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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:
0066-4804(199903)43:3<498:POTEOI>2.0.ZU;2-B
Fonte:
ISI
Lingua:
ENG
Soggetto:
TROVAFLOXACIN CP-99,219; AMPICILLIN-SULBACTAM; 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. 498-502

Abstract

The effect of inoculum size (N-0) 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 12-h interval) were compared at N-0 = 10(6) and 10(9) CFU/ml (S. aureas) and at N-0 = 10(6), 10(7), and 10(9) CFU/ml (E. coli). A series of pharmacokinetic profiles of trovafloxacin and ciprofloxacin with respective half-lives of 9.2 and 4 h mere simulated at different ratios of area under the concentration-time 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 N-0 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 N-0 for both organisms. The N-0-induced reductions of the intensity ofthe antimicrobial effect (I-E, area between control growth, and the killing-regrowth curves) were also relatively small, However, the N-0 effect could not be eliminated either by simple shifting of the time-hill curves obtained at higher N(0)s by the difference between the higher and lowest N-0 or by operating with I(E)s determined within the N-0-adopted upper limits of bacterial numbers (I-E's), By using multivariate correlation and regression analyses, linear relationships between I-E and log AUC/MIC and log N-0 related to the respective mean values [(log AUC/MIC)(average) and (log N-0)(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 N-0 based on the relationship I-E = a + b [(log AUC/MIC)/log AUC/MIC)(average)] - c [(log N-0)/(log N-0)(average)]. Moreover, the relativeimpacts of AUC/MIC and N-0 on I-E 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 ampicillin-sulbactam as examined previously (1.9), the inoculum effect with the quinolones may be much less pronounced than with thebeta-lactams. 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