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Community Acquired Pneumonia Challenges in the New Millenium. Adeel A. Butt, MD Assistant Professor of Medicine University of Pittsburgh Director, VAPHS ID-HIV Clinics Center for Health Equity Research and Promotion. Community Acquired Pneumonia. Definition:

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community acquired pneumonia challenges in the new millenium

Community Acquired PneumoniaChallenges in the New Millenium

Adeel A. Butt, MD

Assistant Professor of Medicine

University of Pittsburgh

Director, VAPHS ID-HIV Clinics

Center for Health Equity Research and Promotion

community acquired pneumonia
Community Acquired Pneumonia
  • Definition:
    • … 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.

Adeel A. Butt, MD

Bartlett. Clin Infect Dis 2000;31:347-82.

community acquired pneumonia1
Community Acquired Pneumonia
  • Epidemiology:
    • 4-5 million cases annually
    • ~500,000 hospitalizations
    • ~45,000 deaths
    • Mortality 2-30%
      • <1% for those not requiring hospitalization

Bartlett. CID 1998;26:811-38.

Adeel A. Butt, MD

community acquired pneumonia2
Community Acquired Pneumonia
  • Epidemiology: (contd)
    • 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 pneumonia3
Community Acquired Pneumonia

Incidence

# in 1000s

Adeel A. Butt, MD

community acquired pneumonia4
Community Acquired Pneumonia

Mortality

# in 1000s

Adeel A. Butt, MD

community acquired pneumonia5
Community Acquired Pneumonia
  • Risk Factors for pneumonia
    • 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 pneumonia6
Community Acquired Pneumonia
  • Risk Factors (contd.)
    • Men: age and smoking, weight gain
        • 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
    • Women: smoking, BMI, weight gain
        • 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 pneumonia7
Community Acquired Pneumonia
  • Risk Factors in Patients Requiring Hospitalization
    • older, unemployed, unmarried
    • common cold in the previous year
    • asthma, COPD; steroid or bronchodilator use
    • Chronic disease
    • amount of smoking
    • alcohol NOT related to increased risk

Adeel A. Butt, MD

community acquired pneumonia8
Community Acquired Pneumonia
  • Risk Factors for Mortality
    • age
    • bacteremia (for S. pneumoniae)
    • extent of radiographic changes
    • degree of immunosuppression
    • amount of alcohol

Adeel A. Butt, MD

community acquired pneumonia9
S. pneumoniae: 20-60%

H. influenzae: 3-10%

Chlamydia pneumoniae: 4-6%

Mycoplasma pneumonaie: 1-6%

Legionella spp. 2-8%

S. aureus: 3-5%

Gram negative bacilli: 3-5%

Viruses: 2-13%

Community Acquired Pneumonia

Microbiology

40-60% - NO CAUSE IDENTIFIED

2-5% - TWO OR MORE CAUSES

Adeel A. Butt, MD

community acquired pneumonia11
Community Acquired Pneumonia
  • Laboratory Tests:
      • 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 pneumonia12
Community Acquired Pneumonia

Diagnostic Evaluation

  • CXR
    • usually needed to establish diagnosis
    • prognostic indicator
    • rule out other disorders
    • may help in etiological diagnosis
  • Only 3% of outpatients and 28% of ER patients with suggestive signs and symptoms actually have pneumonia

Adeel A. Butt, MD

J Chr Dis 1984;37:215-25

community acquired pneumonia13
Community Acquired Pneumonia

Usefulness of Gram Stain

  • Good sputum samples obtained from 39%
  • 83% show one predominant morphotype

Adeel A. Butt, MD

community acquired pneumonia14
Community Acquired Pneumonia

Who should be hospitalized?

Adeel A. Butt, MD

community acquired pneumonia15
Community Acquired Pneumonia
  • PORT Publications:
  • Class I:
      • age < 50; 0/5 co-morbid conditions; normal or mildly deranged VS; normal mental status
  • Class II-V:
      • points assigned based on above, 5 co-morbid conditions, 5 PE findings, 7 lab or X-ray findings

Adeel A. Butt, MD

Fine MJ. NEJM 1997;336:243-50

community acquired pneumonia16
Community Acquired Pneumonia
  • Class I & II:
      • usually do not require hospitalization
  • Class III:
      • may require brief hospitalization
  • Class IV & V:
      • usually do require hospitalization

Fine MJ. NEJM 1997;336:243-50

Adeel A. Butt, MD

community acquired pneumonia18
Community Acquired Pneumonia

Severity of CAP

  • RR > 30
  • PaO2/FiO2 < 250, or PO2 < 60 on room air
  • Need for mechanical ventilation
  • Mulitlobar involvement
  • Hypotension
  • Need for vasopressors
  • Oliguria
  • Altered mental status

