Community acquired pneumonia (CAP): Why is this still a problem? François Boucher MD, FRCPC The complete PowerPoint file of this presentation is available at the following URL: http://tinyurl.com/7uc3m4e francois@boucher.cc Objectives After this presentation, participants will be able to: • Determine appropriate agents, routes and duration of treatment. • Recognize how local epidemiology influences treatment choices. • Manage complications of CAP. Emergent problems in pediatric community-acquired pneumonia • Severe pneumonia • Pulmonary abscess formation: GAS • Pulmonary necrosis & fibrosis: MRSA • Pneumatocoeles: S. aureus • Resistant organisms: S. pneumoniae 19A • Parapneumonic effusion • Increasing incidence • Difficult management IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25 Incidence in Canadian children • 41,000 children <5 years of age treated in the community each year • 9600 hospitalized • older children have decreased incidence • leading cause of mortality and morbidity amongst Canadian Inuit; 1999-2000- outbreak in several communities on Baffin Island (adult and child) Pathogens • CAP generally caused by a single organism • Even with extensive diagnostic testing, most investigators cannot identify a specific etiology for CAP in ≥ 50% of patients. • In those identified, S. pneumoniae is causative pathogen 60-70% of the time Pathogens in pediatric CAP Pediatr Infect Dis J 2002 21: 592-598 Pneumococcal pneumonia • Most common cause of CAP • Gram positive diplococci • “Typical” symptoms (e.g. malaise, shaking chills, fever, pleuritic hest pain, cough) • Lobar infiltrate on CXR • Rarely bacteremic in children Atypical Pneumonia • Second most frequent cause (especially in younger population) • Commonly associated with milder symptoms: subacute onset, non-productive cough, no focal infiltrate on CXR • Mycoplasma: younger Pts, extra-pulmonary symptoms (URI, rash), headache, sore throat • Chlamydia pneumoniae: young adults, year round, URI, sore throat Viral Pneumonia • Most common cause in children • RSV, influenza, parainfluenza • Influenza is the most important viral cause in adults, especially during winter months • Post-influenza pneumonia (secondary bacterial infection) • S. pneumo, Staph aureus Other bacteria • Staphylococcus aureus • Severe disease, prior viral pneumonia • Gram negative bacteria • Klebsiella – neonates • Branhamella catarrhalis - sinus disease, otitis, COPD • H. influenzae - Rare • Anaerobes • Aspiration pneumonia, dental disease IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25 Management of CAP: Antibiotic therapy Child < 5 years old • Presumed bacterial pneumonia • Amoxicillin, oral (90 mg/kg/day in 2 doses) Alternative: oral amoxicillin clavulanate (amoxicillin component, 90 mg/kg/day in 2 doses) • Presumed atypical pneumonia • Azithromycin oral (10 mg/kg on day 1, followed by 5 mg/kg/day once daily on days 2– 5); • Alternatives: oral clarithromycin (15 mg/kg/day in 2 doses for 7-14 days) or oral erythromycin (40 mg/kg/day in 4 doses) IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25 Management of CAP: Antibiotic therapy Child ≥ 5 years old • Presumed bacterial pneumonia • Oral amoxicillin (90 mg/kg/day in 2 doses to a maximum of 4 g/day); 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 to a b-lactam antibiotic for empiric therapy; • alternative: oral amoxicillin clavulanate (amoxicillin component, 90 mg/kg/day in 2 doses to a maximum dose of 4000 mg/day, eg, one 2000-mg tablet twice daily) IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25 Management of CAP: Antibiotic therapy Child ≥ 5 years old • Presumed atypical pneumonia • Oral azithromycin (10 mg/kg on day 1, followed by 5 mg/kg/day once daily on days 2– 5 to a maximum of 500 mg on day 1, followed by 250 mg on days 2–5); alternatives: oral clarithromycin (15 mg/kg/day in 2 doses to a maximum of 1 g/day); erythromycin, doxycycline for children >7 years old IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25 Management of CAP: Antibiotic therapy Inpatient (All ages) • Presumed bacterial pneumonia • Ampicillin or penicillin G; • alternatives: ceftriaxone or cefotaxime; • addition of vancomycin or clindamycin for suspected CA-MRSA IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25 Management of CAP: Antibiotic therapy Inpatient (All ages) • Presumed atypical pneumonia • Azithromycin (in addition to ß-lactam, if diagnosis of atypical pneumonia is in doubt); • alternatives: clarithromycin or erythromycin; doxycycline for children >7 