Pediatric Community-Acquired Pneumonia: Updated Guidelines

Providence 5th Annual Pediatric Conference Septe be 30, 2011 0 September

John Bradley MD Pediatric Infectious Diseases University of California, San Diego Rady Childrens Hospital San Diego

Pediatric Community-Acquired Pneumonia: Updated Guidelines Disclosure Statement: John S. Bradley, MD

The Regents of the University of California (Dr. Bradleys employer) p y ) hold a consulting g contract with Cerexa

Pediatric Pneumonia
We are all experts in Pediatric Pneumonia we know p pneumonia when we see it: Fever, cough, dyspnea, systemic toxicity But how can we most accurately diagnose p pneumonia? and for those who need antibiotics in this era of increasing resistance, but recent availability of Prevnar13, which one should we prescribe?

New Guidelines for Pediatric Pneumonia PIDS/IDSA/AAP/ATS/SCCM/SHM/ACEP/APSA Collaboration between

Pediatric ID Society, IDSA and American Academy of Pediatrics American College of Emergency Physicians American Thoracic Society (ATS) Pediatric Section Society for Hospital Medicine Society of Critical Care Medicine American Pediatric Surgical Association

New Guidelines for Pediatric Pneumonia PIDS/IDSA/AAP/ATS/SCCM/SHM/ACEP/APSA Site of Care (outpatient vs. ward vs. PICU) Diagnostic Testing Anti Anti-infective Treatment Adjunctive Surgical Therapy Discharge Criteria Prevention

Pediatric Pneumonia
One of most common causes of mortality in childhood worldwide

WHO 2005

Pediatric Pneumonia
There are an immense number of pathogens that can infect the lung Every pathogen that a child can inhale with each breath or can arrive in the lung through the bloodstream can cause pneumonia bloodstream,

Pediatric Pneumonia: Etiology

Etiology of pneumonia varies by: Age Clinical characteristics Season Exposures to illness Geographic location Underlying disease state Immunization history

Pediatric Pneumonia
Fungal Coccidioides Histoplasma Cryptococcus And new viruses: Human Metapneumovirus Bocavirus SARS coronavirus

PLUS:

McIntosh K. NEJM 2002

Incidence of Community-Acquired Pneumonia, Finland

Ruuskanen O, Mertsola J, Semin Resp Infect, 1999

Pneumonia is a disease of Preschool/School-aged Children

Glezen P, Denny FW. Epidemiology of acute lower respiratory disease in children. N Engl J Med. 1973

Pediatric Pneumonia
Viruses have been documented to cause the h vast majority j i (>90%) ( 90%) of f pneumonia, i particularly in infants Haemophilus influenzae type b conjugate vaccines have eliminated H. flu pneumonia Prevnar Prevnar vaccines have an efficacy of about 50% for pneumonia (in contrast to > 90% for bacteremia); decreased colonization/infxn colonization/ infxn by PenR strains

Pediatric Pneumonia: Diagnosis

Clues to Pathogen Identification

Clinical (age (age-specific)

Acute vs. slowly progressive illness Clinical toxicity present? Upper respiratory tract symptoms? Bilateral vs. unilateral disease Immunizations complete for H. influenzae, type b and S. pneumoniae?

Etiology of Pediatric Pneumonia, by Age

January 1999 March 2000, Dallas TX

Unk V B+V B

Prevnar licensed in 2000

Michelow I et al. Pediatrics 2004. Pathogen identified in 79% of children studied

Published Studies
Author, Year (nb) Hospitalized Michelow, 2004 (154) Juvn, 2000 (254) Outpatient Wubbel, 1999 (168) Combined (In/Outpt) ( p) Heiskanen-Kosma, 1998 (201 total, 64 hospitalized)
aIncludes

Percent of all children with pneumonia in whom a pathogen was identifieda

Streptococcus pneumoniae
Other bacterial Viral Atypical pneumonia agentsc

44% 37%

3% 10%

58% 80%

23% 8%

27%

nrd

20%

13%

28%

8%

25%

36%

co-infections bNumber of children studied cMycoplasma pneumoniae and Chlamydia (Chamydophila) pneumoniae dNot reported Bradley and McCracken, Clin Infect Dis. 2008 Dec 1;47 Suppl 3:S241-8.

The Role of Mixed Viral Infections

(n=51) Virus RSV Bocavirus Rhinovirus Enterovirus Metapneumovirus Single 24 2 6 2 0 Mixed 13 (35%) 13 (87%) 3 (33%) 1( (33%) ) 0 (no MPV in Germany?)

