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Treatment of uncomplicated gonococcal urethritis by double-dosing of 200 mg cefixime at a 6-h interval

Abstract

 The efficacy of antimicrobial regimens for the treatment of uncomplicated gonococcal urethritis depends partially upon the period of time (therapeutic time) during which the drug concentration in the blood after the concentration peak is greater than four times the minimum inhibitory concentration for 90% of clinical isolates of Neisseria gonorrhoeae (MIC90). A therapeutic time of at least 10 h is suggested as an important determinant for elimination of 95% or more of the infection. In this study, therapeutic times for a single 400-mg dose of cefixime at various MIC90s were calculated, and pharmacokinetic profiles of double-dosing of 200 mg cefixime at various intervals were simulated. Subsequently, a dosing interval of 6 h was tested in 6 healthy Japanese men, and then 93 Japanese men with gonococcal urethritis were treated with a regimen of two 200-mg doses of cefixime given at a 6-h interval. For a single dose of 400 mg cefixime, therapeutic times were calculated to be 12.8, 9.1, 5.4, and 1.7 h for MIC90s of 0.06, 0.125, 0.25, and 0.5 μg/ml, respectively. In the simulation study of double-dosing of 200 mg cefixime at a 6-h interval, the therapeutic times for the MIC90s of ≤0.125 μg/ml were longer than 10 h. Of the 93 patients, 68 were evaluated for microbiological outcome, and N. gonorrhoeae was eradicated in 60 (88.2%). The MIC90 of cefixime for the 61 isolates tested was 0.125 μg/ml. All strains with MICs of ≤0.06 μg/ml were eradicated, whereas 8 of 16 strains with MICs of ≥0.125 μg/ml persisted after treatment. This regimen would not be effective against infection by strains exhibiting cefixime MIC90s of ≥0.125 μg/ml. For such strains, a different regimen with a higher dose of cefixime would be required.

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Received: July 10, 2002 / Accepted: September 21, 2002

Acknowledgments We thank Kohji Ishibashi and Kohji Takeshita, at Fujisawa Pharmaceutical Co., Ltd., for pharmacokinetic analyses.

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Deguchi, T., Yasuda, M., Yokoi, S. et al. Treatment of uncomplicated gonococcal urethritis by double-dosing of 200 mg cefixime at a 6-h interval. J Infect Chemother 9, 35–39 (2003). https://doi.org/10.1007/s10156-002-0204-8

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  • DOI: https://doi.org/10.1007/s10156-002-0204-8

  • Key words Gonococcal urethritis
  • Cefixime
  • Pharmacokinetics