered
and have lower incidence of adverse events relative to the conventional formulation.
However, because lipid complex formulations of amphotericin B are significantly more
expensive than the deoxycholate formulation ($500/day vs <$50/day for a 75 kg patient),
it is necessary to reserve the drug for patients who meet the following criteria:
Evidence of serious systemic fungal infection

Culture/histology evidence for serious systemic fungal infections and/or evidence of
invasive disease in patients at risk for disseminated fungal infections (i.e. BMT patients)
with clinical signs of infection despite antimicrobial therapy.
AND/OR
Evidence of deteriorating renal function

Serum creatinine has doubled since baseline at initiation of therapy or creatinine clearance
is less than 60 mL/minute (hematological malagnancies, BMT patients).
Which is sustained for 48 hours or more despite the use of saline boluses and careful
attention to K and Mg levels and review of other nephrotoxic medications for possible
discontinuation.
AND/OR
The patient is not a candidate for high dose fluconazole or itraconazole because of lack of
efficacy or adverse events or in the case of IV itraconazole lack of availability as well.
NOTE:
Previous exposure of lipid complex amphotericin B does not automatically infer that a
patient will receive the lipid product during a subsequent treatment for fungal infections.
(ie hematology patients).
Procedure for Obtaining Amphotericin B Lipid Complex

• Initial order by ID or hematology physician in consultation.
• Patient must meet criteria for use.
• Each (ABLC) therapy regimen should be reviewed at least twice weekly by an ID or
hematology physician. If renal function appears to be normalizing, the use of
traditional amphotericin B should be strongly considered.
20-31 31 1/10/12, 10:16 AM

Recommendations for the Treatment of
Staphylococcus aureus Bacteremia
Category Criteria Therapy
Simple bacteremia All of the following: 7 d IV antibiotics
1. TEE on d 5-7 of therapy that was negative
for both vegetations and predisposing
valvular abnormalities
2. Negative surveillance blood culture
obtained 2-4 d after starting appropriate
antibiotic therapy and removal of focus
3. Removable focus of infection
4. Clinical resolution (afebrile and no
localizing complaints attributable to
metastatic infection within 72 h of starting
therapy and removal of focus)
5. No indwelling prosthetic devices
Uncomplicated One or more of the following: 14 d IV antibiotics

bacteremia 1. Predisposing valvular abnormalities
(more than mild regurgitation) but no
vegetations shown by TEE
2. Positive surveillance blood culture
3. Superficial, non-removable focus of
infection
4. Persistent signs of infection after 72 h
of antibiotic therapy
Endocarditis According to Duke criteria 4-8 wk IV antibiotics
Extracardiac All of the following: 4-8 wk IV antibiotics

1. TEE negative for vegetations
2. Deep-tissue infection
32-75 32 1/9/12, 3:03 PM

PRE-PRINTED ORDER
Management of Peritonitis
(Nephrology)
Patient: Allergies:
1. Investigations
Within 48–72h of initiating antibiotic therapy, assess clinical improvement. Consult with physician/nurse
practitioner if there is no improvement
Repeat peritoneal dialysis (PD) effluent culture as well as profile with differential q48h for the first week and
until negative culture result obtained
Once negative result obtained, continue sending PD effluent weekly until antibiotic treatment has been
completed
2. Medications:
x Stop empiric antibiotic therapy and choice of subsequent antibiotic therapy based on culture and sensitivity and patient
allergy status. See below for antibiotic options. Intraperitoneal (IP) (6h long dwell) preferred. Intravenous (IV)
administration only for patients where IP antibiotics cannot be utilized
i) Gram-positive organisms on culture (Staphylococcus Aureus, Coagulase-Negative Staphylococcus, Streptococcus
spp.)
CeFAZolin 20 mg/kg IP or IV daily: (Circle Route of Administration)
Weight less than 60 kg = 1 g
Weight 60–80 kg = 1.5 g
Weight greater than 80 kg = 2 g
OR
Vancomycin (cephalosporin allergy and/or bacterial resistance to first-generation cephalosporin)
30 mg/kg IP x _______ kg (most recent total body weight) = _______mg IP EVERY 5 DAYS –
approximately 3–5 doses
20 mg/kg IV x _______ kg (most recent total body weight) = _______mg IV EVERY 5 DAYS –
approximately 3–5 doses
Duration of therapy
Staphylococcus aureus = at least 21 days
Other gram-positive organisms =14 days
Peritonitis with exit site or tunnel infection =14–21 days
Prescriber’s Signature: Date (yyyy/mm/dd):

Prescriber’s Name Reg. No.
Print
PPO0394MR_11_09 Sept 8 2011 Original – chart page 1 of 4
32-75 33 1/9/12, 3:03 PM

PRE-PRINTED ORDER
(Nephrology)
Patient: Allergies:
2. Medications continued…
ii) Enterococcus spp. on culture (Duration of therapy 21 days)
Ampicillin (if sensitive)
Ampicillin 1 g IP daily
Ampicillin 1 g IV daily
OR
Vancomycin (penicillin allergy and/or ampicillin resistance)
30 mg/kg IP x _________ kg (most total body weight) = ________mg IP EVERY 5 DAYS – approximately
3–5 doses
20 mg/kg IV x _________kg (most total body weight) = ________mg IV EVERY 5 DAYS – approximately
3–5 doses
PLUS
Gentamicin
Gentamicin 0.6 mg/kg IP X ____kg (IBW)=_____mg IP daily (round to the nearest 20 mg)
Gentamicin 0.6 mg/kg IV X ____kg (IBW)=_____mg IV daily (round to the nearest 20 mg)
x See Section 3 for gentamicin monitoring
iii) Culture Negative Peritonitis
Continue initial empiric antibiotic therapy for 14 days (from PPO0395MR)
Repeat PD effluent culture and profile with differential
x If culture positive, adjust therapy/duration based on organism identified (see appropriate section i-vii of
this PPO for antibiotic options)
x If culture still negative and no clinical improvement, consult physician to consider catheter removal and
continue initial empiric antibiotic therapy for at least 14 days after catheter removal.
iv) Pseudomonas spp. on culture
Select two anti-pseudomonal antibiotics (if feasible) with differing mechanisms that organism is sensitive to and patient is
not allergic to: (Duration at least 21 days)
Ciprofloxacin 500 mg po bid
If vomiting, ciprofloxacin 400 mg IP daily. Change to po once vomiting resolves
If vomiting, ciprofloxacin 400 mg IV daily. Change to po once vomiting resolves
CeftAZIDime 1 g IP daily
CeftAZIDime 500 mg IV daily
Piperacillin/tazobactam 3.375 g IV q12h
Imipenem/cilastatin 500 mg IV daily (Restricted– See Capital Health Formulary)
Gentamicin 0.6 mg/kg IP x _____kg (IBW)= ______mg IP daily (round to nearest 20 mg)
Gentamicin 0.6 mg/kg IV x _____kg (IBW)= ______mg IV daily (round to nearest 20 mg)
Other Antibiotic Order:

Print
32-75 34 1/9/12, 3:03 PM

PRE-PRINTED ORDER
(Nephrology)
Patient: Allergies:
2. Medications continued…
v) Single Gram-Negative Organisms on culture
E.coli, Proteus, Klebsiella spp. on culture
x Choose two antibiotics (if feasible) based on sensitivity for 14–21 days
CeFAZolin 20 mg/kg IP or IV daily: (Circle route of administration)
Weight less than 60 kg = 1 g
Weight 60–80 kg = 1.5 g
Weight greater than 80 kg = 2 g
CeftAZIDime 1g IP daily
If vomiting, Ciprofloxacin 400 mg IP daily. Change to po once vomiting resolves
If vomiting, Ciprofloxacin 400 mg IV daily. Change to po once vomiting resolves
Stenotrophomonas spp. on culture
x Choose two antibiotics (if feasible) with differing mechanisms based on sensitivity for 21–28 days
Trimethoprim/sulfamethoxazole DS (160 mg/800 mg) 1 tablet po daily
CeftAZIDime 1 g IP daily
Ticarcillin/clavulanate 3.1 g IV q12h (Restricted- See Capital Health Formulary)
Other antibiotic order:
Enterobacter, Citrobacter, Serratia, Morganella and Providentia spp. on culture
x Choose two antibiotics (if feasible) with differing mechanisms based on sensitivity
If vomiting, ciprofloxacin 400 mg IP daily. Change to oral once vomiting resolves for 14 to 21 days
If vomiting, ciprofloxacin 400 mg IV daily. Change to oral once vomiting resolves
Trimethoprim/sulfamethoxazole DS (160 mg/800 mg) 1 tablet po daily
Imipenem/cilastatin 500 mg IV daily (Restricted- See Capital Health Formulary)
Gentamicin 0.6 mg/kg IP x_____ kg (IBW) = ____ mg IP daily (round to nearest 20 mg)
Gentamicin 0.6 mg/kg IV x _____kg (IBW) = ____mg IV daily (round to nearest 20 mg)

Print
32-75 35 1/9/12, 3:03 PM

PRE-PRINTED ORDER
(Nephrology)
Patient: Allergies:
vi) Polymicrobial Peritonitis on Culture

Multiple gram-negative organisms or mixed gram–negative/gram–positive (high index of suspicious for intestinal
origin) (Duration of therapy 14 to 21 days.)
Choose one
Metronidazole 500 mg po q12h
If vomiting, metronidazole 500 mg IV q12h
Plus: Choose one
Ampicillin (if sensitive) 1 g IP daily
Ampicillin (if sensitive) 1 g IV daily
Vancomycin (penicillin allergy and/or ampicillin resistance)
30 mg/kg IP x _______ kg (most recent body weight) = _______mg IP q5days – approximately 3–5 doses
20 mg/kg IV x _______kg (most recent body weight) = ______mg IV q5days – approximately 3–5 doses
Plus: Choose one
CeftAZIDime (if sensitive) 1 g IP daily
CeftAZIDime (if sensitive) 500 mg IV daily
If vomiting, Ciprofloxacin 400 mg IP daily. Change to oral once vomiting resolves
If vomiting, Ciprofloxacin 400 mg IV daily. Change to oral once vomiting resolves
Gentamicin 0.6 mg/kg IP x ______ kg (IBW) = ______ mg IP daily (round to nearest 20 mg)
Gentamicin 0.6 mg/kg IV x ______ kg (IBW) = ______ mg IV daily (round to nearest 20 mg)
Other Antibiotic Order: _____________________________________________________
vii)Fungal Peritonitis
Fluconazole (if sensitive) 200 mg po daily for 10 days
If vomiting, fluconazole 200 mg IV daily for 10 days
Remove catheter once fungi confirmed by culture
3. Monitoring
Pre (trough) gentamicin level before the fourth dose. Additional serum gentamicin sampling should be carried
out twice weekly. Audiograms are recommended at baseline (right away) and again if aminoglycoside therapy
anticipated to exceed 14 days

Print
32-75 36 1/9/12, 3:03 PM

PRE-PRINTED ORDER
Empiric Management of Peritonitis

(Nephrology)
Patient: Allergies:
1) INVESTIGATIONS:
Send cloudy effluent ASAP for gram stain, culture and profile with differential
Repeat above q48h for the first week and until negative culture result obtained
Once negative result obtained, continue sending PD effluent weekly until antibiotic treatment has been completed
2) MEDICATIONS:
a) Initiate Empiric Antibiotic Therapy: Intraperitoneal (IP) (6h long dwell) preferred
IV administration only in patients whom IP antibiotics cannot be utilized
CeFAZolin 20 mg/kg IP or IV daily: (Circle Route of Administration)
Wt less than 60 kg = 1 g
Wt 60–80 kg = 1.5 g
Wt greater than 80 kg = 2 g
OR for patient allergic to cephalosporin:
Vancomycin:
30 mg/kg IP x ______ kg (most recent total body weight) = ______ mg IP EVERY 5 DAYS
20 mg/kg IV x ______ kg (most recent total body weight) = ______ mg IV EVERY 5 DAYS
PLUS All patients should receive one of the following:
If vomiting, ciprofloxacin 400 mg IP daily. Change to po once vomiting resolves
If vomiting, ciprofloxacin 400 mg IV daily. Change to po once vomiting resolves
If patient allergic to ciprofloxacin, ceftAZIDime 1 g IP daily
If patient allergic to ciprofloxacin, ceftAZIDime 500 mg IV daily
b) Non-Antibiotic Medication:
Hold oral iron, phosphate binders such as calcium carbonate (Tums®) until peritonitis has resolved.
Heparin 500 units/L of Dianeal® fluid IP for fibrin in effluent until clear
Ultrafiltration problems: use 2.5% Dianeal® exchanges (with short dwell times of 2-3 hours) as opposed to longer
®
dwells with 4.25% Dianeal
c) Subsequent Antibiotic Therapy: Based on 48–72h culture results (See Management of Peritonitis Pre-Printed Order
PPO0394MR)

Print
32-75 37 1/9/12, 3:03 PM

Treatment of Candidemia
Suspected or confirmed candidemia
No Is the patient neutropenic?
Drug Therapy
➝
1st choice: Amphotericin B 0.6-1.0 mg/kg/day IV
OR
Fluconazole 400-800 mg/day IV or PO if tolerated*
OR Yes
Micafungin 100 mg IV daily
Alternate: Amphotericin B 0.7 mg/kg/day IV plus
Fluconazole 800 mg/day IV or PO for 4-7 days,
then Fluconazole 800 mg/day IV or PO*
❖ Continue therapy for 14 days after the last positive blood
culture and/or resolution of signs and symptoms
➝
➝
❖ Removal of intravascular catheters if possible

❖ Give at least 1 ophthalmologic Drug Therapy
exam to exclude candidal 1st choice: Amphotericin B 0.7-1.0 mg/kg/day IV
endophthalmitis at a time when OR
the candidemia is controlled
❖ If the patient was neutropenic
➝ Lipid formulation Amphotericin B 3.0-6.0 mg/kg/day IV
OR
wait until they have recovered for Micafungin 100 mg IV daily
eye examination Alternate: Fluconazole 6-12 mg/kg/day IV or PO if tolerated*
➝ ➝
❖ Continue therapy for 14 days after the last positive blood culture and/or
resolution of signs and symptoms and resolution of the neutropenia
❖ Failure to respond to therapy ❖ May be necessary to accelerate recovery from neutropenia with GCSF
❖ Consider susceptibility testing if Lipid formulations of Amphotericin B are not

there is a failure to respond to interchangeable and are used when there is a
therapy as azole resistant C. contraindication to conventional Amphotericin B:
albicans, C. glabrata and C. 1. Amphotericin B lipid complex (ABLC); Abelcet
krusei are becoming more 2. Liposomal Amphotericin B; Ambisome
common
If endocarditis is suspected and/or confirmed:

Drug Therapy
1st choice: Amphotericin B 0.6-1.0 mg/kg/day IV
OR
Lipid formulation Amphotericin B 3.0-6.0 mg/kg/day IV
plus 5-flucytosine 25-37.5 mg/kg PO QID*
Alternate: Fluconazole 6-12 mg/kg/day IV or PO if tolerated* References
OR 1. CID 2004:38; 161.
Micafungin 100 mg IV daily 2. Medical Letter 2008:6(65); 1
❖ Continue therapy for 6 weeks after valve replacement
❖ If valve replacement is contraindicated continue fluconazole long term
❖ See also guidelines for fungal infections.
32-75 38 1/9/12, 3:03 PM

Cellulitis Guidelines
Definition:
Acute spreading inflammation involving the soft tissue, excluding muscle,
characterized by recent onset soft-tissue erythema, warmth, swelling and
tenderness, considered to be of infective origin, and acquired in the community.
This does not include infected surgical wounds or previously treated (<3
months) deep diabetic infections.
A four level grading system to guide the intensity of treatment according to the
clinical presentation and underlying predisposition of the patient.
Grading scale:
Grade I - Symptoms/signs restricted to superficial swelling,

erythema, warmth, mild lymphadenopathy, & mild
pain; absence of systemic symptoms in patients
without high risk factors1.
Grade II - Dominant systemic signs – fever, chills lymphangitis

&/or rapidly advancing edge.
- Mild cellulitis (as defined in Grade I) in high-risk
patients1,2 without frank immunocompromise2.
Grade III - Failure to respond to >48 h of adequate oral antibiotic

therapy, severe facial involvement or extensive skin
involvement (i.e. if any dimension of the area of skin
involved is greater than the distance between the
patient’s median wrist crease and the point of the
elbow).
- History of episodes of cellulitis requiring prolonged
intravenous therapy.
- Co-morbid conditions necessitating inpatient therapy.
Grade IV - Orbital, joint, or deep hand involvement.

