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:
 … 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.
Bartlett. Clin Infect Dis 2000;31:347-82.
Adeel A. Butt, MD
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
1171 1207
1200
1000
# in
1000s
1071
898
800
684
600
# of cases
400
200
83
0
<5
5 to 18-24 25-44 45-64 >65
17
Adeel A. Butt, MD
Community Acquired Pneumonia
Mortality
80
74.9
70
60
50
# in 40
1000s 30
# of deaths
20
10
2
5.7
0
<4
5 to 14 15-24
25-44
45-64
>65
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




Women: smoking, BMI, 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
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
J Chr Dis 1984;37:215-25
Adeel A. Butt, MD
Community Acquired
Pneumonia
Usefulness of Gram Stain


Good sputum samples obtained from 39%
83% show one predominant morphotype
Pneumococcus
H. flu.
Sensitivity
57
82
Specificity
97
99
Pos Pred Value
95
93
Neg Pred Value
71
96
Adeel A. Butt, MD
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
Fine MJ. NEJM 1997;336:243-50
Adeel A. Butt, MD
Community Acquired
Pneumonia

Class I & II:


Class III:


usually do not require hospitalization
may require brief hospitalization
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
Points
Mortality
I
Absence of
predictors
0.1%
II
< 70
0.6%
III
71-90
2.8%
IV
91-130
8.2%
V
> 130
Adeel A. Butt, MD
29.2%
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
IDSA guidelines: Clin Infect Dis 2000;31:347-82
Adeel A. Butt, MD
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.
Gleason. Arch Int Med 1999;159:2562-72.
Adeel A. Butt, MD
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

Azithromycin


Cefuroxime +
Erythro
Mean cost - $4,104


CE Ratio per
expected cure $5,265

Mean cost - $4,578
CE Ratio per
expected cure - $
6,145
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%
Vs. Trovafloxacin2


Clinical cure 87% vs. 95%
Radiographic success 95% vs. 95%
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