ANTIBIOTICS • Can be a means of prophylaxis – prevention of

KEY TERMS potential infection

BACTERIA o Undergoing GI surgeries or traveling to malarial
Aerobic countries may be given antibiotics
• Bacteria that depend on oxygen for survival o Usually a large, one-time dose of an antibiotic
Anerobic Drug Therapy across the Lifespan
• Bacteria that survive without oxygen, which are Children
often seen when blood flow is cut off to an area of • very sensitive to the GI and CNS effects
the body • severe reactions and superinfections
Antibiotic • monitor hydration and nutritional status
• Chemical that is able to inhibit the growth of specific • Fluoroquinolones (damage to cartilage) and
bacteria or cause the death of susceptible bacteria tetracyclines (growth of bones and teeth) – extreme
Gram-negative caution of using it
• Bacteria that accept a negative stain and are • Parent education is important
frequently associated with infections of the Adults
genitourinary or gastrointestinal (GI) tract • Many adults believe that antibiotics are a cure-all for
• cell walls lose a stain or are decolorized by alcohol any discomfort and fever
• Escherichia coli – cystitis o Explain that antibiotics are useful against only
Gram-positive specific bacteria
• Bacteria that take a positive stain and are frequently • Cautioned to take the entire course of the
associated with infections of the respiratory tract medication
and soft tissues • Pregnant and BF women – not take antibiotics
• cell wall retains a stain known as Gram’s stain or o Unless the benefit clearly outweighs the potential
resists decolorization with alcohol risk to the fetus or neonate
• Streptococcus pneumoniae • Can interfere with the effectiveness of hormonal
Synergistic contraceptives
• Drugs that work together to increase drug Older Adults
effectiveness • Most important to obtain culture
Bactericidal • More susceptible to the adverse effects
• Causes death of bacteria • Hydration and nutritional status monitor as well as
• Interfering with cell membrane/wall CNS
Bacteriostatic • Hepatic and renal dysfunction (expected)
• Prevents replication or growth of bacteria by • Need to be cautioned to complete the full course
interfering with DNA/RNA synthesis (CHON) of drug therapy
BACTERIA AND ANTIBIOTICS RESISTANCE TO ANTIBIOTICS
Bacteria • Can adapt to their environment
• Invade the human body through many routes • Produce cells that are no longer affected by drug
• Human inflammatory response activates → S&S → 4 • Often patients are given the simplest antibiotic first
signs of inflammation to prevent resistance
• Body becomes host → supplies proteins & enzymes • Altering their cell wall or enzyme systems to
for bacteria become resistant to unfavorable conditions or
Antibiotic Therapy situations
• Goal: decrease the population of invading bacteria • Penicillin – developed an enzyme penicillinase –
to a point at which the human immune system can activated the penicillin-type drugs
effectively deal with it • May result in the development of superinfections
• Identify through culture and sensitivity testing for or overgrowth of resistant pathogens
treatment o An irritating adverse effect
• attempt to administer a drug with a broad spectrum AMINOGLYCOSIDES
of activity if patient too sick to wait for test results • Group of powerful antibiotics used to treat serious
o Gm (+ or -) and anaerobic bacteria infections caused by gram-negative aerobic bacilli
o Associated with adverse effects • Potential adverse effects but have newer and less-
• given in combination because they are synergistic toxic drugs
o Help to reduce adverse effects • Superinfections can occur with any of the
carbapenems.
 o Closely monitor patients to deal with the new • relatively new class of broad-spectrum antibiotics
infection before it becomes overwhelming. effective against gram-positive and gram-negative
Drugs in Focus (GANTS-K, -mycin & -acin) bacteria
Gentamycin (Garamycin) Tx of Pseudomonas infections
• Meropenem: first drug which has limited use -
Amikacin (Amikin) Tx of serious gm (-) infx
GI normal flora (pre-op); skin severe risk for GI toxicities
Neomycin (Maxitrol)
wounds; tx of hepatic coma • Newer carbapenems are not as toxic
IV or IM short tx; ocular infx;
Drugs in Focus (DIME, -penem)
Tobramycin (Tobrex) Pseudomonas aeruginosa infx; cystic
fibrosis Tx of intra-abdominal infx or
Doripenem (Donbax)
4th drug in combination therapy for complicated UTIs
Streptomycin (generic) Tx of serious respiratory, intra-
tuberculosis; severe infections only Imipenem-cilastatin (Tienam,
Tx of hepatic coma; decrease GI ab, UT, gyne, bone and joint,
Kanamycin (Mycifradin) Primaxin)
normal flora septicemia, etc
Tx of bacterial meningitis, skin
Therapeutic Actions and Indications Meropenem (Merrem IV,
and skin structure infx, and
Meronem)
• Bactericidal – inhibit protein synthesis of gm (-) intra-abdominal infx
o Irreversibly bind to bacteria ribosomes → cell Tx of community-acquired
Ertapenem (Invanz)
pneumonia, GU and pelvic infx
death
Therapeutic Actions and Indications
• Indicated for the treatment of serious infections that
• Bactericidal - inhibit cell membrane synthesis → cell
are susceptible to penicillin when penicillin is
