Healthy

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

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;31:347-82.

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
Adeel A. Butt, MD
Bartlett. CID 1998;26:811-38.

4.  Epidemiology: (contd)
 fewest cases in 18-24 yr group
 probably highest incidence in <5 and
>65 yrs
 mortality disproportionately high in
>65 yrs
Community Acquired
Pneumonia
Adeel A. Butt, MD

5. Community Acquired Pneumonia
Adeel A. Butt, MD
898
1071
83
1171 1207
684
0
200
400
600
800
1000
1200
1400
<5 5 to
17
18-24 25-44 45-64 >65
# of cases
# in
1000s
Incidence

6. Community Acquired Pneumonia
Adeel A. Butt, MD
2
5.7
74.9
0
10
20
30
40
50
60
70
80
<4 5 to 14 15-24 25-44 45-64 >65
# of deaths
# in
1000s
Mortality

7.  Risk Factors for pneumonia
 age
 alcoholism
 smoking
 asthma
 immunosuppression
 institutionalization
 COPD
 PVD
 dementia
Community Acquired
Pneumonia
Adeel A. Butt, MD
ID Clinics 1998;12:723.
Am J Med 1994;96:313

8.  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
Community Acquired Pneumonia
Adeel A. Butt, MD

9.  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
Community Acquired
Pneumonia
Adeel A. Butt, MD

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

11.  S. pneumoniae: 20-60%
 H. influenzae: 3-10%
 Chlamydia pneumoniae:
4-6%
 Mycoplasma pneumonaie:
1-6%
Adeel A. Butt, MD
Community Acquired
Pneumonia
 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
Microbiology

12. Community Acquired
Pneumonia
Adeel A. Butt, MD
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

13.  Laboratory Tests:
 CXR
 CBC with differential
 BUN/Cr
 glucose
 liver enzymes
 electrolytes
 Gram stain/culture of sputum
 pre-treatment blood cultures
 oxygen saturation
Community Acquired
Pneumonia
Adeel A. Butt, MD

14. 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
Community Acquired
Pneumonia
J Chr Dis 1984;37:215-25

15. Usefulness of Gram Stain
 Good sputum samples obtained from 39%
 83% show one predominant morphotype
Community Acquired
Pneumonia
Adeel A. Butt, MD
Pneumococcus H. flu.
Sensitivity 57 82
Specificity 97 99
Pos Pred Value 95 93
Neg Pred Value 71 96

16. Community Acquired
Pneumonia
Adeel A. Butt, MD

17.  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
Community Acquired
Pneumonia
Adeel A. Butt, MD
Fine MJ. NEJM 1997;336:243-50

18.  Class I & II:
 usually do not require hospitalization
 Class III:
 may require brief hospitalization
 Class IV & V:
 usually do require hospitalization
Community Acquired
Pneumonia
Adeel A. Butt, MD
Fine MJ. NEJM 1997;336:243-50

19. Adeel A. Butt, MD
Age:
Male
Female
Nursing home resident
Number of years
Number – 10
10
Co-morbid illness
Neoplastic disease
Liver disease
CHF
Cerebrovascular disease
Renal disease
30
20
10
10
10
Physical Exam
Altered mental status
RR > 30
Systolic bp < 90
Temp <35o
C or >40o
C
Pulse >125
20
20
20
15
10
Lab/X-ray findings
Arterial pH <7.35
BUN > 30
Sodium < 130
Hematocrit <30%
Glucose > 250
PaO2 <60
Pleural effusion
30
20
20
10
10
10
10

20. Adeel A. Butt, MD
Risk Class Points Mortality
I Absence of
predictors
0.1%
II < 70 0.6%
III 71-90 2.8%
IV 91-130 8.2%
V > 130 29.2%

21. 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
Pneumonia

22. 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

23.  Outpatient:
 macrolide
 doxycycline
 Fluoroquinolone
NOT IN ANY SPECIFIC ORDER
Adeel A. Butt, MD
Community Acquired
Pneumonia
Empiric Treatment
IDSA guidelines: Clin Infect Dis 2000;31:347-82

24.  Patients in General Medical Ward:
 3GC + macrolide
 B/B-I + macrolide OR B/B-I + FQ
 FQ alone
Adeel A. Butt, MD
Community Acquired
Pneumonia
Empiric Treatment
IDSA guidelines: Clin Infect Dis 2000;31:347-82

25.  Patients in ICU:
 3GC + macrolide
 3GC + FQ
 B/B-I + macrolide
 B/B-I + FQ
Adeel A. Butt, MD
Community Acquired
Pneumonia
Empiric Treatment
IDSA guidelines: Clin Infect Dis 2000;31:347-82

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;122:612-617.

27. 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
Community Acquired
Pneumonia
Adeel A. Butt, MD
IDSA guidelines: Clin Infect Dis 2000;31:347-82

28.  Increased drug efflux
 coded by mefE
 susceptible to
clindamycin
 most cases in US
 may be overcome by
achievable levels of
macrolides
Community Acquired
Pneumonia
Adeel A. Butt, MD
 Ribosomal methylase
 coded by ermAM
 resistant to
clindamycin
 mostly in Europe
 not overcome by
standard doses
Macrolide Resistance

29.  Active against 98% of resistant
pneumococcus
 Resistance has begun to increase
Community Acquired
Pneumonia
Adeel A. Butt, MD
(Newer)Fluoroquinolones
Chen DK. NEJM 1999;341:233-9
Ho PL. Antimicrob Agents Chemother 1999;43:1310-3.
Wise R. Lancet 1996;348:1660

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;346:747-750

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;32:701-707.

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;34:1607-1612.

33.  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.
Adeel A. Butt, MD
Community Acquired
Pneumonia
Gleason. Arch Int Med 1999;159:2562-72.

34.  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)
Adeel A. Butt, MD
Community Acquired
Pneumonia
Stahl. Arch Int Med 1999;159:2576-80.

35.  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
Community Acquired
Pneumonia
Adeel A. Butt, MD
Vergis. Arch Int Med 2000;160:1294-1300.

36.  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
Community Acquired
Pneumonia
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;122:1271-1279.

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%

39. 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)
Community Acquired
Pneumonia
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