This Article
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Right arrowReprints and Permissions
Right arrow Copyright Information
Right arrow Books from ASM Press
Right arrow MicrobeWorld
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Firsov, A. A.
Right arrow Articles by Cornaglia, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Firsov, A. A.
Right arrow Articles by Cornaglia, G.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, Jun 1997, 1281-1287, Vol 41, No. 6
Copyright © 1997 by the American Society for Microbiology. All rights reserved.

Parameters of bacterial killing and regrowth kinetics and antimicrobial effect examined in terms of area under the concentration-time curve relationships: action of ciprofloxacin against Escherichia coli in an in vitro dynamic model

AA Firsov, SN Vostrov, AA Shevchenko and G Cornaglia
Department of Pharmacokinetics, Centre of Science & Technology, LekBioTech, Moscow, Russia. Biotec@glas.apc.org

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 microg/ml) were studied in vitro by simulating a series of ciprofloxacin monoexponential pharmacokinetic profiles. Initial ciprofloxacin concentrations varied from 0.02 to 19.2 microg/ml, whereas the half-life of 4 h was the same in all experiments. The following parameters were calculated and estimated: the time to reduce the initial inoculum (N0) 10-, 100-, and 1,000-fold (T90%, T99%, and T99.9%, respectively), the rate constant of bacterial elimination (k(elb)), the nadir level (Nmin) in the viable count (N)- versus-time (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 under the 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 maximal values 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 AUC or initial concentration of ciprofloxacin rose. Other parameters, especially T90%, T99%, T99.9%, t(min), and log N0 - log Nmin = delta log Nmin, related to 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, may lead to the degeneration of the AUC-response relationships, as expressed by log N0 - log Ntau = delta log Ntau, AUBC, AAC, or ABBC, to a point 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 antimicrobial effect.


This article has been cited by other articles:

  • Smirnova, M. V., Vostrov, S. N., Strukova, E. V., Dovzhenko, S. A., Kobrin, M. B., Portnoy, Y. A., Zinner, S. H., Firsov, A. A. (2009). The impact of duration of antibiotic exposure on bacterial resistance predictions using in vitro dynamic models. J Antimicrob Chemother 64: 815-820 [Abstract] [Full Text]  
  • Firsov, A. A., Lubenko, I. Y., Smirnova, M. V., Strukova, E. N., Zinner, S. H. (2008). Enrichment of Fluoroquinolone-Resistant Staphylococcus aureus: Oscillating Ciprofloxacin Concentrations Simulated at the Upper and Lower Portions of the Mutant Selection Window. Antimicrob. Agents Chemother. 52: 1924-1928 [Abstract] [Full Text]  
  • Zinner, S. H., Gilbert, D., Lubenko, I. Yu., Greer, K., Firsov, A. A. (2008). Selection of linezolid-resistant Enterococcus faecium in an in vitro dynamic model: protective effect of doxycycline. J Antimicrob Chemother 61: 629-635 [Abstract] [Full Text]  
  • Firsov, A. A., Smirnova, M. V., Lubenko, I. Yu., Vostrov, S. N., Portnoy, Y. A., Zinner, S. H. (2006). Testing the mutant selection window hypothesis with Staphylococcus aureus exposed to daptomycin and vancomycin in an in vitro dynamic model. J Antimicrob Chemother 58: 1185-1192 [Abstract] [Full Text]  
  • Ba, B. B., Arpin, C., Vidaillac, C., Chausse, A., Saux, M.-C., Quentin, C. (2006). Activity of Gatifloxacin in an In Vitro Pharmacokinetic-Pharmacodynamic Model against Staphylococcus aureus Strains either Susceptible to Ciprofloxacin or Exhibiting Various Levels and Mechanisms of Ciprofloxacin Resistance.. Antimicrob. Agents Chemother. 50: 1931-1936 [Abstract] [Full Text]  
  • Firsov, A. A., Lubenko, I. Y., Vostrov, S. N., Portnoy, Y. A., Zinner, S. H. (2005). Antistaphylococcal Effect Related to the Area under the Curve/MIC Ratio in an In Vitro Dynamic Model: Predicted Breakpoints versus Clinically Achievable Values for Seven Fluoroquinolones. Antimicrob. Agents Chemother. 49: 2642-2647 [Abstract] [Full Text]  
  • Liu, Y. Q., Zhang, Y. Z., Gao, P. J. (2004). Novel Concentration-Killing Curve Method for Estimation of Bactericidal Potency of Antibiotics in an In Vitro Dynamic Model. Antimicrob. Agents Chemother. 48: 3884-3891 [Abstract] [Full Text]  
  • Ba, B. B., Feghali, H., Arpin, C., Saux, M.-C., Quentin, C. (2004). Activities of Ciprofloxacin and Moxifloxacin against Stenotrophomonas maltophilia and Emergence of Resistant Mutants in an In Vitro Pharmacokinetic-Pharmacodynamic Model. Antimicrob. Agents Chemother. 48: 946-953 [Abstract] [Full Text]  
  • Mueller, M., de la Pena, A., Derendorf, H. (2004). Issues in Pharmacokinetics and Pharmacodynamics of Anti-Infective Agents: Kill Curves versus MIC. Antimicrob. Agents Chemother. 48: 369-377 [Full Text]  
  • Schentag, J. J, Meagher, A. K, Forrest, A. (2003). Fluoroquinolone AUIC Break Points and the Link to Bacterial Killing Rates: Part 1: In Vitro and Animal Models. The Annals of Pharmacotherapy 37: 1287-1298 [Abstract] [Full Text]  
  • Zhanel, G. G, Noreddin, A. M (2003). Fluoroquinolone AUIC Break Points and the Link to Bacterial Killing Rates: In Vitro Models. The Annals of Pharmacotherapy 37: 1331-1334 [Full Text]  
  • Firsov, A. A., Vostrov, S. N., Lubenko, I. Y., Drlica, K., Portnoy, Y. A., Zinner, S. H. (2003). In Vitro Pharmacodynamic Evaluation of the Mutant Selection Window Hypothesis Using Four Fluoroquinolones against Staphylococcus aureus. Antimicrob. Agents Chemother. 47: 1604-1613 [Abstract] [Full Text]  
  • Firsov, A. A., Zinner, S. H., Vostrov, S. N., Portnoy, Y. A., Lubenko, I. Yu. (2002). AUC/MIC relationships to different endpoints of the antimicrobial effect: multiple-dose in vitro simulations with moxifloxacin and levofloxacin. J Antimicrob Chemother 50: 533-539 [Abstract] [Full Text]  
  • Firsov, A. A., Zinner, S. H., Vostrov, S. N., Kononenko, O. V., Portnoy, Y. A., Shustova, L. V., Kadenatsi, I. B. (2002). Comparative pharmacodynamics of azithromycin and roxithromycin with S. pyogenes and S. pneumoniae in a model that simulates in vitro pharmacokinetics in human tonsils. J Antimicrob Chemother 49: 113-119 [Abstract] [Full Text]  
  • Zinner, S. H., Firsov, A. A., Gilbert, D., Simmons, K., Lubenko, I. Yu. (2001). The pharmacodynamics of gatifloxacin and ciprofloxacin for pneumococci in an in vitro dynamic model: prediction of equiefficient doses. J Antimicrob Chemother 48: 821-826 [Abstract] [Full Text]  
