community acquired pneumonia challenges in the new millenium

Community Acquired Pneumonia

Challenges in the New Millenium

DR. Yousef Noaimat MD.FCCPConsultant in pulmonary and internal

medicine.


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, MDBartlett. Clin Infect Dis 2000;31:347-82.


Epidemiology: 4-5 million cases annually ~500,000 hospitalizations ~45,000 deaths Mortality 2-30%

<1% for those not requiring hospitalization

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

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


Adeel A. Butt, MD

898

1071

83

1171 1207

684

0

200

400

600

800

1000

1200

1400

<5 5 to17

18-24 25-44 45-64 >65

# of cases

# in 1000s

Incidence


Adeel A. Butt, MD

25.7

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

Risk Factors for pneumonia age alcoholism smoking asthma immunosuppression institutionalization COPD PVD dementia


Adeel A. Butt, MDID Clinics 1998;12:723. Am J Med 1994;96:313

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

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

Risk Factors for Mortality age bacteremia (for S. pneumoniae) extent of radiographic changes degree of immunosuppression amount of alcohol


Adeel A. Butt, MD

S. pneumoniae: 20-60% H. influenzae: 3-10% Chlamydia pneumoniae:

4-6% Mycoplasma

pneumonaie: 1-6%

Adeel A. Butt, MD


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


Adeel A. Butt, MD

Evaluation for CAP

History, PE, CXR

No infiltratemanage/evaluate for alternate diagnosis Infiltrate + clinical evidence of pneumonia

evaluate for admission

outpatient:empiric treatment with macrolide, doxycycline, FQ

hospitalizelabs

medical ward:abx < 8 hrs ICU: abx < 8 hrs

no pathogen identifiedB-lactam + macrolide

FQ

no pathogen identified B-lactam + macrolide

B-lactam + FQ

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

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

Usefulness of Gram Stain Good sputum samples obtained from 39% 83% show one predominant morphotype


Adeel A. Butt, MD

Pneumococcus H. flu.

Sensitivity 57 82

Specificity 97 99

Pos Pred Value 95 93

Neg Pred Value 71 96


Adeel A. Butt, MD

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, MDFine MJ. NEJM 1997;336:243-50

Class I & II: usually do not require

hospitalization

Class III: may require brief hospitalization

Class IV & V: usually do require hospitalization


Adeel A. Butt, MDFine MJ. NEJM 1997;336:243-50

Adeel A. Butt, MD

Age: Male FemaleNursing home resident

Number of yearsNumber – 1010

Co-morbid illness Neoplastic disease Liver disease CHF Cerebrovascular disease Renal disease

3020101010

Physical Exam Altered mental status RR > 30 Systolic bp < 90 Temp <35oC or >40oC Pulse >125

2020201510

Lab/X-ray findings Arterial pH <7.35 BUN > 30 Sodium < 130 Hematocrit <30% Glucose > 250 PaO2 <60 Pleural effusion

30202010101010

Adeel A. Butt, MD

Risk Class Points Mortality

I Absence ofpredictors

0.1%

II < 70 0.6%

III 71-90 2.8%

IV 91-130 8.2%

V > 130 29.2%

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


Management Rational use of microbiology

laboratory Pathogen directed antimicrobial

therapy whenever possible Prompt initiation of therapy Decision to hospitalize based on

prognostic criteriaAdeel A. Butt, MD


Outpatient: macrolide doxycycline Fluoroquinolone

NOT IN ANY SPECIFIC ORDER

Adeel A. Butt, MD


Empiric Treatment

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

Patients in General Medical Ward: 3GC + macrolide B/B-I + macrolide OR B/B-I + FQ FQ alone

Adeel A. Butt, MD


Empiric Treatment


Patients in ICU: 3GC + macrolide 3GC + FQ B/B-I + macrolide B/B-I + FQ

Adeel A. Butt, MD

Community Acquired PneumoniaEmpiric Treatment


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.

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, MDIDSA guidelines: Clin Infect Dis 2000;31:347-82

Increased drug efflux

coded by mefE susceptible to

clindamycin most cases in US may be overcome by

achievable levels of macrolides


Adeel A. Butt, MD

Ribosomal methylase coded by ermAM resistant to

clindamycin mostly in Europe not overcome by

standard doses

Macrolide Resistance

Active against 98% of resistant pneumococcus

Resistance has begun to increase


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

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.

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


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

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


Stahl. Arch Int Med 1999;159:2576-80.

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, MDVergis. Arch Int Med 2000;160:1294-1300.

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

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%

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

community acquired pneumonia challenges in the new millenium

Documents

pneumoniarisk factors

symptoms of acute infection

onset of symptoms

acute infiltrate

yousef noaimat md

er patients

yrs adeel

increased riskadeel