Abstract
Two beta-lactam antibiotics, cefazolin and cefmenoxime, were administered for 7 days to mice with pneumonia caused by Klebsiella pneumoniae by using dosage regimens that would simulate multiple dosing in usual clinical treatments at dosing intervals of 8 or 12 h. Viable numbers of the bacteria in the lungs were measured at 12- or 24-h intervals. The mathematical model established in a previous single-dose study was applied in this study to explain the time courses of the changes in bacterial count over 7 days. However, because the error in viable count measurements was larger than that in the previous study, the time course of the changes in mean viable count was not regular and the viable count reduction rate changed during multiple dosing, and therefore it was difficult to explain the time course by repeated application of the mathematical model described previously. This study suggests that the changes in pharmacokinetic and pharmacodynamic parameters during multiple dosing need to be considered.
Full text
PDF
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Coonrod J. D. The role of extracellular bactericidal factors in pulmonary host defense. Semin Respir Infect. 1986 Jun;1(2):118–129. [PubMed] [Google Scholar]
- Drusano G. L. Role of pharmacokinetics in the outcome of infections. Antimicrob Agents Chemother. 1988 Mar;32(3):289–297. doi: 10.1128/aac.32.3.289. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hishikawa T., Kusunoki T., Tsuchiya K., Uzuka Y., Sakamoto T., Nagatake T., Matsumoto K. Application of mathematical model to experimental chemotherapy of fatal murine pneumonia. Antimicrob Agents Chemother. 1990 Feb;34(2):326–331. doi: 10.1128/aac.34.2.326. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Leggett J. E., Fantin B., Ebert S., Totsuka K., Vogelman B., Calame W., Mattie H., Craig W. A. Comparative antibiotic dose-effect relations at several dosing intervals in murine pneumonitis and thigh-infection models. J Infect Dis. 1989 Feb;159(2):281–292. doi: 10.1093/infdis/159.2.281. [DOI] [PubMed] [Google Scholar]
- McDonald P. J., Craig W. A., Kunin C. M. Persistent effect of antibiotics on Staphylococcus aureus after exposure for limited periods of time. J Infect Dis. 1977 Feb;135(2):217–223. doi: 10.1093/infdis/135.2.217. [DOI] [PubMed] [Google Scholar]
- Roosendaal R., Bakker-Woudenberg I. A., van den Berg J. C., Michel M. F. Therapeutic efficacy of continuous versus intermittent administration of ceftazidime in an experimental Klebsiella pneumoniae pneumonia in rats. J Infect Dis. 1985 Aug;152(2):373–378. doi: 10.1093/infdis/152.2.373. [DOI] [PubMed] [Google Scholar]
- Tuomanen E., Durack D. T., Tomasz A. Antibiotic tolerance among clinical isolates of bacteria. Antimicrob Agents Chemother. 1986 Oct;30(4):521–527. doi: 10.1128/aac.30.4.521. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Vogelman B., Gudmundsson S., Leggett J., Turnidge J., Ebert S., Craig W. A. Correlation of antimicrobial pharmacokinetic parameters with therapeutic efficacy in an animal model. J Infect Dis. 1988 Oct;158(4):831–847. doi: 10.1093/infdis/158.4.831. [DOI] [PubMed] [Google Scholar]