  • Aviles, P., Falcoz, C., Guillen, M. J., San Roman, R., Gomez De Las Heras, F., Gargallo-Viola, D. (2001). Correlation between In Vitro and In Vivo Activities of GM 237354, a New Sordarin Derivative, against Candida albicans in an In Vitro Pharmacokinetic-Pharmacodynamic Model and Influence of Protein Binding. Antimicrob. Agents Chemother. 45: 2746-2754 [Abstract] [Full Text]  
  • Firsov, A. A., Lubenko, I. Y., Portnoy, Y. A., Zinner, S. H., Vostrov, S. N. (2001). Relationships of the Area under the Curve/MIC Ratio to Different Integral Endpoints of the Antimicrobial Effect: Gemifloxacin Pharmacodynamics in an In Vitro Dynamic Model. Antimicrob. Agents Chemother. 45: 927-931 [Abstract] [Full Text]  
  • Wright, D. H., Brown, G. H., Peterson, M. L., Rotschafer, J. C. (2000). Application of fluoroquinolone pharmacodynamics. J Antimicrob Chemother 46: 669-683 [Abstract] [Full Text]  
  • Firsov, A. A., Lubenko, I. Yu., Vostrov, S. N., Kononenko, O. V., Zinner, S. H., Portnoy, Y. A. (2000). Comparative pharmacodynamics of moxifloxacin and levofloxacin in an in vitro dynamic model: prediction of the equivalent AUC/MIC breakpoints and equiefficient doses. J Antimicrob Chemother 46: 725-732 [Abstract] [Full Text]  
  • MacGowan, A., Rogers, C., Bowker, K. (2000). The use of in vitro pharmacodynamic models of infection to optimize fluoroquinolone dosing regimens. J Antimicrob Chemother 46: 163-170 [Full Text]  
  • MacGowan, A., Rogers, C., Holt, H. A., Wootton, M., Bowker, K. (2000). Assessment of different antibacterial effect measures used in in vitro models of infection and subsequent use in pharmacodynamic correlations for moxifloxacin. J Antimicrob Chemother 46: 73-78 [Abstract] [Full Text]  
  • Vostrov, S. N., Kononenko, O. V., Lubenko, I. Y., Zinner, S. H., Firsov, A. A. (2000). Comparative Pharmacodynamics of Gatifloxacin and Ciprofloxacin in an In Vitro Dynamic Model: Prediction of Equiefficient Doses and the Breakpoints of the Area under the Curve/MIC Ratio. Antimicrob. Agents Chemother. 44: 879-884 [Abstract] [Full Text]  
  • Firsov, A. A., Vasilov, R. G., Vostrov, S. N., Kononenko, O. V., Lubenko, I. Yu., Zinner, S. H. (1999). Prediction of the antimicrobial effects of trovafloxacin and ciprofloxacin on staphylococci using an in-vitro dynamic model. J Antimicrob Chemother 43: 483-490 [Abstract] [Full Text]  
  • Firsov, A. A., Vostrov, S. N., Kononenko, O. V., Zinner, S. H., Portnoy, Y. A. (1999). 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. Antimicrob. Agents Chemother. 43: 498-502 [Abstract] [Full Text]  
  • MacGowan, A. P., Wootton, M., Holt, H. A. (1999). The antibacterial efficacy of levofloxacin and ciprofloxacin against Pseudomonas aeruginosaassessed by combining antibiotic exposure and bacterial susceptibility. J Antimicrob Chemother 43: 345-349 [Abstract] [Full Text]  
  • Firsov, A. A., Vostrov, S. N., Shevchenko, A. A., Portnoy, Y. A., Zinner, S. H. (1998). A New Approach to In Vitro Comparisons of Antibiotics in Dynamic Models: Equivalent Area under the Curve/MIC Breakpoints and Equiefficient Doses of Trovafloxacin and Ciprofloxacin against Bacteria of Similar Susceptibilities. Antimicrob. Agents Chemother. 42: 2841-2847 [Abstract] [Full Text]  
  • Firsov, A. A., Vostrov, S. N., Shevchenko, A. A., Zinner, S. H., Cornaglia, G., Portnoy, Y. A. (1998). MIC-Based Interspecies Prediction of the Antimicrobial Effects of Ciprofloxacin on Bacteria of Different Susceptibilities in an In Vitro Dynamic Model. Antimicrob. Agents Chemother. 42: 2848-2852 [Abstract] [Full Text]  
  • Prieto, J., Aguilar, L., Giménez, M. J., Toro, D., Gómez-Lus, M. L., Dal-Ré, R., Balcabao, I. P. (1998). In Vitro Activities of Co-Amoxiclav at Concentrations Achieved in Human Serum against the Resistant Subpopulation of Heteroresistant Staphylococcus aureus: a Controlled Study with Vancomycin. Antimicrob. Agents Chemother. 42: 1574-1577 [Abstract] [Full Text]  
  • Firsov, A. A., Shevchenko, A. A., Vostrov, S. N., Zinner, S. H. (1998). Inter- and Intraquinolone Predictors of Antimicrobial Effect in an In Vitro Dynamic Model: New Insight into a Widely Used Concept. Antimicrob. Agents Chemother. 42: 659-665 [Abstract] [Full Text]  


Copyright © 2009 by the American Society for Microbiology.   For an alternate route to Journals.ASM.org, visit: http://intl-journals.asm.org | More Info»