Definition Community-acquired pneumonia (CAP) is defined as an acute infection of the lung parenchyma accompanied by symptoms of acute illness, which is not acquired in hospitals or other long-term care facilities. -Clin. infect Dis. 2000;31:347-82
Alphabet Soup for Pneumonia HAP: Hospital-acquired pneumonia ≥ 48 h from admission VAP: Ventilator-associated pneumonia ≥ 48 h from endotracheal intubation HCAP: Healthcare-associated pneumonia Long-term care facility (NH), hemodialysis, outpatient chemo, wound care, etc. CAP: Community-acquired pneumonia Outside of hospital
Epidemiology 8th leading cause of death in US in 2007 4-5 million cases per year in US 25% require hospitalization Almost 916,000 cases annually in pts >65 yo Case fatality rate has not changed substantially since penicillin www.cdc.gov/mmwr cdc.gov/nchs/data/hestat
Microbiology Causative organism established in 60% CAP in research setting, 20% in clinical setting “Typical”: S. pneumoniae, Haemophilus influenzae, Staphylococcus aureus, Group A streptococci, Moraxella catarrhalis, anaerobes, and aerobic gram-negative bacteria “Atypical” - 20-28% CAP worldwide Legionella spp, Mycoplasma pneumoniae, Chlamydophila (formerly Chlamydia) pneumoniae, and C. psittaci Mainly distinguished from typical by not being detectable on Gram stain or cultivable on standard media
Microbiology of CAP amonghospitalized patientsOutpatient Streptococcus pneumoniae Mycoplasma pneumoniae Haemophilus influenzae Chlamydophila pneumoniae Respiratory virusesInpatient (Ward) S. pneumoniae M. pneumoniae H. influenzae C. Pneumoniae Legionella species Respiratory viruses AspirationInpatient (ICU) S. pneumoniae Legionella spp. Staphylococcus aureus Gram-negative bacilli
Age-specificRates ofHospitalAdmission byPathogen Marsten. Community-based pneumonia incidence study group. Arch Intern Med 1997;157:1709-18
Typical vsAtypical CAP CXR patterns Bronchopneumonia: 88% C. pneumo vs 77% Pneumococcal, P=0.67 Lobar or air-space: 29% C. pneumo vs 54% PneumococcalKauppinen et al. Arch Intern Med 1996; 156: 1851.
Exposures & Associated PathogensHotel or cruise ship Legionella sppTravel or residence in US Coccidioides spp HantavirusTravel or residence in Asia Burkolderia pseudomallei Staph aureus H.influenzae Avian influenza A (H5N1)Influenza active in community Influenza S. pneumonae Staph aureus (MRSA) H. influenzaeCough >2 wks with whoop or Bordetella pertussisposttussive vomitting
Diagnosis: Cultures Pretx Blood Cultures Yield 5-15% Stronger indication for severe CAP Host factors: cirrhosis, asplenia, complement deficiencies, leukopenia Pretx expectorated sputum Gs & Cx Yield can be variable Depends on multiple factors: specimen collection, transport, speed of processing, use of cytologic criteria Predominant morphotype seen in only 14% of 1669 hospitalized CAP pts (Garcia-Vasquez, Arch Intern Med 2004) Pretx endotracheal aspirate Gs & Cx Pleural effusions >5 cm on lateral upright CXR
Diagnosis: Other testing Urinary antigen tests S. pneumoniae & L. pneumophila serogroup 1 50-80% sensitive, >90% specific in adults Pros: rapid (15 min), simple, can detect Pneumococcus after abx started Cons: cost, no susceptibility data, not helpful in patients with recent CAP (prior 3 months)
Diagnosis: Other testing Acute-phase serologies C. pneumoniae, Mycoplasma, Legionella spp Not practical given slow turnaround & single acute-phase result unreliable Influenza testing Hospitalized patients: Severe respiratory illness (T> 37.8°C with SOB, hypoxia, or radiographic evidence of pneumonia) without other explanation and suggestive of infectious etiology should get screened during season NP swab or nasal wash/aspirate Rapid flu test (15 min) Distinguishes A vs B Sensitivity 50-70%; specificity >90% Respiratory virus DFA & culture - reflex subtyping for A Respiratory viral PCR panel - reflex subtyping for A Influenza A PCR panel
2009-2010 Influenza Surveillance Seattle - King Countywww.kingcounty.gov/healthservices/health/communicable/immunization/fluactivity.aspx
To Admit or Not?Pneumonia Severity & Deciding Site of Care Using objective criteria to risk stratify & assist in decision re outpatient vs inpatient management PSI CURB-65 Caveats Other reasons to admit apart from risk of death Not validated for ward vs ICU Labs/vitals dynamic
Pneumonia Severity IndexPORT study Fine, N Engl J Med 1997;336:243.
