Sevillano Fernández, DavidAlou Cervera, LuisAguilar, LorenzoEchevarría, OlatzGiménez, María JoséPrieto Prieto, José2024-07-292024-07-292006-04-04Sevillano D, Alou L, Aguilar L, Echevarría O, Giménez MJ, Prieto J. Azithromycin iv pharmacodynamic parameters predicting Streptococcus pneumoniae killing in epithelial lining fluid versus serum: an in vitro pharmacodynamic simulation. J Antimicrob Chemother. 2006 Jun;57(6):1128-33.0305-745310.1093/jac/dkl140https://hdl.handle.net/20.500.14352/107174Objectives: 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. Methods: 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. Results: 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 also with the mef(A) positive strain exhibiting an MIC of 2 mg/L in ELF. Conclusions: The results of this study support that the suggested breakpoint for susceptibility (< or =2 mg/L) may be adequate to predict S. pneumoniae eradication with ELF but not with serum concentrations obtained after a 500 mg iv once a day regimen.engjournal article1460-2091https://doi.org/10.1093/jac/dkl140https://academic.oup.com/jac/article/57/6/1128/734470restricted access611.02in vitro modelsantipneumococcal bactericidal activityresistance genotypesMicrobiología médica2414 Microbiología