- Cellulitis in immunocompromised patients2.
- Suspicion of necrotizing, deep-seated infection or
severe sepsis3.
__________________
1
Age ≥16 years
2
‘High risk patients’, neutropenia, asplenia, active cancer and/or
chemotherapy, SLE, transplant, prosthetic joint or valve, HIV with
CD4 count <200, chronic venous insufficiency, chronic
lymphedema etc. affecting the infected body part
3
Severe sepsis = systemic signs/symptoms with evidence of end
organ dysfunction or hypoperfusion
32-75 39 1/9/12, 3:03 PM

Figure 1: Nova Scotia Adult Cellulitis Algorithm
Confirmed
➝ ➝ Appropriate surgical
management.
Infected bite or infected Diagnosis of Suspicion of Avoid antibiotics except
natural water injury? ➝ Cellulitis1* ➝ Abscess?
if surrounding area of
➝ ➝ cellulitis > 5 cm.
➝
Use the same grading system
Uncertain or
unripe2 or purulent ➝ Begin Rx as Grade
II. See in ED in 24 h
Consider the possibility cellulitis for re-evaluation.
for disposition, but use Table I Consider coverage
of necrotizing infection?
for antibiotic choice.
➝ Yes
Ca-MRSA.
➝
NO
➝
➝
➝
Grade I Grade II Grade III Grade IV

➝
➝
➝
➝
Immediately give
Cephalexin 500 mg Initial dose of Candidate for Clindamycin 600 mg IV
QID po x 7 days or, Cefazolin 2 g IV & home IV therapy4 and Ceftriaxone 1 g IV
Cloxacillin 500 mg Probenecid 1-2 g po2,3 IMMEDIATE REFERRAL
➝
➝
QID po x 7 days
➝
Or, Clarithromycin
500 mg po bid x 7 Cephalexin 500 mg Yes No I M M E D I AT E
days. QID po x 7 days. CONSULTS:
➝
➝
Or, Cloxacillin 500 mg I.D. for all

➝
QID po x 7 days Cefazolin 2 g IV Cefazolin 1-2 g patients plus:

Or, Clarithromycin + Probenecid 1- IV or Cloxacillin
Family doctor 500 mg po bid x Necrotizing
and reliable 2 g po2,3 daily 1-2 g2,3
7 days. infection -
Patient/Family
➝
surgery, Deep
➝
➝
➝
hand infection -
Arrange for Refer to Plastic Surg.
No Family doctor
Yes closely Gen. Med
and reliable Orbital Cellulitis -
supervised home or Fam.
➝
Patient/Family Ophthalmology5
➝
IV therapy. Med for

➝
Cefazolin 2 g IV + admission
Follow-up Return to ED Probenecid 1-2 g
with FD in in 36-48 h No po. Change to po
Yes
48-72 h if no regime as for
➝
➝
improvement Grade 1, if Grade

1 features
Follow-up Return to obtained for > 24
with FD in ED in hours. Follow with
24-36 h 24-36 h if no FD in 5 days.
improvement
Blood Cultures - only in complex infections,

immunocompromised or sepsis
CBC & ‘Lytes - only if indicated for reasons other than cellulitis.
Chem-strips (not lab glucose - to screen for Diabetes Mellitus)
*For cellulitis unresponsive to conventional treatment or that involves an accompanying

abscess or furuncle consider Ca-MRSA (rates in NS purulent SSTI’s ~ 20%). Appropriate
treatment includes incision and drainage and non B-lactam antibiotics such as
doxycycline or trimethoprim/sulfamethoxazole.
____________________________________________________________________________________
1
See definition.
2
Antibiotic treatment must be initiated immediately upon suspicion of diagnosis in patients grade
II to IV.
3
If patient reports shortness of breath or hives within 24 hours of penicillin use, substitute
Cefazolin/Probenecid with Clindamycin 600 mg or Levofloxacin 500 mg IV.
4
Clinical decision by attending physician (patient too sick), or logistical decision (home support
or patient compliance concerns).
5
Consults to several different disciplines may need to be made simultaneously.
32-75 40 1/9/12, 3:04 PM

Nova Scotia Adult Cellulitis Guidelines
Recommendations for Antibiotic Prophylaxis of Bite Wounds
(the use of this algorithm presumes thorough irrigation and
debridement of the wound)
risk pt or
injury
▲
High
risk pt or
Cat
injury
▲
Low
▲
>3h
▲
Uninfected Bite Wounds
immune OK
▲
Human
CFI4
< 3 h and
▲
▲▲
▲
Amox/Clav x 5-7
days. Follow in
Hands/face
Consult ID
○ ○ ○ ○
▲
○
○
24 h3
○
▲▲
▲ ▲
○
○
○
as appropriate, see in 24 h2,3

Flagyl 500 mg tid po, splint
○
○
Ceftriaxone 1-2 g IV and

○
○
▲ ▲
○
○
Antibiotics.
○
○
Follow in
Other
Other
○
○
○ ○ ○
24 h3
○
○
No
▲
○
○
○
○
○
▲
○
○
○
○
○
○
○
○
No
○
○
▲
○
○
▲
○
○
○
○
▲
○
○
○
○
○
○
Grade III1
○
○
Dog
○
risk pt
or
Joint
Yes
▲
○ ○ ○
High
○ ○ ○ ○
▲
○ ○ ○ ○ ○
▲
1
Treat as per Grade III on Cellulitis algorithm.
2
Refer to nearest facility with IV capability, or, if appropriate, contact EHS NS
for emergency home administration of IV antibiotics and splinting.
3
If evidence of active infection at follow-up, apply cellulitis (mammal bite)
guidelines.
4
CFI = clenched fist injury.
5
High Risk patients-see foot note #2 on page 27.
32-75 41 1/9/12, 3:04 PM

32-75
Infections of injuries sustained in natural water or as a result of bite wounds
Circumstance of Original Injury:1
Grade Mammal Bite Salt Water Fresh Water
I Amox/Clav2 875 mg po BID x Doxycycline 200 mg po TMP-Sulpha3 DS x 1 tab
7-10 days OD +/- Ciprofloxacin 500 po BID or Ciprofloxacin
If Pen. Allergy, Ciprofloxacin mg po BID x 7-10 days 500 mg po BID x 7-10 days
500 mg po BID plus Clindamycin
42
300 mg QID x 7 days or Moxifloxacin
400 mg po once daily
42
II Ceftriaxone 1 g IV, then po Ciprofloxacin 400 mg IV, then po as above
regime as above
III4 Ceftriaxone 1-2 g IV OD + Ciprofloxacin 400 mg IV BID
Nova Scotia Adult Cellulitis Guidelines
Metronidazole 500 mg BID x (Step down to PO if functioning gut)

7-10 days
1
Consult ID if pregnant.
2
Amoxicillin/Clavulanate
1/9/12, 3:04 PM
3
Sulfamethoxazole/Trimethoprim
Clindamycin Intervention Project
Due to the frequency of the development of antibiotic associated diarrhea and the high
cost associated with the use of clindamycin, the Antimicrobial Agents Sub-Committee
encourages physicians to consider the following:
Intra-Abdominal and Other Anaerobic Infections

• Unless contraindicated it is suggested that metronidazole 500 mg PO/IV q12 hours be
employed with adjunctive antimicrobials in place of clindamycin.
• Metronidazole has superior coverage of B. fragilis and therefore is the drug of choice.
If staphylococcal/streptococcal coverage is also required,

• Metronidazole can be used in combination with cefazolin as an alternative to
clindamycin.
• Compared to clindamycin the combined use of these agents offers:
i) equivalent staph/strep coverage
ii) better coverage for B. fragilis
iii) additional coverage of E. Coli and Klebsiella
iv) cost savings.
Cautions:
• To avoid the risk of adverse effects, metronidazole should not be administered with
ALCOHOL-containing products or for 48 hours after discontinuation of
metronidazole.
• If metronidazole and WARFARIN are administered concomitantly, the INR should be
monitored more frequently.
• Administration of metronidazole in pregnant patients should be avoided especially
during the first trimester.
• Dosage adjustment for cefazolin is indicated in patients with renal dysfunction.
• Use cefazolin with caution in patients with a history of penicillin allergy.
32-75 43 1/9/12, 3:04 PM

Treatment of Clostridium Difficile-
Associated Disease (CDAD)
CDAD is an infectious disorder that can develop when toxin-producing C. difficile is
acquired as a component of the colonic microflora. If a patient harbouring the organism is
then exposed to certain antimicrobials, C. difficile is able to evade eradication by spore
formation, while many of the bacteria that help maintain normal ecology in the colon are
destroyed. This can result in the uncontrolled overgrowth of C. difficile and the production
of endotoxins that can cause inflammation and cellular damage. When CDAD occurs it
can range from self-limiting diarrhea to life threatening enterocolitis and toxic megacolon.
Diagnosis: Mild to moderate to severe diarrhea accompanied by a positive C. difficile
cytotoxin test result.
Agents implicated in the development of CDAD: All antimicrobials and certain
antineoplastics with antimicrobial activity have in implicated in the precipitation of
CDAD.
Most commonly implicated agents: Clindamycin, ciprofloxacin
Second and third-generation cephalosporins
Onset of development of CDAD: Ranges from one to two days after initiation of therapy
to 10 weeks after drug discontinuation. Most cases occur after several days of therapy of
therapy with the offending agent.
Initial Management of CDAD: Stop the offending agent if feasible and restore fluids and
electrolytes if needed. With mild cases in those who are not elderly or debilitated, the
patient can be monitored for symptomatic improvement for 48 hours before oral
treatment for CDAD is initiated. If symptomatic deterioration occurs, antibiotic therapy
for CDAD should begin immediately.
Drug treatment of CDAD:
Agent Dose/Duration Efficacy Cost for 7 days
Metronidazole 500 mg tid Rapid resolution of $ 0.84 to 1.26

(first line) for 10 to 14 days symptoms within 5 days
Response rate = 95%
Relapse rate = 5 to 15%
Vancomycin 125 mg qid Rapid clinical and $53.67

(second line) for 10 to 14 days bacteriological improvement
within 5 days
Response rate = 97%
Relapse rate = 5 to 15%
Evidence has shown that oral metronidazole to be equivalent to oral vancomycin for the
treatment of mild-moderate CDAD. There appears to be little or no difference in either
response or relapse rates between the two agents. Vancomycin is more costly and the
indiscriminate use of vancomycin may have a role in the emergence of vancomycin-
resistant enterococci (VRE). Thus oral vancomycin is reserved when CDAD fails to
respond to metronidazole or is severe or potentially life-threatening. Vancomycin is also
the preferred agent for pregnant and nursing mothers. Vancomycin may also be
considered for patients who are currently receiving warfarin, alcohol-containing products
and are allergic to or highly intolerant of metronidazole.
32-75 44 1/9/12, 3:04 PM

Treatment of Clostridium Difficile-
Associated Disease (CDAD) (cont’d)
Non-oral therapies: Oral therapy is always preferable for the treatment of CDAD, but the
oral route is sometimes not feasible because of gastrointestinal obstruction or
megacolon. Intravenous metronidazole (500 mg q 12h) is recommended for these
patients. An alternative is vancomycin administered via an nasogastric tube or enemas
(with or without therapy with intravenous vancomycin or metronidazole).
Monotherapy with intravenous vancomycin is almost never recommended because of
unacceptably low concentrations of vancomycin in the gastrointestinal lumen.
Additional strategies:
Antiperistaltic agents such as loperamide should be avoided as they predispose the patient
retention of the C. difficile toxins and possible toxic megacolon or enhance the absorption
of metronidazole and result in treatment failure.
The routine use of bile-sequestering agents such as cholestyramine should be avoided in
the initial management of CDAD. There is lack of evidence to support its role and the drug
may bind oral vancomycin, causing treatment failure. Cholestyramine may have a role in
the treatment of patients with multiple relapse.
The treatment of asymptomatic carriers of C. difficile is not necessary.
Treatment of relapse, reinfection and failure:

15 to 30% of patients will relapse within two months after completing initial therapy.
Relapse is defined as a return of symptoms and positive diagnostic test results after
successful antimicrobial therapy for CDAD. Since relapse is unrelated to antimicrobial
resistance, the same agent used to treat CDAD initially can be used to treat the relapse.
Thus, a patient with relapse treated with oral metronidazole initially should receive a
second 10-day course of metronidazole. Reinfection is difficult to distinguish from relapse
and reusing oral metronidazole is appropriate.
Relapse should be distinguished from treatment failure. Relapses generally manifest within
one to four weeks after cessation of therapy and treatment failure is indicated by a lack of
response. However all patients (unless severely ill) should be treated with a minimum of 72
hours with oral metronidazole before switching to oral vancomycin.
Prevention:
Appropriate antimicrobial selection:
The optimal use of clindamycin, poorly absorbed agents (i.e. cefuroxime) or those with
high biliary tract excretion (i.e. ceftriaxone) is essential for the prevention of CDAD.
Appropriate infection control measures – contact Infection Control
32-75 45 1/9/12, 3:04 PM

Suggested Guidelines for the Treatment of Clostridium difficile-
Associated Diarrhea
Diarrhea
History of prior (1-8 weeks) or concurrent exposure to antimicrobials
Yes No Look for other
▲
▲ ▲ cause
Order assay for C.dificile toxin IBD patient
▲
Positive Negative No Treatment (consider
▲
▲ flexible sigmoidoscopy or other
• Discontinue causative antibiotics, if feasible +/– investigations to determine
substitute with antibiotic less predisposing to CDAD cause if persistent diarrhea)
• Restore fluids & electrolytes as needed
• Avoid antiperistaltic agents
Is diarrhea moderate/severe?
Yes No
Is patient able to tolerate po meds? Is patient elderly or debilitated?
▲
Yes No Yes No
▲ ▲
• Is patients allergic to/or unable Metronidazole 500 mg IV q12h +/— Monitor patient
to tolerate metronidazole? Vancomycin via rectal enema (500 mg for 48 hrs
• Does patient have a severity diluted in 1 L of 0.9% NaCl injection) or
score ≥ 2*? through pigtail catheter directly into
▲
(see below) Resolution Persistent Consider treatment
cecum or ileostomy (200 mg or 500
Diarrhea
mg of vancomycin (400 or 1000 ug/ml)
Yes No
▲ in 0.5 L) QID if tolerated
Vancomycin Metronidazole No further studies
125 mg po qid 500 mg po tid
x 10-14 days x 10-14 days
Patient Responds
Reconfirm diagnosis with

No Relapse Relapse after Therapy
▲
C.difficile cytotoxin test

▲
▲
Positive Negative Further work-up

No further studies
Is CDAD moderate/severe?
Manage without further

Yes No
▲
antimicrobial therapy
Repeat Initial Course of Antibiotic Therapy

(resistance to antimicrobials is exceedingly rare)
No further studies Responds & No Responds &

further Relapse Later Relapses
Vancomycin 500 mg QID x 10 Week Vancomycin Taper Vancomycin po x 14 days Sequential Taper
days + S.boulardii # 500 mg 1 125 mg QID followed by cholestyramine * Vanco 125 mg q6h x 7-10 days
po BID 2 125 mg BID 4 g tid x 21 days Am J Vanco 125 mg q12hrs +
(begininning on day 7 of vanco 3 125 mg OD Gastroenterol 1997;92: 739-50 cholestyramine 4 g q12 hrs x 5-7 days
therapy) x 4 wks 4 125 mg qOD *cholestryramine should be Vanco 125 mg OD + cholestyramine
Clin Infect Dis 2000;31:1012-17 5 & 6 125 mg q3 days spaced from all medications by 4 g q12h x 5-7 days
# Caution in Am J Gastroenterol 1985; at least 2 hours Cholestyramine 4 g q12h x 14 days
immunocompromized patients 80:867-8 Am J Gastroenterol 1982; 77:220-1
* CID 2007;45:302 1 Point 2 Points

• age > 60 • endoscopic evidence of PMC
• T > 38.3°C • ICU admission
• albumin < 25
• WBC > 15,000 cells/mms
32-75 46 1/9/12, 3:04 PM

Prevention of Bacterial Endocarditis 1
Dental procedures that involve manipulation of gingival tissue or the periapical
region of teeth or perforation of the oral mucosa expose patients with the following
cardiac conditions to a risk of developing endocarditis:
i) serious congenital, heart conditions (CHD) - unrepaired or incompletely
repaired cyanotic congenital heart diseases (including palliative shunts and
conduits), any repaired CHD with residual defect at the site or adjacent to the
site of prosthetic patch/device; a completely repaired CHD with prosthetic
material, device during the first 6 months after procedure;
ii) cardiac transplant that develops cardiac valvulopathy;
iii) prosthetic cardiac valve or prosthetic material used for cardiac valve repair;
iv) prior episode(s) of endocarditis.
The following table was adapted from the American Heart Association
recommendations published. Circulation April 19, 2007.
DENTAL AND UPPER RESPIRATORY PROCEDURES

ORAL2 DOSAGE
Amoxicillin3 2 g 1 hour before the procedure
Penicillin allergy:
Clindamycin 600 mg 1 hour before the procedure
OR
Azithromycin or clarithromycin 500 mg one hour before the procedure

OR
Cephalexin ¥ 2 g 1 hour before the procedure only
PARENTERAL2 DOSAGE
Ampicillin 2 g IM* or IV 30 minutes before the procedure
Penicillin Allergy:
Clindamycin 600 mg 30 minutes before the procedure
and 150 mg IV/PO 6 hours later
OR
Cefazolin ¥ 1 g 30 minutes before procedure
¥
Should not be used in individuals with immediate type 1 hypersensitivity reaction
to penicillins (urticaria, angioedema, or anaphylaxis).
* IM administration should be avoided in patients receiving anticoagulation
therapy.
32-75 47 1/9/12, 3:04 PM

Prevention of Bacterial Endocarditis
(cont’d)
1. For patients with previous endocarditis, valvular heart disease, prosthetic heart
valves, most serious forms of congenital heart disease, viridans streptococci are
the most common cause of endocarditis after dental or upper respiratory
procedures; enterococci are the most common cause of endocarditis after
gastrointestinal or genitourinary procedures.*
2. Oral regimens are more convenient and safer. Parenteral regimens are more likely
to be effective; they are recommended especially for patients with prosthetic
heart valves, those who have had endocarditis previously, or those taking
continuous oral penicillin for rheumatic fever prophylaxis.
3. Amoxicillin is recommended because of its excellent bioavailability and good
activity against streptococci and enterococci.
* Antibiotic prophylaxis against infective endocardidits is recommended in the

aforementioned patients for dental procedures that involve manipulation of
gingival tissue or the periapical region of teeth or perforation of the oral mucosa,
procedures on respiratory tract involving incision or biopsy of respiratory
mucosa and procedures in patients with infected skin, skin structures or
musculoskeletal tissue; however, antibiotic prophylaxis against infective
endocardidits is not recommended for genitourinary or gastrointestinal tract
procedures [Circulation 2007; 116: 1736-1754].
32-75 48 1/9/12, 3:04 PM

Treatment of Bacterial Endocarditis
Preface
Bacterial endocarditis is a serious, sometimes life-threatening infection

that may require surgical, as well as medical therapy, for optimal
outcome.
Management requires a multidisciplinary approach involving

infectious disease specialists, cardiologists, and cardiac surgeons, with
other specialists as dictated by the specific clinical situation
These CDHA guidelines for the antimicrobial therapy of bacterial

endocarditis have been arrived at by consensus among ID Division
members based upon the evidence in the literature and our local
epidemiology and susceptibility patterns.
32-75 49 1/9/12, 3:04 PM

