Community Acquired Pneumonia (CAP)Update for 2001/2002John C. Rotschafer, Pharm. D., FCCPProfessorCollege of Pharmacy University of MinnesotaPneumonia! Many different types"Community acquired (CAP)"Hospital acquired (HAP)#Ventilator (VAP)"Aspiration! Diagnosis"Sputum gram stain & culture #<10 epithelial cells & > 25 PMN’s per field#Appropriate cultures of blood and CSF"Chest x-ray infiltrate"Fever, elevated WBC, SOB & pleuritic chest painURTI & LRTI! Introduction"CAP#Annual incidence ~ 4 million cases#Mortality 14%#Direct & indirect cost $23 billion / year "ABS#Annual incidence ~ 30 million cases#Direct & indirect cost $2 billion / year "AECB#Annual incidence ~20 million casesCommunity Acquired Pneumonia - CAP! Hospital cases represent the tip of the iceberg"Diagnosis in office setting confounded#+Gram Stain#+Culture (positive ~50% of the time) & antibiotic sensitivity#+X-ray"Differential Diagnosis#Bronchitis vs Pneumonia +Bacteremia#Viral vs Bacterial! Estimated ~50% of antibiotic Rx’s unnecessary"How should patients be treated? #Oral vs Parenteral"In what setting should patients be treated?CAP Treatment Guidelines! American Thoracic Society"First published 1993 "Revision published Am J Respir Crit Care Med 163:1730-1754, 2001! Infectious Diseases Society of America"First published April 1998"Revision published CID 31:347-382, 2000! Center for Disease Control"Arch Intern Med 160:1399-1408, 2000"Promote macrolides, doxycycline, or beta-lactams"Fluoroquinolones suggested if: 1) Failed previous Tx, 2) Allergy to alternative antibiotics, & 3) PCN MIC > 4mg/LCAP Patient Scoring SystemFine MJ et al NEJM 336:243-250, 1997! Scoring system incorporates "Patient age"Location"Coexisting Illness"Physical Findings"Laboratory Findings"Radiographic Findings! Difficult to use in clinical setting"Point values vary for different parameters"May not have all of the required data"Cumbersome additionCAP Patient Scoring System Fine MJ et al NEJM 336:243-250, 1997Class Score All Patient Mortality I N/A 0.1%II <70 0.6%III 71-90 0.9%IV 91-130 9.3%V > 130 27%Class I, II, & III mortality < 1% Can likely be treated as outpatients with oral antibioticATS CAP 2001 Classification Scheme! Group I (1993 - outpatient <60 yrs no co-morbidity)"Outpatient CAP"No CHF or COPD"No risk factors for other resistant pathogens! Group II (1993 – outpatient with co-morbidity&/or >60yrs)"Outpatient CAP"History of CHF & /or COPD"Risk factors for resistant pathogens may or may not be presentAm J Respir Crit Care Med 163:1730-1754, 2001ATS CAP 2001 Classification Scheme! Group III (1993 – hospitalized with CAP)"Inpatient but does not require ICU setting"No CHF or COPD and/or resistant bacteria risk factors"CHF and/or COPD plus possible risk factors for resistance and may be nursing home patient! Group IV (1993 – hospitalized with severe CAP)"ICU patient"No risk for P. aeruginosa"At risk for P. aeruginosaAm J Respir Crit Care Med 163:1730-1754, 2001CAP Pathogens! Typical"S. pneumoniae"H. influenzae"M. catarrhalis! Atypical"C. pneumoniae"L. pneumophila"MycosplasmaATS Pathogen Risk FactorsAm J Respir Crit Care Med 163:1730-1754, 2001! PCN-NS/R S. pneumoniae"> 65 years"Multiple co-morbidities"Alcoholism"Exposure