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Outpatient treatment of CAP: evidence based findings. Dr. Aykut Çilli Akdeniz U niversity School of Medicine Dept . Of Respiratory Diseases -Antalya. Consultation : Abdi İbrahim Speaking fee : Astra Zeneca , Chiesi , Sanovel , Abdi İbrahim. Conflict of interest.
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Outpatienttreatment of CAP: evidencebasedfindings Dr. Aykut Çilli Akdeniz UniversitySchool of Medicine Dept. Of RespiratoryDiseases-Antalya
Consultation: Abdi İbrahim Speakingfee: AstraZeneca, Chiesi, Sanovel, Abdi İbrahim Conflict of interest
Mildcommunity-acquiredpneumonia • >75% of patientsaretreated as outpatients • Typicallyaged <65 yrs • No significiantcomorbidity • Mortality rate <1% • Empiricaltreatment is directedtowardthemostlikelypathogen
Guidelinesfor CAP treatment • ATS/IDSA • Macrolideordoxycyline • Fluoroquinoloneor ß laktam + macrolide • ERS/ESCMID • Amoxicillinortetracycline • TurkishThorasicSociety • Amoxicillinormacrolide • ß laktam ± macrolide / doxycyline
Azithromycin vs. cefaclor Randomized, double-blindstudy (n=119) Kinasewitz et al. Eur J ClinMicrobiolInfectDis 1991
Randomizedcomparison of sparfloxacin, amoxycillin-clavulanicacidanderythromycin Double-blind, randomized, parallel group study (n=808) Lode et al. EurRespir J 1995
Amoxycillin vs. clarithromycin Macfarlane et al. British Journal of General Practice 1996
Amoxycillin/clavulanate vs.cefuroximeaxetil Multicentre, randomize, investigator-blindedtrial Higuera et al. J AntimicrobChemother 1996
Seventy-four (46%) of the 162 patients enrolled werebacteriologically evaluable. Higuera et al. J AntimicrobChemother 1996
Amoxycillin vs. grepafloxacin Randomized, multicentre, double-blind, double-dummystudy Patients treatedwith grepafloxacin demonstrated a clinical response rate (76%) equivalent to thatseen with amoxycillin (74%) 127 137 O’Doherty et al. Chemotherapy 1997
Roxithromycin vs. cefixime Randomized, doubleblindstudy (n=60) No. of pts (%) Salvarezza et al. J AntimicrobChemother 1998
No. of pts (%) Salvarezza et al. J AntimicrobChemother 1998
High-dosageamoxicillin vs. moxifloxacin Multinational, multicenter, double-blind, randomized study (n=411) Petitpretz et al. Chest 2001
Amoxicillin/clavulanate vs.cefditorenpivoxil Multicenter, prospective, randomized, investigator-blindedtrial (n=802) Fogarty et al. ClinTher 2002
Sparfloxacin vs. clarithromycinorcefaclor Study 1 Study 2 Ramirez et al. ClinTher 1999 Donowitz et al. ClinTher 1997
Moxifloxacin vs. clarithromycin International multi-centre, randomized, prospective, double-blind (n=531) Hoeffken et al. RespirMed 2001
Telithromycin vs. high-doseamoxicillin Randomized, multicentre, double-blind (n=404). Hagberg et al. Infection 2002
Clarithromycin vs. levofloxacin Double-blind, randomized, parallel-group, multicenter study 156 143 Gotfried et al. ClinTher 2002
Clarithromycinextended-releasewithtrovafloxacin Prospective, multicenter, double-blind, double-dummystudy (n=176) Sokol WJ et al. ClinTher 2002
Azithromycin vs. clarithromycinorlevofloxacin [I]Drehobl, Chest 2005 [II]D’Ignasio, AntimicrobAgentsChemother 2005
Gemifloxacin vs. amoxicillin/clavulanicacid Randomized, multicentre, double-blind, phase III study (n=320). Leophontea et al. RespirMed 2004
Cethromycin vs. clarithromycin Randomized, multicentre, double-blind, phase III noninferiority studies Study CL05-001 Study CL06-001 English et al. AntimicrobAgentsandChemother 2012
Meta-analysis-1 18 trials 6749 patients Mildtomoderate CAP Mills et al. BMJ 2005
Meta-analysis-2 13 studies, 4314 outpatienttreated CAP patients Macrolides vs. fluoroquinolones Cephalosporins vs. β-lactams/ β-lactamaseinhibitors Atypicalcoveragevs. no atypical coverage Maimon et al. EurRespir J 2008
Mortality in studies of outpatient-treated CAP by empirical antibacterial therapy Atypical vs. noatypicalcoverage. Macrolides vs. fluoroquinolones Maimon et al. EurRespir J 2008
3 trials • 622 outpatienttreated CAP patients • Anderson (1991) Clarithromycin vs. Erythromycin • Chien (1993) Clarithromycin vs. Erythromycin • Ramirez (1999) Clarithromycin vs. Sparfloxacin
Conclusion • Evidence is lacking that antibiotics active against atypicalpathogens improve clinical outcomes in adults withmildtomoderate CAP • It’s not possibletodemonstrateanyadvantage of specificantibacterialsforoutpatienttreatment of CAP