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Titolo: Prediction of the effects of inoculum size on the antimicrobial action of trovafloxacin and ciprofloxacin against Staphylococcus aureus and Escherichia coli in an in vitro dynamic model
Autore: Firsov, AA; Vostrov, SN; Kononenko, OV; Zinner, SH; Portnoy, YA;
 Indirizzi:
 Ctr Sci & Technol LekBioTech, Dept Pharmacokinet, Moscow 117246, Russia Ctr Sci & Technol LekBioTech Moscow Russia 117246 Moscow 117246, Russia Brownnce,v, Rhode Isl Hosp, Roger Williams Med Ctr, Div Infect Dis, Provide Brown Univ Providence RI USA 02903 liams Med Ctr, Div Infect Dis, Provide
 Titolo Testata:
 ANTIMICROBIAL AGENTS AND CHEMOTHERAPY
fascicolo: 3,
volume: 43,
anno: 1999,
pagine: 498  502
 SICI:
 00664804(199903)43:3<498:POTEOI>2.0.ZU;2B
 Fonte:
 ISI
 Lingua:
 ENG
 Soggetto:
 TROVAFLOXACIN CP99,219; AMPICILLINSULBACTAM; PHARMACOKINETICS;
 Tipo documento:
 Article
 Natura:
 Periodico
 Settore Disciplinare:
 Life Sciences
 Citazioni:
 14
 Recensione:
 Indirizzi per estratti:
 Indirizzo: Firsov, AA Ctr117246,Technol LekBioTech, Dept Pharmacokinet, 8 Nauchny Proezd, Moscow Ctr Sci & Technol LekBioTech 8 Nauchny Proezd Moscow Russia 117246



 Citazione:
 A.A. Firsov et al., "Prediction of the effects of inoculum size on the antimicrobial action of trovafloxacin and ciprofloxacin against Staphylococcus aureus and Escherichia coli in an in vitro dynamic model", ANTIM AG CH, 43(3), 1999, pp. 498502
Abstract
The effect of inoculum size (N0) on antimicrobial action has not been extensively studied in in vitro dynamic models. To investigate this effect andits predictability, killing and regrowth kinetics of Staphylococcus aureusand Escherichia coli exposed to monoexponentially decreasing concentrations of trovafloxacin las a single dose) and ciprofloxacin (two doses at a 12h interval) were compared at N0 = 10(6) and 10(9) CFU/ml (S. aureas) and at N0 = 10(6), 10(7), and 10(9) CFU/ml (E. coli). A series of pharmacokinetic profiles of trovafloxacin and ciprofloxacin with respective halflives of 9.2 and 4 h mere simulated at different ratios of area under the concentrationtime curve (AUC) to MIC (in [micrograms x hours/milliliter]/[micrograms/milliliter]) 58 to 466 with trovafloxacin and 116 to 932 with ciprofloxacin fur S, aureus and 58 to 233 and 116 to 466 for E, coli, respectively. Although the effect of N0 was more pronounced for E. coli than for S, aureus, only a minor increase in minimum numbers of surviving bacteria and an almost negligible delay in their regrowth were associated with an increase ofthe N0 for both organisms. The N0induced reductions of the intensity ofthe antimicrobial effect (IE, area between control growth, and the killingregrowth curves) were also relatively small, However, the N0 effect could not be eliminated either by simple shifting of the timehill curves obtained at higher N(0)s by the difference between the higher and lowest N0 or by operating with I(E)s determined within the N0adopted upper limits of bacterial numbers (IE's), By using multivariate correlation and regression analyses, linear relationships between IE and log AUC/MIC and log N0 related to the respective mean values [(log AUC/MIC)(average) and (log N0)(average)] were established far both trovafloxacin and ciprofloxacin against each of the strains (r(2) = 0.97 to 0.99). The antimicrobial effect may be accurately predicted at a given AUC/MIC of trovafloxacin or ciprofloxacin andat a given N0 based on the relationship IE = a + b [(log AUC/MIC)/log AUC/MIC)(average)]  c [(log N0)/(log N0)(average)]. Moreover, the relativeimpacts of AUC/MIC and N0 on IE may be evaluated. Since the db ratios for trovafloxacin and ciprofloxacin against E, coli were much lower (0.3 to 0.4) than that for ampicillinsulbactam as examined previously (1.9), the inoculum effect with the quinolones may be much less pronounced than with thebetalactams. The described approach to the analysis of the inoculum effect in in vitro dynamic models might be useful in studies with other antibiotic classes.
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Documento generato il 03/12/20 alle ore 16:08:32