to children in day care"Immunosuppressed"Use of beta-lactam within last 90 days! P. aeruginosa"Use of broad spectrum antibiotic for > 1 week in last month"Structural lung disease"Steroid use"Malnutrition!Gram Negatives"Nursing home resident"Cardiopulmonary disease"Multiple co-morbidities"History of recent antibiotic therapyPneumococcal Sentinel Surveillance System Definition of PCN-R S. pneumoniae"Sensitive #PCN MIC < 0.06 mg/L"Non-susceptible#PCN MIC = 0.12 to 1.0 mg/L"Resistant #PCN MIC > 2.0 mg/L#Mechanism of resistance is an alteration of penicillin binding proteins (PBP)Penicillin (MIC≥≥≥≥ 2µµµµg/mL)AzithromycinCeftriaxoneLevofloxacinNo. of institutionsNo. of isolates% R14.722.73.40.6964,296TRUST 3(1999)% R16.023.43.80.52389,499TRUST 4(2000)% R16.927.53.00.82406,362TRUST 5(2001)TRUST Studies 1999-2001: Comparison of Antimicrobial Resistance of S. pneumoniae*6,362 isolates, 240 labs.Kelly LJ, et al. 41st ICAAC, 2001, abstract 2109. Data on file, Ortho-McNeil Pharmaceutical, Inc. DCDCS. pneumoniaePenicillin Resistance(Resistant, MIC ≥≥≥≥2 µg/mL)S. pneumoniaeAzithromycin Resistance(Resistant, MIC ≥≥≥≥2 µg/mL)National Rates:Azithromycin=28% RClarithromycin=28% RErythromycin=28% RNational Rate:Penicillin=17% R≥≥≥≥20% R12-19.9% RStates not participating<12% RS. pneumoniae Antimicrobial Resistance: TRUST 5 (2000-2001) Respiratory SeasonLab report vs Clinical Outcome Disconnect! In-vitro susceptibility does not seem to correlate with clinical outcome in LRTI"Clinical failures with conventional antibiotics & resistant pathogens are rare for RTI’s"Phenomena poorly studied#Cultures & susceptibility studies rarely done"Question as to the timeframe where PCN & multiply antibiotic resistant strains will become an issueMacrolide Resistant S. pneumoniae! Three Types"Ribosomal resistance (erm ~30% of strains)#Alters the binding of macrolide to the 50S ribosome#Conveys resistance to all macrolides"Efflux pump (mef ~70% of strains)#Macrolide pumped out of bacteria#Resistance is macrolide dependent"23S r RNA or ribosomal protein mutations, only 20 strains reported (AAC 44:3395-3401, 2000)! Testing is problematic "Erythromycin used as class disk"Quick check erythromycin vs clindamycin susceptibility#Many labs do not report clindamycin resultFluoroquinolone Resistant Respiratory Pathogens! S. pneumoniae"Canada (Chen D.K. N Engl J Med 341:233-239,1999)#0% FQ-R in 1993 to 1.7% in 1997/1998"Hong Kong (Ho, P.L. AAC 43:1310-1313,1999)PCN-R (MIC>0.06) 69.1%Cipro-R(MIC>2) 12.1%Levo-R(MIC>2) 5.5%Trova-R(MIC>1) 2.2%! H. influenzae & M. catarrhalis(Biedenbach, D.J. Diagn Micro & Infect Dis 36:255-259,2000)"4 FQ-R H. influenzae (Sentry Data 1997-1999)"1 FQ-R M. catarrhalisClonal ProblemIDSA CAP Guidelines Bartlett,J.G. CID 31:347-382, 2000!Outpatient Empiric Selection"Macrolide"Fluoroquinolone (expanded spectrum)"DoxycylineATS GuidelinesAm J Respir Crit Care Med 163:1730-1754, 2001! Group I "Clarithromycin or Azithromycin or Doxycycline! Group II "Oral#Cefpodoxime, Cefuroxime, HD Amoxicillin, or Augmentin plus macrolide or doxycycline #Antipneumococcal fluoroquinolone"Parenteral#Ceftriaxone followed by oral cefpodoximeIDSA CAP Guidelines Bartlett,J.G. CID 31:347-382,