years old; levofloxacin for children who have reached growth maturity, or who cannot tolerate macrolides IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25 Management of CAP: Antibiotic therapy Not completely immunized • Presumed bacterial pneumonia: • Ceftriaxone or cefotaxime; addition of vancomycin or clindamycin for suspected CAMRSA; • alternative: levofloxacin; addition of vancomycin or clindamycin for suspected CAMRSA IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25 Management of CAP: Antibiotic therapy Not completely immunized • Presumed atypical pneumonia • Azithromycin (in addition to ß-lactam, if diagnosis in doubt); • alternatives: clarithromycin or erythromycin; doxycycline for children >7 years old; levofloxacin for children who have reached growth maturity or who cannot tolerate macrolides IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25 Management of CAP: Antibiotic therapy Mild case or step-down therapy • Preferred: amoxicillin (90 mg/kg/day in 2 doses or 45 mg/kg/day in 3 doses); • Alternatives: second- or third-generation cephalosporin (cefpodoxime, cefuroxime, cefprozil); oral levofloxacin, if susceptible (16– 20 mg/kg/day in 2 doses for children 6 months to 5 years old and 8–10 mg/kg/day once daily for children 5 to 16 years old; maximum daily dose, 750 mg) or oral linezolid (30 mg/kg/day in 3 doses for children <12 years old and 20 mg/kg/day in 2 doses for children ≥12 years old) IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25 Management of CAP: Antibiotic therapy Highly resistant S.pneumoniae Parenteral therapy • Preferred: ceftriaxone (100 mg/kg/day every 12– 24 hours); • Alternatives: ampicillin (300–400 mg/kg/day every 6 hours), levofloxacin (16–20 mg/kg/day every 12 hours for children 6 months to 5 years old and 8–10 mg/kg/day once daily for children 5–16 years old; maximum daily dose, 750 mg), or linezolid (30 mg/kg/day every 8 hours for children <12 years old and 20 mg/kg/day every 12 hours for children ≥12 years old); • may also be effective: clindamycin (40 mg/kg/day every 6–8 hours) or vancomycin (40– 60 mg/kg/day every 6–8 hours) IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25 Management of CAP: Antibiotic therapy Highly resistant S.pneumoniae Oral therapy • Preferred: oral levofloxacin (16–20 mg/kg/day in 2 doses for children 6 months to 5 years and 8–10 mg/kg/day once daily for children 5–16 years, maximum daily dose, 750 mg), if susceptible, or oral linezolid (30 mg/kg/day in 3 doses for children <12 years and 20 mg/kg/day in 2 doses for children ≥12 years); • Alternative: oral clindamycin (30–40 mg/kg/day in 3 doses) IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25 Levofloxacin (Levaquin™) • Wide-spectrum fluoroquinolone: • S pneumoniae, • Haemophilus influenzae (nontypeable), • Moraxella catarrhalis • M pneumoniae, C pneumoniae, Legionella • M. tuberculosis • Excellent bioavailability: 100% absorbed • Well tolerated by children • 5-year safety study reported 11-03-23 • Many interactions • Medications: anticoagulants • Natural products Linezolid (Zyvox™) • Narrow-spectrum oxazolidinone: Gram+ • S pneumoniae, • S. aureus, MRSA • VRE • Excellent bioavailability: ≈100% absorbed • Well tolerated for short courses of therapy • Headache, diarrhea, nausea • Long-term use: Bone marrow suppression, thrombocytopenia • > 2 weeks: neuropathy, lactic acidosis, mitochondrial toxicity Management of CAP: Antibiotic therapy Mycoplasma pneumoniae Parenteral therapy • Preferred: intravenous azithromycin (10 mg/kg on days 1 and 2 of therapy; transition to oral therapy if possible); • Alternatives: intravenous erythromycin lactobionate (20 mg/kg/day every 6 hours) or levofloxacin (16-20 mg/kg/day every 12 hours; maximum daily dose, 750 mg) IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25 Management of CAP: Antibiotic therapy Mycoplasma pneumoniae Oral therapy • Preferred: azithromycin (10 mg/kg on day 1, followed by 5 mg/kg/day once daily on days 2–5); • Alternatives: clarithromycin (15 mg/kg/day in 2 doses) or oral erythromycin (40 mg/kg/day in 4 doses); • for children >7 years old, doxycycline (2–4 mg/kg/day in 2 doses; • for adolescents with skeletal maturity, levofloxacin (500 mg once daily) or moxifloxacin (400 mg once daily) IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25 Pneumonia caused by MRSA François Boucher MD, FRCPC MRSA pneumonia in children: When to suspect… • For children hospitalized with severe CAP empiric therapy for MRSA is recommended (pending sputum and/or blood culture