32-75
Anatomic Site/Diagnosis/ Etiologies Suggested Regimens* Adjunct Diagnostic or Therapeutic Measures
Modifying Circumstances (usual) Primary and Comments
Alternative
Infective endocarditis - NOTE: Diagnostic criteria include evidence of continuous bacteremia (multiple positive blood cultures), new murmur (worsening of old murmur) or valvular
Native valve - empirical rx insufficiency, definite emboli, and echocardiographic (transthoracic or transesophageal) evidence of valvular vegetations. Review: NEJM 345: 1318, 2001.
awaiting cultures
Viridans strep 30-40%, [(Pen G 20 mU qd IV, div. q4h) or Vanco 15 mg/kg q12h IV If patient not acutely ill or not in heart failure, we prefer to wait for blood
“other” strep 15-25%, (AMP 12 g qd IV, continuous or div. culture results. If initial 3 blood cultures neg. after 24-48 hrs, obtain 2-3
(cont’d)
enterococci 5-18%, q4h) + (cloxacillin 2.0 g q4h IV) + more blood cultures before empiric rx started. Cloxacillin + gentamicin
staphylococci 20-35% gentamicin 1.0 mg/kg q8h IV] may not be adequate coverage of enterococci, hence addition of penicillin
G pending cultures. When blood cultures +, modify regimen from empiric
to specific based on organism, in vitro susceptibilities clinical experience.
Infective endocarditis - S. aureus Cloxacillin 2 g IV q4h + Vanco 15 mg/kg q12h IV If MRSA carrier, vancomycin replaces cloxacillin as the empiric choice.
Native-valve-IV illicit drug All others rare gentamicin 1.0 mg/kg q8h
use ± evidence rt-sided
endocarditis-empiric rx
50
Infective endocarditis - Native valve - culture positive (Consensus opinion on rx by organism: JAMA 274: 1706, 1995)(Review: NEJM 345: 1318, 2001)(Combination rx: CID 36: 615, 2003)
Viridans strep, S. bovis with Viridans strep, S. bovis [(Pen G 12-18 mU/d IV, q4h x 2 (Ceftriaxone 2 g qd IV + Target gent levels: peak 3 μg/mL, trough <1 μg/mL. Infuse vanco over ≥1
penicillin G MIC ≤0.1 μg/mL weeks) PLUS (gentamicin 1 mg/ gentamicin 1 mg/kg IV q8h h to avoid red man syndrome.
50
kg q8h IV x 2 weeks) if both x 2 weeks). If allergy S. bovis suggests occult bowel pathology. (New name: S. gallolyticus)
uncomplicated pen G or ceftriax, use vanco
OR (Pen G 12-18 mU/d IV, q4h x 4 30 mg/kg/d in 2 div. doses x 4
weeks) if complicated weeks
Viridans strep, S. bovis with Viridans strep, S. bovis, Pen G 18 mU/d IV (q4h) x 4 weeks Vanco 15 mg/kg IV q12h x 4 Can use cefazolin for Pen G in patient with allergy that is not IgE-
penicillin G MIC >0.1 to <0.5 nutritionally variant PLUS gentamicin 1 mg/kg q8h IV weeks mediated (e.g. anaphylaxis). Alternatively, can use vanco. Target gent
μg/mL streptococci, tolerant x 2 weeks. levels: peak 3 μg/mL, trough <1 μg/mL.
strep
Viridans strep or S. bovis Susceptible enterococci, [(Pen G 18-30 mU/24h IV, q4h x 4- Vanco 15 mg/kg IV q12h 4 weeks of rx if symptoms <3 months; 6 weeks of rx if symptoms >3
with pen G MIC ≥0.5 and viridans strep, S. bovis, 6 weeks) PLUS (gentamicin 1 mg/ PLUS gentamicin 1-1.5 mg/ months.
enterococci susceptible to nutritionally variant kg q8h IV x 4-6 weeks)] OR (AMP kg q8h IV x 4-6 weeks. Do not give gent once-daily for enterococcal endocarditis. Target gent
AMP/pen G, vanco streptococci 12 g/d IV, q4h + gent as above x 4- levels: peak 3 μg/mL, trough <1 μg/mL.
6 weeks)
* Baseline and weekly audiometry recommended if aminoglycosides used > 2 weeks.
1/9/12, 3:04 PM
32-75
Alternative
Enterococci: Enterococci, high-level Pen G or AMP IV as above x 8- If prolonged pen G/AMP fails, 10-25% E. faecalis and 45-50% E. faecium resistant to high gent levels.
MIC streptomycin >2000 μg/ aminoglycoside 12 weeks (approx. 50% cure) consider surgical removal of May be sensitive to streptomycin, check MIC.
mL; MIC gentamicin >500- resistance infected valve. Case report of success with combination of AMP, MER, and vanco (Scand
2000 μg/mL; no resistance to J Inf Dis 29: 628, 1997).
penicillin
(cont’d)
Enterococci: Enterococci, intrinsic Vanco 15 mg/kg q12h Plus gent 1-1.5 mg/kg q8h (no single dose)
pen G MIC >16 μg/mL; no pen G/AMP resistance x 4-6 weeks
gentamicin resistance
Enterococci: Enterococci, vanco- No reliable effective rx. Can try
51
Pen/AMP resistant + high- resistant, usually E. linezolid 600 mg IV or po q12h
level gent/strep resistant + faecium
vanco resistant; usually VRE
Consultation suggested
Staphylococcal Staph. aureus, cloxacillin 2 g q4h-6 IV x 4-6 [(Cefazolin 2.0 g q8h IV x 4-6 Avoid cephalosporins in patients with immediate allergic reaction to
endocarditis methicillin-sensitive weeks +/- (gentamicin 1.0 mg/ weeks) +/- (gentamicin 1.0 mg/ penicillin; cefazolin failures reported (CID 37: 1194, 2003).
Aortic and/or mitral valve kg q8h IV x 3-5 d). kg q8h IV x 3-5 d)]. No definite data, pro or con, on once-daily gentamicin for S. aureus
infection NOTE: Low dose of gent endocarditis. At present, favor q8h dosing x 3-5 d.
51
OR
↑ recognition of IV catheter-associated S. aureus endocarditis. May need
Vanco 15 mg/kg q12h x 4-6 weeks TEE to detect endocarditis. 23% of S. aureus bacteremia in assocation
with IV catheter had endocarditis (CID 115: 106 & 115, 1999); if TEE neg,
only need 2 weeks of therapy for IV-related S. aureus bacteremia.
Aortic and/or mitral valve- Staph. aureus methicillin Vanco 1 g IV q12h x 4-6 weeks Linezolid 600 mg IV q12h
MRSA resistant +/- gentamicin if susceptable
Tricuspid valve infection Staph. aureus, cloxacillin 2 g q4-6h IV plus If penicillin allergy: Not clear. 2-week regimen not recommended if metastatic infection (e.g.
(usually IVDUs): methicillin-sensitive gentamicin 1 mg/kg q8h IV x 2 High failure rate with 2 weeks of osteo), left-sided endocarditis, or MRSA.
MSSA weeks. NOTE: Low dose of vanco + gentamicin (CID 33: 120, 2 reports of success with 4-week oral regimen; CIP 750 mg bid + RIF 300
gent 2001). Can try longer duration of mg bid. Less than 10% pts had MRSA (LN 2: 1071, 1989; AJM 101: 68,
vanco ± RIF (if sensitive). 1996).
S. pneumonia S. pneumonia Test penicillin susceptibility

and consult with ID
1/9/12, 3:04 PM
S. pyogenes S. pyogenes Penicillin G 18 mu/24 h (q4h)
X 4 weeks
B, C, and G Streptococci B, C, and G Streptococci Penicillin G 18 mu/24 h (q4h)

X 4-6 weeks +/- gentamicin
for 2 weeks
32-75
Alternative
Methicillin resistance Staph. aureus, methicillin- Vanco 15 mg/kg q12h x 4-6 weeks Fails/intolerant to vanco, can For MRSA, no difference in duration of bacteremia or fever between pts rx
(MRSA) resistant try linezolid 600 mg IV or po with vanco or vanco + RIF (AnIM 115: 674, 1991).
q12h
Slow-Growing fastidlous HACEK group (see Ceftriaxone 2.0 g qd IV x 4 weeks AMP 12 g qd (div. q4h) x 4 HACEK (acronym for Hemophylus parainfluenzae, H. aphrophilus,
(cont’d)
Gm-neg. bacilli Comments) (Mayo Clin Proc weeks + gentamicin 1.0 mg/ Actinobacillus, Cardiobacterium, Elkenella, Kingella). H. aphrophilus
72: 532, 1997) kg q8h IV x 4 weeks resistant to vanco, clinda and methicillin. For Hemophilus, see CID 24:
1087, 1997.
Bartonella species B. henselae, B. quintana Optimal rx evolving. Retrospective & open prospective trials support Dx: Immunofluorescent antibody titer ≥1:800; blood cultures only occ.
gentamicin 3 mg/kg IV once daily x minimum of 14 days + doxy 100 positive, or PCR.
mg po q12h x 4-6 weeks Surgery: Over 50% pts require valve surgery; relation to cure unclear.
B. quintana transmitted by body lice among homeless; asymptomatic
colonization of RBCs described (Ln 360: 226, 2002).
52
Infective endocarditis - Etiology in 348 cases studied by serology, culture, histopath & molecular detection: C burnetii 48%, Bartonella sp. 28% and rarely (Abiotrophia elegand, Mycoplasma
culture negative hominis, Legionella pneumophila, Tropheryma whipplei — together 1%) & rest without etiology identified (most on antibiotics). Emphasis is on diagnosis. See specific
Fever, valvular disease, and organism for treatment regimens.
ECHO vegetations ± emboli
and neg. cultures
52
Infective endocarditis -
Prosthetic valve - empiric
therapy (cultures pending)
Early (<2 months post-op) S. epidermidis, S. aureus. Vanco 15 mg/kg q12h IV + gentamicin 1.0 mg/kg q8h IV Early surgical consultation advised. Watch for evidence of heart failure.
Rarely, Enterobactenaceae,
diphtheroids, fungi
Late (>2 months post-op) S. epidermidis, viridans

strep, enterococci, S. aureus
1/9/12, 3:04 PM
32-75
Alternative
Infective endocarditis - Staph. epidemidis (Vanco 15 mg/kg q12h IV+ RIF 600 mg BID) x 6 weeks + If S. epidermidis is susceptible to Cloxacillin in vitro (not common), then
Prosthetic valve - positive gentamicin 1 mg/kg q8h IV x 14 d substitute Cloxacillin for vanco.
blood cultures
Surgical consultation advised: Staph. aureus Methicillin sensitive: (cloxacillin 2.0 g q4h IV + RIF 600 mg BID) x 6 weeks + gentamicin 1.0 mg/kg q8h IV x 14 d.
retrospective analysis shows Methicillin resistant: (Vanco 15 mg/kg q12h IV + RIF 600 mg BID) x 6 weeks + gentamicin 1.0 mg/kg q8h IV x 14 d.
(cont’d)
↓ mortality of pts with S.

aureus endocarditis if valve Viridans strep. enterococci See infective endocarditis, native valve, culture positive
replaced during antibiotic rx
(CID 26: 1302 & 1310, 1998); Enterobacteriaceae or P. Aminoglycoside (tobra if P. aeruginosa) + (Piperacillin or In theory, could substitute Cipro for Piperacillin, but no clinical data.
also, retrospective study aeruginosa Ceftazidime)
showed ↑ risk of death 2°
53
neuro events in assoc. with Candida, aspergillus Ampho B ± an azole, e.g. fluconazole High mortality. Valve replacement plus antifungal therapy standard
Coumadin rx therapy but some success with antifungal therapy alone (CID 22: 262,
1996).
Infective endocarditis -Q Coxiella burnettii Doxy 100 mg po bid + hydroxychloroquine 600 mg/d x 1.5-3 years Dx: IgG CF antibody of 1:200 to phase I antigen diagnostic of chronic Q
fever fever (LnID 3:709, 2003).
53
Outpatient Treatment
Patients with organisms susceptible to Ceftriaxone would benefit from once daily dosing of Ceftriaxone 2 g to facilitate home IV therapy once
discharged from hospital.
1/9/12, 3:04 PM
Febrile Neutropenia - High Risk Inpatient
Temp (po) ≥38.5°C or >38°C X 2 in 12

hours and ANC ≤0.5 x 109 1
➝
1. Clinical assessment2
2. Microbiological assessment cultures
of blood, urine, sputum and other
obvious sites of infection
3. Radiological assessment (Cxray)
➝
Imipenem 500 mg IV q 6h3
➝
Afebrile
➝ Day
➝ Persistent Fever
➝
(Temp < 38.5°C) 3-5 (Temp ≥38.5 C) °
➝
➝
➝
Modify Therapy2-6
No Clinically Clinically or
➝
Defined Infection2 Microbiologically
Defined Infection2
➝
Reassess
ANC >0.5 ANC ≤0.5 by day 7 ANC ≤0.5 by day 7 &
Continue broad spectrum Day
rising X 48 h and clinically well high risk (ANC ≤0.1,
antibiotics (modify coverage 5-78
mucositis, unstable)
➝
if necessary) until afebrile ≥

➝
➝
total of 5-7 days OR ANC

D/C Ab- 48 h Continue ≥0.5. Treat specific infection
Continue original Persistent Fever
AF& ANC antibiotics until for at least 7-10 days2,4,7
empiric regimen (Temp ≥38.5°C) and
>0.5 afebrile for 5-7
until ANC ≥0.5 unresolving neutropenia
days.
➝
➝
Consider Amphotericin
Continue antibiotics for
2 weeks max. OR ANC
Reassess10
➝ B 0.6-1 mg/kg IV daily9
➝
>0.5
Intolerance/
nephrotoxicity
➝
➝ ABLC (Abelcet)
Micafungin
100 mg daily ➝ Intolerance/
nephrotoxicity ➝ 5 mg/kg daily
32-75 54 1/9/12, 3:04 PM

High Risk Febrile Neutropenia
Footnotes
1. ANC: Absolute Neutrophil Count.
2. Clinically defined infections: It is important to remember that patients with

chemotherapy induced febrile neutropenia need both broad spectrum cover-
age, as well as coverage for specific infections. For initial management of
clinically defined infections. In addition to meropenem, consider:
(i) Severe Mucositis/Oral Lesions: Yeast/fungal, and HSV cultures.
(ii) Documented Line Infection or Sepsis: Vancomycin 1 g IV q12h if
Coagulase-negative staphylococcus (CNST) or MRSA isolated. If suspected
line infection, may consider adding Vancomycin. Discontinue if cultures
are negative after 48 hours and/or decrease in clinical suspicion.
(iii) C. difficile diarrhea suspected or documented, ADD metronidazole.
(iv) Pulmonary Infiltrates: Consider BAL: for RSV, CMV, PCP, Legionella &
fungus.
3. Documented Hypersensitivity to B-Lactam Antibiotics: Ciprofloxacin 400 mg

IV q12h +/- gentamicin 6 mg/kg IV q24h. Vancomycin should be added for
broader gram positive coverage: Consider an ID consult.
4. Deterioration: Patients who deteriorate (e.g. become hypotensive or confused)

while still neutropenic and on any combination of antibiotics need careful
reassessment for a source of infection, as well as the addition/change of
antibiotics. Vancomycin may be added empirically in this instance pending
culture results. If culture(s) negative after 48 hours, discontinue.
5. Pathogen Isolated (microbiologically defined infection): Maintain initial

broad-spectrum regimen, unless sensitivities indicate that a pathogen is
inadequately covered. Culture documented Pseudomonas infections should
always be treated with two agents to which the bacteria is susceptible. Add
Vancomycin for documented gram positive infections until susceptibility
confirmed.
6. Renal Function: Monitor serum creatinine at least 3x per week while on an

aminoglycoside. If baseline SCr >200 mmol/L or estimated ClCr <70 mL/min
avoid adding an aminoglycoside; add ceftazidime to meropenem if double
coverage required (ie Pseudomonas).
7. Clinically or Microbiologically Defined Infection and Afebrile at Day 4:

Continue broad spectrum coverage until afebrile 5-7 days OR ANC ≥0.5 x 109/L.
Continue coverage for specific infection for at least 7-10 days AND until clinical
symptoms have resolved AND ANC >0.5 x 109/L, AND afebrile for 5 days.
Duration of antibiotics should be assessed on an individual basis.
8. If still persistently febrile and ANC >0.5, antimicrobials may be stopped after 4-5
days of treatment and patient reassessed.
9. Amphotericin B: Consult hospital guidelines for the use of amphotericin B.
10. Consider stopping antimicrobials after 2 weeks of treatment for ANC 0.2-0.5 if
no infectious etiology identified and condition is stable.
32-75 55 1/9/12, 3:04 PM

Low Risk Febrile Neutropenia
{Paraphrased from Finberg RW, Talcott JA. N Eng J Med 1999; 341: 362-3}
The treatment of fever and neutropenia has evolved with the development of both
new antimicrobial drugs and new strategies for using them. The first effective treatment
for patients with fever and neutropenia was the combination of an antipseudomonal
penicillin, carbenicillin, and gentamicin in a strategy of early empirical therapy triggered
by fever alone.
In the 1980’s, the options for antibiotic treatment improved. A large, randomized
study demonstrated that a single broad-spectrum drug, ceftazidime, could safely replace
the standard combination of an antipseudomonal penicillin and an aminoglycoside.
Despite this finding, because of their previous experience with rapidly fatal pseudomonas
infections, wary clinicians were reluctant to use ceftazidime alone in patients who
often were very ill from intensive chemotherapy.
However, risk-assessment studies began to refine clinicians intuitions about the medical
instability of their patients. A retrospective study by Talcott et al. of 261 episodes of
fever and neutropenia treated in the hospital provided justification, in part, for the
anxiety of clinicians. In one of five episodes, serious, potentially life-threatening medical
complications developed, such as hypotension, respiratory failure and altered mental
status. However, not all patients were at similarly high risk. Within 24 hours of
hospitalization, three high-risk groups, could be identified: 1. Patients who were already
inpatients when fever and neutropenia developed; 2. Outpatients who needed acute
hospital care for problems in addition to the fever and neutropenia; and 3. Clinically
stable outpatients with uncontrolled cancer (those with acute anticancer therapy). All
the remaining patients - a group that comprised 70 percent of the outpatients - were
by default at low risk. The validity of these risk groups was later confirmed. For patients
in the three high-risk groups, the rate of medical complications was 36 percent, and
20 percent of such patients died. For the low-risk patients, the complication rate was 2
percent, and none died.
The ability to make distinctions about risk offered new possibilities for treatment. If
fever and neutropenia do not always have the same clinical significance, then the
strategy for treating them may vary according to circumstance. For example, clinicians
who initially were wary of singe-drug therapy with ceftazidime often were more
comfortable using it for low-risk patients. But there were other possible innovations
with important economic implications. If a single intravenous antibiotic could be used
to treat low-risk patients, why not still cheaper and more convenient oral antibiotics?
Even more radically, why not send apparently stable patients home for treatment and
avoid incurring the cost of an inpatient bed? A more recent paper validated a scoring
system to predict risk.
Attached are two recent reports from the N Eng J Med1,2 which involve large, prospective,
randomized studies of low-risk patients (defined variously by the investigators) that
expand our options for the management of fever and neutropenia in patients with
cancer. The results of these studies show that oral antibiotics may be safely substituted
for intravenous antibiotics in low-risk patents with fever and neutropenia. Now that
these studies have provided us with more convenient, versatile antibiotic strategies for
treating low-risk patients with fever and neutropenia, when should we use them? Do
these studies of oral therapy justify our using outpatient treatment? The authors of
32-75 56 1/9/12, 3:04 PM

both of these rigorous, careful studies, which were designed to assess the relative
efficacy of antibiotic regimens given to inpatients, caution that they do not. Although
clinical experience with the treatment of patient with fever and neutropenia on an
outpatient basis has grown in the past decade, this approach has yet to be validated in
large, randomized studies designed to assess this critical question: Is outpatient treatment
of fever and neutropenia, away from the watchful eyes and readily available emergency
equipment of the hospital, as safe as inpatient treatment, or at least safe enough?
In the largest study conducted to date, Malik3 and colleagues examined 169 episodes
of fever and neutropenia and found that inpatients and outpatients treated with
ofloxacin alone were equally likely to have their fever and neutropenia resolve without
requiring a change in their antibiotic regimen. Although this finding indicates that
identical regimens have equal efficacy in inpatients and outpatients, it says little about
the safety of outpatient treatment. Three patients in the outpatient group died; at least
one of these deaths was apparently preventable.
1. N Engl J Med, July 29, 1999; 341: 305-11.

