Lower Respiratory Tract Infections David Wong, MD I. Epidemiology A. 4,000,000 episodes/year B. Community acquired pneumonia (CAP) 1. 250-260 hospitalization/105 population 2. Mortality rate 8.8-14%, increases with age C. Hospital associated pneumonia (HAP) 1. 5-10/1000 hospital admissions. 2. Mortality 70%: Attributable 33-50% II. Community Acquired Pneumonia (Cap) A. Etiology 1. Causes of community acquired pneumonia Organisms 1966-95† (N= 7057)Bacterial S. pneumoniae H. influenzae Mixed bacterial S. aureus Enterobacteriaceae P. aeruginosa Streptococci Aspiration Atypical Legionella M. pneumoniae C. pneumoniae C. psittaci Coxiella burnetti P. carinii M. tuberculosis Viruses Influenza Other viruses No diagnosis 4432 (65) 893 (12) 301 (4) 157 (2) 85 (1) 18 6 272 (4) 507 (7) 41 (1) 32 (0.5) 182 (3) 128 (2) 69 (1) [11,229] 2. Syndrome presentation -atypical vs. typical -not sufficiently diagnostic 3. Chlamydia pneumoniae, Mycoplasma pneumoniae, Legionella occur at all ages and are not seasonal 4. Pathogens attributed causality a. Legionella spp. b. M. tuberculosis c. Influenza, RSV, hantavirus, parainfluenza, Coxsackie, adenovirus d. Strongyloides, toxoplasma e. Pneumocystis carinii, endemic fungi, Cryptococcus neoforrnans 5. Environmental and epidemiologic events can be clues to etiology Morbidity assessment as guide to place of care 1. Mortality by etiologic agent. Pneumococcal pneumonia is major cause of deathCommunity-Acquired Pneumonia: Microbial Agents and Mortality* Agent No. of Cases (%) Mortality (%) All Deaths (%) S. pneumoniae H. influenzae M. pneumoniae Mixed bacterial species Legionella Coxiella burnetii S. aureus Influenza Enterobacteriaceae Viral agents (not influenza)* C. pneumoniae Chlamydia psittaci P. aeruginosa Total 4,432 (65%) 833 (12%) 507 (7%) 301 (4%) 272 (4%) 182 (3 %) 157 (2%) 128 (2%) 85 (1%) 69 (1%) 41 (1%) 32 – 18 ---7057 545 (12%) 61 (7%) 7 (1%) 71 (24%) 39 (15%) 1 ---50 (32%) 9 (7%) 26 (31%) 3 ---4 (10%) 0 — 11 (61%) 827 (12 %) 66% 7% 1% 9% 5% ---6% 1% 3% ---------1% ---*Meta-analysis of community-acquired pneumonia: 122 studies reported 1966-1995 (Fine MJ, et al. JAMA 1996; 275:134) 2. Laboratory evaluation based on morbidity assessment a. Suitable for outpatient therapy -chest radiograph b. Anticipated hospitalization -define etiology, further refine risk assessment i. Sputum Gram stain and culture ii. Blood cultures: Positive 8 to 10% cases c. Criteria for ICU admission C. Antimicrobial susceptibility of major CAP pathogens 1. S. pneumoniae Antibiotic Resistance Among PneumococciAntibiotic (MIC) Percent Resistant U.S.A.1994-95# Penicillin (> 0.12-1.0) (> 2) Cefotaxime (> 1 ) Erythromycin (>1) TMP/SMZ (> 1) Tetracycline (> 4) Ofloxacin (>4) 14 9.5 310 18 7.5 4.5 2. H. influenzae a. Beta-lactamase production (ampicillin resistance) 15-25 % 3. Moraxella catarrhalis -85 % beta-lactamase producers 4. Legionella, Chlamydia pneumoniae, Mycoplasma pneumoniae a. Susceptible to macrolides b. Susceptible to fluoroquinolones 5. Unique considerations of antimicrobial agents a. Levofloxacin, sparfloxacin, trovafloxacin enhanced activity against pneumococci both penicillin susceptible and resistant, active vs. H. influenzae, C. pneumoniae, M. pneumoniae, Legionella b. Macrolides -azithromycin most active against H. influenzae c. Cephalosporin activity versus S. pneumoniae D. Treatment of CAP 1. Reassessment of the American Thoracic Society Guidelines a. Enhanced role for new fluoroquinolones b. Limited role for empiric use of TMP/SMZ as anti-pneumococcal agent c. Increased emphasis on anti-pneumococcal therapy in most severely ill CAP Outpatient Treatment: < 60 Yr -No ComorbidityOrganisms‡: S. pneumoniae, M. pneumoniae viruses C. pneumoniae, H. influenzae Misc: Legionella, S. aureus, M.tb, endemic fungi, Enterobacteriaceae ATS IDSA** Macrolide* Macrolide or Fluoroquinolone# Tetracycline or Doxycycline †30-50% no etiology defined *Erythromycin (Clarith/Azith-H. influenzae) # If suspect PRP -levofloxacin 500 mg qd; sparfloxacin 400 mg, then 200 mg qd PO **Aspiration BL-BL inhibitor Cap: Outpatient Treatment-Comorbidity. > 60 Y/O Organisms: S. pneumoniae, viruses, H. infiuenzae Enterobacteriaceae, S. aureus Misc: M. catarrhalis, Legionella, M. tb ATS IDSA 2nd gen ceph Macrolide or Fluoroquinolone** TMP/SMZ? or or Doxycycline BL/BL-inhibitor Macrolide †Resistance in S. pneurnoniae: TMP/SMZ > 269 **Preferred if suspect PRP: Levofloxacin 500 q d, sparfloxacin 400 mg then 200 q d Hospitalized Patients with Cap (Mild/moderate) Organisms: S. pneumoniae, H. influenzae, polymicrobial (not anaerobes), Enterobacteriaceae, Legionella, S. aureus, C. pneumoniae, viruses Mise: M. pneumoniae, M. catarrhalis, M. tb, endemic fungi ATS IDSA 2nd/3rd Gen Ceph Ceftriaxone or cefotaximeor 4-BL/BL-inhibitor Macrolide 4-or Macrolide Fluoroquinolone* *Levofloxacin 500 mg q d (IV/PO) S. aureus primarily after influenzae AfB HOSPITALIZED PATIENTS WITH SEVERE CAP Organisms: S. pneumoniae, Legionella, Enterobacteriaceae M. pneumoniae, viruses Misc: H. influenzae, M. tb, endemic fungi ATS IDSA Macrolide Macrolide plus or 3rd gen ceph (ceftazidime) Fluoroquinolone//or plus Antipseudomonal agents: Cefotaxirne, ceftriaxone, imipenem, ciprofloxacin ticar/clav, pip/tazo #Levofloxacin 500 mg IV q d †Structural lung disease -cover P. aeruginosa (with 2 agents) + Legionella Aspiration -Levofloxacin + clinda or BL/BL-inhibitor 2. Clinical clues to aspiration pneumonia a. Agents of choice: Clindamycin, beta-lactam-beta-lactamase inhibitor 3. Chlamydia pneumoniae a. Recurrent disease common among adults b. Laboratory confirmation problematic 4. Legionella a. Risk factors: Age (> 50), smokers, diabetes, end stage renal disease, lung cancer, hematologic malignancy, AIDS b. Among isolates major species is L. pneumophila (90%), serogroup 1 (7%)c. Urine antigen detection identifies only serogroup 1 E. Treatment of pleural effusion 1. Thoracentesis if fluid layer > 10 mm on lateral decubitus film 2. Criteria for drainage of parapneumonic effusions. a. pH > 7.30, glucose > 60 mg/dl, LDH < 1,000 U/L, resolves with antibiotic therapy b. pH < 7.10, glucose < 40 mg/dl, LDH > 1,000 U/L, or frank pus; tube drainage 3. Fibrinolytic therapy (urokinase, streptokinase) of loculated parapneumonic effusion, controversial 4. Organized parapneumonic effusion or empyema with pleural fluid requires surgical drainage and possible decortication III. Hospital Acquired Pneumonia (Hap) A. Microbiology differs from CAP 1. Increased role of S. aureus, Gram-negative bacilli, P. aeruginosa Microbiology of Ventilator Associated Pneumonia Antibiotics No Antibiotics Total (Died) S. aureus S. pneumoniae Enterococci CN Staphylococci H. influenzae P. aeruginosa GNB E. coli Anaerobic flora Fungi/yeast Unknown 6 00 1 3 21 15 0 3 3 13 22 5 2 1 17 3 6 3 1 1 27 28 5 2 2 20 24 (9) 21 (6) 34 4 (3) 40 (3) Rello, et al., Chest 1993; 104:1230.B. Empiric treatment strategy based on duration of hospitalization and presence of risk factors, including prior antibiotic exposure, all of which increases the risk of antibiotic resistant bacteria causing HAP Initial Treatment of Group I Hospital-acquired Pneumonia Mild/moderate pneumonia: No risk factors, onset any time Severe pneumonia: No risk factors, onset < 5 days Organisms Treatment Enterobacteriaceae 2nd gen ceph or H. infiuenzae 3rd gen ceph (not anti-P, aeurg) S. aureus (MS) or S. pneumoniae BL/BL-inhibitor or Fluoroquinolone* Aztreonam/clindamycin (Pen allergy) Revise with microbiologic data Enterobacter spp. -combination Rx *Newer anti-& pneumoniae Am J Respir Crit Care Med 1996; 153:1711-1725 Initial Therapy of Group II Hospital Acquired Pneumonia Mild/moderate pneumonia with risk factors-onset any time Risk Factors Organisms Core Organisms Treatment Core Treatment Abdominal surgery, aspiration Coma, head trauma, CRF, diabetes Steroids, outbreak-endemic Long ICU, steroids, antibiotics, lung dis Anaerobes S. aureus Legionella P. aeruginosa Clindamycin BL/BL-inhibitor Vancomycin (r/o MRSA) Erythromycin + Rifampin Enterobacter spp. -combination therapy Am J Respir Crit Care Med 1996; 153:1711-1725. Initial Therapy of Hospital-acquired Pneumonia Severe pneumonia: No risk factors, late onset Severe pneumonia: Risk factors, onset any timeOrganisms Treatment Core Organisms* Aminoglycoside or ciprofloxacin P. aeruginosa plus Acinetobacter Antipseudomonal penicillin S. aureus (MRSA) BL/BL-inhibitor Ceftazidime Imipenem Aztreonam and Vancomycin (r/o MRSA) C. Controversies in diagnosis of ventilator associated pneumonia 1. Colonization of airway confounds etiologic diagnosis 2. Fever, leukocytosis, purulent sputum, and radiologic changes may not be pneumonia 3. Quantitative microbiology from lower respiratory tract secretions helps to diagnose pneumonia in ventilated patients IV. Treatment of Specific Pathogens Causing Pneumonia A. Pneumococci 1. Penicillin susceptible and intermediately resistant strains -penicillin and ampicillin are effective a. Resistance to macrolides, tetracycline, TMP/SMZ common with intermediate and highly penicillin resistant strains 2. Penicillin resistant strains (MIC > 2 µg/ml) a. Fluoroquinolones b. Vancomycin c. Ceftriaxone/cefotaxime -may be significant cross resistance VI. Prevention of Pneumonia A. Influenza vaccine 1. Patients: Prevent hospitalization, deaths from influenza/pneumonia, deaths from respiratory and all causes2. Physicians and personnel in long term care facilities B. Pneumococcal vaccine -overall efficacy for preventing infection -57 % References 1. Bartlett JG, Mundy LM. Community-acquired pneumonia. N Engl J Med 1995; 333:1618-1624 2. Fine MJ, Smith MA, Carson CA, Mutha SS, Sankey SS, Weissfeld LA, et al. Prognosis and outcomes of patients with community-acquired pneumonia: A meta-analysis . JAMA 1996; 275:134-141. 