Community Acquired Pneumonia Challenges in the New Millenium

Community Acquired Pneumonia Challenges in the New Millenium DR. Yousef Noaimat MD. FCCP Consultant in pulmonary and internal medicine.

Community Acquired Pneumonia n Definition: n … an acute infection of the pulmonary parenchyma that is associated with at least some symptoms of acute infection, accompanied by the presence of an acute infiltrate on a chest radiograph, or auscultatory findings consistent with pneumonia, in a patient not hospitalized or residing in a long term care facility for > 14 days before onset of symptoms. Bartlett. Clin Infect Dis 2000; 31: 347 -82. Adeel A. Butt, MD

Community Acquired Pneumonia n Epidemiology: n n 4 -5 million cases annually ~500, 000 hospitalizations ~45, 000 deaths Mortality 2 -30% n <1% for those not requiring hospitalization Bartlett. CID 1998; 26: 811 -38. Adeel A. Butt, MD

Community Acquired Pneumonia n Epidemiology: (contd) n n n fewest cases in 18 -24 yr group probably highest incidence in <5 and >65 yrs mortality disproportionately high in >65 yrs Adeel A. Butt, MD

Community Acquired Pneumonia Incidence # in 1000 s Adeel A. Butt, MD

Community Acquired Pneumonia Mortality # in 1000 s Adeel A. Butt, MD

Community Acquired Pneumonia n Risk Factors for pneumonia n n n n n age alcoholism smoking asthma immunosuppression institutionalization COPD PVD dementia ID Clinics 1998; 12: 723. Am J Med 1994; 96: 313 Adeel A. Butt, MD

Community Acquired Pneumonia n Risk Factors (contd. ) n Men: age and smoking, weight gain n n Women: smoking, BMI, weight gain n RR 1. 5 for age 50 -54, 4. 17 for > 70 Smoking, current: RR 1. 5; heavy: 2. 54; Quit <10 yrs: 1. 5 Weight gain >40 lbs since age 21 BMI 25 -26. 9, RR 1. 53: BMI >30, RR 2. 22 Exercise protective: RR 0. 66 for most active Alcohol consumption NOT associated with increased risk in men or women Adeel A. Butt, MD

Community Acquired Pneumonia n Risk Factors in Patients Requiring Hospitalization n older, unemployed, unmarried n common cold in the previous year n asthma, COPD; steroid or bronchodilator use n Chronic disease n amount of smoking n alcohol NOT related to increased risk Adeel A. Butt, MD

Community Acquired Pneumonia n Risk Factors for Mortality n n n age bacteremia (for S. pneumoniae) extent of radiographic changes degree of immunosuppression amount of alcohol Adeel A. Butt, MD

Community Acquired Pneumonia Microbiology n n n S. pneumoniae: 20 -60% H. influenzae: 3 -10% Chlamydia pneumoniae: 4 -6% n Mycoplasma pneumonaie: 1 -6% n n Legionella spp. 28% S. aureus: 3 -5% Gram negative bacilli: 3 -5% Viruses: 2 -13% 40 -60% - NO CAUSE IDENTIFIED 2 -5% - TWO OR MORE CAUSES Adeel A. Butt, MD

Community Acquired Pneumonia Evaluation for CAP History, PE, CXR No infiltrate manage/evaluate for alternate diagnosis Infiltrate + clinical evidence of pneumonia evaluate for admission outpatient: empiric treatment with macrolide, doxycycline, FQ hospitalize labs medical ward: abx < 8 hrs ICU: abx < 8 hrs no pathogen identified B-lactam + macrolide FQ no pathogen identified B-lactam + macrolide B-lactam + FQ Adeel A. Butt, MD

Community Acquired Pneumonia n Laboratory Tests: n n n n n CXR CBC with differential BUN/Cr glucose liver enzymes electrolytes Gram stain/culture of sputum pre-treatment blood cultures oxygen saturation Adeel A. Butt, MD

Community Acquired Pneumonia Diagnostic Evaluation n n CXR n usually needed to establish diagnosis n prognostic indicator n rule out other disorders n may help in etiological diagnosis Only 3% of outpatients and 28% of ER patients with suggestive signs and symptoms actually have pneumonia J Chr Dis 1984; 37: 215 -25 Adeel A. Butt, MD

Community Acquired Pneumonia Usefulness of Gram Stain n n Good sputum samples obtained from 39% 83% show one predominant morphotype Adeel A. Butt, MD

Community Acquired Pneumonia Adeel A. Butt, MD

Community Acquired Pneumonia n n PORT Publications: Class I: n n age < 50; 0/5 co-morbid conditions; normal or mildly deranged VS; normal mental status Class II-V: n points assigned based on above, 5 comorbid conditions, 5 PE findings, 7 lab or X-ray findings Fine MJ. NEJM 1997; 336: 243 -50 Adeel A. Butt, MD

Community Acquired Pneumonia n Class I & II: n n Class III: n n usually do not require hospitalization may require brief hospitalization Class IV & V: n usually do require hospitalization Fine MJ. NEJM 1997; 336: 243 -50 Adeel A. Butt, MD

Adeel A. Butt, MD

Adeel A. Butt, MD

Community Acquired Pneumonia Severity of CAP n n n n RR > 30 Pa. O 2/Fi. O 2 < 250, or PO 2 < 60 on room air Need for mechanical ventilation Mulitlobar involvement Hypotension Need for vasopressors Oliguria Adeel A. Butt, MD Altered mental status

Community Acquired Pneumonia Management n Rational use of microbiology laboratory n Pathogen directed antimicrobial therapy whenever possible n Prompt initiation of therapy n Decision to hospitalize based on prognostic criteria Adeel A. Butt, MD