2. N Engl J Med, July 29, 1999; 341: 312-18.
3. Am J Med, 1995; 98: 224-31.
4. Klastersky J, Paesmans M, Rubenstein EB et al. The multinational association for
supportive care in cancer risk index: A multinational scoring system for identifying
low-risk febrile neutropenic cancer patients. JCO 2000; 18 (16); 3038-3051.
32-75 57 1/9/12, 3:04 PM

A Potential Step by Step Management
Program for Low-Risk Febrile Neutropenia
This protocol should only be activated after discussion
with the medical oncologist or hematologist on call
Outpatient Management of the Low Risk Febrile Neutropenic (FN) Patient
Safe management of the FN patient relies on a careful risk assessment to identify those
individuals who can be treated in the outpatient setting. Outpatient management is intended
only for stable patients who can be expected to do well. Patients with acute leukemia are not
candidates for outpatient management of febrile neutropenia.
Definitions:
• Fever is an oral temperature ≥38°C on 2 occasions at least 12 hours apart or a single oral
temperature ≥38.5°C.
• Neutropenia is an absolute neutrophil count (ANC) ≤0.5x109/L as determined by an
automated differential.
Patient Assessment:
If the patient will be compliant with outpatient management recommendations AND
Lives within 30 minutes of a hospital and has 24 hour live-in support, AND
Can be assessed daily by a physician, he/she may be eligible for outpatient therapy.
Answer all of the following questions about the patient:
Yes No
1. The patient has hypotension (systolic BP <90 mmHg systolic or 40 mmHg ___ ___
less than patient’s normal)
2. The patient has a compromised mental status or is incompetent ___ ___
3. The patient has respiratory distress ___ ___
4. The patient has abdominal pain, vomiting, mucositis or diarrhea ___ ___
5. The patient has gross bleeding or severe bruising ___ ___
6. The patient needs parental fluid therapy or pain control ___ ___
7. The ANC is expected to take >10 days to recover ___ ___
8. There is evidence of deep organ or tissue infection (e.g.: pneumonia, ___ ___
pyelonephritis)
9. The temperature is >39°C and the ANC ≤ 0.1x109/L ___ ___
10. There is a coexistent medical condition requiring admission ___ ___
11. The patient has recently received prophylactic or therapeutic antibiotics ___ ___
(other than sulfamethoxazole-trimethoprim)
If the answer to any of the above is YES, the patient is NOT a candidate for outpatient
antibiotic therapy for febrile neutropenia.
Patient Scoring:
If the patient is a candidate for outpatient antibiotic therapy, complete the following checklist:
Characteristic Value
• Burden of illness: no or mild symptoms 5
• No hypotension 5
• No chronic obstructive lung disease 4
• Solid tumour or no previous fungal infection 4
• No dehydration 3
• Burden of illness: moderate symptoms 3
• Outpatient status 3
• Age <60 years 2
If the score adds to ≥21 the patient may be considered for outpatient antibiotic therapy
32-75 58 1/9/12, 3:04 PM

Management
1. Order a CBC and differential, BUN, creatinine, urinalysis, blood and urine cultures, and
chest XRAY.
2. The patient should be given the first dose of antibiotics and observed in the medical day
unit (MDU) or Emergency Department (ED) for 4 hours, monitoring heart and
respiratory rates, blood pressure with orthostatic measurements, temperature, and pulse
oximetry every 2 hours at a minimum.
3 If the patient remains clinically stable and fulfills all criteria, the patient can be discharged
to home with the appropriate prescription (5 day supply with 1 repeat) and specific
instructions on how to take the antibiotics and on follow up with the MDU at 10AM the
following day.
4. Dose adjustments are required for ciprofloxacin and amoxicillin clavulanate in the
presence of renal insufficiency. Give the first doses and contact pharmacy for advice on
further dosing recommendations.
5. The patient will be seen daily by the physician or physician clinical associate for the
patient’s service until afebrile and asymptomatic, or hospitalized if necessary.
6. If the patient remains febrile for more than 5 days, admission is required and antibiotics
reassessed.
7. Antibiotics will be continued for 5-10 days and until the ANC is >0.5x109/L and the
patient afebrile for ≥72 hours. Oral antibiotics should replace IV as soon as tolerated.
8. The patient should have a CBC with differential and creatinine every 48 hours at a
minimum.
Outpatient Antibiotic Therapy
Oral * consider potential for

drug interactions
Ciprofloxacin* 750 mg BID

and
Amoxicillin-Clavulanate
875 mg BID
If penicillin allergic
Moxifloxacin* 400 mg OD
Prepared by the Divisions of Infectious Diseases, Medical Oncology, and

Hematology and the Pharmacy Department, CDHA
March 2005/Revised 07/05, 12/05, 05/06, 05/06, 06/06
32-75 59 1/9/12, 3:04 PM

32-75
Infection Usual Pathogens Recommended Empiric Therapy Recommended Dose Recommended Duration Comments
Candida
Candiduria Candida spp* Asymptomatic • Usually associated with foreign body in urinary
Treatment not recommended tract. Removal of urinary catheter or stent results
unless high risk† in 40% eradication of candiduria but only 20%
if subsequently replaced.
Symptomatic/High Risk† * Fluconazole may not be effective against C.
Fluconazole 200 mg PO daily 7-14 days krusei and some strains of C. glabrata.
C. lusitaniae may be resistant to amphotericin B.
Alternative ** Bladder irrigation with amphotericin B has
Amphotericin B2** 0.3-0.5 mg/kg/d IV 7-14 days been used to treat candidal cystitis but does not
treat infections beyond the bladder.
- Persistent candiduria in immunocompromised
patients warrants US or CT of kidney.
60
† High Risk:
• neutropenia
• renal transplant patients
• patients undergoing urological procedures.
60
Esophageal Candida albicans Fluconazole 200 mg PO first day - Always indicative of immunosuppression
Candidiasis Occasionally then 100 mg PO daily
non-albicans spp Refractory 2-3 weeks after clinical
Fluconazole 400-800 mg po daily-bid improvement
or
Amphotericin B or 0.5 mg/kg/d IV
Micafungin 100 mg IV daily
Invasive General Management
Candidiasis/ - Removal of central venous and/or peritoneal dialysis catheters generally recommended in non-neutropenic patients but controversial for neutropenic
Candidemia patients as source often from GI tract.
- Discontinue broad spectrum antibiotics if possible.
- Serial blood cultures (minimum daily x3) to ensure sterilization every 2-3 days until blood cultures negative.
- Fundoscopic examination should be done.
- For positive Candida spp cultures:
Empiric Therapy of Fungal Infections
• C. glabrata - some resistance with low dose fluconazole but can be overcome with high dose therapy.
• C. krusei - resistant to fluconazole
1/9/12, 3:04 PM
• C. lusitaniae, C. guilliermondii - usually resistant to amphotericin B.
32-75
Infection Usual Pathogens Recommended Recommended Dose Recommended Duration Comments
Empiric Therapy
Candidia albicans Fluconazole 800 mg IV loading dose minimum 14 days after last * Usually associated with prosthetic
Candidia tropicalis* or then 400-800 mg IV/PO daily positive blood culture device, especially central venous catheters.
Candida parapsilosis* Amphotericin B 0.6-1 mg/kg/d IV and resolution of signs and - Amphotericin B or caspofungin
Candida glabrata symptoms recommended empirically if:
Candida krusei Micafungin 100 mg IV daily • hemodynamically unstable
• neutropenic (ANC <0.5 x109/L)
• suspect non-albicans Candida spp.
Empiric Treatment of Candida spp Amphotericin B 0.6-0.7 mg/kg/d IV
61
Persistent Febrile Aspergillus Alternative
Neutropenia Protocol Micafungin 100 mg IV daily
(High Risk) or
ABLC 5 mg/kg/d IV
Empiric Treatment of Candida spp Fluconazole 400 mg IV/PO daily
Persistent Febrile Alternative
61
Neutropenia Protocol Micafungin 100 mg IV daily
(Low Risk) or
ABLC 5 mg/kg/d IV
Candida
Hepatosplenic Candida spp Amphotericin B 0.6-0.7 mg/kg/d IV 3-6 months and resolution - Fluconazole may be given after
Candidiasis or or calcification of radiologic 1-2 weeks of amphotericin B if
Fluconazole 400-800 mg daily lesions clinically stable and improved.
Invasive Aspergillosis Aspergillus fumigatus Voriconazole 6 mg/kg IV q12h first day ≥10 weeks - Infectious Diseases consult recommended.
Aspergillus flavus then 4 mg/kg IV q12h - For central nervous system infection,
Other Aspergillus spp or then 200 mg PO bid* voriconazole recommended and
ABLC 5 mg/kg/d IV ≥10 weeks*** neurosurgery often required.
Salvage*** *** Combination antifungal therapy may
1/9/12, 3:04 PM
Micafungin 100 mg IV daily ≥10 weeks be needed. Consult Infectious Diseases.
Empiric Therapy of Fungal Infections (cont’d)
32-75
Infection Usual Pathogens Recommended Recommended Dose Recommended Duration Comments
Empiric Therapy
Fungal Sinusitis Aspergillus spp Immunocompetent - In immunocompetent host, fungi in sinuses
Antifungal therapy not may be associated with nasal polyposis and
routinely recommended do not routinely require antifungal therapy.
- In immunocompromised patients/diabetic
Immunocompromised ketoacidosis, a fungal infection can present as
Aspergillus as a cellulitis that may rapidly progress and
Voriconazole 6 mg/kg IV q12h first day be fatal. Surgical debridement is necessary.
then 4 mg/kg IV q12h or * Use the higher dose if neutropenic.
200 mg PO bid ** Other Azoles and micafungin not
or active against Rhizopus/Mucor spp.
Amphotericin B 1-1.25 mg/kg/d* IV
62
Rhizopus/Mucor** Amphotericin B 0.8-1.5 mg/kg/d IV
Posaconazole (NF) 200 mg PO qid
62
Endemic Mycoses* Cryptococcus spp** - Infectious Diseases consult strongly recommended.
Histoplasma spp*** * Therapy/dose/duration dependent on clinical picture.
Blastomyces spp ** Caspofungin not active against Cryptococcus spp.
Coccidioides spp *** Fluconazole less effective then itraconazole against Histoplasma spp.
1/9/12, 3:04 PM
Empiric Therapy of Fungal Infections (cont’d)
Immunization for Adults
Childhood immunization programs have proven to be an effective and safe method of
preventing many infectious diseases. The delivery and implementation of adult
immunization programs have not matched the successes achieved in the pediatric
population. However given increased emphasis on disease prevention, healthcare
providers must be made aware of the need to improve immunization among adults.
Immunization status should be considered an integral part of the health assessment of any
adult. Opportunities to provide vaccines to adults are being missed in the healthcare
setting. Prevention of infection by immunization is a lifelong process that should be
tailored to meet individual variations in risk resulting from age, illness, travel, occupation
and lifestyle.
Canadian recommendations for vaccination can be found in the Canadian
Immunization Guide, sixth edition 2006 or at http://phac-aspe.gc.ca/publicat/cig-gci/
index.html or e-CPS-Clin-Info “vaccines”.
Opportunities for Immunization in Acute Care Institutions

A vaccination history taken on admission to hospital provides an important opportunity
to ensure that up-to-date immunization is maintained in all individuals.
In acute care hospitals the admission of elderly patients and others at risk for complications
from influenza and other diseases should be seen as opportunity to ensure protection
against these diseases. All routine vaccines should be up to date and consideration should
be given to other vaccines as needed.
(see next page for more information on individual vaccines, toxoids)
Opportunities for Immunization in Long-Term Health Care Facilities

Annual vaccination against influenza is strongly recommended for individuals in nursing
homes and chronic care institutions. Pneumococcal vaccine is recommended for the
elderly and chronically ill, particularly in closed populations. A single dose should be
administered to all unvaccinated individual admitted to such facilities. All routine vaccines
should be up to date and consideration should be give to other vaccines as needed.
(see next page for more information on individual vaccines, toxoids)
32-75 63 1/9/12, 3:04 PM

32-75
Vaccine or Indication Timing Comments
toxoid
Diphtheria All adults Every 10 years, as Td Adverse events: Transient local and febrile reactions (usually mild and self-limiting)
(IM) Contraindications: Allergy to any component of the vaccine
Tetanus All adults Every 10 years, as Td Adverse events: Local erythema and swelling. Severe local reactions are associated
(IM) with high levels of antitoxin, often as a result of over vaccination
Contraindications: Allergy to any component of the vaccine. No booster dose in the last five
years or 10 years if major local reaction or avoid use at all if previous major systemic reaction
Pertussis Adults who have not Give once as dTap (it is Adverse events: Transient, local pain, erythema and swelling were generally mild
previously received a dose recommemded that a single Contraindications: Hypersensitivity to any compont of the vaccine
of acellular Pertussis vaccine Td booster be replaced with
the combined dTap vaccine)
64
Influenza Adults >65 yrs or <65 Give yearly between Contraindications: Anaphylaxis to eggs, previous allergic reaction to influenza
(IM, SC) yrs with chronic September and vaccine
medical conditions1 December
Pneumococcal Adults >65 yrs Once in a life-time Adverse events: Local soreness and erythema are common
64
(polysaccaride) or <65 yrs with Re-vaccination once in Contraindications: Previous allergic reaction to pneumococcal vaccine
(IM, SC) chronic medical 5 years for the following:
conditions2 patients with asplenia,
sickle cell disease, severe
cardiopulmonary disease,
cirrhosis, chronic renal
failure, HIV infection, or
immunosuppression
Measles All adults born in 1970 or All adults born in 1970 or Adverse events: Fever, transient thrombocytopenia and very rarely encephalitis
(preferable to later who are susceptible later who are susceptible Contraindications: Immunosuppression. Previous allergic reaction to measles or MMR vaccines,
give as MMR) to measles to measles (by serology) neomycin allergy
Immunization for Adults (cont’d)
(SC)
Rubella Susceptible women of One dose, no further Adverse events: Rash, lymphadenopathy, transient arthralgia
(SC) childbearing age and doses needed Contraindications: Pregnancy, immunosuppression, allergy to neomycin
health care workers
1/9/12, 3:04 PM
Mumps Adults born in One dose, no further Adverse events: Fever, parotitis, rash
(SC) 1970 or later doses needed Contraindications: Pregnancy, immunosuppression, allergy to neomycin
32-75
Varicella Susceptible health Two doses separated Adverse events: Fever, local reactions, rash
(SC) care workers, and by 4 to 8 weeks Contraindications: Hypersensitivity to any vaccine component including neomycin, malignant
certain patient neoplasms affecting the bone marrow, immunosuppression, active untreated TB, pregnancy
populations4 Warnings: Avoid salicylates for 6 weeks
Hepatitis B3 Occupational, life-style or Series of three doses Adverse events: Fever, local reactions
(IM) environmental exposure4 Contraindications: Hypersensitivity to any vaccine component
Haemophilus B Patients with anatomic or One dose Adverse events: Fever, local reactions
(HIB) functional asplenia and Currently no Contraindications: Hypersensitivity to any vaccine component
(IM) other immunosuppressed recommendations for
patients at risk for invasive revaccination are
65
HIB infection available
Menactra Patients with anatomic Patients with anatomic or Adverse events: Fever, local reactions
A,C,Y and W-135 or functional asplenia functional asplenia Contraindications: Hypersensitivity to any vaccine component
(conjugate) (IM) Preferred to give dose x 1 (instead
of C-conjugate followed by A, C,
Y, W-135 polysaccharide)
65
Meningococcal Patients with anatomic One dose (2 weeks after conjugate) Adverse events: Fever, local reactions
A,C,Y and W-135 or functional asplenia The need for repeat doses and Contraindications: Hypersensitivity to any vaccine component
(polysaccharite) their optimal timing is unknown
(SC) (effectiveness of vaccine is
probably 2 years or less)
Meningococcal Patients with anatomic Give dose (2 weeks prior to Adverse events: Fever, local reactions
C (conjugate) (IM) or functional asplenia polysaccharide vaccine) Contraindications: Hypersensitivity to any vaccine component
Hepatitis A3 Occupational, life-style or Series of two to three doses Adverse events: Fever, local reactions
(IM) environmental exposure4 (depending on the product) Contraindications: Hypersensitivity to any vaccine component
Immunization for Adults (cont’d)
1. Cardiorespiratory disease, diabetes mellitus, hepatic or renal disease, cancer, immunosuppression, alcoholism, residence in an institution
1/9/12, 3:04 PM
2. Cardiorespiratory disease (except asthma), diabetes mellitus, alcoholism, cirrhosis, renal disease, cancer, asplenia, sickle cell disease, CSF leak, HIV infection, homelessness, IVDU
3. There is combination Hepatitis A/B vaccine available
4. Please call Pharmacy or refer to Canadian Immunization Guideline 7th ed 2006 for more information.
PRE-PRINTED ORDER
Department of Medicine, Infectious Diseases
Pneumonococcal & Influenza Vaccination
Patient: Allergies:
THE FOLLOWING ORDERS:
• May be used on any nursing unit and will be carried out by a qualified health professional ONLY ON THE
AUTHORITY OF A PHYSICIAN
• All orders to be carried out must be checked/completed as appropriate.
• All dates must be written yyyy/mm/dd. All times must be on the 24-hour clock (hhmm hr).
1. Risk assessment for INFLUENZA: At high risk due to: (check all applicable)
a. ■ Age 65 or older
b. ■ Chronic cardiovascular or pulmonary disease (i.e. asthma*, COPD)
c. ■ Resident in nursing home
d. ■ Chronic condition such as diabetes mellitus, cancer, immunodeficiency, immunosuppression, renal
disease, anemia or hemoglobinopathy
e. ■ HIV
f. ■ Foreign travel to destination where influenza is likely circulating
g. ■ Health care occupation or contact with people at high risk
2. Risk assessment for PNEUMONOCOCCAL disease: At high risk due to: (check all applicable)
■ At risk for influenza (any of box a. through e. above checked; exception – box f. or g.)
■ Asplenia, splenic dysfunction, sickle cell disease, cirrhosis, alcoholism or chronic leak of cerebrospinal fluid
* Asthma alone has not been associated with increased risk for pneumococcal disease
3. Contraindications (check all applicable)

■ Anaphylactic reaction to a previous dose
■ Hypersensitivity to eggs (influenza only) or other components of the vaccine
■ Acute febrile illness
■ Previously received pneumococcal vaccine. [Some sub-groups require re-immunization (See Canadian
Immunization Guide)]
4. ■ Administer pneumococcal vaccine (0.5 mL intra-muscularly or subcutaneously in deltoid)
5. ■ Administer influenza vaccine [0.5 mL intramuscularly in deltoid (subcutaneously also permissible)]
6. ■ Do not administer vaccines
Physician’s Signature: Date (YYYY/MM/DD):
Physician’s Name: CPSNS No.