death
contraindicated
• Used to treat serious infections caused by
Pharmacokinetics
susceptible strains
• Poorly absorbed from the GI tract but rapidly
• Indicated for treating serious intra-abdominal,
absorbed after intramuscular (IM) injection (1hr on
urinary tract, skin and skin structure, bone and joint,
peak levels)
and gynecological infections
• average half-life: 2-3 hours
Pharmacokinetics
• enter placenta and breastmilk; excreted unchanged
• Rapidly absorbed if given IM
in the urine
• Peak levels: at the end of infusion
Contraindications and Cautions
• Not known whether they cross the placenta or enter
• known allergy; renal and hepatic disease
breast milk
• preexisting hearing loss
• Average half-life: 1-4 hours
• active infections with herpes or mycobacterial
Contraindications and Cautions
infections
• Known allergy to carbanems or beta-lactams
• myasthenia gravis or parkinsonism
• Seizure disorder and lactation
• lactation
• Caution on pregnancy and test urine function
• Caution: pregnancy and test for urine function
• Ertapenem – not recommend below 18 years old
• Amikacin: nephron and ototoxicity
• Meropenem: associated with the development of
• Streptomycin: reserved in specific situations
pseudomembranous colitis
o Toxic to 8th cranial nerve and kidney
o Caution: inflammatory bowel disorders
Adverse Effects
Adverse Effects
• Black box warning: risk of ototoxicity and
• GI toxicity
nephrotoxicity
• Pseudomembranous colitis, Clostridium difficile
• Renal toxicity
diarrhea → serious dehydration and electrolyte
• Bone Marrow Depression: leading to immune
imbalances
suppression and resultant superinfections
• CNS effects: seizures
• GI effects: loss of bacteria (normal flora)
Clinically Important Drug–Drug Interactions
• Cardiac effects: palpitations, hypo & hypertension
• Give alternative treatment if patient is on valproic
• Hypersensitivity reactions: purpura, rash urticaria, acid; Risk for seizures
and exfoliative dermatitis
• Avoid imipenem with ganciclovir – seizures
Clinically Important Drug–Drug Interactions
• Avoid meropenem with probenecid – lead to
• Synergistic bactericidal effect with penicillin and
toxicity
cephalosporins
CEPHALOSPORINS
• Avoid combining aminoglycosides with potent
• Introduced in the 1960s
diuretics; increase adverse effects
• Similar to the penicillin in structure and activity
• With anesthetics: increased neuromuscular
• 4 generations with its own spectrum activity
blockade with paralysis is possible
First Generation
CARBAPENEMS
• Largely effective against the same gram-positive • Susceptible species: interfere with the cell wall–
bacteria that are affected by penicillin G, and gm(-) building ability of bacteria when they divide
• Proteus mirabilis, Escherichia coli, and Klebsiella o prevent the bacteria from biosynthesizing
pneumoniae (PEcK) the framework of their cell walls → burst
Cefadroxil (generic)
UTI, pharyngitis, and tonsillitis – group A from osmotic pressure
beta-hemolytic streptococci, skin infx
• Important to reserve cephalosporins for
Respiratory, skin, bone, GU infx; otitis
Cephalexin (Keflex) appropriate situations
media for children
Second Generation o cephalosporin-resistant bacteria are
• Less effective against gram-positive bacteria appearing in increasing
• Effective against the previously mentioned strains • Culture and sensitivity test should be performed
with Haemophilus influenzae, Enterobacter Pharmacokinetics
aerogenes, and Neisseria spp. (HENPeCK) • Well-absorbed from the GI tract
Respiratory tract infx, skin infx, UTIs, o 1st gen: cefadroxil and cephalexin
Cephaclor (Ceclor) Otitis media, typhoid fever, anthrax o 2nd gen: cefaclor and cefprozil
exposure
Severe infx; prophylaxis for CS, o 3rd gen: cefdinir, cefpodoxime, and
Cefoxitin (generic) abdominal, vaginal, biliary, or colorectal ceftibuten
surgery o 4th gen: cefditoren and cefepime
Pharyngitis, tonsillitis, otitis media,
Cefprozil (generic) sinusitis, secondary bronchial infx, and • Others: after IM injection or IV administration
skin infections • Primarily metabolized in the liver and excreted in
Cefuroxime For wide range of infx, Lyme disease,
the urine
(Zinacef) from parenteral to oral drug use
Third Generation • Cross the placenta and enter breast milk
• effective against all of the previously mentioned Contraindications and Cautions
strains • Known allergies to cephalosporins and penicillin –
• relatively weak against gram-positive bacteria but cross-sensitivity is common
are more potent against the gram-negative bacilli • Hepatic or renal impairment
and against Serratia marcescens (HENPeCKS) • Pregnant or lactating patients
Respiratory infx, otitis media, sinusitis, Adverse Effects
Cefdinir (Omnicef)
laryngitis, bronchitis, skin infx, • GI tract toxicity: nausea, vomiting, diarrhea,
Moderate to severe skin infx, UT, and
anorexia, abdominal pain, and flatulence
Cefotaxime respiratory infx, PID, intra-abdominal infx,
(Claforan) peritonitis, septicemia; bone infx, CNS • Pseudomembranous colitis
infx, preoperative prophylaxis • Discontinued immediately: any sign of violent,
Cefpodoxime Respiratory infx, UTIs, gonorrhea, skin infx,
(Vantin) and otitis media
