Azithromycin iv pharmacodynamic parameters predicting Streptococcus pneumoniae killing in epithelial lining fluid versus serum: an in vitro pharmacodynamic simulation

The Journal of Antimicrobial Chemotherapy
David SevillanoJosé Prieto

Abstract

To investigate the azithromycin pharmacodynamic parameters predicting bacterial killing in epithelial lining fluid (ELF) versus serum against macrolide-susceptible and -resistant Streptococcus pneumoniae isolates (with different resistance genotypes), through the simulation of concentrations achieved after a 500 mg intravenous (iv) once a day regimen. An in vitro computer-controlled pharmacodynamic simulation of human azithromycin concentrations in serum and ELF was carried out, and colony counts were determined over 24 h. Four strains with MIC values (mg/L) of 0.5 [mef(A) and erm(B) negative], 2 [mef(A) positive and erm(B) negative], 8 [mef(A) positive and erm(B) negative] and 256 [mef(A) negative and erm(B) positive] were used. Significant (P < 0.05) azithromycin antibacterial activity versus antibiotic-free controls was found in serum and ELF against the susceptible and mef(A) positive strains, but not against the erm(B) positive strain. AUC(0-24)/MIC values around or higher than 25 were needed to achieve (time to 99.9% reduction of initial inocula of around 6 h) and maintain (24 h inocula reduction > or =3 log(10)cfu/mL) bactericidal activity without regrowth. This was achieved only with the susceptible strain in serum, but...Continue Reading

Citations

Mar 17, 2009·Journal of Ocular Pharmacology and Therapeutics : the Official Journal of the Association for Ocular Pharmacology and Therapeutics·Lyle M BowmanMitchell Friedlaender
Jan 1, 2011·International Journal of Pharmaceutical Investigation·Ritu Mehra GilhotraDina Nath Mishra
Mar 20, 2015·Drug Delivery and Translational Research·Shunmugaperumal TamilvananAshutosh Thakur
Jan 6, 2016·American Journal of Transplantation : Official Journal of the American Society of Transplantation and the American Society of Transplant Surgeons·D NakajimaS Keshavjee
Sep 30, 2016·Frontiers in Microbiology·Rita Teixeira-SantosCidália Pina-Vaz

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