Consensus Guidelines on the Management of Community-Acquired Pneumonia Site-of-Care Decisions • Hospital admission decision - Severity-of-illness scores, such as the CURB-65 criteria (confusion, uremia, respiratory rate, low blood pressure, age 65 years or greater), or prognostic models, such as the Pneumonia Severity Index (PSI), can be used to identify patients with CAP who may be candidates for outpatient treatment (Strong recommendation; Level I evidence) - Objective criteria or scores should always be supplemented with physician determination of subjective factors, including the ability to safely and reliably take oral medication and the availability of outpatient support resources (Strong recommendation; Level II evidence) - For patients with CURB-65 scores ≥ 2, more-intensive treatement – that is, hospitalization or, where appropriate and available, intensive in-home health care services – is usually warranted (Moderate recommendation; Level III evidence)Mandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
Consensus Guidelines on the Management of Community-Acquired Pneumonia Site-of-Care Decisions • ICU admission decision - Direct admission to an ICU is required for patients with septic shock requiring vasopressors or with acute respiratory failure requiring intubation and mechanical ventilation (Strong recommmendation; Level II evidence) - Direct admission to an ICU or high-level monitoring unit is recommended for patients with 3 of the minor criteria for severe CAP listed in table 4 (Moderate recommendation; Level II evidence)Mandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
Criteria for Severe CAP Minor criteria Respiratory rate ≥30 breaths/min PaO2/FiO2 ratio ≥ 250 Multilobar infiltrates Confusion/disorientation Uremia (BUN ≥20 mg/dL) Leukopenia (WBC <4000 cells/mm3) Thrombocytopenia (platelets <100,000 cells/mm3) Hypothermia (core T <36°C) Hypotension requiring aggressive fluid resuscitation Major criteria Invasive mechanical ventilation Septic shock with the need for vasopressors
Consensus Guidelines on the Management of Community-Acquired Pneumonia Table 5: Clinical Indications for More Extensive Diagnostic Testing Indication Blood culture Sputum culture Legionella UAT Pneumococcal UAT Other Intensive care unit X X X X Xa admission Failure of outpatient X X X antibiotic therapy Cavitary infiltrates X X Xb Leukopenia X X Active alcohol abuse X X X X Chronic severe liver X X disease Severe X obstructive/structural lung disease Asplenia (anatomic or X X functional Recent travel (within X Xc past 2 weeks) Positive Legionella UAT Xd NA result Positive pneumococcal X X NA UAT result NOTE. NA, not Pleural effusionapplication; UAT urinaryXantigen test X X X Xe a Endotracheal aspirate if intubated, possibly bronchoscopy or nonbronchoscopic bronchoalveolar lavage. b Fungal and tuberculosis cultures. c See table 8 for details d Special media for Legionella e Thoracentesis and pleural fluid culturesMandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
Outpatient Empiric CAP Abx Healthy; no abx x past 3 months Macrolide e.g. azithromycin 2nd choice: doxycycline Comorbidities; abx x past 3 mon (use alternative abx) Respiratory fluoroquinolone: Moxifloxacin, levofloxacin 750 mg, gemifloxacin Beta-lactam + macrolide Regions with >25% high-level macrolide-resistant S. pneumo, consider alternative agents 2007 IDSA/ATS Guidelines for CAP in Adults.
Inpatient Empiric CAP Abx Inpatients in ward Respiratory fluoroquinolone ß-lactam + macrolide Inpatients in ICU ß-lactam (cefotaxime/ceftriaxone or ampicillin/sulbactam) + macrolide Respiratory fluoroquinolone for PCN-allergic pts Pseudomonas Anti-pneumococcal & anti-pseudomonal ß-lactam + azithromycin + cipro/levofloxacin Can substitute quinolone for aminoglycoside PCN-allergic: can substitute aztreonam CA-MRSA: Add vanco or linezolid 2007 IDSA/ATS Guidelines for CAP in Adults.