results): • Those requiring an intensive care unit (ICU) admission, • OR Necrotizing or cavitary infiltrates, • OR Empyema Lui C, et al. Clin Infect Dis. 2011;52:1-38 Management of CAP: Antibiotic therapy MRSA susceptible to clindamycin Parenteral therapy • Preferred: vancomycin (40–60 mg/kg/day every 6–8 hours or dosing to achieve an AUC/MIC ratio of >400) or clindamycin (40 mg/kg/day every 6–8 hours); • Alternatives: linezolid (30 mg/kg/day every 8 hours for children ,12 years old and 20 mg/kg/day every 12 hours for children $12 years old) IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25 Management of CAP: Antibiotic therapy MRSA susceptible to clindamycin Oral therapy • Preferred: oral clindamycin (30–40 mg/kg/day in 3 or 4 doses); • Alternatives: oral linezolid (30 mg/kg/day in 3 doses for children >12 years and 20 mg/kg/day in 2 doses for children ≥12 years) IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25 Management of CAP: Antibiotic therapy MRSA resistant to clindamycin Parenteral therapy • Preferred: vancomycin (40–60 mg/kg/day every 6-8 hours or dosing to achieve an AUC/MIC ratio of >400); • Alternatives: linezolid (30 mg/kg/day every 8 hours for children <12 years old and 20 mg/kg/day every 12 hours for children ≥12 years old) IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25 Management of CAP: Antibiotic therapy MRSA resistant to clindamycin Oral therapy • Preferred: oral linezolid (30 mg/kg/day in 3 doses for children <12 years and 20 mg/kg/day in 2 doses for children ≥12 years old); • Alternatives: none; entire treatment course with parenteral therapy may be required IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25 Management of CAP: Antibiotic therapy for other etiologic agents The guideline offers specific therapy recommendations for pediatric CAP caused by •GAS •MSSA… •H. influenzae, typable or not •Chlamydia & Chlamydophila •Etc IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25 Empyema Empyema: definition • Empyema is inflammatory fluid and debris in the pleural space. It results from an untreated pleuralspace infection that progresses from free-flowing pleural fluid to a complex collection in the pleural space. Pathophysiology • Exudative stage • Fibrinolytic stage • Organization stage Epidemiology • Increase in incidence since the mid-nineties (USA) • Particularly among certain age groups Finlay C et al. Can Respir J 2008 Finlay C et al. Can Respir J 2008 Finlay C et al. Can Respir J 2008 Variables associated with parapneumonic effusions • Pneumococcal serotype? NO • Age ≥ 3 years (p<0,0001)* • Varicella (p<0,0001)* • Fever ≥ 7 days (p<0,0001)* • Medication use: • Ibuprofen (p<0,0001)* • Ceftriaxone (p<0,0001)* *: Multivariate regression analysis Parapneumonic effusions management Small effusions • Size of effusion: Small: <10 mm on lateral decubitus radiograph or opacifies less than onefourth of hemithorax • Bacteriology: Bacterial culture and Gram stain results unknown or negative • Risk of poor outcome: Low • Tube drainage: No; sampling of pleural fluid is not routinely required IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25 Parapneumonic effusions management Moderate effusions • Size of effusion: Moderate: >10 mm rim of fluid but opacifies less than half of the hemithorax • Bacteriology: Bacterial culture and/or Gram stain results negative or positive (empyema) • Risk of poor outcome: Low to moderate • Tube drainage: • No, if the patient has no respiratory compromise and the pleural fluid is not consistent with empyema; • Yes, if the patient has respiratory compromise or if pleural fluid is consistent with empyema IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25 Parapneumonic effusions management Large effusions • Size of effusion: Large: opacifies more than half of the hemithorax • Bacteriology: Bacterial culture and/or Gram stain results positive (empyema) • Risk of poor outcome: High • Tube drainage: Yes, in most cases IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25 Parapneumonic effusions management Antibiotic therapy • In the case of culture-negative parapneumonic effusions, antibiotic selection should be based on the treatment recommendations for patients hospitalized with CAP • The duration of antibiotic treatment depends on the adequacy of drainage and on the clinical response demonstrated for each patient. In most children, antibiotic treatment for 2–4 weeks is adequate IDSA Pediatric Community Pneumonia Guidelines. CID 2011;53:e25 Merci! François Boucher MD, FRCPC