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
Oct 7, 2008·British Poultry Science·G LiliaH Sumano
Aug 24, 2013·The Journal of Antimicrobial Chemotherapy·Aleksandra K WierzbowskiUNKNOWN Canadian Antimicrobial Resistance Alliance
Jul 28, 2010·Antimicrobial Agents and Chemotherapy·Tomoyuki HommaShogo Kuwahara
Nov 26, 2009·Antimicrobial Agents and Chemotherapy·Hidetoshi FuruieJingoro Shimada
Apr 28, 2005·Antimicrobial Agents and Chemotherapy·George G ZhanelDaryl J Hoban
Nov 10, 2006·Journal of Clinical Microbiology·David J FarrellStephen G Jenkins
Sep 8, 2011·Clinical Pharmacokinetics·Keith A RodvoldLiz Yoo
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
Feb 13, 2007·Lancet·Surbhi Malhotra-KumarHerman Goossens
Dec 30, 2006·International Journal of Antimicrobial Agents·Wanchai TreyaprasertHartmut Derendorf
Sep 18, 2004·International Journal of Clinical Practice·T J Marrie
Jun 28, 2007·Journal of Chemotherapy·O EcheverriaJ Prieto
Jun 5, 2004·Clinics in Laboratory Medicine·Michael R JacobsPeter C Appelbaum
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
Nov 9, 2004·The Journal of Antimicrobial Chemotherapy·George G ZhanelDaryl J Hoban
Dec 22, 2006·Expert Review of Anti-infective Therapy·Daryl J Hoban, George G Zhanel
Jan 19, 2008·European Journal of Ophthalmology·F ChiambarettaI Cochereau
Jun 11, 2019·Journal of Chemotherapy·Maria V GolikovaAlexander A Firsov