Pharmacodynamic activity of azithromycin against macrolide-susceptible and -resistant Streptococcus pneumoniae simulating clinically achievable free serum, epithelial lining fluid and middle ear fluid concentrations

The Journal of Antimicrobial Chemotherapy
George G ZhanelDaryl J Hoban

Abstract

The association between macrolide resistance mechanisms and bacteriological eradication of Streptococcus pneumoniae remains poorly studied. The present study, using an in vitro pharmacodynamic model, assessed azithromycin activity against macrolide-susceptible and -resistant S. pneumoniae simulating clinically achievable free serum (S), epithelial lining fluid (ELF) and middle ear fluid (MEF) concentrations. Two macrolide-susceptible [PCR-negative for both mef(A) and erm(B)] and six macrolide-resistant [five mef(A)-positive/erm(B)-negative displaying various degrees of macrolide resistance and one mef(A)-negative/erm(B)-positive] S. pneumoniae were tested. Azithromycin was modelled simulating a dosage of 500 mg/250 mg by mouth, once a day [free S: maximum concentration (Cmax) 0.2 mg/L, t1/2 68 h; free ELF Cmax 1.0 mg/L, t1/2 68 h] and 10 mg/kg by mouth, once a day (free MEF: Cmax 1.0 mg/L, t1/2 68 h) using a one compartment model. Starting inocula were 1 x 10(6) cfu/mL in Mueller-Hinton broth with 2% lysed horse blood. Sampling at 0, 2, 4, 6, 12, 24 and 48 h assessed the extent of bacterial killing (decrease in log10 cfu/mL versus initial inoculum). Free azithromycin concentrations in serum, ELF and MEF simulating time above th...Continue Reading

Citations

May 31, 2008·European Journal of Clinical Microbiology & Infectious Diseases : Official Publication of the European Society of Clinical Microbiology·M EisenblätterH Lode
Aug 24, 2013·The Journal of Antimicrobial Chemotherapy·Aleksandra K WierzbowskiUNKNOWN Canadian Antimicrobial Resistance Alliance
Nov 26, 2009·Antimicrobial Agents and Chemotherapy·Hidetoshi FuruieJingoro Shimada
Jun 21, 2005·Emerging Infectious Diseases·Keith P Klugman, John R Lonks
Jun 30, 2009·International Journal of Antimicrobial Agents·James A KarlowskyGeorge G Zhanel
Jun 26, 2007·International Journal of Antimicrobial Agents·Jerome J SchentagJoseph A Paladino
Dec 30, 2006·International Journal of Antimicrobial Agents·Wanchai TreyaprasertHartmut Derendorf
Dec 3, 2008·International Journal of Infectious Diseases : IJID : Official Publication of the International Society for Infectious Diseases·Ayman M NoreddinGeorge G Zhanel
Nov 29, 2017·Antimicrobial Agents and Chemotherapy·Brian T TsujiTimothy F Murphy
Dec 22, 2006·Expert Review of Anti-infective Therapy·Daryl J Hoban, George G Zhanel

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