Adeel A. Butt, MD

community acquired pneumonia19
Community Acquired Pneumonia

Management

  • Rational use of microbiology laboratory
  • Pathogen directed antimicrobial therapy whenever possible
  • Prompt initiation of therapy
  • Decision to hospitalize based on prognostic criteria

Adeel A. Butt, MD

community acquired pneumonia20
Community Acquired Pneumonia

Empiric Treatment

  • Outpatient:
    • macrolide
    • doxycycline
    • Fluoroquinolone

NOT IN ANY SPECIFIC ORDER

IDSA guidelines: Clin Infect Dis 2000;31:347-82

Adeel A. Butt, MD

community acquired pneumonia21
Community Acquired Pneumonia

Empiric Treatment

  • Patients in General Medical Ward:
    • 3GC + 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 pneumonia22
Community Acquired Pneumonia

Empiric Treatment

  • Patients in ICU:
    • 3GC + macrolide
    • 3GC + 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
Deviation From Guidelines
  • 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 pneumonia23
Community Acquired Pneumonia

Concerns about multiply resistant pneumococcus:

  • 25-40% overall penicillin resistance
  • intermediate resistance of questionable significance
  • high level resistance associated with in vitro macrolide and 3GC resistance
  • clinical failures not really documented

Adeel A. Butt, MD

IDSA guidelines: Clin Infect Dis 2000;31:347-82

community acquired pneumonia24
Increased drug efflux

coded by mefE

susceptible to clindamycin

most cases in US

may be overcome by achievable levels of macrolides

Ribosomal methylase

coded by ermAM

resistant to clindamycin

mostly in Europe

not overcome by standard doses

Community Acquired Pneumonia

Macrolide Resistance

Adeel A. Butt, MD

community acquired pneumonia25
Community Acquired Pneumonia

(Newer)Fluoroquinolones

  • 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
FQ Resistance
  • 4 cases from Canada with pneumococcal pneumonia
  • 1 died
  • 2 developed resistance while on Rx
  • 2 had resistantbugs 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 resistance1
FQ Resistance
  • In a case control study, colonization or infection by FQ resistant pneumococci was independently associated with:
    • COPD
    • Nosocomial origin of bacteremia
    • Residence in a nursing home
    • Prior exposure to FQ

Ho. Clin Infect Dis 2001;32:701-707.

other concerns
Other Concerns
  • Delay in diagnosis and treatment of TB
    • Johns Hopkins study
    • 33 patients with TB
    • 16 received FQ for empiric Rx of CAP
    • TB treatment initiation time:
      • 21 days in the FQ group
      • 5 days in the non-FQ group

Dooley. Clin Infect Dis 2002;34:1607-1612.

community acquired pneumonia26
Community Acquired Pneumonia
  • Choice of Initial Antimicrobial Regimen
    • Second generation generation cephalosporin plus a macrolide, non-pseudomonal 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 pneumonia27
Community Acquired Pneumonia
  • Macrolide Use and LOS:
    • 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 pneumonia28
Community Acquired Pneumonia
  • Azithromycin vs. Cefuroxime + Erythromycin
    • prospective, randomized trial
    • 145 patients
    • Clinical cure 91% in each group.
    • 4 S. pneumoniae strains with MIC 0.064-2 ug/ml: 1/1 in azithromycin group cured, 2/3 in cef/erythro group cured

Adeel A. Butt, MD

Vergis. Arch Int Med 2000;160:1294-1300.

community acquired pneumonia29
Community Acquired Pneumonia
  • IV followed by Oral Azithromycin
    • 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
Azithromycin

Mean cost - $4,104

CE Ratio per expected cure - $5,265

Cefuroxime + Erythro

Mean cost - $4,578

CE Ratio per expected cure - $ 6,145

Cost-Effectiveness of IV-Oral Switch Therapy

Paladino. Chest Oct 2002;122:1271-1279.

clarithromycin er
Clarithromycin ER
  • Head-to-head comparison with FQ
    • Vs. Levofloxacin1
      • 252 patients
      • Clinical cure 88% in Clarithro; 86% levo
      • Radiographic success 95% vs. 88%
    • Vs. Trovafloxacin2
      • Clinical cure 87% vs. 95%
      • Radiographic success 95% vs. 95%
community acquired pneumonia30
Community Acquired Pneumonia

Report from the DRSP Therapeutic Working Group

  • Use a macrolide or doxycycline for outpatients
  • Beta-lactam for inpatient
  • Reserve FQ for:
    • if above fails
    • if allergic to any of the above
    • documented high level resistance (pen MIC >4)

Adeel A. Butt, MD

summary
Summary
  • 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