bloody diarrhea, and abdominal pain
Moderate to severe skin infx, UT, and • CNS toxicity: headache, dizziness, lethargy, and
Ceftazidime
respiratory infx, intra-abdominal infx; paresthesias
(Ceptaz, Tazicef)
septicemia, bone infx, CNS infx
Pharyngitis, tonsillitis, exacerbations of
• Nephrotoxicity
Ceftibuten (Cedax)
bronchitis, otitis media • Superinfections: death of protective bacteria of
Moderate to severe skin infx, UT, and normal flora
respiratory infx, PID, intra-abdominal infx,
Ceftriaxone
peritonitis, septicemia; bone infx, CNS Clinically Important Drug–Drug Interactions
(Rocephin)
infx, preoperative prophylaxis • Concurrent administration increases risk for
Off-label use for tx of Lyme Disease nephrotoxicity
Fourth Generation • Monitor patients and evaluate serum blood urea
• In development; effective with some methicillin- nitrogen (BUN) and creatinine levels
resistant organisms • Oral anticoagulants + cephalosporin: increased
• Cefepime: gm (+ or -) organisms bleeding
• cephalosporin-resistant staphylococci and o Monitor blood loss
Pseudomonas aeruginosa • Avoid ETOH for up to 72 hours – Prevention of
Acute exacerbations of chronic
Cefditoren (Spectracef) bronchitis; pharyngitis and tonsillitis;
disulfram-like reaction: flushing, throbbing
skin and skin structure infx headache, nausea and vomiting, chest pain,
Moderate to severe skin, UT, palpitations, dyspnea, syncope, vertigo, blurred
Cefepime (Maxipime)
respiratory infx
skin and skin structure infx;
vision, and, in extreme reactions, cardiovascular
Ceftaroline (Teflaro) collapse, convulsions, or even death
community-acquired pneumonia
Therapeutic Actions and Indications FLUOROQUINOLONES
• Both bactericidal and bacteriostatic • Relatively new synthetic class of antibiotics with a
broad spectrum of activity
Drugs in Focus (GOLF-CM, -floxacin) o avoid sun and ultraviolet light exposure
Ciprofloxacin (Cipro) Wide spectrum of gm (-) bacteria and to use protective clothing and
Acute otitis externa (S. aureus, P.
Finafloxacin (Xtoro) sunscreens
aeruginosa)
Acute exacerbations of chronic Clinically Important Drug–Drug Interactions
Gemifloxacin (Factive)
bronchitis, CA pneumonia • taken concurrently with iron salts, sucralfate,
Respiratory, UT, skin, sinus infx;
mineral supplements, or antacids: therapeutic
Levofloxacin (Levaquin) by susceptible gm (-); tx after
anthrax exposure effect is decreased
Moxifloxacin (Avelox)
Sinusitis, bronchitis, or CA • administration of two agents: separated by at least
pneumonia
4 hours
Respi, UT, skin infx; PID, ocular
Ofloxacin (Floxin, Ocuflox) • Taken with drugs that increase QTc interval or
infx; otitis media (in otic form)
Therapeutic Actions and Indications cause torsades de pointes (quinidine,
• Enter the bacterial cell by passive diffusion through procainamide, amiodarone, sotalol, erythromycin,
channels in the cell membrane → interfere action terfenadine, pentamidine, tricyclics,
of DNA enzymes of bacteria → leads to cell death phenothiazines) → severe-to-fatal cardiac reactions
• Little cross-resistance with other forms of o Monitor cardiac
antibiotics but misuse may lead to resistant strains • With theophylline → increased theophylline levels
• Gm (-) bacteria – infections include urinary tract, o Should be decreased by one-half, and
respiratory tract, and skin infections serum theophylline levels monitored
• Ciproflaxin: effective against a wide spectrum of carefully
gram-negative bacteria • With NSAIDs → increased risk of CNS stimulation
o Prevention of anthrax infections o Monitor patients with history of seizures
o Effective against typhoid fever • With corticosteroids → increased risk of tendonitis
Pharmacokinetics and tendon rupture
• Absorbed from the GI tract, metabolized in the o Patient to report any tendon pain or
liver, and excreted in the urine and feces weakness
• Cross placenta and breastmilk PENICILLINS AND PENICILLINASE-RESISTANT
• Ciproflaxin: injectable, oral, and topical forms ANTIBIOTICS
• Oral agents: Gemifloxacin, lomefloxacin, and • First antibiotic introduced for clinical use
moxifloxacin • Sir Alexander Fleming used Penicillium during
• Levofloxacin: oral and IV forms 1920s
• Ofloxacin: oral and IV for treatment of ocular • Subsequent versions were developed to decrease
infections the adverse effects of the drug and to modify it to
• Newest drug: finafloxacin – otic drops for topical act on resistant bacteria
treatment of swimmer’s ear • Prolonged use of penicillin: bacteria synthesized
Contraindications and Cautions the enzyme penicillinase to counteract effects of
• Known allergy; pregnant/lactating women penicillin
• Presence of renal dysfunction o Develop group of drugs to still have an
• Associated with lesions in developing cartilage and effect of the penicillin
not recommended below 18 years old • Penicillinase-resistant antibiotics: nafcillin and
Adverse Effects oxacillin
• Relatively mild adverse reactions o depends on the sensitivity of the
• Most common: headache, dizziness, insomnia, and bacteria causing the infection, the desired and
depression available routes, and the personal experience
• GI effects: nausea, vomiting, diarrhea, and dry of the clinician with the particular agent.
