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

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 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 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 Pneumonia

Incidence
1400 1200 1000 1071 898 684 # of cases 1171 1207

# in 1000s

800 600 400 200 0 <5 83

5 to 18-24 25-44 45-64 >65 17 Adeel A. Butt, MD

Community Acquired Pneumonia

Mortality
80 70 60 50 74.9

# in 40 1000s 30
20 10 0 <4 5 to 14 15-24 25-44 45-64 >65 2 5.7

# of deaths

Adeel A. Butt, MD

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 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 BMI 25-26.9, RR 1.53: BMI >30, RR 2.22 Exercise protective: RR 0.66 for most active

Women: smoking, BMI, weight gain

Alcohol consumption NOT associated with increased risk in men or women

Adeel A. Butt, MD

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 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 Pneumonia

Microbiology

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%

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

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 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 Pneumonia

Usefulness of Gram Stain

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

Pneumococcus Sensitivity Specificity Pos Pred Value Neg Pred Value 57 97 95 71

H. flu. 82 99 93

Adeel A. Butt, MD

96

Community Acquired Pneumonia

Adeel A. Butt, MD

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 comorbid conditions, 5 PE findings, 7 lab or X-ray findings
Adeel A. Butt, MD

Fine MJ. NEJM 1997;336:243-50

Community Acquired Pneumonia

Class I & II:

usually do not require hospitalization may require brief hospitalization

Class III:

Class IV & V:

usually do require hospitalization

Fine MJ. NEJM 1997;336:243-50

Adeel A. Butt, MD

Age: Male Female Nursing home resident Co-morbid illness Neoplastic disease Liver disease CHF Cerebrovascular disease Renal disease Physical Exam Altered mental status RR > 30 Systolic bp < 90 Temp <35oC or >40oC Pulse >125 Lab/X-ray findings Arterial pH <7.35 BUN > 30 Sodium < 130 Hematocrit <30% Glucose > 250 PaO2 <60 Pleural effusion

Number of years Number 10 10 30 20 10 10 10 20 20 20 15 10 30 20 20 10 10 10 10

Adeel A. Butt, MD

Risk Class I II III IV V

Points Absence of predictors < 70 71-90 91-130 > 130

Mortality 0.1% 0.6% 2.8% 8.2% 29.2%

Adeel A. Butt, MD

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 Adeel A. Butt, MD Altered mental status

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 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 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 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

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:

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 Pneumonia

Macrolide Resistance

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
Adeel A. Butt, MD

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

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

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

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 Pneumonia

Choice of Initial Antimicrobial Regimen

Second generation 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.
Adeel A. Butt, MD

Gleason. Arch Int Med 1999;159:2562-72.

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 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

Vergis. Arch Int Med 2000;160:1294-1300. Adeel A. Butt, MD

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

Cefuroxime + Erythro

Azithromycin

Mean cost - $4,104 Mean cost - $4,578 CE Ratio per expected cure - $ 6,145 CE Ratio per expected cure $5,265

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

Clarithromycin ER

Head-to-head comparison with FQ

Vs. Levofloxacin1

252 patients Clinical cure 88% in Clarithro; 86% levo Radiographic success 95% vs. 88% Clinical cure 87% vs. 95% Radiographic success 95% vs. 95%

Vs. Trovafloxacin2

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

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