Bonzel L et al. PIDJ 2008. Childrens Hospital Duesseldorf, Germany (PCR test)

New Guidelines for Pediatric Pneumonia PIDS/IDSA/AAP/ATS/SCCM/SHM/ACEP/APSA Diagnostic tests in children well enough to be managed as outpatients:
Blood cultures are rarely positive and are discouraged WBC, ESR, CRP do not need to be routinely performed p CXR does not need to be routinely performed (an experienced ED pediatrician in Philadelphia is able to accurately predict pneumonia on exam (confirmed by CXR)

Inpatient Diagnosis to Promote Specific Therapy Blood cultures recommended WBC/ESR/CRP may be helpful

Pediatric Pneumonia:

CXR recommended

Virus tests (antigen, culture, PCR) Influenza A and B, hMPV, RSV, etc Pertussis tests (culture, DFA, PCR) Bacterial/Mycoplasma/Fungal serologies AFB cultures/PCR, PPD, QuantiFERON test

How good are fever and cough for diagnosing bacterial pneumonia? Pneumococcus vs RSV vs Mixed: Not very good: Finland

Pediatric Pneumonia: Signs/Sx

Juven T et al. PIDJ 2001

Pediatric Pneumonia: Laboratory Dx

High WBC and CRP are helpful, but not sensitive enough for diagnosis; negative tests helpful to dx virus
Juven T et al. PIDJ 2001

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Pediatric Pneumonia: Diagnosis

Juven T et al. PIDJ 2001

How good are chest auscultation/CXR for diagnosing pneumonia? Dismal for Pneumococcal; not bad for RSV!

New Guidelines for Pediatric Pneumonia PIDS/IDSA/AAP/ATS/SCCM/SHM/ACEP/APSA When should you hospitalize a child with pneumonia from a clinic or ED?
Respiratory distress, of course Or: When the peripheral oxygen saturation is 90% or less

OxyMedical.com

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New Guidelines for Pediatric Pneumonia PIDS/IDSA/AAP/ATS/SCCM/SHM/ACEP/APSA How does the community rate of penicillin resistance in pneumococcus impact the dose of amoxicillin or ampicillin?

Easy: the higher the resistance, the greater the dose needed to achieve cure [For penicillins penicillins, , you need antibiotic at the site of infection for 40% of dosing interval; higher concentrations at the site will not improve cure rates. TID vs BID

Serotypes of Invasive Pneumococci: 8 Pediatric Hospitals

*
Kaplan S et al. Pediatrics 2010

In Prevnar13

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Resistance in 19A Pneumococci

90 80 70 60 50 19A 40 30 20 10 0 0.01 0.02 0.03 0.06 0.13 0.25 0.5 1 2 4 8 non 19A

Penicillin MIC (mcg/mL)

Kaplan S et al. Pediatrics 2010

How Does The Community Rate Of Penicillin Resistance Impact The Dose Of Amox/Ampicillin?
Time that ampicillin concentrations are above MIC in the serum, given a 30 mg/kg dose 88% of children given 30 mg/kg k every 8 hours will be cured of an infection caused by pneumococci in Kansas City (with 20% of strains having an MIC of 2 or greater)

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New Guidelines for Pediatric Pneumonia PIDS/IDSA/AAP/ATS/SCCM/SHM/ACEP/APSA Outpatient empiric therapy of community pneumonia:
Amoxicillin!
90 mg/kg/day divided bid OR 40 40-45 mg/kg/day divided tid OR 90 mg/kg/day divided tid

I Inpatient ti t empiric i i th therapy:

Ampicillin (or penicillin G)!

150 150-200 mg/kg/day div q 6 hours (ampicillin)

Table 7 - Empiric Therapy for Pediatric CAP Site of Care Empiric Therapy for Bacterial Pneumonia Empiric Therapy for Atypical Pneumonia

Outpatient: Fully immunized with conjugate vaccines for: Haemophilus influenzae, type b, and S. pneumoniae Amoxicillin, oral Less than 5 years of age (90 mg/kg/day div bid) (Preschool)

Azithromycin oral

Alternative: Alternatives: Clarithromycin Amoxicillin/clavulanate, oral (90 oral; erythromycin oral mg/kg/day amox component div bid) Azithromycin oral (10 mg/kg on d 1, followed by 5 mg/kg daily, d 2-5 Alternatives: Clarithromycin oral (15 mg/kg/day div bid to a max of 1 gm daily); erythromycin; doxycycline for older than 7 years Azithromycin IV (in addition to beta-lactam, if bacterial diagnosis in doubt) Alternatives***: Clarithromycin; erythromycin; doxycycline Azithromycin IV (in addition to beta-lactam, if diagnosis in doubt) Alternatives***: Clarithromycin; erythromycin; doxycycline

5 Years of age and older

Amoxicillin, oral (90 mg/kg/day div bid to a max of 4gm/day)* Alternative: Amoxicillin/clavulanate, oral (90 mg/kg/day amox component div bid to a max dose of 4g amox/day)

