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 Mouton, J. W.
Right arrow Articles by Punt, N. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mouton, J. W.
Right arrow Articles by Punt, N. C.

 Previous Article  |  Next Article 

Antimicrobial Agents and Chemotherapy, Apr 1997, 733-738, Vol 41, No. 4
Copyright © 1997 by the American Society for Microbiology. All rights reserved.

Pharmacokinetic-pharmacodynamic modeling of activity of ceftazidime during continuous and intermittent infusion

JW Mouton, AA Vinks and NC Punt
Department of Medical Microbiology & Infectious Diseases, Erasmus University Hospital Rotterdam, The Netherlands. Mouton@bacl.azr.nl

We developed and applied pharmacokinetic-pharmacodynamic (PK-PD) models to characterize in vitro bacterial rate of killing as a function of ceftazidime concentrations over time. For PK-PD modeling, data obtained during continuous and intermittent infusion of ceftazidime in Pseudomonas aeruginosa killing experiments with an in vitro pharmacokinetic model were used. The basic PK-PD model was a maximum- effect model which described the number of viable bacteria (N) as a function of the growth rate (lambda) and killing rate (epsilon) according to the equation dN/dt = [lambda - epsilon x [Cgamma(EC50gamma + Cgamma)]] N, where gamma is the Hill factor, C is the concentration of antibiotic, and EC50 is the concentration of antibiotic at which 50% of the maximum effect is obtained. Next, four different models with increasing complexity were analyzed by using the EDSIM program (MediWare, Groningen, The Netherlands). These models incorporated either an adaptation rate factor and a maximum number of bacteria (Nmax) factor or combinations of the two parameters. In addition, a two- population model was evaluated. Model discrimination was by Akaike's information criterion. The experimental data were best described by the model which included an Nmax term and a rate term for adaptation for a period up to 36 h. The absolute values for maximal growth rate and killing rate in this model were different from those in the original experiment, but net growth rates were comparable. It is concluded that the derived models can describe bacterial growth and killing in the presence of antibiotic concentrations mimicking human pharmacokinetics. Application of these models will eventually provide us with parameters which can be used for further dosage optimization.


This article has been cited by other articles:

  • Bulitta, J. B., Ly, N. S., Yang, J. C., Forrest, A., Jusko, W. J., Tsuji, B. T. (2009). Development and Qualification of a Pharmacodynamic Model for the Pronounced Inoculum Effect of Ceftazidime against Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 53: 46-56 [Abstract] [Full Text]  
  • Venisse, N., Gregoire, N., Marliat, M., Couet, W. (2008). Mechanism-Based Pharmacokinetic-Pharmacodynamic Models of In Vitro Fungistatic and Fungicidal Effects against Candida albicans. Antimicrob. Agents Chemother. 52: 937-943 [Abstract] [Full Text]  
  • De Jongh, R., Hens, R., Basma, V., Mouton, J. W., Tulkens, P. M., Carryn, S. (2008). Continuous versus intermittent infusion of temocillin, a directed spectrum penicillin for intensive care patients with nosocomial pneumonia: stability, compatibility, population pharmacokinetic studies and breakpoint selection. J Antimicrob Chemother 61: 382-388 [Abstract] [Full Text]  
  • Mouton, J. W., Punt, N., Vinks, A. A. (2007). Concentration-Effect Relationship of Ceftazidime Explains Why the Time above the MIC Is 40 Percent for a Static Effect In Vivo. Antimicrob. Agents Chemother. 51: 3449-3451 [Abstract] [Full Text]  
  • Roberts, J. A., Boots, R., Rickard, C. M., Thomas, P., Quinn, J., Roberts, D. M., Richards, B., Lipman, J. (2007). Is continuous infusion ceftriaxone better than once-a-day dosing in intensive care? A randomized controlled pilot study. J Antimicrob Chemother 59: 285-291 [Abstract] [Full Text]  
  • Nielsen, E. I., Viberg, A., Lowdin, E., Cars, O., Karlsson, M. O., Sandstrom, M. (2007). Semimechanistic Pharmacokinetic/Pharmacodynamic Model for Assessment of Activity of Antibacterial Agents from Time-Kill Curve Experiments. Antimicrob. Agents Chemother. 51: 128-136 [Abstract] [Full Text]  
  • Bull, J. J, Regoes, R. R (2006). Pharmacodynamics of non-replicating viruses, bacteriocins and lysins. Proc R Soc B 273: 2703-2712 [Abstract] [Full Text]  
  • Chung, P., McNamara, P. J., Campion, J. J., Evans, M. E. (2006). Mechanism-Based Pharmacodynamic Models of Fluoroquinolone Resistance in Staphylococcus aureus.. Antimicrob. Agents Chemother. 50: 2957-2965 [Abstract] [Full Text]  
  • Olofsson, S. K., Geli, P., Andersson, D. I., Cars, O. (2005). Pharmacodynamic Model To Describe the Concentration-Dependent Selection of Cefotaxime-Resistant Escherichia coli. Antimicrob. Agents Chemother. 49: 5081-5091 [Abstract] [Full Text]  
  • Campion, J. J., Chung, P., McNamara, P. J., Titlow, W. B., Evans, M. E. (2005). Pharmacodynamic Modeling of the Evolution of Levofloxacin Resistance in Staphylococcus aureus. Antimicrob. Agents Chemother. 49: 2189-2199 [Abstract] [Full Text]  
  • Tam, V. H., Schilling, A. N., Nikolaou, M. (2005). Modelling time-kill studies to discern the pharmacodynamics of meropenem. J Antimicrob Chemother 55: 699-706 [Abstract] [Full Text]  
  • Campion, J. J., McNamara, P. J., Evans, M. E. (2005). Pharmacodynamic Modeling of Ciprofloxacin Resistance in Staphylococcus aureus. Antimicrob. Agents Chemother. 49: 209-219 [Abstract] [Full Text]  
  • Regoes, R. R., Wiuff, C., Zappala, R. M., Garner, K. N., Baquero, F., Levin, B. R. (2004). Pharmacodynamic Functions: a Multiparameter Approach to the Design of Antibiotic Treatment Regimens. Antimicrob. Agents Chemother. 48: 3670-3676 [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]  
  • Mager, D. E., Wyska, E., Jusko, W. J. (2003). Diversity of Mechanism-Based Pharmacodynamic Models. Drug Metab. Dispos. 31: 510-518 [Abstract] [Full Text]  
  • Traunmuller, F., Schenk, P., Mittermeyer, C., Thalhammer-Scherrer, R., Ratheiser, K., Thalhammer, F. (2002). Clearance of ceftazidime during continuous venovenous haemofiltration in critically ill patients. J Antimicrob Chemother 49: 129-134 [Abstract] [Full Text]  
  • Robaux, M.-A., Dube, L., Caillon, J., Bugnon, D., Kergueris, M.-F., Navas, D., Le Conte, P., Baron, D., Potel, G. (2001). In vivo efficacy of continuous infusion versus intermittent dosing of ceftazidime alone or in combination with amikacin relative to human kinetic profiles in a Pseudomonas aeruginosa rabbit endocarditis model. J Antimicrob Chemother 47: 617-622 [Abstract] [Full Text]  
  • Aviles, P., Falcoz, C., San Roman, R., Gargallo-Viola, D. (2000). Pharmacokinetics-Pharmacodynamics of a Sordarin Derivative (GM 237354) in a Murine Model of Lethal Candidiasis. Antimicrob. Agents Chemother. 44: 2333-2340 [Abstract] [Full Text]  
  • Aviles, P., Aliouat, E.-M., Martinez, A., Dei-Cas, E., Herreros, E., Dujardin, L., Gargallo-Viola, D. (2000). In Vitro Pharmacodynamic Parameters of Sordarin Derivatives in Comparison with Those of Marketed Compounds against Pneumocystis carinii Isolated from Rats. Antimicrob. Agents Chemother. 44: 1284-1290 [Abstract] [Full Text]  
  • Thalhammer, F., Traunmuller, F., El Menyawi, I., Frass, M., Hollenstein, U. M., Locker, G. J., Stoiser, B., Staudinger, T., Thalhammer-Scherrer, R., Burgmann, H. (1999). Continuous infusion versus intermittent administration of meropenem in critically ill patients. J Antimicrob Chemother 43: 523-527 [Abstract] [Full Text]  
  • Lipman, J., Gomersall, C. D., Gin, T., Joynt, G. M., Young, R. J. (1999). Continuous infusion ceftazidime in intensive care: a randomized controlled trial. J Antimicrob Chemother 43: 309-311 [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»