Community Acquired Pneumonia Empiric Treatment n Outpatient: n n n macrolide doxycycline Fluoroquinolone NOT IN ANY SPECIFIC ORDER IDSA guidelines: Clin Infect Dis 2000; 31: 347 -82 Adeel A. Butt, MD

Community Acquired Pneumonia Empiric Treatment n Patients in General Medical Ward: n n n 3 GC + macrolide B/B-I + macrolide OR B/B-I + FQ FQ alone IDSA guidelines: Clin Infect Dis 2000; 31: 347 -82 Adeel A. Butt, MD

Community Acquired Pneumonia Empiric Treatment n Patients in ICU: n n 3 GC + macrolide 3 GC + FQ B/B-I + macrolide B/B-I + FQ IDSA guidelines: Clin Infect Dis 2000; 31: 347 -82 Adeel A. Butt, MD

Deviation From Guidelines n n n n Not many Studies done to assess this Prospective study in a tertiary care hospital Adherence to ATS guidelines was 88% No significant difference in mortality or LOS Mortality in Class V patients higher in nonadherent treatments Adherence to ATS associated with decreased mortality Mortality in Class I, II & III was ZERO. Menendez. Chest 2002; 122: 612 -617.

Community Acquired Pneumonia Concerns about multiply resistant pneumococcus: n n 25 -40% overall penicillin resistance intermediate resistance of questionable significance high level resistance associated with in vitro macrolide and 3 GC resistance clinical failures not really documented IDSA guidelines: Clin Infect Dis 2000; 31: 347 -82 Adeel A. Butt, MD

Community Acquired Pneumonia Macrolide Resistance n n n Increased drug efflux coded by mef. E susceptible to clindamycin most cases in US may be overcome by achievable levels of macrolides n n n Ribosomal methylase coded by erm. AM resistant to clindamycin mostly in Europe not overcome by standard doses Adeel A. Butt, MD

Community Acquired Pneumonia (Newer)Fluoroquinolones n n Active against 98% of resistant pneumococcus Resistance has begun to increase Chen DK. NEJM 1999; 341: 233 -9 Ho PL. Antimicrob Agents Chemother 1999; 43: 1310 -3. Wise R. Lancet 1996; 348: 1660 Adeel A. Butt, MD

FQ Resistance n n n 4 cases from Canada with pneumococcal pneumonia 1 died 2 developed resistance while on Rx 2 had resistant bugs to begin with Authors suggested that recent FQ use should be a contra-indication to using a FQ for empiric treatment of CAP Davidson. NEJM 2002; 346: 747 -750

FQ Resistance n In a case control study, colonization or infection by FQ resistant pneumococci was independently associated with: n n COPD Nosocomial origin of bacteremia Residence in a nursing home Prior exposure to FQ Ho. Clin Infect Dis 2001; 32: 701 -707.

Other Concerns n Delay in diagnosis and treatment of TB n n Johns Hopkins study 33 patients with TB 16 received FQ for empiric Rx of CAP TB treatment initiation time: n n 21 days in the FQ group 5 days in the non-FQ group Dooley. Clin Infect Dis 2002; 34: 1607 -1612.

Community Acquired Pneumonia n Choice of Initial Antimicrobial Regimen n Second generation cephalosporin plus a macrolide, nonpseudomonal third generation cephalosporin plus a macrolide, or a fluoroquinolone alone were all associated with a lower 30 day mortality in patients with CAP. Gleason. Arch Int Med 1999; 159: 2562 -72. Adeel A. Butt, MD

Community Acquired Pneumonia n Macrolide Use and LOS: n Patients who received macrolides within first 24 hours of admission had a shorter LOS (2. 8 days vs. 5. 3 days) Stahl. Arch Int Med 1999; 159: 2576 -80. Adeel A. Butt, MD

Community Acquired Pneumonia n Azithromycin vs. Cefuroxime + Erythromycin n prospective, randomized trial n 145 patients n Clinical cure 91% in each group. n 4 S. pneumoniae strains with MIC 0. 064 -2 ug/ml: 1/1 in azithromycin group cured, 2/3 in cef/erythro group cured Vergis. Arch Int Med 2000; 160: 1294 -1300. Adeel A. Butt, MD

Community Acquired Pneumonia n IV followed by Oral Azithromycin n n 615 patients: Azithromycin given to 414 202 in a comparison trial with ATS recommended cefuroxime + erythromycin 77% vs 74% clinical cure or improvement Microbiological cure rates similar or better in azithromycin group Adeel A. Butt, MD

Cost-Effectiveness of IV-Oral Switch Therapy n Azithromycin n n Cefuroxime + Erythro Mean cost - $4, 104 n n CE Ratio per expected cure $5, 265 n Mean cost - $4, 578 CE Ratio per expected cure - $ 6, 145 Paladino. Chest Oct 2002; 122: 1271 -1279.

Clarithromycin ER n Head-to-head comparison with FQ n Vs. Levofloxacin 1 n n 252 patients Clinical cure 88% in Clarithro; 86% levo Radiographic success 95% vs. 88% Vs. Trovafloxacin 2 n n Clinical cure 87% vs. 95% Radiographic success 95% vs. 95%

Community Acquired Pneumonia Report from the DRSP Therapeutic Working Group n Use a macrolide or doxycycline for outpatients n Beta-lactam for inpatient n Reserve FQ for: n n n if above fails if allergic to any of the above documented high level resistance (pen MIC >4) Adeel A. Butt, MD

Summary n n n We have some really good drugs available Use antibiotics judiciously Do consider local and national resistance patterns For Class I, II and possibly III, first line recommendations are a macrolide or doxycycline Revise therapy based on clinical and microbiological response Consider prior exposure when choosing an Abx