-Fully immunized -Local penicillin resistance in invasive strains of pneumococcus low -Not fully immunized -Local penicillin resistance in invasive strains of pneumococcus is significant

Inpatient (all ages)

Ampicillin IV; penicillin G IV**

Alternatives**: Ceftriaxone; cefotaxime Ceftriaxone; cefotaxime**

Alternative: Levofloxacin

*For children with presumed bacterial CAP who do not have clinical, laboratory, or radiographic evidence that distinguishes bacterial CAP from atypical CAP, a macrolide can be added **Addition of vancomycin or clindamycin for suspected CA-MRSA ***Levofloxacin for children who have reached growth maturity, or those who cannot tolerate macrolides

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Pathogen

Parenteral Therapy

Table 5: Selection of Antimicrobial Therapy for Specific Pathogens

S. pneumoniae with MIC values to penicillin 2.0 mcg/mL

Preferred: Ampicillin (150-200 mg/kg/day div q 6 hours), or penicillin G (200-300,000 u/kg/day div q 4-6 hours) Alternatives: Ceftriaxone (50 to 100 mg/kg/day q 12-24 hours) (Preferred for parenteral outpatient therapy) or cefotaxime (150 mg/kg/day div q 8 hours) May also be effective: Clindamycin (40 mg/kg/day div q 6-8 hours) or vancomycin (40-60 mg/kg/day div q 6-8 hours)

Preferred: Amoxicillin (90 mg/kg/day div bid, or 45 mg/kg/day div tid)

Oral Therapy (Step-Down Therapy or Mild Infection)

to penicillin > 4.0 mcg/mL (resistant)

S. pneumoniae, with MIC values

Alternatives: A second or third generation cephalosporin (cefpodoxime, cefuroxime, cefprozil); levofloxacin PO, if susceptible, (1620 mg/kg/day div bid for children 6 months to 5 years and 8-10 mg/kg/day once daily for children 5 to 16 years, max daily dose 750 mg), or linezolid PO (30 mg/kg/day div tid for children < 12 years and 20 mg/kg/day div bid for children >12 years). Preferred: Ceftriaxone (100 mg/kg/day q 12- Preferred: Levofloxacin PO (16 -20 mg/kg/day 24 hours) div bid for children 6 months to 5 years and 810 mg/kg/day once daily for children 5 to 16 years, max daily dose 750 mg), if susceptible, or linezolid PO (30 mg/kg/day div tid for children < 12 years and 20 mg/kg/day div bid for children >12 years). Alternatives: te at es Ampicillin pc (300-400 (300 00 mg/kg/day g/ g/day Alternative: te at e C Clindamycin da yc PO* O (30-40 (30 0 div q 6 hours), levofloxacin (16-20 mg/kg/day mg/kg/day div tid) div q 12 hours for children 6 months to 5 years and 8-10 mg/kg/day once daily for children 5 to 16 years, max daily dose 750 mg) or linezolid (30 mg/kg/day div q 8 hours for children < 12 years and 20 mg/kg/day div q 12 hours for children >12 years) May also be effective: Clindamycin* (40 mg/kg/day div q 6-8 hours) or vancomycin (40-60 mg/kg/day div q 6-8 hours),

AntiAnti -infective Treatment

Amoxicillin should be used as firstfirst-line empiric therapy for previously healthy, appropriately immunized infants and prepre-school aged children with mild to moderate CAP suspected p to be of bacterial origin. g Amoxicillin provides p appropriate coverage for Streptococcus pneumoniae, the most prominent invasive bacterial pathogen. (strong

recommendation, moderate moderate-quality evidence)

Ampicillin or penicillin G should be administered to the fully immunized infant or schoolschool-aged child admitted to a hospital ward with CAP. Assuming local epidemiologic data document lack of substantial high high-level penicillinpenicillinresistance for invasive Streptococcus pneumoniae, empiric therapy with ampicillin or penicillin G is moderate-quality appropriate (strong recommendation, moderate-

evidence)

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New Guidelines for Pediatric Pneumonia PIDS/IDSA/AAP/ATS/SCCM/SHM/ACEP/APSA And for suspected Mycoplasma, in schoolschool -aged children or adolescents adolescents, use azithromycin or add azithromycin to amox/ampicillin for children with presumed bacterial CAP who do not p have clinical, laboratory, or XX-ray evidence that distinguishes bacterial CAP from atypical CAP

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New Guidelines for Pediatric Pneumonia Conclusions

We have a critical need for accurate data on the pathogens causing pneumonia in all age groups, using better noninvasive diagnostic techniques (PCR) We need information on just how clinically effective amoxicillin is against g pneumococcus at current levels of PenR; PenR; how long do we need to treat? This is just the first version!!

Thank you!

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Questions???? Q ti ????

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