Outpatient treatment of CAP: evidence based findings

Dr. Aykut ÇilliAkdeniz University School of Medicine Dept. Of Respiratory Diseases-

Antalya

• Consultation: Abdi İbrahim• Speaking fee: Astra Zeneca, Chiesi, Sanovel,

Abdi İbrahim

Conflict of interest

Mild community-acquired pneumonia

• >75% of patients are treated as outpatients• Typically aged <65 yrs• No significiant comorbidity• Mortality rate <1%• Empirical treatment is directed toward the

most likely pathogen

Guidelines for CAP treatment

• ATS/IDSA– Macrolide or doxycyline– Fluoroquinolone or ß laktam + macrolide

• ERS/ESCMID– Amoxicillin or tetracycline

• Turkish Thorasic Society– Amoxicillin or macrolide– ß laktam ± macrolide / doxycyline

azithromycin cefaclor

Satisfactory clinical response, % 97.3 100

Bacteriological eradication, % 80.4 92.6

Azithromycin vs. cefaclor

Randomized, double-blind study (n=119)

Kinasewitz et al. Eur J Clin Microbiol Infect Dis 1991

Randomized comparison of sparfloxacin, amoxycillin-clavulanic acid and erythromycin

Double-blind, randomized, parallel group study (n=808)

Lode et al. Eur Respir J 1995

Lode et al. Eur Respir J 1995

Amoxycillin vs. clarithromycin

Macfarlane et al. British Journal of General Practice 1996

Amoxycillin/clavulanate vs.cefuroxime axetil

Higuera et al. J Antimicrob Chemother 1996

Multicentre, randomize, investigator-blinded trial

Higuera et al. J Antimicrob Chemother 1996

Seventy-four (46%) of the 162 patients enrolled were bacteriologically evaluable.

Amoxycillin vs. grepafloxacin

O’Doherty et al. Chemotherapy 1997

Patients treated with grepafloxacin demonstrated a clinical response rate (76%) equivalent to that seen with amoxycillin (74%)

127 137

Randomized, multicentre, double-blind, double-dummy study

curepartial

response failure

0102030405060708090

100

roxithromycincefixime

Roxithromycin vs. cefiximeRandomized, double blind study (n=60)

Salvarezza et al. J Antimicrob Chemother 1998

No. of pts (%)

satisfa

ctory

satisfa

ctory

with co

loniz.

failure

not acce

ssable

0102030405060

roxithromycincefixime

Salvarezza et al. J Antimicrob Chemother 1998

No. of pts (%)

High-dosage amoxicillin vs. moxifloxacin

Petitpretz et al. Chest 2001

Multinational, multicenter, double-blind, randomized study (n=411)

Petitpretz et al. Chest 2001

Amoxicillin/clavulanate vs.cefditoren pivoxil

Fogarty et al. Clin Ther 2002

Multicenter, prospective, randomized, investigator-blinded trial (n=802)

Sparfloxacin vs. clarithromycin or cefaclor

Sparfloxacin (n=167)

Clarithromycin (n=175)

Sparfloxacin (n=168)

Cefaclor (n=162)

Clinical successes, % 79.6 82.9 72.6 71.0

Bacteriological response, % 97 91 88.6 81.8

Study 1 Study 2

1) Ramirez et al. Clin Ther 19992) Donowitz et al. Clin Ther 1997

Moxifloxacin vs. clarithromycin

Hoeffken et al. Respir Med 2001

International multi-centre, randomized, prospective, double-blind (n=531)

Hoeffken et al. Respir Med 2001

Hoeffken et al. Respir Med 2001

Telithromycin vs. high-dose amoxicillin

Hagberg et al. Infection 2002

Randomized, multicentre, double-blind (n=404).

Hagberg et al. Infection 2002

Clarithromycin vs. levofloxacin

Gotfried et al. Clin Ther 2002

156 143

Double-blind, randomized, parallel-group, multicenter study

Gotfried et al. Clin Ther 2002

Clarithromycin extended-release with trovafloxacin

Sokol WJ et al. Clin Ther 2002

Prospective, multicenter, double-blind, double-dummy study (n=176)

Sokol WJ et al. Clin Ther 2002

Azithromycin vs. clarithromycin or levofloxacin

[I] Drehobl, Chest 2005[II] D’Ignasio, Antimicrob Agents Chemother 2005

Gemifloxacin vs. amoxicillin/clavulanic acid

Leophontea et al. Respir Med 2004

Randomized, multicentre, double-blind, phase III study (n=320).

Leophontea et al. Respir Med 2004

Cethromycin(n=261)

Clarithromycin (n=254)

Cethromycin (n=257)

Clarithromycin (n=253)

Clinical successes, % 94.0 93.8 91.5 95.9

Bacteriological response, % 90-100 90.9-100 66.7-100 80-100

Study CL05-001 Study CL06-001

English et al. Antimicrob Agents and Chemother 2012

Cethromycin vs. clarithromycin

Randomized, multicentre, double-blind, phase III noninferiority studies

Meta-analysis-1

Mills et al. BMJ 2005

18 trials6749 patientsMild to moderate CAP

Mills et al. BMJ 2005

Meta-analysis-2

Atypical coverage vs. no atypical coverage

Macrolides vs. fluoroquinolones Cephalosporins vs. β-lactams/β-lactamase inhibitors

13 studies, 4314 outpatient treated CAP patients

Maimon et al. Eur Respir J 2008

Mortality in studies of outpatient-treated CAP by empirical antibacterial therapy

Atypical vs. no atypical coverage. Macrolides vs. fluoroquinolones

Maimon et al. Eur Respir J 2008

• 3 trials• 622 outpatient treated CAP patients

1. Anderson (1991) Clarithromycin vs. Erythromycin2. Chien (1993) Clarithromycin vs. Erythromycin 3. Ramirez (1999) Clarithromycin vs. Sparfloxacin

Conclusion

• Evidence is lacking that antibiotics active against atypical pathogens improve clinical outcomes in adults with mild to moderate CAP

• It’s not possible to demonstrate any advantage of specific antibacterials for outpatient treatment of CAP