Skip to main content
PMC home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1997 May;41(5):927–930. doi: 10.1128/aac.41.5.927

Suspicion of quinolone active metabolite following discrepancy between predicted and experimental urine bactericidal activities.

L Aguilar 1, M J Giménez 1, J Costa 1, R Dal-Ré 1, J Prieto 1
PMCID: PMC163827  PMID: 9145846

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.

Full Text

The Full Text of this article is available as a PDF (218.3 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aguilar L., Balcabao I. P., Salvá P., Martín M., Costa J., Prieto J., Dal-ré R. Ex vivo antibacterial properties of rufloxacin compared with those of norfloxacin in a study with healthy volunteers. Antimicrob Agents Chemother. 1996 Jan;40(1):17–21. doi: 10.1128/aac.40.1.17. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bergeron M. G., Bernier M., L'Ecuyer J. In vitro activity of clarithromycin and its 14-hydroxy-metabolite against 203 strains of Haemophilus influenzae. Infection. 1992 May-Jun;20(3):164–167. doi: 10.1007/BF01704612. [DOI] [PubMed] [Google Scholar]
  3. Blaser J., Stone B. B., Groner M. C., Zinner S. H. 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. Antimicrob Agents Chemother. 1987 Jul;31(7):1054–1060. doi: 10.1128/aac.31.7.1054. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Del Río G., Dalet F., Aguilar L., Caffaratti J., Dal-Ré R. Single-dose rufloxacin versus 3-day norfloxacin treatment of uncomplicated cystitis: clinical evaluation and pharmacodynamic considerations. Antimicrob Agents Chemother. 1996 Feb;40(2):408–412. doi: 10.1128/aac.40.2.408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. Drusano G., Standiford H., Ryan P., McNamee W., Tatem B., Schimpff S. Correlation of predicted serum bactericidal activities and values measured in volunteers. Eur J Clin Microbiol. 1986 Feb;5(1):88–92. doi: 10.1007/BF02013475. [DOI] [PubMed] [Google Scholar]
  7. Kisicki J. C., Griess R. S., Ott C. L., Cohen G. M., McCormack R. J., Troetel W. M., Imbimbo B. P. Multiple-dose pharmacokinetics and safety of rufloxacin in normal volunteers. Antimicrob Agents Chemother. 1992 Jun;36(6):1296–1301. doi: 10.1128/aac.36.6.1296. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Klastersky J., Daneau D., Swings G., Weerts D. Antibacterial activity in serum and urine as a therapeutic guide in bacterial infections. J Infect Dis. 1974 Feb;129(2):187–193. doi: 10.1093/infdis/129.2.187. [DOI] [PubMed] [Google Scholar]
  9. Kowalsky S. F., Echols R. M., McCormick E. M. Comparative serum bactericidal activity of ceftizoxime/metronidazole, ceftizoxime, clindamycin, and imipenem against obligate anaerobic bacteria. J Antimicrob Chemother. 1990 May;25(5):767–775. doi: 10.1093/jac/25.5.767. [DOI] [PubMed] [Google Scholar]
  10. Norrby S. R. Short-term treatment of uncomplicated lower urinary tract infections in women. Rev Infect Dis. 1990 May-Jun;12(3):458–467. doi: 10.1093/clinids/12.3.458. [DOI] [PubMed] [Google Scholar]
  11. Rubin R. H., Shapiro E. D., Andriole V. T., Davis R. J., Stamm W. E. Evaluation of new anti-infective drugs for the treatment of urinary tract infection. Infectious Diseases Society of America and the Food and Drug Administration. Clin Infect Dis. 1992 Nov;15 (Suppl 1):S216–S227. doi: 10.1093/clind/15.supplement_1.s216. [DOI] [PubMed] [Google Scholar]
  12. Saginur R., Nicolle L. E. Single-dose compared with 3-day norfloxacin treatment of uncomplicated urinary tract infection in women. Canadian Infectious Diseases Society Clinical Trials Study Group. Arch Intern Med. 1992 Jun;152(6):1233–1237. [PubMed] [Google Scholar]
  13. Shumaker R. C. PKCALC: a BASIC interactive computer program for statistical and pharmacokinetic analysis of data. Drug Metab Rev. 1986;17(3-4):331–348. doi: 10.3109/03602538608998295. [DOI] [PubMed] [Google Scholar]
  14. Stamey T. A., Fair W. R., Timothy M. M., Millar M. A., Mihara G., Lowery Y. C. Serum versus urinary antimicrobial concentrations in cure of urinary-tract infections. N Engl J Med. 1974 Nov 28;291(22):1159–1163. doi: 10.1056/NEJM197411282912204. [DOI] [PubMed] [Google Scholar]
  15. Trautmann M., Ruhnke M., Borner K., Wagner J., Koeppe P. Pharmacokinetics of sparfloxacin and serum bactericidal activity against pneumococci. Antimicrob Agents Chemother. 1996 Mar;40(3):776–779. doi: 10.1128/aac.40.3.776. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Wise R., Andrews J. M., Matthews R., Wolstenholme M. The in-vitro activity of two new quinolones: rufloxacin and MF 961. J Antimicrob Chemother. 1992 Jun;29(6):649–660. doi: 10.1093/jac/29.6.649. [DOI] [PubMed] [Google Scholar]
  17. Zeiler H. J., Beermann D., Wingender W., Förster D., Schacht P. Bactericidal activity of ciprofloxacin, norfloxacin and ofloxacin in serum and urine after oral administration to healthy volunteers. Infection. 1988;16 (Suppl 1):S19–S23. doi: 10.1007/BF01650502. [DOI] [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES