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Titolo: PARAMETERS OF BACTERIAL KILLING AND REGROWTH KINETICS AND ANTIMICROBIAL EFFECT EXAMINED IN TERMS OF AREA UNDER THE CONCENTRATIONTIME CURVERELATIONSHIPS  ACTION OF CIPROFLOXACIN AGAINST ESCHERICHIACOLI IN AN INVITRO DYNAMICMODEL
Autore: FIRSOV AA; VOSTROV SN; SHEVCHENKO AA; CORNAGLIA G;
 Indirizzi:
 CTR SCI & TECHNOL LEKBIOTECH,DEPT PHARMACOKINET,8 NAUCHNY PROEZD MOSCOW 117246 RUSSIA UNIV VERONA,INST MICROBIOL I37100 VERONA ITALY
 Titolo Testata:
 Antimicrobial agents and chemotherapy
fascicolo: 6,
volume: 41,
anno: 1997,
pagine: 1281  1287
 SICI:
 00664804(1997)41:6<1281:POBKAR>2.0.ZU;29
 Fonte:
 ISI
 Lingua:
 ENG
 Soggetto:
 PHARMACOKINETIC INVITRO MODEL; STAPHYLOCOCCUSAUREUS; PSEUDOMONASAERUGINOSA; ANTIBACTERIAL ACTIVITY; STREPTOCOCCUSPNEUMONIAE; DOSING REGIMENS; PHARMACODYNAMICS; LOMEFLOXACIN; ELIMINATION; COMBINATION;
 Tipo documento:
 Article
 Natura:
 Periodico
 Settore Disciplinare:
 Science Citation Index Expanded
 Science Citation Index Expanded
 Citazioni:
 39
 Recensione:
 Indirizzi per estratti:



 Citazione:
 A.A. Firsov et al., "PARAMETERS OF BACTERIAL KILLING AND REGROWTH KINETICS AND ANTIMICROBIAL EFFECT EXAMINED IN TERMS OF AREA UNDER THE CONCENTRATIONTIME CURVERELATIONSHIPS  ACTION OF CIPROFLOXACIN AGAINST ESCHERICHIACOLI IN AN INVITRO DYNAMICMODEL", Antimicrobial agents and chemotherapy, 41(6), 1997, pp. 12811287
Abstract
Although many parameters have been described to quantitate the killing and regrowth of bacteria, substantial shortcomings are inherent in most of them, such as low sensitivity to pharmacokinetic determinants of the antimicrobial effect, an inability to predict a total effect, insufficient robustness, and uncertain interrelations between the parameters that prevent an ultimate determination of the effect. To examine different parameters, the kinetics of killing and regrowth of Escherichia coli (MIC, 0.013 mu g/ml) were studied in vitro by simulating a series of ciprofloxacin monoexponential pharmacokinetic profiles. Initial ciprofloxacin concentrations varied from 0.02 to 19.2 mu g/ml, whereas the halflife of 4 h was the same in all experiments. The followingparameters were calculated and estimated: the time to reduce the initial inoculum (N0) 10, 100, and 1,000fold (T90%, T99%, and T99.9%, respectively), the rate constant of bacterial elimination (k(elb)),the nadir level (Nmin) in the viable count (N)versustime (t) curve, the time to reach Nmin (t(min)), the numbers of bacteria that survived (Ntau) by the end of the observation period (tau), the area underthe bacterial killing and regrowth curve (log NAt curve) from the zero point (time zero) to tau (AUBC), the area above this curve (AAC), the area between the control growth curve (log NCt curve) and the bacterial killing and regrowth curve (log NAt curve) from the zero point to tau (ABBC) or to the time point when log NA reaches the maximalvalues observed in the log NCt curve (IE; intensity of the effect), and the time shift between the control growth and regrowth curves (TE; duration of the effect). Being highly sensitive to the AUC, IE and TE showed the most regular AUC relationships: the effect expressed by IE or TE increased systematically when the AUG or initial concentration of ciprofloxacin rose. Other parameters, especially T90%, T99%, T99.9%, t(min), and log N0  log Nmin = Delta log Nmin, relatedto the AUC less regularly and were poorly sensitive to the AUC. TE proved to be the best predictor and t(min) proved to be the worst predictor of the total antimicrobial effect reflected by IE. Distinct feedback relationships between the effect determination and the experimental design were demonstrated. It was shown that unjustified shortening of the observation period, i.e., cutting off the log NAt curves, maylead to the degeneration of the AUGresponse relationships, as expressed by log N0  log Ntau = Delta log Ntau, AUBC, AAC, or ABBC, to apoint where it gives rise to the false idea of an AUC or concentrationindependent effect. Thus, use of IE and TE provides the most unbiased, robust, and comprehensive means of determining the antimicrobialeffect.
ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 22/09/20 alle ore 08:00:47