3. Marston B J, Plouffe JF, File TM, Jr., Hackman BA, Salstrom S J, Lipman HB, et al. Incidence of community-acquired pneumonia requiring hospitalization. Arch Intern Med 1997; 157:1709-1718. 4. Fine MJ, Auble TE, Yealy DM, Hanusa BH, Weissfeld LA, Singer DE, et al. A prediction rule to identify low-risk patients with community-acquired pneumonia. N Engl J Med 1997; 336:250 5. Butler JC, Hofmann J, Cetron MS, Elliott JA, Facklam RR, Breiman RF, et al. The continued emergence of drug-resistant Streptococcus pneumoniae in the United States: An update from the Centers for Disease Control and Prevention's pneumococcal sentinel surveillance system. J Infect Dis 1996; 174:986-993. 6. Hofmann J, Cetron MS, Farley MM, Baughman WS, Facklam RR, Elliott JA, et al. The prevalence of drug-resistant Streptococcus pneumoniae in Atlanta. N Engl J Meal 1995; 333:481486. 7. Doern GV, Brueggemann A, Holley HP, Jr., Rauch AM. Antimicrobial resistance of Streptococcus pneumoniae recovered from outpatients in the United States during the winter months of 1994 to 1995: Results of a 30-center national surveillance study. Antimicrob Agents Chemother i996; 40:1208-I213. 8. Clavo-Sanchez A J, Giron-Gonzalez JA, Lopez-Prieto D, Canueto-Quintero J, Sanchez-Porto A, Vergara-Campos A, et al. Multivariate analysis of risk factors for infection due to penicillin-resistant and multidrug-resistant Streptococcus pneumoniae: A multicenter study. Clin Infect Dis 1997; 24:1052-1059. 9. Marston BJ, Lipman HB, Breiman RF. Surveillance for Legionmires' disease: Risk factors for morbidity and mortality. Arch Intern Med 1994; 154:2417-2422. 10. Bartlett JG. Anaerobic bacterial infections of the lung and pleural space. Clin Infect Dis 1993; 16 (Suppl 4):S48-S55.11. Gudiol F, Manresa F, Pallares R, Dorea J, Ruff G, Boada J, et al. Clindamycin vs. penicillin for anaerobic lung infections: Highrate of penicillin failures associated with penicillin-resistant Bacteroides melaninogenicus. Arch Intern Med 1990; 150:2525-2529. 12. Hammerschlag MR. Antimicrobial susceptibility and therapy of infections caused by Chlamydia pneurnoniae. Antimicrob Agents Chemother 1994; 38:1873-1878. 13. Niederman MS, Bass JB, Jr., Campbell GD, Fein AM, Grossman RF, Mandell LA, et al. Guidelines for the initial management of adults with community-acquired pneumonia: Diagnosis, assessment of severity, and initial antimicrobial therapy. Atn Rev Respir Dis 1993; 148:1418-1426. 14. Plouffe JF, Herbert MT, File TM, Jr., Baird I, Parsons JN, Kahn JB, et al. Ofloxacin versus standard therapy in treatment of community-acquired pneumonia requiring hospitalization. Antimicrob Agents Chemother 1996; 40:1175-1179. 15. Salm SA. Management of complicated parapneumonic effusions. Am Rev Respir Dis1993;148:813-817. 16. Rello J, Ausina V, Ricart M, Castella J, Prats G. Impact of previous antimicrobial therapy on the etiology and outcome of ventilator-associated pneumonia. Chest 1993; 104:1230-1235. 17. Campbell GD, Niederman MS, Broughton WA. Hospital-acquired pneumonia in adults: Diagnosis, assessment of severity, initial antimicrobial therapy, and preventive strategies: A consensus statement. Am J Respir Crit Care Med 1996; 153:1711-1725.