Lower Respiratory Tract Infections

Lower Respiratory Tract Infections David Wong, MD

I.

Epidemiology A.

4,000,000 episodes/year

B.

Community acquired pneumonia (CAP)

C.

II.

1.

250-260 hospitalization/105 population

2.

Mortality rate 8.8-14%, increases with age

Hospital associated pneumonia (HAP) 1.

5-10/1000 hospital admissions.

2.

Mortality 70%: Attributable 33-50%

Community Acquired Pneumonia (Cap) A. Etiology 1.

Organisms

Causes of community acquired pneumonia 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

5.

a.

Legionella spp.

b.

M. tuberculosis

c.

Influenza, RSV, hantavirus, parainfluenza, Coxsackie, adenovirus

d.

Strongyloides, toxoplasma

e.

Pneumocystis carinii, endemic fungi, Cryptococcus neoforrnans

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 death

Community-Acquired Pneumonia: Microbial Agents and Mortality* Agent 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

No. of Cases (%)

Mortality (%)

All Deaths (%)

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

c. C.

i.

Sputum Gram stain and culture

ii.

Blood cultures: Positive 8 to 10% cases

Criteria for ICU admission

Antimicrobial susceptibility of major CAP pathogens 1.

S. pneumoniae

Antibiotic Resistance Among Pneumococci

Antibiotic (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 3 10 18 7.5 4.5

2.

H. influenzae a.

3.

Moraxella catarrhalis - 85 % beta-lactamase producers

4.

Legionella, Chlamydia pneumoniae, Mycoplasma pneumoniae

5.

a.

Susceptible to macrolides

b.

Susceptible to fluoroquinolones

Unique considerations of antimicrobial agents a.

D.

Beta-lactamase production (ampicillin resistance) 15-25 %

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

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 Comorbidity

Organisms‡: S. pneumoniae, M. pneumoniae viruses C. pneumoniae, H. influenzae Misc: Legionella, S. aureus, M.tb, endemic fungi, Enterobacteriaceae ATS

IDSA**

Macrolide* or Tetracycline

Macrolide Fluoroquinolone# 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 or TMP/SMZ? or BL/BL-inhibitor

Macrolide Fluoroquinolone** or Doxycycline

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 cefotaxime

or BL/BL-inhibitor 4Macrolide

4Macrolide or 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 plus 3rd gen ceph (ceftazidime) or Antipseudomonal agents: imipenem, ciprofloxacin

Macrolide or Fluoroquinolone// plus Cefotaxirne, ceftriaxone, 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.

3.

4.

Agents of choice: Clindamycin, beta-lactam-beta-lactamase inhibitor

Chlamydia pneumoniae a.

Recurrent disease common among adults

b.

Laboratory confirmation problematic

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. E.

Urine antigen detection identifies only serogroup 1

Treatment of pleural effusion 1.

Thoracentesis if fluid layer > 10 mm on lateral decubitus film

2.

Criteria for drainage of parapneumonic effusions.

3. parapneumonic

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

Fibrinolytic therapy (urokinase, streptokinase) of loculated 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

S. aureus S. pneumoniae Enterococci CN Staphylococci H. influenzae P. aeruginosa GNB E. coli Anaerobic flora Fungi/yeast Unknown

Antibiotics

No Antibiotics

Total (Died)

6 0 0 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) 3 4 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 H. infiuenzae S. aureus (MS) S. pneumoniae

2nd gen ceph or 3rd gen ceph (not anti-P, aeurg) or 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

Anaerobes

Coma, head trauma, CRF, diabetes Steroids, outbreak-endemic Long ICU, steroids, antibiotics, lung dis

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 time

C.

Organisms

Treatment

Core Organisms* P. aeruginosa Acinetobacter S. aureus (MRSA)

Aminoglycoside or ciprofloxacin plus Antipseudomonal penicillin BL/BL-inhibitor Ceftazidime Imipenem Aztreonam and Vancomycin (r/o MRSA)

Controversies in diagnosis of ventilator associated pneumonia 1.

2.

Fever, leukocytosis, purulent sputum, and radiologic changes may not be pneumonia 3.

IV.

Colonization of airway confounds etiologic diagnosis

Quantitative microbiology from lower respiratory tract secretions helps to diagnose pneumonia in ventilated patients

Treatment of Specific Pathogens Causing Pneumonia A.

Pneumococci 1.

Penicillin susceptible and intermediately resistant strains - penicillin and ampicillin are effective a.

2.

VI.

Resistance to macrolides, tetracycline, TMP/SMZ common with intermediate and highly penicillin resistant strains

Penicillin resistant strains (MIC > 2 µg/ml) a.

Fluoroquinolones

b.

Vancomycin

c.

Ceftriaxone/cefotaxime - may be significant cross resistance

Prevention of Pneumonia A.

Influenza vaccine 1.

Patients: Prevent hospitalization, deaths from influenza/pneumonia, deaths from respiratory and all causes

2. B.

Physicians and personnel in long term care facilities

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, SanchezPorto 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.