mouth Penicillins
Penicillin G benzathine Syphilis and erysipeloid
• Black box: risk of tendinitis and tendon rupture (Bicillin, Permapen) infections
o Increased in patients over 60 years old, Penicillin G potassium Severe infections; used for
concurrent steroids, and renal, heart, or (Pfizerpen) several days
Penicillin G procaine Moderately severe infections;
lung transplants (Wycillin) daily for 8-12 days
• Immunological effects: bone marrow depression Prophylaxis for bacterial
• Other: fever, rash, and photosensitivity (skin Penicillin V (generic) endocarditis, Lyme disease,
UTIs
reactions)
Extended-Spectrum Penicillin
Amoxicillin (Amoxil, Trimox) Broad spectrum of uses for
adults and children
 Ampicillin (Principen) Broad spectrum of activity; • Drugs that inhibit folic acid synthesis
switch from parenteral to oral;
monitor for nephritis
Drugs in Focus
Sulfadiazine (generic) tx of a broad spectrum of infx
Penicillinase-Resistance Antibiotics
Ulcerative colitis and Crohn’s
Nafcillin Infx by penicillinase-producing Sulfasalazine (Azulfidine)
disease; rheumatoid arthritis
staphylococci and group A Otitis media, bronchitis, UTI,
hemolytic streptococci plus S. Cotrimoxazole
and pneumonitis
viridans; drug of choice if (Septra, Bactrim)
(Pneumocystis jiroveci)
switch to oral form is
anticipated Therapeutic Actions and Indications
Oxacillin Infx by penicillinase-producing • Folic acid: necessary for the synthesis of purines
staphylococci; switch to oral and pyrimidines, which are precursors of RNA and
form is anticipated
DNA
• Folic acid depends on the diet
Therapeutic Actions and Indications • Bacteria - impermeable to folic acid and must
synthesize it inside the cell
• produce bactericidal effects by interfering with the
ability of susceptible bacteria to build their cell • Competitively block para-aminobenzoic acid to
walls when they are dividing prevent the synthesis of folic acid in susceptible
bacteria
• prevent the bacteria from biosynthesizing →
weakened cell walls → burst from osmotic pressure • Gm (+ or -) - Chlamydia trachomatis and Nocardia
and some strains of Haemophilus influenzae,
• Treatment of streptococcal infections: pharyngitis,
Escherichia coli, and Proteus mirabilis
tonsillitis, scarlet fever, and endocarditis
• Sulfa drugs – no longer used much
• Pneumococcal infections; staphylococcal
infections; fusospirochetal infections; rat-bite fever; • Remain inexpensive and effective for treatment for
diphtheria; anthrax; syphilis; and uncomplicated UTIs and trachoma (leading cause of blindness)
gonococcal infections o Nocardiosis and STDs as well
• High dose: treat meningococcal meningitis • Sulfasalazine – tx of ulcerative colitis and
Pharmacokinetics rheumatoid arthritis
Pharmacokinetics
• Rapidly absorbed from the GI tract
• Teratogenic; distributed into breastmilk
• Peak levels: 1 hour
• Given orally and absorbed from GI → liver → urine
• Sensitive to gastric acid levels taken on an empty
stomach • Vary of the peak level & half-life
• Excreted unchanged in the urine, making renal • Sulfadiazine: oral agent absorbed from GI tract
function an important factor in safe use of the drug o Peak level: 3-6 hours
• Enter breast milk and cause adverse reactions • Sulfasalazine: sulfapyridine that is carried by
Contraindications and Cautions aminosalicylic acids (aspirin)
o Release acid in the colon where anti-
• Allergies to penicillin or cephalosporins or other
inflammatory effects
allergens
• Delayed release form: treat rheumatoid arthritis
• Caution with renal disease
o Rapidly absorbed from GI tract
• Limited with pregnant or lactating
o Peak level: 2-6 hours
Adverse Effects
o Half-life: 5-10 hours
• Penicillin therapy: Involve GI tract
• Cotrimoxazole: contains sulfamethoxazole and
• Adverse effect: nausea, vomiting, diarrhea,
trimethoprim, another antibacterial drug
abdominal pain, glossitis, stomatitis, gastritis, sore
o Absorbed from GI tract
mouth, and furry tongue
o Peak level: 2 hours
o Related to the loss of bacteria
o Half-life: 7-12 hours
• Superinfections
Contraindications and Cautions
• Pain and inflammation at injection site
• Allergy to sulfonamide, sulfonylureas or thiazide
• Hypersensitivity reactions: rash, fever, wheezing,
diuretics
and with repeated exposure anaphylaxis
• Pregnancy and lactation: kernicterus
Clinically Important Drug–Drug Interactions
• Renal disease
• With tetracyclines: decrease in the effectiveness of
• Caution in elderly: increased incidence of CNS
the penicillins results
effects
• Inactivation of aminoglycosides - combination with
Adverse Effects
any of the parenteral aminoglycosides
• GI effects: death of normal bacteria
SULFONAMIDES
• Renal effects: crystalluria, hematuria, and Contraindications and Cautions
proteinuria • known allergy to tetracyclines or to tartrazine
• CNS effects: headache, dizziness, vertigo, ataxia, • pregnancy and lactation
convulsions, and depression • ophthalmic preparation - fungal, mycobacterial, or
