title: 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 (MIC(90)). 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 MIC(90)s 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 MIC(90)s of 0.06, 0.125, 0.25, and 0.5 microg/ml, respectively. In the simulation study of double-dosing of 200 mg cefixime at a 6-h interval, the therapeutic times for the MIC(90)s of < or =0.125 microg/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 MIC(90) of cefixime for the 61 isolates tested was 0.125 microg/ml. All strains with MICs of < or =0.06 microg/ml were eradicated, whereas 8 of 16 strains with MICs of > or =0.125 microg/ml persisted after treatment. This regimen would not be effective against infection by strains exhibiting cefixime MIC(90)s of > or =0.125 microg/ml. For such strains, a different regimen with a higher dose of cefixime would be required.
authors.affiliation: Department of Urology, Gifu University School of Medicine, 40 Tsukasa-machi, Gifu 500-8705, Japan. deguchit@cc.gifu-u.ac.jp
authors.forename: Takashi
authors.initials: T
authors.lastname: Deguchi
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Yasuda
authors.forename: Shigeaki
authors.initials: S
authors.lastname: Yokoi
authors.forename: Ken-Ichiro
authors.initials: K
authors.lastname: Ishida
authors.forename: Masayasu
authors.initials: M
authors.lastname: Ito
authors.forename: Satoshi
authors.initials: S
authors.lastname: Ishihara
authors.forename: Ken
authors.initials: K
authors.lastname: Minamidate
authors.forename: Yoshimasa
authors.initials: Y
authors.lastname: Harada
authors.forename: Kanhin
authors.initials: K
authors.lastname: Tei
authors.forename: Kentaro
authors.initials: K
authors.lastname: Kojima
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Tamaki
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Maeda
mesh_terms: D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D020682:Cefixime / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D004334:Drug Administration Schedule; D006069:Gonorrhea / Q000188:drug therapy / Q000382:microbiology; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D009344:Neisseria gonorrhoeae / Q000187:drug effects*; D016896:Treatment Outcome; D014526:Urethritis / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000900:Anti-Bacterial Agents; D020682:Cefixime