Print
CD0880MR 10/05 Top copy – chart Bottom copy – pharmacy Page 1 of 1
32-75 66 1/9/12, 3:04 PM

Risk assessment for pneumococcal vaccine only (as all patients are at risk for influenza disease and qualify for vaccine
unless there is a contraindication)
Assess contraindications
Obtain Informed Consent

Discuss:
- Benefits of vaccine s)
- Risks of not getting vaccinated
- Common and expected side effects of the vaccine (s)
- Possible serious adverse effects and their frequency
- Potential need and consent for anaphylaxis management
- Provide opportunity for questions
- Patient appears to understand and knowingly consents
Administer vaccine(s)
Document administration of vaccine including lot number and site of injection(s) either in MAR
32-75 67 1/9/12, 3:04 PM

32-75
Infection Patient Criteria Usual Pathogens Recommended Alternatives Duration Comments
Empiric Tharpy
Acute Cholecystitis Mild Usually does not require

antimicrobial therapy
a
Moderate to severe E. coli Cefazolin + Penicillin-allergic: 7-10 days Enterococcus should
B. fragilis metronidazoleb Clindamycin + be treated only if
Enterococcusa OR gentamicinc 3-5 days isolated bCefoxitin is
Ampicillin + OR if no interchanged to
gentamicinc + Ciprofloxacin + perforation, cefazolin + metronidazole
c
metronidazole metronidazole abcess, or Aminoglycosides should
cholangitis be avoided in the elderly,
Oral Stepdown: Oral Stepdown: critically ill, or those
Amoxicillin/ Ciprofloxacin + with renal impairment.
clavulanate metronidazole
68
a
Acute Cholangitis Uncomplicated E. coli Cefazolin + Penicillin-allergic: 10 days Enterococcus should
(no perforation B. fragilis metronidazoleb Clindamycin + be treated only if
or abscess) Enterococcusa OR gentamicinc isolated bCefoxitin is
68
Ampicillin + OR interchanged to
gentamicinc + Ciprofloxacin + cefazolin + metronidazole
c
metronidazole metronidazole Aminoglycosides should
be avoided in the elderly,
Oral Stepdown: Oral Stepdown: critically ill, or those
Amoxicillin/ Ciprofloxacin + with renal impairment.
Intra-abdominal Infections
clavulanate metronidazole
Performation/
abscess
See Secondary
Peritonitis
Post-ERCP P. aeruginosa Piperacillin/ Penicillin-allergic:

tazobactam Ciprofloxacin +
metronidazole
1/9/12, 3:04 PM
* Cultures and sensitivities should always be used to guide antimicrobial therapy when available
Guidelines for the Empiric Treatment of
32-75
Empiric Tharpy
a
Acute Mild-moderate E. coli Oral Therapy:b Penicillin-allergic: 7-10 days, Only amoxicillin-
Diverticulitis B. fragilis Amoxicillin-clavulanate Ciprofloxacin + according clavulanate covers
Enterococcusa OR metronidazole to clinical Enterococcus
b
Trimethoprim/ response. Oral therapy is
sulfamethoxazole + appropriate for mild
metronidazole uncomplicated
IV Therapy: infections
Cefazolin + metronidazole
69
Severe
See Secondary Peritonitis
Acute Pancreatitis Complicated- E. coli Piperacillin/ Penicillin-allergic: Dependent Tailor antimirobials

abscess, infected Enterococcus spp tazobactam Ciprofloxacin + on clinical to C&S results.
pseudocyst, infected S. aureus OR metronidazole picture,
necrotic pancreas Coagulase Meropenem may be
negative Staph prolonged.
69
Anaerobes
Candida spp
Intra-abdominal Infections (cont’d)
1/9/12, 3:04 PM
32-75
Empiric Tharpy
Acute Appendicitis Uncomplicated Empiric therapy

not required
Complicated
(gangrene,
perforation,
abscess or
peritionitis)
See Secondary
Peritonitis
Liver Abscess Bacterial E. coli Drainage and: Piperacillin/ 4 weeks or

B. fragilis Cefazolin + tazobactam until CT
70
Enterococcus metronidazole resolution
Streptococcus Penicillin-allergic:
anginosus/ Oral Stepdown: Ciprofloxacin +
milleri group Amoxicillin/clavulanate metronidazole
70
Spontaneous Enterobacteriaceae Cefotaxime Penicillin-allergic: 10-14 days
Bacterial S. pneumoniae Ciprofloxacin
Peritonitis Streptococcus spp Oral Stepdown:
Amoxicillin/clavulanate Oral Stepdown:
Ciprofloxacin
1/9/12, 3:04 PM
32-75
Empiric Tharpy
a
Secondary Community- E. coli Ampicillin + Ceftriaxonee + Dependent Treat if isolated.
a
Peritonitis acquired B. fragilis gentamicinb + metronidazole on clinical Aminoglycosides should
(e.g. bowel Enterococcus metronidazole picture be avoided in the elderly,
perforation, Streptococcus spp OR Penicillin-allergic: criticall ill, or those with
ruptured Candida sppa Cefazolin + Clindamycin + renal impairment.
c
appendix) metronidazolec gentamicina Cefoxitin is interchanged to
OR cefazolin + metronidazole.
d
Oral Stepdown:d Ciprofloxacin + Oral stepdown appropriate
Amoxicillin/ metronidazole in patients with a working
71
clavulanate GI tract and normalizing
Oral Stepdown:d WBC and temp.
e
*Ciprofloxacin + High incidence of diarrhea
metronidazole and biliary sludging.
f
Treat with a different
Hospital-acquired E. coli Cefazolin + Piperacillin/ Dependent antimicrobial class and
and no previous B. fragilis metronidazoleb tazobactam on clinical consider Infectious
antimicrobial Enterococcus spp picture Diseases consult.
71
therapy, or intra- Klebsiella spp Penicillin-allergic:
abdominal abscess Proteus spp Ciprofloxacin +
P. aeruginosa metronidazole
Candida spp
Hospital-acquired, E. coli Piperacillin/ Meropenem Dependent

previous antimicrobial B. fragilis tazobactam on clinical
therapyf, or ICU Enterococcus spp Penicillin-allergic: picture
admission Klebsiella spp *Ciprofloxacin +
Proteus spp metronidazole
P. aeruginosa
Serratia spp
Acinetobacter spp
S. epidermis
1/9/12, 3:04 PM
Candida sppa
*Ciprofloxacin + metronidazole does not cover enterococcus

32-75
Empiric Tharpy
a
Tertiary P. aeruginosa Treat according Continue Treat if isolated.
Peritonitis E. faecium to C&S results until afebrile,
Coagulase normal WBC/
negative Staph differential,
Candida sppa no residual
fluid collections,
dependent on
the clinical
picture.
References available upon request from Pharmacy.
72
72
1/9/12, 3:04 PM
32-75
Etiologies Treatment
Suggested Regimens Alternative Regimens
Inpatient Note: Hospitalization Criteria: pregnancy, when surgical emergencies (i.e., appendicitis) are not excluded, patient not responding clinically to
oral therapy, patient not able to follow or tolerate outpatient regimens, severe illness, nausea and vomiting, high fever, or tubo-ovarian abscess.
Consider hospitalization for oral or parenteral therapy in HIV infected patients or youth/adolescents.
Sexually Transmitted: A) Ceftriaxone 1 g IV q24h + doxycycline 100 mg IV or A) Ofloxacin 400 mg IV q12h ± metronidazole 500 mg IV
Chlamydia trachomatis PO* q12h. IV therapy can be discontinued 24 h after clinical q12h
Neisseria gonorrhoeae improvement, and doxycycline 100 mg BID PO should B) Levofloxacin 500 mg IV q24h ± metronidazole 500 mg
Herpes simplex virus continue for a total of 14 days of treatment. IV q12h
Trichomonas vaginalis B) Clindamycin 900 mg IV q8h + gentamicin 6 mg/kg IV C) Ertapenem 1 g IV every 24 h + doxycycline 100 mg IV
73
Endogenous organisms: q24h. IV therapy can be discontinued 24 h after clinical or PO* every 12 h
Mycoplasma genitalium improvement, and doxycycline 100 mg BID PO or Note: Due to concerns of anaerobic coverage of
Mycoplasma hominis clindamycin 450 mg QID PO should continue for a total of quinolones, metronidazole should be added to quinolone
Ureaplasma urealyticum 14 days of treatment. regimens
Anaerobic bacteria: A) Ceftriaxone 250 mg IM single dose + doxycycline 100 A) Ofloxacin 400 mg PO BID x 14 d ± metronidazole 500
Bacteroides spp. mg BID PO x 14 d mg PO BID for 14 d
73
Outpatient Peptostreptococcus spp. B) Other parenteral 3rd generation cephalosporin (i.e., B) Levofloxacin 500 mg PO QD ± metronidazole 500 mg
Prevotella spp. cefotaxime) + doxycycline 100 mg PO BID x 14 d. PO BID x 14 d
Facultative (aerobic) bacteria:
Escherichia coli Patients with contraindications to cephalosporins or
(Metronidazole 500 mg PO BID x 14 d may be added to quinolones can be treated with azithromycin 250 mg PO
Gardnerella vaginalis these regimens for more anaerobic coverage)
Haemophilus influenzae once daily x 7 d or 1 g PO weekly x 2 weeks + oral
Pelvic Inflammatory Disease
Streptococcus spp. metronidazole

Note: Quinolones are considered as an alternative only if
Most cases are associated susceptibility testing is available and has demonstrated
with more than one organism susceptibility or a test of cure can be completed.
• *Most experts recommend doxycycline can be administered orally in hospitalized patients due to painful and costly IV administration. Oral and IV administration
1/9/12, 3:04 PM
also have similar bioavailability.
• Efficacy and complication rates are not significantly different between parenteral versus oral therapy or inpatient versus outpatient treatment.
• If patient does not recover, consider differential diagnosis and laparoscopy.
• Improvement in pain and tenderness from acute PID should begin within 2-3 days after initiating therapy.
Reference: Wong T, editor. Canadian guidelines on sexually transmitted infections. Ottawa: Public Health Agency of Canada; 2008.
Penicillin Allergy – An Overview
Clinical situations for which penicillin is indicated as the sole effective treatment arise frequently in
hospital practice. The evaluation of suspected penicillin allergy is therefore essential in making
decisions about alternative antibiotic therapy verses penicillin. Up to 20% of hospitalized
individuals claim allergy to penicillin. However, penicillin can also cause non-allergic intolerance
(most commonly manifested as GI effects) and it is this intolerance that is often misinterpreted as
allergy by many patients. Other reasons for misdiagnosis of penicillin allergy may include a
patient’s faulty recall or natural declining hypersensitivity over time. Three to seven percent of
patients taking ampicillin or amoxicillin develop maculopapular rashes. These rashes are not IgE-
mediated however, and develop more commonly (up to 100%) in a patient with mononucleosis
or with concurrent allopurinol therapy (up to 30%).
After a careful review of past penicillin usage and subsequent outcomes, all patients with
suspected allergies can be classified into one of three categories represented in the following table:
ALLERGIC POSSIBLY ALLERGIC ALLERGY NOT LIKELY

• Anaphylactic reactions: IgE • Mild skin rash • Nausea, vomiting,
swelling of throat, lips, or • Itchiness alone without diarrhea
face; difficulty breathing, rash • Negative rechallenge
wheezing; urticaria • Unknown reaction • Injection site reactions:
• Serum Sickness pain, phlebitis
• Stevens-Johnson • Seizures
• Unknown reaction
• Those patients found to be “Allergic” should avoid penicillins.

• There is less chance of a serious reaction in the “Possibly Allergic” category because
these symptoms are consistent with reactions to the drug’s primary metabolites, not
minor determinants, and are less likely to result in anaphylaxis.
• An “Allergy Not Likely” patient implies that the effects previously experienced, are
GI or infusion-related and not allergy-related; penicillin and related drugs may be
considered.
• Patients with chronic urticaria may have urticaria exacerbated by any antimicrobials
or infection - patient can be referred to Immunology.
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Penicillin Allergy (cont’d)
Reaction to any penicillin
➝ ➝
History of urticarial rash, History of other type of reaction
angioedema,
➝
bronchospasm,
or hypotension Challenge with a penicillin,
cephalosporin*, or carbapenem**
➝
Do penicillin skin test before giving any penicillin

(consult Immunology) consider cephalosporin*,
consider carbapenem **, or other class of antibiotics
➝
➝
Positive skin test result Negative skin test result
➝
➝
Avoid penicillins or Challenge with a penicillin

desensitize patient (see PPO)
*In the general population, the risk of serious allergic reactions to cephalosporins appears to be
<0.02%; the risk is lowest for third-generation cephalosporins (possibly because free drug
competes with bound drug for antibodies to the side chain). Therefore, even if patients with a
history of penicillin allergy have twice as great a risk of have a serious reaction to cephalosporins
that do control subjects; this risk may be lower than the risk that they will have a serious reaction
to any alternative antibiotic.1
**Patients with a history of a reported or documented penicillin allergy appeared to
demonstrate an 11% incidence of hypersensitivity when treated with a carbapenem, compared
with an incidence of 2.7% for patients without a reported history of penicillin allergy.2 However,
it is important to note these statistics are based on a variety of reaction severities, and lower rates
have been observed in other studies (1.5-5%)4,5
References
1. Robinson, J.L., Hameed, T. and Carr S. Practical Aspects of Choosing an Antibiotic for Patients with a Reported Allergy to an
Antibiotic. CID 2002;35:26-31.
2. Prescott W.A. et al. Incidence of Carbapenem-Associated Allergic-Type Reactions among Patients with versus Patients
without a Reported Penicillin Allergy. CID 2004;38:1102-1107.
3. Romano, A. et al. Cross-Reactivity and Tolerability of Cephalosporins in Patients with Immediate Hypersensitivity to
Penicillins. Ann Intern Med. 2004;141:16-22.
4. Schiavino, D. Cross reactivity and tolerability of imipenem Allergy 2009;64:1644.
5. Atanaskovic M. Tolerability of imipenem in children with IgE mediated hypersentivity to penicilin Allergy 2008;63:237.
32-75 75 1/9/12, 3:04 PM

76-85 76 1/9/12, 3:15 PM

Pentamidine
– Suggested Dosing Guidelines
Pentamidine Therapy:
Pentamidine, 3-4 mg/kg/d IV as a single daily dose, infused over at least 1 hour (preferably
over 2-3 hours).
Side Effects of Pentamidine Therapy:

The use of injectable pentamidine is associated with a variety of serious adverse effects in
approximately 50% of treated patients. Medical staff should be consulted when abnormalities
in laboratory data occur or if questions concerning change in management arise.
Side Effect Incidence (%)
Skin rash or thrombophlebitis 1–2
Hypotension (positioning patient in a
supine position during administration
may decrease incidence) 9 – 10
Arrhythmias (ventricular tachycardia) 1–2
Hypoglycemia, usually after first
5-7 days of treatment 6 – 40
Hyperglycemia may occur up to months
after treatment, in about 5% of patients
with a history of hypoglycemia
Hypocalcemia 1–2
Myelotoxicity, neutropenia, pancytopenia 14 – 15
Nephrotoxicity, possibly progressing to
acute renal failure including hyperkalemia,
hypomagnesemia 23 – 25
Acute Pancreatitis rare, but serious
Elevated Liver Enzymes 9 – 11
Management of Pentamidine Therapy:

• prior to therapy and daily: glucose (by chemstrip or blood) anytime of the day.
• prior to therapy and twice weekly: CBC with differential and platelets; calcium,
magnesium; liver function tests; urea, creatinine, electrolytes.
• vitals: beginning, and at end of infusion. Ambulatory patients should have BP checked
sitting at the completion of infusion to check for postural hypotension.
• assure adequate fluid status before administering pentamidine, preloading with 500
mL of NaCL 0.9% may decrease the incidence of nephrotoxicity/hypotension.
• avoid other nephrotoxic drugs (amphotericin B, aminoglycosides, vancomycin)
whenever possible.
• counsel patient on signs and symptoms of acute pancreatitis i.e. acute abdominal pain,
nausea and vomiting.
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Empiric Therapy of Pneumonia
EMPIRIC ANTIBIOTIC THERAPY OF PNEUMONIA IS DETERMINED
BY THREE MAIN FACTORS:
1. Where was the infection acquired?
• Community vs Chronic Care Facility vs Acute Care Hospital vs Intensive Care Unit.
2. What are the patient’s age and underlying conditions?

• Alcoholism, COPD, chronic bronchitis, altered level of consciousness or impaired
swallowing, influenza, chronic debilitating conditions (malignancy, chronic renal
failure, etc.), cystic fibrosis.
3. What is the severity of the illness?