• Bone Marrow Depression viral ocular infections
• Dermatological effects: photosensitivity and rash • used with caution in children below 8 years old
• Wide range of hypersensitivity reactions o damage bones and teeth
• Steven Johnson Syndrome • hepatic and renal dysfunction
Clinically Important Drug–Drug Interactions Adverse Effects
• With tolbutamide, tolazamide, glyburide, glipizide, • GI effects: nausea, vomiting, diarrhea, abdominal
or chlorpropamide: risk of hypoglycemia increases pain, glossitis, and dysphagia
o Dose adjustment of antidiabetic agent • Fatal hepatoxicity
• With cyclosporine: risk of nephrotoxicity rises • Skeletal effects: teeth and bones
TETRACYCLINES • Dermatological Effects: photosensitivity and rash
• developed as semisynthetic antibiotics based on • Superinfections: yeast infections
the structure of a common soil mold • Local Effects: pain and stinging with topical or
• composed of four rings ocular application
• newer tetracyclines: increase absorption and tissue • Hematological effects: hemolytic anemia and bone
penetration marrow depression
• Widespread resistance: limited their use in recent • Hypersensitivity reactions: urticaria to anaphylaxis
years and intracranial hypertension
Drugs in Focus: (-cycline, Dom-TDe) Clinically Important Drug–Drug Interactions
Demeclocycline Tx of wide variety of infx when penicillin • When penicillin G and tetracyclines are taken
(generic) cannot be used
Doxycycline Tx of wide variety of infx, including
concurrently the effectiveness of penicillin G
(Doryx, traveler’s disease, and STDS; periodontal decreases
Vibramycin) disease o Dose of penicillin should be increased:
Minocycline Tx of meningococcal carriers and of
(Arestin, Minocin) various uncomplicated GU and gyne infx
combination
Tx of wide variety of infx when penicillin is • With oral contraceptives: effectiveness of OC
contraindicated; acne vulgaris and minor decreases
Tetracycline skin infx, ocular lesions; prophylactic agent
(generic) for ophthalmia neonatorum caused by • Digoxin toxicity rises: tetracyclines are taken
Neiserria gonorrhoeae, and Chylamydia concurrently
trachomatis • Decreased absorption of tetracyclines: oral
Oxytetracycline
combination with calcium salts, magnesium salts,
Therapeutic Actions and Indications
zinc salts, aluminum salts, bismuth salts, iron,
• Work by inhibiting protein synthesis in a wide
urinary alkalinizers and charcoal
range of bacteria – inability to multiple
Clinically Important Drug–Food Interactions
• Treated on psittacosis, ornithosis,
• Administered on an empty stomach 1 hour before
lymphogranuloma venereum, and granuloma
or 2 to 3 hours after meal or other medication
inguinale; when penicillin is contraindicated
ANTIMYCOBACTERIALS
• Treatment for acne and uncomplicated GU infx
Mycobacteria
• Treatment of certain protozoal infx
• Group of bacteria that contain the pathogens that
Pharmacokinetics
cause tuberculosis and leprosy
• absorbed adequately, but not completely, from the
• Classified on the basis of their ability to hold a stain
GI tract
even in the presence of a “destaining” agent such
• affected by food, iron, calcium, and other drugs in
as acid
the stomach
o Called “acid-fast” bacteria
• concentrated in the liver and excreted unchanged
• Have an outer coat of mycolic acid that protects
in urine
them from many disinfectants and allows them to
• half-lives: 12-25 hours
survive for long periods in the environment
• cross placental and pass into breast milk
• Treat these slow-growing bacteria for several years
• available in oral and topical forms; ophthalmic
before they can be eradicated
agent
Mycobacterium tuberculosis
• demeclocycline: oral form
• Leading cause of death from infectious disease in
• Doxycycline and minocycline: IV and oral forms the world
• Increasing number of people with compromised • Act on the DNA and/or RNA of the bacteria → lack
immune systems and the emergence of resistant of growth → cell death
bacterial strains = rise of tuberculosis • Isoniazid (INH): affects the mycolic acid coat
Mycobacterium leprae around the bacterium
• Leprosy or Hansen’s disease • Always used in combination to affect the bacteria
• Characterized by disfiguring skin lesions and at various stages and to help to decrease the
destructive effects on the respiratory tract emergence of resistant strains
• Worldwide health problem: invade skin or Pharmacokinetics
respiratory tract • generally well absorbed from the GI tract
Mycobacterium avium-intracellulare • Given orally; cross placenta and breastmilk
• Causes mycobacterium avium complex – AIDS or Contraindications and Cautions
severely immunocompromised • contraindicated for patients with any known allergy
• Rifabutin (Mycobutin): antituberculosis drug, is to these agents
most effective against M. avium-intracellulare • severe renal or hepatic failure
ANTITUBERCULOSIS DRUGS • severe CNS dysfunction
