Affiliation:
1. Medical Department, SmithKline Beecham Pharmaceuticals, Madrid, Spain.
Abstract
The prediction of urine antibacterial activity from pharmacological and microbiological parameters was assessed by using experimental urine levels and urine bactericidal titers determined up to 72 h after a 400-mg single dose of two quinolones in a phase I study. The area under the bactericidal curve (AUBC) was accurately predicted for norfloxacin but significantly (P < 0.001) underestimated for rufloxacin (actual value was four times higher than the predicted value against Escherichia coli and two times higher against Staphylococcus aureus). In vitro susceptibility differences between the two strains predicted the ex vivo AUBC differences for norfloxacin but not for rufloxacin, where ex vivo differences were greater than expected. Urine bactericidal titers for up to 72 h were accurately predicted for norfloxacin against E. coli and S. aureus and for rufloxacin against S. aureus, but experimental activity for up to 48 h was four times higher (P < 0.001) than the predicted activity for rufloxacin against E. coli. In the case of norfloxacin, the duration of adequate urine antibacterial activity against S. aureus was overestimated. Inaccurate estimations of ex vivo antibacterial activity of a suspected active metabolite (as with rufloxacin) when an adequate cutoff is not established may have dosing implications.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Reference27 articles.
1. Acar J. F. and F. W. Goldstein. 1996. Disk susceptibility test p. 1-51. In V. Lorian (ed.) Antibiotics in laboratory medicine 4th ed. The Williams & Wilkins Co. Baltimore Md.
2. Ex vivo antibacterial properties of rufloxacin compared with those of norfloxacin in a study with healthy volunteers;Aguilar L.;Antimicrob. Agents Chemother.,1996
3. Barry A. L. 1991. Procedures and theoretical considerations for testing antimicrobial agents in agar media p. 1-16. In V. Lorian (ed.) Antibiotics in laboratory medicine 3rd ed. The Williams & Wilkins Co. Baltimore Md.
4. Comparative study with enoxacin and netilmicin in a pharmacodynamic model to determine importance of ratio of antibiotic peak concentration to MIC for bactericidal activity and emergence of resistance;Blaser J.;Antimicrob. Agents Chemother.,1987
5. Singledose rufloxacin versus 3-day norfloxacin treatment of uncomplicated cystitis: clinical evaluation and pharmacodynamic considerations;Del Río G.;Antimicrob. Agents Chemother.,1996
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