Community acquired pneumonia: Update and review for the hospitalist

Community acquired pneumoniaBharat Awsare MD FCCPDivision of Pulmonary and Critical Care MedicineAssistant Professor of MedicineDirector, Medical Intensive Care UnitThomas Jefferson University HospitalPneumonias ClassificationNosocomial Pneumonias-Acute infection of parenchyma-Symptoms of infection-Acute infiltrate or auscultatory findings consistent with pneumoniaCAP Two Types of PresentationsClassicalSudden onset of CAPHigh fever, shaking chillsPleuritic chest pain, SOBProductive coughRusty sputum, blood tingePoor general conditionHigh mortality up to 20% in patients with bacteremiaS.pneumoniae causative Gradual & insidious onsetLow grade feverDry cough, No blood tingeWalking CAPLow mortality 1-2%; except in cases of LegionellosisMycoplasma, Chlamydiae, Legionella, Ricketessiae, Viruses are causative

AtypicalScope of the problem5 million cases/year10 million office visits1 million admissions/year100,000 ICU admissionsEstimated cost: $12 billion*Inpatient (20%)$10 billionOutpatient (80%) $2 billion

*Colice GL et al. Am J Resp Crit Care Med (2006)176:913-920.Incidence of CAP per age (in 1000s)

CAP mortality per age (in 1000s)

Mortality in CAPMost common cause of severe sepsis6th leading cause of deathLeading cause of death from infectionMortality has not changed in 4 decadesOutpatient1%Inpatient5-10%ICU20-40%Age adjusted death rates

www.cdc.gov/mmwrRisk factorsMajorCOPD/smokingAlcoholismChronic heart diseaseDiabetes1/3 patients previously healthy

Other risk factorsPoor dentitionRenal failureHepatic diseaseCVAImmunodeficiencyMalnutrition

MicrobiologyOutpatientInpatient (non-ICU)Inpatient (ICU)S pneumoniaeS pneumoniaeS pneumoniaeM pneumoniaeM pneumoniaeLegionella sppH influenzaeC pneumoniaeH influenzaeC pneumoniaeH influenzaeGram negative bacilliM catarrhalisLegionella sppS aureusViruses*

Viruses**Influenza A and BAdenovirusRespiratory syncitial virusParainfluenza

40-70% of patients with CAP have no organism identified (fastidious growth of S. pneumoniae, H. influenzae)

Modern methods to determine etiology of CAPAdults admitted with CAP over 1 yearMicrobiologic testingSputum cultureBlood cultureNasopharyngeal samplingSputum samples analyzed by PCRNasal samples analyzed by PCRSerologic testing for M pneumoniae and Chlamydophila pneumoniae, and virusesUrine antigen assay for S pneumoniae, Legionella

ResultsN = 184Organism identified in 124 (67%)35% of these had 2+ organismsFor complete sampling, organism identified in 89%Sputum PCR increased yield over traditional methods

Bacterial and viral yields

Incidence of co-infections

Etiology in special situationsAlcohol, poor dental hygiene: anaerobesSick hunting dogs: blastomycosisBats, bird droppings: histoplasmosisTravel to SW US: coccidiomycosisBirds: Chlamydia psittaciRabbits: Francisella tularensisFarm animals, parturient cats: Coxiella burnetii (Q fever)Post-influenza: S. aureus, S. pneumoniae, S. pyogenes, H. influenzaeH1N1 outbreak April 200961 million affected13,000 deaths90% hospitalizations, 87% deaths occurred in patients less than 65ObesityPregnancyAsthmaYoung age

Community acquired MRSANew strain of MRSA (USA 300 strain)Not traditional risk factors for MRSAOften follow influenza viral infectionInfluenza with bilateral cavitary pneumoniaSkin/soft tissue infectionRisk factorsYoung ageClose living conditionsSkin contact, cuts/abrasionsNecrotizing pneumonia (CA-MRSA)

Eur Respir J 2009; 34: 14701476CA-MRSA virulence factorsPanton-Valentine leukocidin (PVL) geneSkin/soft tissue infectionsSevere cavitary pneumoniaType IV mecA geneResistance to beta lactams/methicillinCA-MRSA therapyAntibioticsVancomycin (reports of poor outcomes with monotherapy*)LinezolidAnti-toxinClindamycinLinezolid

*Micek et al. Chest 2005(128):2732.Assessment of severityPhysicians overestimate risk of deathUnnecessary admissionsIncreased costPotential for morbidity related to hospitalizationMultiple tools availablePORT/Pneumonia Severity IndexCURB-65ATS/IDSAPORT Pneumonia Severity Index

EDs using PSI reduced rate of hospitalization in low risk groups

NO DIFFERENCES IN MORTALITYCURB-65 algorithm

CRB-65 algorithm

ATS/IDSA: site of care decisionsSeverity scores should be used to identify patients for outpatient therapyCURB-65PSIScores should always be supplemented by physician determination of other factorsPsychosocial factorsSupport resourcesComplianceAbility to tolerate oral therapyFailure of outpatient therapyLaboratory testing (hospitalization)Chest X-rayCBC with differentialElectrolytesBUN/creatinineGlucoseLiver enzymesOxygen saturationGram stain/cultures of sputum (??)Blood cultures (??)Chest x-rayRadiology + clinical scenario are gold standard for diagnosisNot mandatory (outpatient)Information providedExtent of diseaseCavitationComplications (effusion)Alternate or co-existing diagnosis (neoplasm)Information not providedCausative organismCXR PatternPossible PathogensLobarS.pneumo, Kleb, H. influ, Gram NegPatchyAtypicals, Viral, LegionellaInterstitialViral, PCP, Legionella, mycoplasma, chlamydiaCavitationAnerobes, Kleb, TB, S.aureus, Fungi, caMRSA, NocardiaLarge effusionStaph, Anaerobes, KlebsiellaMiliary patternMtb, FungiWidened mediastinum with effusionsInhalational anthraxChest Xray in CAP