• Lead to serious damage in the lungs, the GU tract, • Pregnancy: combination of isoniazid, ethambutol,
bones, and the meninges and rifampin is considered the safest
• Slow growing the treatment must be continued 6 Adverse Effects
months – 2 years • CNS effects: neuritis, dizziness, headache, malaise,
• Combination: decrease the emergence of resistant drowsiness, and hallucinations
strains and to affect the bacteria at various phases • GI effects: nausea, vomiting, anorexia, stomach
Antituberculosis Drugs upset, and abdominal pain
First-Line Drugs • Rifampin, rifabutin, and rifapentine: discoloration
• used in combinations of two or more agents until of body fluids from urine to sweat and tears
bacterial conversion occurs or maximum o instances orange-tinged: permanently stain
improvement is seen contact lenses
Ethambutol (Myambutol) • Hypersensitivity reactions
INH (Nydrazid)
Pyrazinamide (generic) Treatment of Mycobacterium
• Bedaquiline: black box → increased risk of death
Rifampin (Rifadin, tuberculosis o QTc intervals may increase
Rimactane) Clinically Important Drug–Drug Interactions
Rifapentine (Priftin)
Treatment of Mycobacterium
• Rifampin + INH - possibility of toxic liver reactions
Streptomycin (generic) tuberculosis, tularemia, plague, increases
subacute bacterial endocarditis • Increased metabolism and decreased drug
Second-Line Drugs effectiveness: combination with rifampin or
• if the disease continues to progress because of the rifabutin
emergence of a resistant strain • Patients taking bedaquiline should avoid any other
• ciproflaxin, ofloxacin, and levofloxacin – effective drugs that prolong the QTc interval
for 2nd line treatment OTHER ANTIBIOTIC
Second-Line treatment of M.
tuberculosis, not use in
• Other antibiotics that do not fit into the large
Bedaquiline (Sirturo) antibiotic classes
extrapulmonary, latent, or
drug-sensitive TB DRUGS IN FOCUS
Capreomycin (Capastat)
KETOLIDES
Cycloserine (Seromycin) Second-Line treatment of M.
Ethionamide (Trecator-SC) tuberculosis Mild to moderate community-acquired
Telithromycin (Ketek)
pneumonia caused by susceptible
Rifabutin (Mycobutin) (2016)
bacteria
Leprostatic Drug
• First introduced in 2004
Leprosy; Pneumocystic
Therapeutic Actions and Indications
Dapsone (generic) jiroveci; pneumonia in
• block protein synthesis within susceptible bacteria
AIDS patients
→ cell death which can be related to macrolide
• inhibits folate synthesis in susceptible bacteria
antibiotics
• used for brown recluse spider bites
• binds to specific ribosome subunits → cell death
• Thalidomide (Thalomid) – approved for use after
• effective against Streptococcus pneumoniae,
treatment of Leprosy
including certain multidrug-resistant strains,
Therapeutic Actions and Indications
Haemophilus influenzae, Moraxella catarrhalis,
 Chlamydophila pneumoniae, and Mycoplasma LIPOGLYCOPEPTIDES
pneumoniae Dalbavancin (Dalvance) Complicated skin and skin structure
infections caused by susceptible
Pharmacokinetics Oritavancin (Orbitiv)
strains of gm (+) bacteria
• oral drug that is absorbed through the GI tract Complicated skin and skin structure
• peak levels in 1 hour infections caused by susceptible
Televancin (Vibativ)
strains of gm (+) organisms
• crosses placenta and pass into breastmilk including methicillin-resistant strains
• Half-life: 10 hours • first introduced in 2010
Contraindications and Cautions Therapeutic Actions and Indications
• allergy to any component of the drug or to • Semisynthetic derivatives of vancomycin
macrolide antibiotics • Inhibit bacterial cell wall synthesis by interfering
• known congenital prolonged QT interval, with the polymerization and cross-linking of
bradycardia, or any proarrhythmic condition peptidoglycans
(hypokalemia) • Bind to the bacterial membrane and disrupt the
• with concurrent use of pimozide, cardiac membrane barrier → cell death
antiarrhythmics, simvastatin, atorvastatin, or • Effective against susceptible strains of the gram-
lovastatin positive organisms: Staphylococcus aureus
• with myasthenia gravis (black box – respiratory (including methicillin-susceptible and methicillin-
failure) resistant isolates), Streptococcus pyogenes,
• caution of renal or hepatic impairment & pregnant Streptococcus agalactiae, Streptococcus anginosus,
and lactating patients Enterococcus faecalis (vancomycin-susceptible
Adverse Effects isolates only), Streptococcus intermedius, and
• Largely secondary to toxic effects on GI tract Streptococcus constellatus
• Superinfection, hypersensitivity rxs (anaphylaxis) Pharmacokinetics
Clinically Important Drug–Drug Interactions • IV drugs only; excreted in the urine
• Combined with pimozide, simvastatin, lovastatin, • Peak levels occurring at end of infusion
or atorvastatin: risk of increased serum levels of • Half-life range to (4-8-9 hours)
telithromycin Contraindications and Cautions
o risk of increased serum levels of digoxin • with known allergy to any component of the drug