Influenza pneumoniaSome things to keep in mind… Antiviral treatment within 48 hrs Reduce likelihood of lower tract complications & antibacterial use in outpatients Impact on hospitalized pts less clear Possible exceptions to <48 h rule: Immunocompromised patients To reduce viral shedding for infection control in hospitalized patients
Influenza pneumoniaSome things to keep in mind… Influenza B Oseltamavir 75 mg PO BID x 5 days Zanamavir 2 INH BID x 5 days Influenza A H3N2 - general seasonal Resistant to adamantane antivirals H1N1 - general seasonal High rate of oseltamavir resistance in 2008-2009 Still susceptible to zanamavir Novel H1N1 (Swine flu) Sensitive to neuraminidase inhibitors Resistant to adamantanes
Drug-resistant Strep pneumoniaeß-lactam resistance Risk factors Age >65 yrs ß-lactam x previous 3 mon Medical comorbidities Exposure to child in day care Current levels of ß-lactam resistance do not generally result in treatment failure with amoxicillin, ceftriaxone or cefotaxime As opposed to macrolide or fluoroquinolone resistance Clinically relevant threshold - MIC 4?
Consensus Guidelines on the Management of Community-Acquired Pneumonia Time to First Antibiotic Dose • For patients admitted through the emergency department (ED), the first antibiotic dose should be administered while still in the ED (Moderate recommendation; Level III evidence)Mandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
Consensus Guidelines on the Management of Community-Acquired Pneumonia Switch from Intravenous to Oral Therapy • Patients should be switched from intravenous to oral therapy when they are hemodynamically stable and improving clinically, are able to ingest medications, and have a normally functioning gastrointestinal tract (Strong recommendation; Level II evidence) • Patients should be discharged as soon as they are clinically stable, have no other active medical problems, and have a safe environment for continued care. Inpatient observation while receiving oral therapy is not necessary (Moderate recommendation; Level II evidence)Mandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
Consensus Guidelines on the Management of Community-Acquired Pneumonia Duration of Antibiotic Therapy • Patients with CAP should be treated for a minimum of 5 days (Level I evidence), should be afebrile for 48-72 h, and should have no more than one CAP-associated sign of clinical instability (Table 10) before discontinuation of therapy (Moderate recommendation; Level II evidence) • A longer duration of therapy may be needed if initial therapy was not active against the identified pathogen or if it was complicated by extrapulmonary infection, such as meningitis or endocarditis (Weak recommendation ; Level III evidence)Mandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
Consensus Guidelines on the Management of Community-Acquired Pneumonia Table 10. Criteria for clinical stability Temperature ≤ 37.8oC Heart rate ≤ 100 beats/min Respiratory rate ≤ 24 breaths/min Systolic blood pressure ≥ 90 mmHg Arterial oxygen saturation ≥ 90% or pO2 ≥ 60 mmHg on room air Ability to maintain oral intakea Normal mental statusa NOTE. Critera are from [268, 274, 294]. pO2 oxygen partial pressure. a Important for discharge or oral switch decision but not necessarily for determination of nonresponseMandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
Consensus Guidelines on the Management of Community-Acquired Pneumonia Other Treatment Considerations I • Patients with CAP who have persistent septic shock despite adequate fluid resuscitation should be considered for treatment with drotrecogin alfa activated within 24h of admission (Weak recommendation; Level II evidence) • Hypotensive, fluid-resuscitated patients with severe CAP should be screened for occult adrenal insufficiency (Moderate recommendation; Level II evidence)Mandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
Consensus Guidelines on the Management of Community-Acquired Pneumonia Other Treatment Considerations II • Patients with hypoxemia or respiratory distress should receive a cautious trial of noninvasive ventilation unless they require immediate intubation because of severe hypoxemia (PaO2/FiO2 ratio, <150) and bilateral alveolar infiltrates (Moderate recommendation; Level I evidence) • Low-tidal-volume ventilation (6 cm3/kg of ideal body weight) should be used for patients undergoing ventilation who have diffuse bilateral pneumonia or acute respiratory distress syndrome (Strong recommendation; Level I evidence)Mandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