• Respiratory function (blood gases, need for ventilatory support, degree of distress).
• Progression of the illness (stable vs deteriorating).
An assessment of the first two factors will help determine the most likely pathogen.
Empiric therapy should be initiated based on the above factors pending results of Gram
stain and cultures. Therapy must be modified to the most effective and least costly therapy,
once culture results are known.
The greatest cost savings are achieved by an early switch from intravenous to oral therapy.
See Sequential Antibiotic Therapy and Pharmacist Initiation Route of Administration
Therapeutic Interchange.
The following guidelines will assist in selecting the most cost-effective empiric therapy for
most clinical situations.
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Suggested Guidelines for the Treatment of
Community-Acquired Pneumonia
Patient with community acquired pneumonia
➝
CXR, CBC, lytes, urea, glucose,
O2 sat (if <90% ABG)
➝
Pneumonia severity scoring system
➝
➝
➝
≤ 70 points 71-90 points ≥ 91 point
➝
➝
➝
Fits extra discharge 1st dose IV/PO antibiotic in Admit to
criteria emergency dept. hospital
➝
➝
No Yes Start drug
therapy
➝
Admit to 1. D/C home

hospital 2. Suggested antibiotic choices:
- Clarithromycin 500 mg po bid x 10 days
➝
- Azithromycin 500 mg po once then 250 mg po od x 4

days
Start drug - Pts >65yrs can use Cefuroxime 500 mg po BID
therapy (↓ likelihood mycoplasma, chlamydia pneumoniae)
3. All patients should follow-up with their Family Physician
4. Follow-up CXR if:
- Patient ≥55yrs old
- Patient ≥45yrs old and smokes
5. Pneumonia education booklet
Organisms
No Comorbidity Comorbidity
S.pneumoniae Legionella species S.pneumoniae S.aureus
H.Influenzae Mycoplasma pneumoniae H.influenzae Gram-negative rods
S.aureus Chlamydia pneumoniae Oral anaerobes Legionella species
Extra Discharge Criteria

1.The patient’s O2 sat >90% on R/A (or if COPD paO2>55) yes or no
2. Will the patient tolerate oral medications? yes or no
3. Will the patient likely be compliant? yes or no
4. Are home supports sufficient? yes or no
If you have answered NO to any of these questions, consider admission.
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Treatment of Community-Acquired
Pneumonia (cont’d)
Drug Therapy
* Levofloxacin 500 mg IV/PO Once daily*
OR
* Ceftriaxone 1 g IV once daily + Azithromycin 500 mg IV/PO Once daily
* If patient has received a fluoroquinolone in the past 3 months, then choose an antibiotic from
another class.
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Suggested Guidelines for the Management
of Hospital-Acquired Pneumonia1,2,3
Definitions
Hospital-acquired pneumonia (HAP): Pneumonia that occurs 48 hours or more after
admission, which was not incubating at the time of admission.
Diagnosis
Common Causative Pathogens:
• Gram negative rods: Haemophilus influenzae, Escherichia coli, Klebsiella pneumoniae,
Proteus species, Enterobacter species, Serratia marcescens, Pseudomonas aeruginosa and
Acinetobacter species.
• Gram positive cocci: Staphylococcus aureus, Streptococcus pneumoniae.
• Anaerobes: May play a role when there has been macroaspiration.
Clinical Strategy:
• Diagnostic investigations (sputum and blood cultures) should be obtained prior to
antibiotic initiation or change.
TABLE 2
Centers for Disease Control and Prevention criteria for nosocomial pneumonia
Pneumonia must meet one of the criteria (only in patients >12 months of age)
1. Rales or dullness to percussion on physical examination of chest and any of the following:
• new onset of purulent sputum or change in character of sputum;
• organism isolated from blood culture;
• isolation of pathogen from specimen obtained by transtracheal aspirate, bronchial
brushing or biopsy.
2. Chest radiographic examination shows new or progressive infiltrate, consolidation,
cavitation or pleural effusion and any of the following:
• new onset of purulent sputum or change in character of sputum;
• organism isolated from blood culture;
• isolation of pathogen from specimen obtained by transtracheal aspirate, bronchial
brushing or biopsy;
• isolation of virus or detection of viral antigen in respiratory secretions;
• diagnostic single antibody titre (IgM) or four-fold increase in paired serum samples (IgG)
for pathogen.
Ig Immunoglobulin. Adapted from reference 3.
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Treatment
Empiric Therapy:
• The treatment of HAP is usually empirical. Studies have shown that delayed or
inappropriate administration of empiric antimicrobial therapy is associated with
increased mortality. Therefore it is imperative that optimal treatment be initiated as
soon as possible.
• Choice of agent should be based on our local patterns of susceptibility, anticipated side
effects, and what antibiotics the patient has recently received, striving not to repeat the
same antimicrobial class if possible.
• Intravenous therapy should be used in all patients initially. A switch to oral/enteral
therapy can be made in patients with good clinical response and functioning
gastrointestinal tract.
• Legionnaires’ Disease
• Legionella pneumophila should be suspected in severe or rapidly progressing
pneumonia. Sputum for Legionella culture should be specifically requested in this
situation.
• Patients with suspected or diagnosed legionnaires’ disease should be treated with IV
azithromycin, or a fluoroquinolone.
Ward patient (No risk factors for multi-drug resistant (MDR) pathogens*):
• Initial Treatment: Ceftriaxone
• Stepdown: Amoxicillin/clavulanic acid, cefuroxime, or ciprofloxacin
*Risk factors for MDR pathogens:

(Antibiotic therapy should be tailored to reflect individual patient’s risk factors.)
• Current hospitalisation of 4 days or more;
• Antimicrobial therapy in preceding 30 days;
• Patients hospitalized in an acute care hospital for 2 or more days within 90 days of the
infection;
• Recent ICU admissions.
De-escalation:
• Clinical improvement usually takes 48–72 hours, and thus therapy should not be
changed during this time unless there is rapid clinical decline.
• Broad spectrum empiric antibiotic therapy should be accompanied by a commitment
to streamline antibiotics, on the basis of clinical microbiologic data, to limit the
emergence of resistance in the hospital and the potential for adverse effects.
Duration of Therapy:
• If patients receive an initially appropriate antibiotic regimen, duration of therapy may
be shortened from 10-14 days to as short as 7 days, provided that the pathogen is not P.
aeruginosa, S aureus and that the patient has a good clinical response with resolution
of clinical features of infection.
References:
1. Am J Respir Crit Care Med 2005;171:388-416
2. Microbiology Susceptibility Reports 2000, Antimicrobial Handbook, QEII
3. Can J Infec Dis Med Micro January 2008; 19 (1): 19.
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Diagnostic Algorithm HAP/VAP
Screen patient for clinical features: Does patient have two or more of the following features that are
suggestive of an infection?
a. temperature >38°C or <36°C

b. leukopenia/leukocytosis
c. purulent tracheal secretions NO
d. decreased PaO2
No further investigation is required;

however, it is recommended that the
YES patient be monitored for any changes
to their condition
Order chest x-ray
Review patient’s chest x-ray: Were any of the abnormalities listed below observed
on the patient’s chest x-ray?
a. evidence of alveolar infiltrates

b. evidence of air bronchograms
c. new or worsened infiltrates NO
Recommended that the patient be

monitored and that an investigation into
YES other possible causes be conducted
Is the patient in the ICU?
YES
Is the patient mechanically ventilated? NO
YES
Calculate patient’s CPIS Calculate patient’s CPIS
YES
Is the CPIS ≤6? Is the CPIS ≤6?
NO
YES Is the CPIS <4?

Are trachobronchial
YES secretions available
for Gram stain?
NO
YES
Initiate therapy NO
NO
Are pus cells and
Recalculate organisms present?
CPIS daily
YES
Continue Treat based

Stop Stop therapy
therapy if on Gram stain
therapy if if CPIS ≤6
CPIS >6 and local
started on day 3
on day 3 epidemiology
Diagnostic algorithm for hospital-acquired pneumonia and ventilator-associated pneumonia.

Please note that there is no definitive scientific evidence or expert consensus that quantitative
testing produces better clinical outcomes than empirical treatment. Scientific evidence of
improved specificity, supplemented by expert opinion, supports the performance of invasive
tests to avoid the use of antibiotics for clinically insignificant organisms, but there is no direct
evidence or consensus regarding the superiority of one invasive test over another. Factors to
consider in choosing an appropriate test include sensitivity and specificity, ability to improve
patient outcome, potential adverse effects, test availability and cost. CPIS Clinical pulmonary
infection score; ICU Intensive care unit; PaO2 Partial pressure of oxygen in arterial blood.3
76-85 83 1/9/12, 3:15 PM

Treatment Guidelines for the Management
of Ventilator-Associated Pneumonia
Summary
Prompt appropriate therapy for critically ill patients with VAP and other infections reduces
mortality. However, antibiotic resistant organisms are an increasing threat to the health
care system. Within the hospital environment, critical care areas have the highest
incidence of antibiotic resistant organisms.1 It is important therefore, to minimize the use
of antibiotics whenever possible. This must be balanced with the fact that prompt
adequate therapy for critically ill patients with VAP affects clinical outcome.2
Developing this approach to the management of VAP was based on the following
points from the literature:
1. Mortality is lower in patients who initially receive the correct antimicrobial for
their pneumonia, as shown in a number of studies.3-6 Initial treatment should be
based on local flora and antibiotic susceptibility patterns, the duration of prior
hospital and ICU stay (“early” or “late”), and history of previous antibiotic
therapy.7
2. There is to date no “gold standard” for the diagnosis of VAP. Clinical criteria for
diagnosing VAP are not very specific and often patients have non-infectious
causes of their pulmonary infiltrates.9,10 As a result, antibiotics may be prescribed
unnecessarily, with the potential for increased costs, adverse effects, and the
future development of infection with resistant organisms.11 Prior receipt of
antibiotics is a risk factor for infection with resistant organisms in studies of
VAP. Bacteriological sampling is usually required to confirm clinically suspected
pneumonia and direct therapy.
3. Although not consistently done, various studies have shown that antibiotics can
safely be stopped in patients with negative bronchoscopic specimen
cultures.11,14,15
4. In selected patients with VAP, a 7 or 8 day course of treatment is as effective as

longer courses, and does not result in adverse patient outcomes.16,17
5. A comprehensive evaluation or algorithmic approach to VAP incorporating

formal reassessment of the need or tailoring of antibiotic therapy based on
culture results, results in decreased antibiotic use, a decreased length of ICU stay,
and a decreased rate of secondary infections.11,18
Conclusion
The optimization of the management of VAP (i.e. improved diagnosis, prompt, adequate
initiation of antibiotics, reassessment or narrowing of antibiotic therapy based on cultures
and shorter duration of therapy) should lead to improved patient outcomes and a
decreased risk of antibiotic resistance.
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CDHA Algorithum for the Diagnosis and
Management of VAP
Infection
Suspected
➝
VAP Criteria: New pulmonary infiltrate after 48
hrs of intubation, not otherwise explainable,
with at least one of: T >38oC,↑ WBC and two or
more of: new change in sputum purulence or ➝ Pneumonia
Diagnosed
volume, rales or bronchial breath sounds,
worsening gas exchange
➝
Draw Cultures: Blood and
pulmonary secretions for
culture should be sent on
every patient with VAP
➝
START ANTIBIOTICS: Early

(≤4 days in hosp): cefotaxime;
Late (>4 days in hosp): pip/
tazo or cipro + cefazolin; if
prev abx course: pip/tazo or
ceftazidime with either an AG
or cipro
➝
Pathogen isolated Cultures Negative, and no abx

within 72 hrs of specimen
Adjust abx
based on C&S# ➝ Check culture results
in 48-72 hours ➝ D/C Abx
Cultures Negative; pt had

Pseudomonas, Acinetobacter, severe sepsis &/or abx
Patient responding
clinically, initial abx
S.aureus, or initial abx did
not cover pathogen
➝ prior to obtaining culture
covered organism(s) Continue or adjust

➝
D/C abx after

➝ abx; look for
alternate source of
Treat for 10-14 days, infection
8 days
or 3 days after
clinical
improvement
* If tracheal aspirate cultures performed, use CPIS (who is going to do this; can we do this regularly when
VAP suspected?) score and re-evaluate after cultures available; D/C abx if CPIS ≤ 6
# change to narrowest spectrum agent which will adequately cover organism; use 2 agents for Pseudomonas
aeruginosa; for Serratia, Acinetobacter, Citrobacter or Enterobacter, use septra or cipro, or change to
piperacillin + gentamicin
Can J Infect Dis Med Micro Apr 2007; 19(1): 19
76-85 85 1/9/12, 3:15 PM

SEPSIS
Suspect
SEVERE SEPSIS or SEPTIC SHOCK
Suspect Severe Sepsis Or Septic Shock In A Patient Who Has:
1. A suspected infection (bacterial, fungal or viral)

2. Two or more vital sign abnormalities* *Vital Sign Abnormalities
3. A lactate equal to or greater than 4 mmol/L and/or MAP a) Temp less than 36°C or greater than
less than 55 mmHg after a 2 L bolus 38°C
b) HR greater than 90 BPM
c) RR greater than 20 or PaCO2 less than
32
9
d) WBC less than 4x10 /L or greater than
9
12x10 /L, or greater than 10% bands
Evidence of Organ Dysfunction:

1. Lactate equal to or greater than 4
2. Alteration in level of consciousness
3. Urine less than 0.5 mL/kg/h x 6h or increased creatinine 1.5 x baseline
4. Elevation of AST, ALT
Empiric Antibiotic Therapy For Patients With Suspected Severe Sepsis Or Septic Shock
Note: Every effort should be made to ensure that antibiotics are administered WITHIN 1 HOUR of the diagnosis of severe sepsis or
septic shock
If possible, obtain appropriate cultures prior to antibiotic administration; however, DO NOT DELAY ANTIBIOTICS FOR
CULTURES
Sepsis Origin Empiric Initial Intravenous Antibiotic

Unknown Vancomycin 20 mg/kg IV AND piperacillin/tazobactam 3.375 g IV
Lung (pneumonia)
A) Community Acquired / Nursing Home cefTRIAXone 1 g IV AND azithromycin 500 mg IV OR
levofloxacin 750 mg IV
B) Hospital Acquired piperacillin/tazobactam 3.375 g IV
**If MRSA suspected (homeless/incarceration/IV drug ADD vancomycin 20 mg/kg IV
use)
Intra-abdominal piperacillin/tazobactam 3.375 g IV
Urologic ampicillin 2 g IV AND gentamicin 4 mg/kg IV
Skin (rapidly progressing/necrotizing fasciitis) cefTRIAXone 1 g IV AND clindamycin 900 mg IV
Central Nervous System cefTRIAXone 2 g IV AND vancomycin 20 mg/kg IV
**ADD dexamethasone 10 mg IV before antibiotic
Febrile Neutropenia piperacillin/tazobactam 3.375 g IV
86-93 86 1/9/12, 3:03 PM

PRE-PRINTED ORDER
Severe Sepsis / Septic Shock Resuscitation

Patient: Allergies:
1. Intravenous Fluid Resuscitation
x Insert 2 large bore peripheral IV cannulas (#16 and #18 gauge)
x Administer 1 L 0.9% sodium chloride IV rapid infusion over 15±30 min IMMEDIATELY
x After 1 L 0.9% sodium chloride, if MAP is equal to or less than 55 mmHg, then repeat 1 L 0.9% sodium chloride IV
infusion over 15±30 min IMMEDIATELY
x After 2 L 0.9% sodium chloride, if MAP is still equal to or less than 55 mmHg and/or the patient has evidence of organ
dysfunction (see reverse), physician to assess need for:
x repeat IV fluid bolus
x insertion of central venous catheter (check platelets, INR and patient's FiO 2)
x insertion of arterial catheter
x initiation of vasopressor medications
x consultation to ICU
x Maintenance IV fluid/rate (after IV Fluid Bolus) mL/h
2. Antibiotics (see reverse forAntimicrobial Section
)
Every effort should be made to have blood cultures collected before the initiation of antibiotics. However, DO NOT DELAY
ANTIBIOTICS IF UNABLE TO COLLECT CULTURES FIRST
Antibiotics should be given within 1h of diagnosis of severe sepsis/septic shock
x
x
x
3. Vital Signs
x Attach patient to a cardiac monitor. Arrange transfer to a step-down or ICU bed if patient on the floor or in the emergency
department
x BP, HR, RR, O2 saturation q15min. Temperature q4h
x Ins and Outs q1h
x Foley to urometer
4. Investigations± STAT
x ABG and lactate
x Profile and differential, BUN, creatinine, blood glucose
x Sodium, potassium, chloride, magnesium
x CK and troponin, EKG
x AST, ALT, alkaline phosphatase, bilirubin and amylase
x Type and screen
x Blood cultures x 2 using two sites. First site both aerobic and anaerobic vials
x Urine dip, microscopy, culture and susceptibility
Sputum for culture and sensitivity
Cultures (other)
Special cultures (viral)
Chest x-ray
Other x-ray
Other investigation (for e.g., CT)
Prescriber¶V6LJQDWXUH Date (yyyy/mm/dd):

PrescULEHU¶V Name Reg. No.
Print
PPO0365MR_11_06 Jul 05 2011 Original ± chart page 1 of 1
86-93 87 1/9/12, 3:03 PM

Splenectomy Vaccination Guidelines
Splenectomy Vaccine Kit (all items go up to floor for patient)
1) Post-splenectomy vaccinations Pre-Printed Order.
2) One dose of each vaccine plus package insert
• Pneumococcal polysaccharide vaccine (Pneumovax®)
• Meningococcal ACYW conjugate (Menactra®)
• Hemophilus influenzae B (Act-Hib®)
3) Splenectomy vaccines - Documentation for Family Physicians form.
4) Splenectomy - Information for Patients sheet.
5) Wallet card for Asplenic Patients sheet.
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86-93 89 1/9/12, 3:03 PM

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Surgical Prophylaxis
PRINCIPLES OF ANTIMICROBIAL PROPHYLAXIS
The accepted principles of antimicrobial prophylaxis for surgical procedures involve:
• Surgical procedures for which antimicrobial prophylaxis has been demonstrated to be
beneficial.
• Antimicrobial prophylaxis for “clean” surgical procedures is generally unnecessary. For
the majority of surgical procedures in which antimicrobial prophylaxis is indicated, a
single 2 g dose of cefazolin given immediately prior to induction of anaesthesia is
appropriate.
• Timing and duration of the administration of the antimicrobial is important. In
general, a single dose of a parenteral antimicrobial given within 30 minutes before skin
incision (i.e. immediately prior to induction of anaesthesia) provides adequate tissue
concentrations for several hours. “On call” dosing is not acceptable, as it may result in
premature administration of the antibiotic regimen and insufficient tissue
concentrations of the drug during surgery. An intra-operative dose of antibiotics should
be given when surgery is prolonged (i.e. more than 3 hours when the antibiotic, such as
cefazolin, has a reasonably long half-life or sooner for an antibiotic with shorter half-
life). If massive blood loss occurs, a second dose should be given promptly. Post-
operative doses of prophylactic antibiotics are generally unnecessary. However, dosing
beyond the operative period is still recommended in such areas as cardiac surgery.
86-93 93 1/9/12, 3:03 PM

