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Titolo:
PARAMETERS OF BACTERIAL KILLING AND REGROWTH KINETICS AND ANTIMICROBIAL EFFECT EXAMINED IN TERMS OF AREA UNDER THE CONCENTRATION-TIME CURVERELATIONSHIPS - ACTION OF CIPROFLOXACIN AGAINST ESCHERICHIA-COLI IN AN IN-VITRO DYNAMIC-MODEL
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 I-37100 VERONA ITALY
Titolo Testata:
Antimicrobial agents and chemotherapy
fascicolo: 6, volume: 41, anno: 1997,
pagine: 1281 - 1287
SICI:
0066-4804(1997)41:6<1281:POBKAR>2.0.ZU;2-9
Fonte:
ISI
Lingua:
ENG
Soggetto:
PHARMACOKINETIC INVITRO MODEL; STAPHYLOCOCCUS-AUREUS; PSEUDOMONAS-AERUGINOSA; ANTIBACTERIAL ACTIVITY; STREPTOCOCCUS-PNEUMONIAE; 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 CONCENTRATION-TIME CURVERELATIONSHIPS - ACTION OF CIPROFLOXACIN AGAINST ESCHERICHIA-COLI IN AN IN-VITRO DYNAMIC-MODEL", Antimicrobial agents and chemotherapy, 41(6), 1997, pp. 1281-1287

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 half-life of 4 h was the same in all experiments. The followingparameters were calculated and estimated: the time to reduce the initial inoculum (N-0) 10-, 100-, and 1,000-fold (T-90%, T-99%, and T-99.9%, respectively), the rate constant of bacterial elimination (k(elb)),the nadir level (N-min) in the viable count (N)-versus-time (t) curve, the time to reach N-min (t(min)), the numbers of bacteria that survived (N-tau) by the end of the observation period (tau), the area underthe bacterial killing and regrowth curve (log N-A-t curve) from the zero point (time zero) to tau (AUBC), the area above this curve (AAC), the area between the control growth curve (log N-C-t curve) and the bacterial killing and regrowth curve (log N-A-t curve) from the zero point to tau (ABBC) or to the time point when log N-A reaches the maximalvalues observed in the log N-C-t curve (I-E; intensity of the effect), and the time shift between the control growth and regrowth curves (T-E; duration of the effect). Being highly sensitive to the AUC, I-E and T-E showed the most regular AUC relationships: the effect expressed by I-E or T-E increased systematically when the AUG or initial concentration of ciprofloxacin rose. Other parameters, especially T-90%, T-99%, T-99.9%, t(min), and log N-0 - log N-min = Delta log N-min, relatedto the AUC less regularly and were poorly sensitive to the AUC. T-E proved to be the best predictor and t(min) proved to be the worst predictor of the total antimicrobial effect reflected by I-E. 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 N-A-t curves, maylead to the degeneration of the AUG-response relationships, as expressed by log N-0 - log N-tau = Delta log N-tau, AUBC, AAC, or ABBC, to apoint where it gives rise to the false idea of an AUC- or concentration-independent effect. Thus, use of I-E and T-E 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 30/10/20 alle ore 10:01:19