Cavitary pneumonia

Parapneumonic effusion

CXR PA and Lateral Views

PA - RML Lateral - RML Round Pneumonic Consolidation

RUL RLL, LLL Special Forms of Pneumonia

PCP/ CMV

Empyema

Empyema RCT EmpyemaSplit pleura signMicrobiologic testingUtility for all CAP uncertainFalse negativesNot cost effectiveDiagnosis may not affect outcomeIDSA/ATS recommendationsSevere CAP (ICU)Optional for outpatientDiagnosis uncertainStructural lung diseasePleural effusion

Biomarkers for CAPProcalcitonin (available)C-reactive protein (available)Pro-adrenomedullinCo-peptinNatriuretic peptidesCortisolPro-atrial natriuretic peptideCoagulation markersBrar NK and Niederman MS, Ther Adv Respir Dis (2011) 61-78ProcalcitoninPrecursor of calcitoninNo hormonal effectsIncreased with bacterial infectionToxin mediated (lipopolysaccaride)Cytokine mediated (IL-6, IL-1, TNF)Cell mediated response mediatedDecreased with viral infectionCytokine mediated (IFN-gamma)Also increased with trauma, burns

Procalcitonin: Pros/consProsHelps reduce antibiotic durationHelps antibiotic exposureHelps convert to oral therapyMay help with early dischargeConsInadequate accuracy to discriminate bacterial vs. viral infectionAccuracy too low to withhold therapyTiming of antibioticsMultiple studies show delayed antibiotics associated with increased mortality (Houck et al 2004, Meehan et al 1997)4 hour antibiotic was adopted as quality core measureImplementation of 4 hours had problems:Misdiagnosis of CAP*Inappropriate antibiotics*Antibiotic toxicity including C difficile*Kanwar et al. Chest 2007:1865-1869.Timing of antibioticsIDSA/ATS guidelines recommendationFirst dose of antibiotics in ED (6-8 hrs)Earlier antibiotics probably better with severe sepsis

Factors influencing antibioticsSettingOutpatientInpatientICUComorbiditiesRisk factors for certain pathogensResistant pneumococcusResistant gram negativesPseudomonasCommunity acquired MRSA

Monotherapy vs. combination therapyMultiple recent studies show improved outcomes with combination therapy1-5Odds ratio of death with monotherapy ranged from 1.5-6x adjusted for severityBenefit most in those with severe CAPBenefit only seen when macrolides used6

1Waterer et al. Arch Int Med 2001(161):1837.2Baddour et al. Am J Respir Crit Care Med 2004(170):440.3Tessmer et al. J Antimicrob Chemother 2009(63):1025.4Rodriguez et al. Crit Care Med 2007(35):1493.5Restrepo et al.Eur Respir J 2009(33):153.6Martin-Loeches et al. Intensive Care Med 2010(36):612.Beneficial effects of macrolidesAtypical pathogen co-infection seen in 1/3 of pneumococcal CAPQuinolones, tetracyclines do not offer same benefitAnti-inflammatory propertiesModification of heat shock protein-70 and p38 signaling pathwaysImprove chemotactic and phagocytic function of macrophagesMucociliary function enhancementReduce virulence factorsToxin productionBiofilmMay reduce bacterial load with less cell wall lysis by beta-lactams = less pro-inflammatory response

Antimicrobial therapyOutpatientPreviously healthyNo antibiotics within last 3 months

MacrolideDoxycyclineAntimicrobial therapyOutpatientComorbiditiesPrevious antibiotics within 3 monthsHigh resistance to S pneumoniae

Respiratory fluoroquinolone Beta-lactam plus macrolideAntimicrobial therapyInpatient, non-ICU

Beta-lactam plus macrolideRespiratory fluoroquinoloneAntimicrobial therapyInpatient, ICU

Beta lactam plus:Respiratory fluoroquinolone orMacrolidePCN allergic:Aztreonam plus fluoroquinoloneAntimicrobial therapyPseudomonas is considerationAnti-pseudomonal/pneumococcal beta-lactam (Pip-tazo, cefepime, imipenem, meropenem) PLUS one of the following:Ciprofloxacin or LevofloxacinAzithromycin plus aminoglycosideAntipneumococcal fluroquinolone plus aminoglycosidePCN allergy: substitute aztreonam for beta-lactamAntimicrobial therapyIf CA-MRSA is consideration

Add vancomycin or linezolidIf vancomycin, consider clindamycin for anti-toxin therapyFactors for switch to oral therapyHemodynamic stabilityClinical improvement Cough, dyspnea betterAfebrile > 8 hoursWBC normalizingAdequate oral intakeNo GI absorption issuesPatients do not need to be observed overnight after switch to oral txDuration of antibioticsTreated for minimum 5 days (ATS), 7 days (BTS)Longer if resistant organism, extra-pulmonary diseaseAfebrile for 48-72 hoursNo more than 1 sign of clinical instability

Number of signs of instability correlate with mortality, readmission

Halm EA, et al.. Arch Intern Med 2002; 162:127884.

Does everyone need follow up chest Xray?Cohort study in 3398 patients1.1% risk of lung cancer at 90 days2.3% risk of lung cancer at 5 yearsMultivariate analysisAge > 50 most strongly associatedMale sexSmokingConclusion: follow-up CXR not necessary in patients 1 Instability46.2To resize chart data range, drag lower right corner of range.