1. 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
Salutations:
I am going to talk mainly about the work-up of CAP and the IDSA guidelines for the treatment of CAP.

2. 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:

3. 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:
Adeel A. Butt, MD

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

5. Community Acquired Pneumonia
Incidence
# in 1000s
NCHS Data:
Adeel A. Butt, MD

6. Community Acquired Pneumonia
Mortality
# in 1000s
NCHS Data:
Adeel A. Butt, MD

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

8. 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 , 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
Baik et al. Arch Int Med 2000;160:
Adeel A. Butt, MD

9. 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
Farr BM. Respir Med 2000;94:954-63
Adeel A. Butt, MD

10. Community Acquired Pneumonia
Risk Factors for Mortality
age
bacteremia (for S. pneumoniae)
extent of radiographic changes
degree of immunosuppression
amount of alcohol
Fine. JAMA 1996;275:
Adeel A. Butt, MD

11. Community Acquired Pneumonia
Microbiology
Legionella spp %
S. aureus: 3-5%
Gram negative bacilli: 3-5%
Viruses: 2-13%
S. pneumoniae: 20-60%
H. influenzae: 3-10%
Chlamydia pneumoniae: 4-6%
Mycoplasma pneumonaie: 1-6%
Bartlett. NEJM 1995;333:
40-60% - NO CAUSE IDENTIFIED
2-5% - TWO OR MORE CAUSES
Adeel A. Butt, MD

12. Community Acquired Pneumonia
Adeel A. Butt, MD

13. 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

14. 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

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

16. Community Acquired Pneumonia
Who should be hospitalized?
Adeel A. Butt, MD

17. 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

18. 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

19. Community Acquired Pneumonia
Fine MJ. NEJM 1997;336:243-50
Adeel A. Butt, MD

20. Fine MJ. NEJM 1997;336:243-50
Adeel A. Butt, MD

21. 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

22. 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

23. 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

24. 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

25. 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

26. 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:

27. 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

28. 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
Amsden GW. J Antimicrob Chemother 1999;44:1-6.
Adeel A. Butt, MD

29. 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:
Wise R. Lancet 1996;348:1660
Adeel A. Butt, MD

30. 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:

31. 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:

32. 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:

33. 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:
Adeel A. Butt, MD

34. 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:
Adeel A. Butt, MD

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

36. 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
Plouffe. Antimicrob Agents Chemother 2000;44:
Adeel A. Butt, MD

37. 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
Paladino. Chest Oct 2002;122:

38. 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%
1. Gotfried. Clin Ther 2002;24:
2. Sokol. Clin Ther 2002;24:

39. 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)
Heffelfinger. Arch Int Med 2000;160:
Adeel A. Butt, MD

40. 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