and metoprolol • with pregnant and lactating patients
• With rifampin, phenytoin, carbamazepine, or • Televancin: black box warning: fetal risk
phenobarbital: risk of decreased serum levels of Adverse Effects
telithromycin and loss of therapeutic effects • largely secondary to toxic effects on the GI tract:
• With theophylline: Increased GI toxicity Nausea, vomiting, taste alterations, diarrhea, loss of
• Separate does by at least 1 hour appetite, and risk of Clostridium difficile diarrhea
LINCOSAMIDES • Nephrotoxicity
Clindamycin (Cleocin) Severe infx when penicillin or others,
less toxic antibiotics cannot be used
• Risk of prolonged QTc Interval
Lincomycin (Lincocin)
• Red man syndrome - flushing, sweating, and
• similar to the macrolides but are more toxic
hypotension can occur with rapid infusion
Therapeutic Actions and Indications
• Rxs – pain and redness
• react at almost the same site in bacterial protein
Clinically Important Drug–Drug Interactions
synthesis and are effective against the same strains
• Increased risk of prolonged QT interval and
of bacteria
resultant arrhythmias
Pharmacokinetics
• Combined with other drugs known: monitor ECG
• Rapidly absorbed: GI tract and IM injections
• Increased risk of nephrotoxicity
• Crosses placenta and enter breatmilk
OXAZOLIDINONES
• Clindamycin: half life (2-3 hours); parenteral and
Pneumonia, skin and skin structure
oral forms infections caused by susceptible strains
Linezolid (Zyvox)
• Lincomycin: half-life (5 hours); IM or IV including resistant strains; diabetic foot
ulcers
Contraindications and Cautions Acute skin and skin structure infections
• hepatic or renal impairment Tedizolid (Sivextro)
by susceptible strains
• pregnancy and lactating patients Therapeutic Actions and Indications
Adverse Effects • Interfere with protein synthesis on the bacterial
• GI toxicity: fatal pseudomembranous colitis ribosome
• Pain, skin infections, and bone marrow depression • Act as MAO (monoamine oxidase) inhibitors
Pharmacokinetics Pharmacokinetics
• Tedizolid: oral or IV use; half-life of 12 hours • Absorbed in the GI tract
o Feces and urine • Widely distributed throughout the body; they cross
• Linezolid: oral or IV use; half-life of 5 hours the placenta and enter the breast milk
o Urine • Erythromycin: excretion in the bile to feces
Contraindications and Cautions o Half-life: 1.6 hours
• with any known allergy to the drug or drug • Azithromycin and clarithromycin: excreted
components; with phenylketonuria unchanged in the urine
• taking MAO inhibitors because these drugs can act o A: half-life 68 hours
as reversible MAO inhibitors o C: half-life 3-7 hours
• breastfeeding women and pregnant
• Hepatic impairment; pheochromocytoma, Contraindications and Cautions
hypertension, hyperthyroidism, and bone marrow • known allergy to any macrolide
suppression • Ocular preparations are contraindicated for viral,
Adverse Effects fungal, or mycobacterial infections of the eye
• CNS effects: headache, insomnia, dizziness • hepatic dysfunction and renal disease
• GI effects: dry mouth, nausea, vomiting, and • Lactating and pregnant women
diarrhea with the potential for pseudomembranous Adverse Effects
colitis; and thrombocytopenia and hypertension • GI tract toxiticity
Drug–Drug Interactions • Neurological symptoms
• With other drugs: risk of hypertension and related • Hypersensitivity rxs: ash to anaphylaxis;
adverse effects superinfections
• With drugs that affect bleeding including Clinically Important Drug–Drug Interactions
nonsteroidal anti-inflammatory drugs (NSAIDs) and • With digoxin: Increased serum levels of digoxin
platelet inhibitors: increased risk of bleeding and • With oral anticoagulants, theophyllines,
further thrombocytopenia carbamazepine, or corticosteroids: increased
• With other serotogenic drugs: serious serotonin metabolic changes in the liver
syndrome • With cycloserine: increased serum levels of
o serotogenic drugs should be stopped 2 cycloserine → renal toxicity
weeks before therapy begins Clinically Important Drug–Food Interactions
Drug–Food Interactions • Food in the stomach decreases absorption of oral
• Tyramine-containing foods avoided: life- macrolides
threatening hypertension • Empty stomach with 8oz of water 1 hour before or
MACROLIDES at least 2-3 hours after meals
Mild to moderate respiratory infections and MONOBACTAM
Azithromycin
urethritis in adults and otitis media and
(Zithromax) Gm (-) enterobacterial infx; safe alternative for
pharyngitis/tonsillitis in children
Aztreonam treating infx caused by susceptible bacteria in
Clarithromycin Various respi, skin, sinus, and maxillary infx;
(Azactam) px who may be allergic to penicillins or
(Biaxin) effective against mycobacteria
cephalosporins
Infx in px allergic to penicillin; drug of choice for tx of
Erythromycin Legionnaire’s disease, infx caused by Therapeutic Actions and Indications
(Ery-Tab, Eryc) Corynebacterium diphtheriae, Ureaplasma spp.
