This Article
Right arrow Full Text
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 Portnoy, Y. A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Firsov, A. A.
Right arrow Articles by Portnoy, Y. A.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, March 1999, p. 498-502, Vol. 43, No. 3
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.

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

Alexander A. Firsov,1,* Sergey N. Vostrov,1 Olga V. Kononenko,1 Stephen H. Zinner,2 and Yury A. Portnoy1

Department of Pharmacokinetics, Center for Science and Technology LekBioTech, Moscow 117246, Russia,1 and Division of Infectious Diseases, Roger Williams Medical Center, Rhode Island Hospital, Brown University, Providence, Rhode Island2

Received 6 March 1998/Returned for modification 30 September 1998/Accepted 17 December 1998

The effect of inoculum size (N0) on antimicrobial action has not been extensively studied in in vitro dynamic models. To investigate this effect and its predictability, killing and regrowth kinetics of Staphylococcus aureus and Escherichia coli exposed to monoexponentially decreasing concentrations of trovafloxacin (as a single dose) and ciprofloxacin (two doses at a 12-h interval) were compared at N0 = 106 and 109 CFU/ml (S. aureus) and at N0 = 106, 107, and 109 CFU/ml (E. coli). A series of pharmacokinetic profiles of trovafloxacin and ciprofloxacin with respective half-lives of 9.2 and 4 h were simulated at different ratios of area under the concentration-time curve (AUC) to MIC (in [micrograms × hours/milliliter]/[micrograms/milliliter]): 58 to 466 with trovafloxacin and 116 to 932 with ciprofloxacin for 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 of the N0 for both organisms. The N0-induced reductions of the intensity of the antimicrobial effect (IE, area between control growth and the killing-regrowth curves) were also relatively small. However, the N0 effect could not be eliminated either by simple shifting of the time-kill curves obtained at higher N0s by the difference between the higher and lowest N0 or by operating with IEs determined within the N0-adopted 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 for both trovafloxacin and ciprofloxacin against each of the strains (r2 = 0.97 to 0.99). The antimicrobial effect may be accurately predicted at a given AUC/MIC of trovafloxacin or ciprofloxacin and at 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 relative impacts of AUC/MIC and N0 on IE may be evaluated. Since the c/b 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 the beta -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.

* Corresponding author. Mailing address: Department of Pharmacokinetics, Center for Science and Technology LekBioTech, 8 Nauchny proezd, Moscow 117246, Russia. Phone: 011-7-095-332-3435. Fax: 011-7-095-331-4116. E-mail: firsov{at}dol.ru.

Antimicrobial Agents and Chemotherapy, March 1999, p. 498-502, Vol. 43, No. 3
0066-4804/99/$04.00+0
Copyright © 1999, American Society for Microbiology. All rights reserved.


This article has been cited by other articles:

  • Launay, E., Joram, N., Jacqueline, C., Miegeville, A. F., Caillon, J., Potel, G., Roze, J. C., Gras-Le Guen, C. (2009). Efficacy of Ciprofloxacin in an Experimental Model of Escherichia coli Chorioamnionitis in Rabbits. Antimicrob. Agents Chemother. 53: 1624-1627 [Abstract] [Full Text]  
  • Ferran, A., Dupouy, V., Toutain, P.-L., Bousquet-Melou, A. (2007). Influence of Inoculum Size on the Selection of Resistant Mutants of Escherichia coli in Relation to Mutant Prevention Concentrations of Marbofloxacin. Antimicrob. Agents Chemother. 51: 4163-4166 [Abstract] [Full Text]  
  • Wiuff, C., Zappala, R. M., Regoes, R. R., Garner, K. N., Baquero, F., Levin, B. R. (2005). Phenotypic Tolerance: Antibiotic Enrichment of Noninherited Resistance in Bacterial Populations. Antimicrob. Agents Chemother. 49: 1483-1494 [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]  
  • 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]  
  • MacGowan, A. P., Rogers, C. A., Holt, H. A., Bowker, K. E. (2003). Activities of Moxifloxacin against, and Emergence of Resistance in, Streptococcus pneumoniae and Pseudomonas aeruginosa in an In Vitro Pharmacokinetic Model. Antimicrob. Agents Chemother. 47: 1088-1095 [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»