Peri-operative Antibiotic Prophylaxis
Table
Patient selection Pre-op IV antibiotic Post-op IV
Standard Penicillin antibiotic
Regimen Allergy duration
Appendectomy
All patients Metronidazole 500 mg Metronidazole 500 mg • No antibiotic
Plus Plus • If gangrenous or
Cefazolin 2 g✿45 Gentamicin 2 mg/kg* perforated appendix
or intestine,
treatment course
must start
Breast
High risk patients only14,15 Cefazolin 2 g✿ Vancomycin 1 g No antibiotic
• Recent neoadjuvant
chemotherapy or radiation
therapy
• Prosthetic material or mesh
• Re-operation or recent prior
breast surgery
• Reconstruction surgeries
• Operation duration ≥2 hours
• Immunocompromised patients
(diabetics, steroids, etc)
Cardiac
All patients Cefazolin 2 g✿ Vancomycin 1 g 24 hours
30
Colorectal
All patients Metronidazole 500 mg Metronidazole 500 mg No antibiotic
Plus Plus
Cefazolin 2 g✿ Gentamicin 2 mg/kg*
Gastroduodenal
High risk patients only Cefazolin 2 g✿ Clindamycin 600 mg No antibiotic
(decreased gastric acidity and Plus
GI motility) Gentamicin 2 mg/kg*
• obstruction
• hemorrhage
• gastric ulcer or malignancy
• therapy with H2 blocker or PPI
• morbid obesity
Hand
Complex Clean Procedures: Cefazolin 2 g✿ Vancomycin 1 g 24 hours
• Mutilating and crushing injuries
from home & industrial source
• Bone, joint, tendon (except
open flexor tendon injuries - see
below) and nerve involvements
• Implants/prosthesis
• Flap reconstruction
• Injuries require amputations
• High risk patients with medical
comorbidities and/or
immunosuppressive drugs
94-102 94 12/12/11, 2:02 PM

Table (cont’d)
Hand (cont’d)
Clean-contaminated and Cefazolin 2 g✿ Clindamycin 600 mg • 24 hours20,26
Contaminated Procedures: Plus Plus • For grossly
• Mutilating and crushing Gentamicin 2 mg/kg* Gentamicin 2 mg/kg* contaminated/dirty
injuries from farm environment Plus wounds and injuries
• Grossly contaminated and Metronidazole longer than 6 hours
dirty injuries 500 mg consider a course of
• Animal and human bites treatment with
• Open fractures broad spectrum
• Use of leeches antibiotics.
Simple Clean Procedures: No antibiotics21,22,25

• Clean simple soft tissue
lacerations 18
• Open flexor tendon injuries
Exception:
✥ Beyond zone IV
Head and Neck (Major)

Clean procedures: Cefazolin 2 g✿ Clindamycin 600 mg Oncology patients9
• no incision of the oral or Benign patients
pharyngeal mucosa • 24 hours
• no implantation of prosthetic • No antibiotics
material
• exceptions (no antibiotics):
- thyroidectomy
- parotidectomy
- submandibular gland excision
- all of above with no neck
dissections and/or skull base
involvement
Clean-contaminated procedures: Cefazolin 2 g✿ Clindamycin 600 mg Oncology patients9

• Require penetration of the Plus Plus • 24 hours
oral or pharyngeal mucosa Metronidazole Gentamicin 2 mg/kg* Benign patients
• Complex resection with 500 mg • No antibiotics
reconstruction procedures
• Revision and salvage surgeries
Hepatic Pancreatic Biliary Tract (HPB)

Minor Procedures Cefazolin 2 g✿ Clindamycin 600 mg No antibiotics for
(Cholecystectomy etc.) Plus most patients except:
• High risk patients only Gentamicin 2 mg/kg* • Acute Cholecystitis:
- age >70 - 2-5 days
- acute cholecystitis • Emphysematous
- non functioning gall bladder acute cholecystitis:
- obstructive jaundice - 5-7 days
- common bile duct stones • Gangrene or
perforated
gallbladder:
- change to a broad
spectrum antibiotic
for treatment
94-102 95 12/12/11, 2:02 PM

Table (cont’d)
Hepatic Pancreatic Biliary Tract (HPB) (cont’d)
Major Procedures Metronidazole 500 mg Metronidazole 500 mg No antibiotics
Plus Plus
Hernia Repair
High risk patients only Cefazolin 2 g✿ Vancomycin 1 g No antibiotic16,17
• prosthetic material or mesh
• age ≥70
• immune compromised patients
(diabetes, neoplasm, HIV/AIDS)
• corticosteroid use
• recurrent repairs
• operative time ≥2 hours
• routine use of drainage and
prosthesis
Neurosurgery
Craniotomy Cefazolin 2 g✿ Vancomycin 1 g No antibiotic
• clean, non-implant
Craniotomy13 Cefazolin 2 g✿ Vancomycin 1 g No antibiotic
• clean-contaminated Plus Plus
• crosses sinuses or naso/ Metronidazole 500 mg Metronidazole 500 mg
oropharynx
• emergency surgery
• operation ≥2 hours
• CSF leakage
• Subsequent operation
Transsphenoidal surgery11,12
• all patients
CSF Shunting32 Cefazolin 2 g✿ Vancomycin 1 g 24 hours46,47
Obstetrics and Gynaecology2,29

Abortion1,2
• First trimester • Chlamydia - positive • Chlamydia - positive For Doxycycline
or suspected or suspected only: Doxycycline
• Previous pelvic • Previous pelvic 200 mg po half
inflammatory disease, inflammatory disease, hour post-op
gonorrhea or multiple gonorrhea or multiple
sex partners sex partners
Oral to be given 1 h Oral to be given 1 h
pre-op: pre-op:
Azithromycin 1 g po Azithromycin 1 g po
Or Or
Doxycycline 100 mg po Doxycycline 100 mg po
• Bacterial vaginosis - • Bacterial vaginosis -
positive or suspected positive or suspected
ADD ADD
Metronidazole Metronidazole
500 mg po 500 mg po
All other patients: All other patients:
Cefazolin 2 g✿ Clindamycin 600 mg
Plus
Gentamicin 2 mg/kg*
94-102 96 12/12/11, 2:02 PM

Table (cont’d)
Obstetrics and Gynaecology2,29 (cont’d)
• Radical and total hysterectomy Cefazolin 2 g✿ Clindamycin 600 mg No antibiotic7
(abdominal, laparoscopic or Plus
vaginal) Gentamicin 2 mg/kg*
• caesarean section
- administer antibiotics prior to
skin incision NOT after cord
clamping8
• vulvectomy with or without
lymphadenectomy
• vaginectomy
• urogynecological procedures
- laparoscopic Burch
- 2-Team sling
• endometriosis (laparoscopy Metronidazole 500 mg Metronidazole 500 mg No antibiotic
and open) Plus Plus
Cefazolin 2 g✿ Gentamicin 2 mg/kg* No antibiotic
Oral and Maxillofacial

• No oral or sinus cavity Cefazolin 2 g✿ Clindamycin 600 mg No antibiotics
involvement
• Oral cavity or sinus cavity Cefazolin 2 g✿ Clindamycin 600 mg No antibiotics19
involvement Plus
• Comminuted and Metronidazole 500 mg
compounded fractures
• Implants/prosthesis; bone graft
• Orthognathic
• Gun shot wound Cefazolin 2 g✿ Clindamycin 600 mg • 24 hours23,24
• Animal or human bite injuries Plus Plus • For grossly
• Grossly contaminated and Gentamicin 2 mg/kg* Gentamicin 2 mg/kg* contaminated/dirty
dirty injury Plus wounds, consider a
Metronidazole 500 mg course of treatment
with broad spectrum
antibiotics.
Orthopedic
Major procedures: Cefazolin 2 g✿ Clindamycin 600 mg 24 hours
• Difficult fracture reconstruction
• total hip & knee replacement
• other procedures requiring
prophylaxis
Minor procedures: No antibiotics
• arthroscopy
• procedures not involving
implantation or prosthetic
material
Spine10
• Fusion Cefazolin 2 g✿ Vancomycin 1 g No antibiotic
• Decompression
• Instrumentation
94-102 97 12/12/11, 2:02 PM

Table (cont’d)
Thoracic
Pulmonary resection only Cefazolin 2 g✿ Vancomycin 1 g No antibiotic
Trauma (Orthopedics)27
Gun shot fracture wound Cefazolin 2 g✿ Vancomycin 1 g 48 hours
Gun shot fracture wound with Cefazolin 2 g✿ Vancomycin 1 g 48 hours
• large soft tissue defects or Plus Plus
cavitary lesions Gentamicin 2 mg/kg* Gentamicin 2 mg/kg*
AND/OR
• fracture of the extremities
(about the hand, foot and ankle)
Gun shot fracture wound with Cefazolin 2 g✿ Vancomycin 1 g • 48 hours
• large soft tissue defects or Plus Plus • For grossly
cavitary lesions Gentamicin 2 mg/kg* Gentamicin 2 mg/kg* contaminated/dirty
AND/OR Plus Plus wounds and injuries
• fracture of the extremities Metronidazole 500 mg Metronidazole 500 mg longer than 6 hours
(about the hand, foot and ankle) consider a course of
PLUS treatment with
• gross contamination of the broad spectrum
wound and environment antibiotics.
- occurred in rural/wooded area
- grossly dirty skin and clothes
- bowel communication
Trauma (Abdomen)28,31
Penetrating abdominal trauma Metronidazole 500 mg Metronidazole 500 mg 24 hours
• hollow viscus injury Plus Plus
Penetrating abdominal trauma Metronidazole 500 mg Metronidazole 500 mg No antibiotic
• non hollow viscus injury Plus Plus
Urinary Diversion Procedures Involving Bowel Segments

(assuming all patients have urine culture performed and all positive urine culture patients are treated before surgery)
5
• Ileal conduit procedures or Oral antibiotics: Oral antibiotics: 24 hours
procedures involving bowel • metronidazole • metronidazole
segments 500 mg po x 3 doses 500 mg po x 3 doses
• Oral AND IV antibiotics at 1, 2 & 4 hours at 1, 2 & 4 hours
Plus Plus
• erythromycin • erythromycin
500 mg po x 3 doses 500 mg po x 3 doses
at 1, 2 & 4 hours after at 1, 2 & 4 hours after
gastric lavage gastric lavage
AND 6
AND
IV antibiotics: IV antibiotics:
• Metronidazole • Metronidazole
500 mg 500 mg
Plus Plus
• Cefazolin 2 g✿ Gentamicin 2 mg/kg*
94-102 98 12/12/11, 2:02 PM

Table (cont’d)
Urology3
(assuming all patients have urine culture performed and all positive urine culture patients are treated before surgery)
• TURP and retropubic total Oral to be given Oral to be given 24 hours4
prostatectomy 1-2 h pre-op: 1-2 h pre-op:
• Transrectal and core biopsy 1. Ciprofloxacin 1. Ciprofloxacin
of the prostate 500 mg po 500 mg po
• Ureteroscopy & percutaneous or or
stone surgery 2. Co-trimoxazole DS - 2. Co-trimoxazole DS -
• implantation of prosthetic 1 tab po 1 tab po
device OR OR
• impaired immune status IV regimen: IV regimen:
• other open and laparoscopy 1. Cefazolin 2 g✿ 1. Gentamicin 2 mg/kg*
procedures or
- clean-contaminated 2. Gentamicin 2 mg/kg*
procedures (open and/or entry
via urinary tract)
➢ all patients
- clean procedures (no urinary
tract entry)
➢ high risk patients only3
✥ advanced age
✥ poor nutritional status
✥ diabetes mellitus
✥ smoking
✥ obesity
✥ coexisting infection at a
remote body site
✥ colonization with
microorganisms
• oral OR IV antibiotics
• ureteroscopy No antibiotics
• cystoscopy
• open and laparoscopy
procedures
- clean (no urinary tract entry)
- exception: high risk patients –
see above risk factors3
Vascular Surgery43,44
• lower limb amputation Cefazolin 2 g✿ Vancomycin 1 g 24 hours
• abdominal and lower limb
vascular surgery
• procedures involving groin
incision or prosthetic material
• carotid endarterectomy and
brachial arterial repair with
prosthetic graft only
94-102 99 12/12/11, 2:02 PM

Intra-operative Antibiotic Prophylaxis
Table:42
Antibiotic Duration of operation Blood loss >1.5L Pre-op administration
>3 hours time
Cefazolin✿ Repeat 1 g q3H33,34,36 Repeat 1 g x 1 dose 0-60 minutes prior to skin

Exception: CrCL ≤30 mL/min only39,40 incision
• repeat 1 g q6h
Ciprofloxacin po Operation >6 hours, No data – 60-120 minutes prior to
administer Cefazolin 1g q3h no recommendation skin incision
CrCL ≤30 mL/min, operation >120 minutes prior to skin
>12 hours, administer incision, repeat
Cefazolin 1 g q6h ciprofloxacin 500 mg po x
1 dose at induction
Clindamycin Repeat q6h No data – 0-60 minutes prior to skin
no recommendation incision
Co-trimoxazole Operation >6 hours, No data – 60-120 minutes prior to
Ds po administer Cefazolin 1 g q3h no recommendation skin incision
CrCL ≤30 mL/min, operation No data – >120 minutes prior to skin
>24 hours, administer no recommendation incision, repeat
Cefazolin 1 g q6h co-trimoxazole DS 1 tab
po x 1 dose at induction
Gentamicin* Repeat 1 dose only intra-op Repeat 1 dose only38,40 60 minutes prior to skin
at 3h after initial dose 37 incision allow
Exception: CrCL ≤60 mL/min Exception: CrCL ≤60 mL/ 30 minutes for infusion
or min or of drugs allow
Males: SCr ≥135 μmol Males: SCr ≥135 μmol another 30 minutes
Females: SCr ≥125 μmol Females: SCr ≥125 μmol for distribution of drugs
• no intra-op dose • no intra-op dose
Metronidazole Repeat q12h No data – 0-60 minutes prior to skin
no recommendation incision
Vancomycin Repeat q12h41 No intra-op dose 60-120 minutes prior to
Exception: CrCL ≤30 mL/min needed35 skin incision allow
• repeat q24h 60 minutes infusion
time for dose of 1 g
* All gentamicin doses will be rounded to the nearest 20 mg.

✿ Cefazolin 2 g is for pre-operative dosing only. Intra-operative and post-operative dosing for cefazolin
will remain 1 g.
Post-operatively resume regular treatment frequency. Adjust as needed for renal impairment
patients.
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46. Costa RB et al. Antibiotic Prophylaxis for Surgical Introduction of Intracranial Ventricular
Shunts; The Cochrane Database of Systematic Reviews; 4, 2007
47. Langley JM, LeBlanc JC et al. Efficacy of Antimicrobial Prophylaxis in Placement of
Cerebrospinal Fluid Shunts: Meta-Analysis. Clinical Infectious Diseases; 17: 98-103, 1993
Adapted from Sunnybrook Health Sciences Centre
94-102 102 12/12/11, 2:02 PM

103-114 103 12/12/11, 2:05 PM

Urinary Tract Infections (UTIs)
UTI Classifications
Lower urinary tract
• Urethritis
• Cystitis
• Prostatitis
Upper urinary tract
• Pyelonephritis
Infection Type
• Acute: recent onset of UTI symptoms
• Chronic: ongoing, unresolved infection, may be due to structural defects or
obstructions and/or resistant or multiple organisms
• Recurrent: symptomatic infection that recurs within 2 weeks of a prior infection with
the same organism or reinfection with a new organism
• Complicated: Acute or chronic UTI with complicating factors such as relapsing
infection, diabetes, pregnancy, altered immune status, structural abnormalities, or
catheterization
• Uncomplicated: UTI without presence of complicating factors
Diagnosis
Must be confirmed by laboratory tests because of the unreliability of symptoms.
Urinalysis
• The presence of leukocytes is non specific and may be indicative of inflammation only
• WBC casts may indicate pyelonephritis
• The following degrees of bacteriuria are often considered to be clinically significant:
Greater than 102 CFU coliforms/mL in symptomatic women
Greater than 103 CFU coliforms/mL in symptomatic men
Greater than 105 CFU coliforms/mL in asymptomatic patients on two consecutive
specimens
Greater than 102 CFU coliforms/mL in a catheterized patient with symptoms
Any growth of bacteria on a suprapubic catheterization in a symptomatic patient
Nitrite test is used as a marker for bacteriuria, but not all uropathogens reduce nitrates to
nitrites. (i.e. Enterococci, S. Saprophyticus and Acetinobacter do not and thus give false-
negative results.)
Culture and sensitivity allows identification of the infecting organism(s) and the
determination of antibiotic sensitivities
Blood cultures should be considered with pyelonephritis and severe complicated UTIs
Asymptomatic Bacteriuria
• Presence of bacteria in voided urine with no symptoms of urinary tract infection
• Treatment is not recommended in the non-catheterized elderly, unless the patient is
symptomatic
• Pregnant women, patients about to undergo urological surgery, immunocompromised
patients should be treated for asymptomatic UTIs.
103-114 104 12/12/11, 2:05 PM

103-114
Category Potential pathogens First line therapy (cost) Second line therapy (cost)
Acute uncomplicated E.coli, S. saprophyticus, Sulfamethoxazole/Trimethoprim DS tab q12h x Ciprofloxacin* 250 mg q12h x 3 days1
cystitis◊ Proteus, Klebsiella 3 days or Nitrofurantoin 50-100 mg q6h x 7 days Cephalexin 500 mg qid x 7 days
Acute cystitis in men requires 7 days of Fosfomycin 3 g x 1 dose
therapy no matter what agent is used Acute cystitis in men requires 7 days of
therapy no matter what agent is used
Acute cystitis E.coli, Proteus, Klebsiella, Amoxicillin 250- 500 mg q8h x 7 days Sulfamethoxazole/Trimethoprim DS tab q12h
(pregnant women) Enterococci (avoid 1st/late 3rd trimesters) or
Cephalexin 250 mg q6h or Nitrofurantoin
105
50-100 mg q6h for 3-7 days
Avoid tetracyclines and quinolones
Acute pyelonephritis E.coli, Proteus, Klebsiella, Severe: Ceftriaxone 1 g q24h1,4 or
(The results of pre- Enterococci, Enterobacter, Ampicillin 1-2 g q6h IV + Ciprofloxacin* 400 mg IV q12h2,4
treatment C/S should be S.saprophyticus Gentamicin 6 mg/kg IV daily (adjusted Step down to oral therapy for a total of
used to direct therapy) to renal function) Step down to oral 14 days3: Ciprofloxacin 500 mg q12h1,4
105
Management of UTIs
Consider the use of therapy for a total of 14 days 3 : or Amoxicillin/Clavulanate 875 mg q12h1
blood cultures Sulfamethoxazole/Trimethoprim DS tab q12h
Do not use nitrofurantoin
Mild to moderate:
Ciprofloxacin 500 mg po q12h x 10-14 days
Complicated UTIs E.coli, Proteus, Klebsiella, Oral therapy: Sulfamethoxazole/Trimethoprim Oral therapy: Ciprofloxacin* 250-500 mg
(The results of pre- Enterococci, Enterobacter, DS tab q12h or Nitrofurantoin q12h1 or Amoxicillin/Clavulanate
treatment C/S should be S.saprophyticus, 50-100 mg for 10-14 days 875 mg q12h1 for 10-14 days.
used to direct therapy) Pseudomonas aeuruginosa IV therapy: IV therapy:
Remove catheter if Ampicillin 1-2 g q6h IV + Ceftriaxone 1 g q24h1 or
catheter-related UTI Gentamicin 6 mg/kg IV daily Ciprofloxacin* 200-400 mg IV q12h2
Consider the use of (adjusted to renal function) Step down to oral therapy
12/12/11, 2:05 PM
blood cultures Step down to oral therapy for a total of 10-14 days3
3
for a total of 10-14 days
*If due to resistant organisms, patient allergies, or contraindications to other agents (as per Antimicrobial Order Form).
◊Note for multidrug resistant, E. coli, fosfomycin can be used.
103-114
Severity Potential pathogens First line therapy (cost) Second line therapy (cost)
Recurrent cystitis E.coli, Proteus, Klebsiella, Early recurrence (< 30 days): Consider prophylaxis for 3 or more recurrences
Enterococci, Enterobacter, Retreat for acute cystitis but per year: Sulfamethoxazole/Trimethoprim one-half
S.saprophyticus for 10-14 days to one tab or nitrofurantoin 50 mg qhs daily
Candiduria in Candida Oral therapy: Fluconazole 200 mg IV therapy: Fluconazole 200 mg daily for
symptomatic patients daily for 3 to 7 days 3 to 7 days2
with risk factors such
as ICU setting,
immunosuppression
106
1. Treatment of UTIs due to resistant organisms or for patients with renal impairment or allergies which preclude the use of other agents
2. Restricted to ID or ICU physicians
3. May be possible to initiate therapy with oral agents in the absence of nausea and vomiting
106
4. The addition of ampicillin/amoxicillin may be necessary in the presence of enterococci
Management of UTIs (cont’d)
12/12/11, 2:05 PM
Vancomycin Usage Guidelines
Recommendations for Appropriate Use of Vancomycin
Prudent antibiotic use is critical to stem the rise of vancomycin-resistant enterococci (VRE),
and even hospitals where the pathogen has not been detected should develop plans to
curtail inappropriate use of vancomycin. Situations in which the use of vancomycin is
appropriate and inappropriate are summarized below.
Using vancomycin is appropriate:

• for treatment of serious infections due to beta-lactam resistant, gram-positive
microorganisms. (Clinicians should be aware that vancomycin may be less rapidly
bactericidal than beta-lactam agents for beta-lactam susceptible staphylococci.);
• for treatment of infections due to gram-positive microorganisms in patients with
serious allergy to beta-lactam antimicrobials;
• when antibiotic-associated colitis (AAC) fails to respond to metronidazole therapy, or
if AAC is severe and potentially life-threatening;
• for prophylaxis, as recommended by the American Heart Association, for endocarditis
following certain procedures in high-risk patients;2
• as prophylaxis for surgical procedures involving implantation of prosthetic materials
or devices at institutions with a high rate of infections due to methicillin-resistant
Staphylococcus aureus (MRSA) or Staphylococcus epidermidis (MRSE). A single dose
administered immediately before surgery is sufficient unless the procedure lasts more
than six hours, in which case the dose should be repeated. Prophylaxis should be
discontinued after a maximum of two doses.
Using vancomycin is inappropriate for:

• routine surgical prophylaxis;
• empiric antimicrobial therapy for a febrile neutropenic patient, unless there is strong
evidence at the onset that the patient has an infection due to gram-positive
microorganisms and the prevalence of infections due to beta-lactam-resistant, gram-
positive microorganisms (e.g. MRSA or MRSE) in the hospital is substantial;
• treatment in response to a single blood culture positive for coagulase-negative
Staphylococcus, if other blood cultures drawn in the same time frame are negative.
(Contamination of blood cultures with skin flora may cause vancomycin to be
administered inappropriately to patients. Phlebotomists and other personnel who
obtain blood cultures should be trained properly to minimize microbial contamination
of specimens.);
• continued empiric use for presumed infections in patients whose cultures are negative
for beta-lactam-resistant, gram-positive microorganisms;
• systemic or local prophylaxis for infection or colonization of indwelling central or
peripheral intravascular catheters and vascular grafts;
• selective decontamination of the digestive tract;
• eradication of MRSA colonization;
• primary treatment of AAC, except if moderate to severe or contains binary toxin;
• routine prophylaxis for patients on continuous ambulatory peritoneal dialysis.
103-114 107 12/12/11, 2:05 PM

Vancomycin Dosing Guidelines (cont’d)
1. INITIAL DOSAGE REGIMEN
The usual initial dose is 15 mg/kg of total body weight (round to the nearest 250 mg),
unless seriously ill (20-25 mg/kg).
The interval should be based on the patient’s estimated creatinine clearance.
There is a degree of patient variability in volume of distribution and drug clearance which
makes it difficult to determine the ideal dosing regimen for an individual. There are many
nomograms available for dosing based on creatinine clearance and weight but individual
patient response remains somewhat unpredictable.
CLcr (mL/min) >75 40-75 25-39 15-24 <15
dosing interval 12 hours 24 hours 48 hours 72 hours 5-7 days
Hemodialysis 20 mg/kg IV then 500 mg post dialysis (as a supplemental dose), (aim for levels
pre-dialysis 7.5 - 20 mg/L) or 1 g post dialysis (if severe infection or MRSA) aim for level 15-25
mg/L.
2. RATIONALE FOR USE OF PRE (Trough) SAMPLES FOR THERAPEUTIC

DRUG MONITORING
Efficacy – Vancomycin exhibits time-dependant killing at concentrations >0.5 mg/L with
a minimum inhibitory concentration (MIC) for susceptible bacteria usually <2 mg/L.
Vancomycin exhibits minimal post-antibiotic effect and does not display concentration
dependant killing. There seems to be general consensus in the current literature that
maintaining a trough concentration above 10 mg/L is desirable for optimal therapeutic
response. There is no evidence to suggest that the peak serum concentration has any
bearing on efficacy. In some cases pre/post pairs may be preferable to provide dosage
adjustment recommendations based on calculated pharmacokinetic data. The post results
in this case should be drawn post-distribution (i.e. 2 hours after the end of infusion).
Ototoxicity – This problem is less frequent than originally feared, especially when
vancomycin is used alone.
Nephrotoxicity – There appears to be a very low incidence of nephrotoxicity when
vancomycin is used alone. However, when used in combinations with aminoglycosides
the incidence increases beyond that of either drug used alone. There is recent evidence to
suggest that the number of nephrotoxic agents used may be one of the most important
factors in predisposing a patient to nephrotoxicity.
3. THERAPEUTIC RANGE
Optimal predose vancomycin level depends on the organism and type of infection
being treated:
• 5-10 mg/L - mild to moderate infections; infections involving coagulase negative
staphylococci or enterococci
• 10-15 mg/L - Staphylococcus aureus NOT MRSA
• 15-20 mg/L - severe infections including osteomyelitis, meningitis and en-
docarditis or infection with MRSA
• For organisms with an MIC ≥2 consult ID as an alternate agent should be
considered.
103-114 108 12/12/11, 2:05 PM

Vancomycin Dosing Guidelines (cont’d)
4. SERUM DRUG CONCENTRATION MONITORING
All patients started on vancomycin should have a steady state pre (trough) level
obtained. To assure steady state has been achieved, the level should be drawn just
before the 4th or 5th dose, not sooner. Adjustments to the dosage regimen may be
made as follows:
Continued monitoring could be achieved by following the Scr (M,W,F) and
drawing a pre (trough level) if Scr increases 25% above baseline or every five days if
therapy is continued.
Additional monitoring is required for the following patients:

1. Patients with severe renal impairment (CLcr <25 mL/min) - trough level every
second dose.
2. Burn patients, intravenous drug abusers, or dehydrated patients - pre and post
levels should be drawn due to high variability of clearance and/or volume of
distribution within an individual patient.
3. Dialysis patients - trough levels drawn prior to dialysis.
103-114 109 12/12/11, 2:05 PM

Sequential Antibiotic Therapy and
Pharmacist Initiated Route of
Administration Therapeutic Interchange
SEQUENTIAL ANTIBIOTIC THERAPY (SAT) refers to the practice of limiting intravenous
(IV) antimicrobials to the early stages of infection and then converting to oral agents for
the duration of treatment. The concept of sequential antibiotic therapy or “stepping
down”or “switching” is a natural sequence in patient care, with many potential benefits:
• Provides similar blood/tissue levels as IV (with some agents identical levels)
• Maintains the same spectrum of activity
• Is well tolerated by the patient
• Improves patient comfort
• Involves less nursing time
• Decreases the risk of line-related phlebitis and infections
• May facilitate an earlier discharge
• Is less expensive
The following Therapeutic Interchange policies enable the pharmacist to change the route
of administration of a drug when, following an assessment of the patient, this is deemed
clinically appropriate. Drug therapy initiated intravenously can often be switched to a
suitable oral regimen, particularly those drugs that are well-known to exhibit a high degree
of oral bioavailability. Selecting the oral administration route over the more expensive
intravenous route can be appropriate in many situations.
For drugs affected by this policy, the pharmacist may change the route of administration
for an ordered medication when he or she has personally assessed the patient, and the
patient meets the following criteria:
• The patient is tolerating oral medications, is receiving as a minimum a clear fluid diet or is
enterally fed, and
• The patient does not have/is not experiencing any of the following;
➝ severe nausea and/or vomiting
➝ malabsorption syndrome
➝ severe sepsis
➝ GI obstruction.
Preparation/regimen ordered Dispensed as

Ciprofloxacin 200 mg IV Ciprofloxacin 250 mg po (same frequency)
Ciprofloxacin 400 mg IV Ciprofloxacin 750 mg po (same frequency) or in the
case of UTI, cirpofloxacin 500 mg po (same frequency)
Fluconazole _____ mg IV Fluconazole _____mg po (same frequency)
Levofloxacin 500 mg IV daily Levofloxacin 500 mg po daily
Levofloxacin 250 mg IV daily Levofloxacin 250 mg po daily
Metronidazole 500 mg IV q12h or bid Metronidazole 500 mg po q8h
103-114 110 12/12/11, 2:05 PM

Potential Savings Intravenous-to-Oral
(IV to PO) Stepdown Program1
IV Drug/Dosage/Cost per Day2 PO Drug/Dosage/Cost per Day Daily Cost
Savings3
4
Acyclovir 5 mg/kg q8h $18.45 Acyclovir 400 mg q8h $3.90 $14.55
OR Valacyclovir 500 mg q12h $3.18 $6.36
Ampicillin 1 g q6h $7.04 Amoxicillin 500 mg q8h $0.03 $7.69

OR Amoxicillin/Clavulanate
875/125 mg q12h $4.56 $2.48
Azithromycin 500 mg q24h $20.36 Azithromycin 250 mg q24h $4.74 $15.62
Cefazolin 1 g q8h $7.68 Cephalexin 500 mg q6h $0.68 $7.00
Cefuroxime Sodium 750 mg q8h $13.05 Cefuroxime Axetil 500 mg q12h $5.16 $7.89
Ceftriaxone 1 g q24h $35.15 Cefuroxime Axetil 500 mg q12h $5.16 $16.86-$29.99

OR OR
Cefotaxime 1 g q8h $22.02 Ciprofloxacin 500 mg q12h +
Cephalexin 500 mg q6h $2.00 $20.02-$33.15
Ciprofloxacin 200-400 mg q12h $33.00-66.00 Ciprofloxacin 250-750 mg q12h $0.60 $32.40-$65.73
Clindamycin 600 mg q8h $10.59 Clindamycin 300-450 mg q6h $4.28-6.42 $4.17-$6.31
Cloxacillin 1-2 g q6h $8.80-$11.60 Cloxacillin 500 mg q6h $0.32 $8.48-$11.28
Doxycycline 100 mg once daily $15.15 Doxycycline 100 mg once daily$0.30 $14.85
Levofloxacin 500 mg q24h $35.15 Levofloxacin 500 mg q24h $4.00 $31.15
Linezolid 600 mg q12h $191.02 Linezolid 600 mg q12h $143.14 $47.88
Imipenem 500 mg q6h $24.40 Ciprofloxacin 500-750 mg q12h +

Metronidazole 500 mg q8h $2.64 $21.00
OR
Ciprofloxacin 500-750 mg q12h +
Clindamycin 300 mg q6h $6.77 $18.00
Piperacillin/Tazobactam 4.5 g q8h $67.05 Ciprofloxacin 500-750 mg q12h +

Metronidazole 500 mg q8h $2.64 $64.41-$65.56
OR OR
Piperacillin/Tazobactam 3.375 g q6h $68.20 Ciprofloxacin 500-750 mg q12h +
Clindamycin 300 mg q6h $6.77 $60.28-$61.43
Trimethoprim/Sulfamethoxazole Trimethoprim/Sulfamethoxazole
4
5/25 mg/kg q6h $64.00 1 DS q12h $0.16 $32.00-$64.00
Voriconazole 400 mg q12h $560.00 Voriconazole 200 mg q12h $100.00 $460.00
1. These are examples only, choice of stepdown therapy must be individualized.

2. Assumes fixed cost of $1.15 per IV dose for IV bag (exceptions: ciprofloxacin, fluconazole, linezolid and
metronidazole available ready to administer).
3. Does not include saving in nursing/pharmacy time, IV tubing, etc.
4. IV cost based on a 80 kg patient.
103-114 111 12/12/11, 2:05 PM

Bioavailability of Oral Antibiotics
Name Bioavailablility t1/2 (h) Administration
Penicillins
Amoxicllin 60-89 1 <->
Amoxicillin/Clavulanate 60-89 1 <->
Cloxacillin 35-70 1 ES
Penicillin VK 35-70 1 < - >1
Cephalosporins
Cephalexin 80-100 0.5-1.3 <->
Cefuroxime axetil 30-50 1.2-1.3 Food2
Fluoroquinolones
Ciprofloxacin 69-85 3-5 < - >3,4
Levofloxacin 99 6-8 < - >1,3,4
Macrolides
Clarithromycin 50 3.4 < - >1
Erythromycin 18-45 1.4 ES
Tetracyclines
Doxycycline 90-100 18 < - >1
Tetracycline 75-80 8.5 ES1,4
Miscellaneous
Clindamycin 90 2.4 <->
Linezolid 100 4-5 <->
Metronidazole 90-100 6-14 < - >1
Trimethoprim/Sulfamethoxazole 85-90 11/9 <->
Antivirals
Amantadine 86-90 12 <->
Acyclovir 15-30 2.2-5.0 <->
Valacyclovir 55 3 <->
Valganciclovir 60 4 Food2
Antifungals
Fluconazole 90 24 <->
Itraconazole 55 17-24 Food2
Ketoconazole Variable
(↑ with ↓ pH) 6.5-9.6 Food2
Voriconazole 96 6 ES
Food = take with food

ES = empty stomach
< - > = without regards to meals
1. The presence of food in the GI tract results in lower and delayed peak serum
concentrations but the total amount of drug absorbed is unaffected.
2. Bioavailability increases with food or milk.
3. Calcium, aluminum, magnesium and iron salts decrease oral bioavailability; milk/
yogurt decrease bioavailability by 30-50%.
4. Calcium, aluminum, magnesium and iron salts should be spaced.
103-114 112 12/12/11, 2:05 PM

Notes
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Notes
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103-114 114 12/12/11, 2:05 PM

Capital Health promotes a smoke-free and scent-free environment.
Please do not use perfumed products. Thank you!
Capital Health, Nova Scotia

www.cdha.nshealth.ca
Prepared by: Department of Pharmacy, Division of Infectious Diseases, Capital Health, Halifax©
Designed and Printed by: CH Audio Visual and Printing Departments
QV85-0173 Rev.01/2012
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1-19 1 1/9/12, 3:05 PM

* For use in urinary tract infection only.

GRAM NEGATIVE ISOLATES - % SUSCEPTIBLE

* For use in urinary tract infection only.

1-19 2 1/9/12, 3:05 PM

IR - Usually not active either because of intrinsic or acquired resistance.

1-19 3 1/9/12, 3:05 PM

1-19 4 1/9/12, 3:05 PM

Gram-Negative Bacilli (GNB)

1-19 5 1/9/12, 3:05 PM

1-19 6 1/9/12, 3:05 PM

1-19 7 1/9/12, 3:05 PM

1-19 8 1/9/12, 3:05 PM

1-19 9 1/9/12, 3:05 PM

1-19 10 1/9/12, 3:05 PM

Table I: Defining Obesity

Equation 1: IBW(male) = 50 kg + 2.3 kg x (inches over 5ft tall)

Since obesity can impact the distribution and clearance of

1-19 15 1/9/12, 3:05 PM

Calculating the Vd (see Equation 3) can help to determine an

Equation 3: Vd(obese) = Vd(non-obese) x Adjusted Body Weight

1-19 16 1/9/12, 3:05 PM

Antibacterial Primary Considerations Adult, non-obese, Recommendation(s)

1-19 17 1/9/12, 3:05 PM

Antibacterial Primary Considerations Adult, non-obese, Recommendation(s)

1-19 18 1/9/12, 3:05 PM

Antibacterial Primary Considerations Adult, non-obese, Recommendation(s)

1-19 19 1/9/12, 3:05 PM

20-31 20 1/10/12, 10:16 AM

(c)crushed 750 mg cipro tab suspension Zn 1.2 mg when adminstering ciprofloxacin.

20-31 22 1/10/12, 10:16 AM

4. ONCE-DAILY DOSING GUIDELINES

Creatinine Clearance (mL/min) Dosing Interval

20-31 23 1/10/12, 10:16 AM

CYSTIC FIBROSIS PATIENTS

Maximum Tobramycin Dosage

20-31 24 1/10/12, 10:16 AM

5. TRADITIONAL DOSING GUIDELINES

20-31 25 1/10/12, 10:16 AM

Table 2. Maintenance Dose Nomogram for Aminoglycoside Antibiotics (Adults)

Determine the recommended Dosing Interval using the Estimated Creatinine

Table 3. Target Serum Aminoglycoside Concentrations

Urinary tract infections 4-6 16-20

Desired Pre (trough) <2 <8

20-31 26 1/10/12, 10:16 AM

Patient Information Sheet - Aminoglycoside Treatment

20-31 27 1/10/12, 10:16 AM

SIDE EFFECTS MANAGEMENT/PREVENTION MEASURES

20-31 28 1/10/12, 10:16 AM

High (>146 mmol/L)

Investigate cause Consider 0.45% NaCl Recommend 0.9% NaCl EXCEPTIONS

depletion and pulmonary edema,

Assess K and Mg status

High Normal Low

No High-Risk for Hypokalemia/Hypomagnesemia or consequences of same?:

Receiving loop/thiazide diuretics, long-term steroids, laxatives

20-31 29 1/10/12, 10:16 AM

Routine Monitoring of Amphotericin B Therapy1