• Structure is unique and little cross-resistance
Syphilis, mycoplasma pneumonia, and chlamydial infx
• Antibiotics that bind to the subunit of the ribosome • Effective against gm (-) enterobacteria and has no
within the bacterial cell and interfere with protein effect on gm (+) or anaerobic bacteria
synthesis in susceptible bacteria • disrupts bacterial cell wall synthesis → promotes
Therapeutic Actions and Indications leakage of cellular contents and cell death
• May be bactericidal or bacteriostatic • For treatment of urinary tract, skin, intra-abdominal,
• Binding to the ribosomes within the cell and and gynecological infections, septicemia
changing protein synthesis Pharmacokinetics
• may be used as prophylaxis for endocarditis before • IV and IM – peak levels (1-1.5 hours)
dental procedures in high-risk patients with • Half-life – 1.5-2 hours; excreted in urine
valvular heart disease who are allergic to penicillin • Crosses the placenta and enters breast milk
• Topical macrolides: tx for ocular infections for acne Contraindications and Cautions
vulgaris • With any known allergy to aztreonam
• May be used as a prophylaxis for skin minor • History of acute allergic reaction to penicillins or
abrasions cephalosporins
• With renal or hepatic dysfunction • RNA virus that invades tissues of the respiratory
Adverse Effects tract, causing the signs and symptoms of the
• Relatively mild – GI effects common cold or “flu”
• Hepatic enzyme elevations Integrase inhibitor
• Inflammation, phlebitis, and discomfort at injection • a drug that inhibits the activity of the virus-specific
sites and anaphylaxis enzyme integrase, an encoded enzyme needed for
Clinically Important Drug–Drug Interactions viral replication; blocking this enzyme prevents the
• Incompatible in solution with nafcillin, cephradine, formation of the HIV-1 provirus
and metronidazole Interferon
**READ ON NEW ANTIBIOTICS AND ADJUNCTS** • tissue hormone that is released in response to viral
ANTIVIRAL AGENTS invasion; blocks viral replication
KEY TERMS
Acquired Immunodeficiency Syndrome (AIDS) Nonnucleoside reverse transcriptase inhibitors
• Collection of opportunistic infections and cancers • drugs that bind to sites on the reverse transcriptase
that occurs when the immune system is severely within the cell cytoplasm, preventing RNA- and
depressed by a decrease in the number of DNA-dependent DNA polymerase activities
functioning helper T cells; caused by infection with needed to carry out viral DNA synthesis; prevents
human immunodeficiency virus (HIV) the transfer of information that allows the virus to
AIDS-related complex (ARC) replicate and survive
• Collection of less serious opportunistic infections Nucleoside reverse transcriptase inhibitors
with HIV infection; the decrease in the number of • drugs that prevent the growth of the viral DNA
helper T cells is less severe than in fully developed chain, preventing it from inserting into the host
AIDS DNA, so viral replication cannot occur
CCR5 coreceptor antagonist: Protease inhibitors
• a drug that blocks the receptor site on the T cell • drugs that block the activity of the enzyme
membrane that the HIV virus needs to interact with protease in HIV; protease is essential for the
in order to enter the cell maturation of infectious virus, and its absence
Cytomegalovirus (CMV) leads to the formation of an immature and
• DNA virus that accounts for many respiratory, noninfective HIV particle
ophthalmic, and liver infections Virus
Fusion inhibitor • particle of DNA or RNA surrounded by a protein
• a drug that prevents the fusion of the HIV-1 virus coat that survives by invading a cell to alter its
with the human cellular membrane, preventing it functioning
from entering the cell Herbal and Alternative Therapies
Helper T cell St. John’s wort
• human lymphocyte that helps to initiate immune • Anti-inflammatory, antidepressant, diuretic, and
reactions in response to tissue invasion treatment for gastritis and insomnia
Hepatitis B •
• a serious to potentially fatal viral infection of the
liver, transmitted by body fluids
Hepatitis C
• a usually mild viral infection of the liver that can
progress to chronic inflammation; most often seen
hepatitis after blood transfusions
Herpes
• DNA virus that accounts for many diseases,
including shingles, cold sores, genital herpes, and
encephalitis
Human immunodeficiency virus (HIV)
• retrovirus that attacks helper T cells, leading to a
decrease in immune function and AIDS or ARC
Influenza A