Consensus Guidelines on the Management of Community-Acquired Pneumonia Table 11. Patterns and Etiologies of Types of Failure to Respond Failure to Improve Early (<72h of treatment) • Normal response Delayed • Resistant microorganism - Uncovered pathogen - Inappropriate by sensitivity • Paraneumonic effusion/empyema • Nosocomial superinfection - Nosocomial pneumonia - Extrapulmonary • Noninfectious - Complication of pneumonia (e.g., BOOP) - Misdiagnosis: PE, CHF, vasculitis - Drug feverMandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
Consensus Guidelines on the Management of Community-Acquired Pneumonia Management of Non-responding Pneumonia • The use of systematic classification of possible causes of failure to respond, based on time of onset and type of failure (Table 11), is recommended. (Moderate recommendation; Level II evidence)Mandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
Consensus Guidelines on the Management of Community-Acquired Pneumonia Table 11. Patterns and Etiologies of Types of Failure to Respond Deterioration or Progression Early (<72h of treatment) • Severity of illness at presentation • Resistant microorganism - Uncovered pathogen - Inappropriate by sensitivity • Metastatic infection - Empyema/parapneumonic - Endocarditis, meningitis, arthritis • Inaccurate diagnosis - PE, aspiration, ARDS - Vasculitis (e.g. SLE) Delayed • Nosocomial superinfection - Nosocomial pneumonia - Extrapulmonary • Exacerbation of comorbid illness • Intercurrent noninfectious disease - PE - Myocardial infarction - Renal failureMandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
Consensus Guidelines on the Management of Community-Acquired Pneumonia Table 12 Factors Associated with Non-responding Pneumonia Overall Failure a Early failure b Risk Factor Decreased Risk Increased Risk Decreased Risk Increased Risk Older Age(>65 years) ... ... 0.35 ... COPD 0.60 ... ... ... Liver disease ... 2.0 ... ... Vaccination 0.30 .... ... ... Pleural effusion ... 2.7 ... ... Multilobar infiltrates ... 2.1 ... 1.81 Cavitation ... 4.1 ... … Leukopenia ... 3.7 ... ... PSI class ... 1.3 ... 2.75 … Legionella pneumonia ... ... ... 2.71 Gram-negative pneumonia ... ... ... 4.34 Fluoroquinolone therapy 0.50 ... .... ... Concordant therapy ... ... 0.61 ... Discordant therapy ... .... ... 2.51NOTE. Data are relative risk values. COPD, chronic obstructive pulmonary disease; PSI, Pneumonia Severity Indexa From . b From .Mandell LA, Wunderlink RJ, Anzueto A et al 2007; 44:S27-72
Case-control study from Canada - review of fluoroquinolone (FLQ) use among Cx-proven TB cases. Of 148 isolates of M. TB, 3 were FLQ resistant. Patients who had received multiple FLQ prescriptions were more likely than patients who had received a single FLQ prescription to be infected with FLQ-resistant M. tuberculosis (15.0% vs. 0.0%; odds ratio, 11.4; P<.04) Long, Clin Infect Dis 2009. May 15; 48: 1355.
Follow-up ResponseExpected improvement? Clinical improvement w/ effective abx: 48-72 hrs Fever can last 2-5 days with Pneumococcus, longer with other etiologies, esp Staph aureus CXR clearing If healthy & <50 yo, 60% have clear CXR x 4 wks If older, COPD, bacteremic, alcoholic, etc. only 25% with clear CXR x 4 wks Switch from IV to PO Hemodynamically stable, improving clinically Able to ingest meds with working GI tract
Question…What is far & away the most common reason for non-response to antibiotics in CAP?1. Cavitation2. Pleural effusion3. Multilobar involvement4. Discordant antibiotic/etiology5. None of the above
Inadequate Response to TherapyWhat to consider Consider S. aureus, virus, resistant organism, TB, endemic fungi, Pneumocystis More unusual pathogens, atypical mycobacteria, higher bacteria (Nocardia, actinomycetes), fungi Noninfectious illness: Lung neoplasms with bronchial obstruction Lymphoma Systemic autoimmune disorders PE w/ infarct, pulm edema, ARDS Consider other testing: Lower tract sampling (bronch) CT chest PE work-up? Serologic testing Open lung biopsy