Characteristics of murine model of genital infection with Chlamydia trachomatis and effects of therapy with tetracyclines, amoxicillin-clavulanic acid, or azithromycin.
Following intravaginal inoculation of progesterone-treated outbred mice with Chlamydia trachomatis MoPn, 4 to 6 log10 inclusion-forming units were recovered in vaginal swabs for 21 days but all animals were culture negative after 28 days. Serum antibody titers were elevated and remained high for at least 70 days. Between 28 and 70 days, upper tract infection (inflammation and distension of the uterine horns, occlusion of oviducts with inflammatory exudate, pyosalpinx, and hydrosalpinx) was seen in > 80% of the animals. Mice were dosed orally, commencing at 7 days after infection, with minocycline, doxycycline, or amoxicillin-clavulanate. Further groups received azithromycin either as a single high dose or as lower once-daily doses. In addition, minocycline and amoxicillin-clavulanate were administered at 24 h after infection, and this early treatment prevented elevation of antibody titers whereas delayed therapy did not. Vaginal swabs from mice in all treatment regimens were culture negative except for 25% of mice receiving either early amoxicillin-clavulanate or low-dose azithromycin, which yielded low numbers (20 to 70 inclusion-forming units) of chlamydiae. Numbers of fertile mice in the early treatment regimens and their litter sizes were similar to those of noninfected controls, although 25% of amoxicillin-clavulanate-treated mice had unilateral hydrosalpinges. In comparison, 88% of untreated mice developed hydrosalpinges and only 25% conceived. Delayed dosing did not affect the outcome of amoxicillin-clavulanate therapy but did diminish the protective efficacy of minocycline such that 50% of treated mice had either unilateral hydrosalpinges or ovarian abscesses. Doxycycline and azithromycin were highly effective in restoring fertility. This model makes possible the study of both short- and long-term outcomes of chlamydial infection.
Beale
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SmithKline Beecham Pharmaceuticals, Brockham Park, Betchworth, Surrey, United Kingdom.
Upshon
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PA
D000658:Amoxicillin / Q000627:therapeutic use; D019980:Amoxicillin-Potassium Clavulanate Combination; D000818:Animals; D017963:Azithromycin / Q000627:therapeutic use*; D002690:Chlamydia Infections / Q000188:drug therapy* / Q000503:physiopathology; D002692:Chlamydia trachomatis / Q000187:drug effects*; D002969:Clavulanic Acids / Q000627:therapeutic use; D004195:Disease Models, Animal; D004318:Doxycycline / Q000627:therapeutic use*; D004359:Drug Therapy, Combination / Q000627:therapeutic use*; D005260:Female; D005298:Fertility / Q000187:drug effects; D005831:Genital Diseases, Female / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D008826:Microbial Sensitivity Tests; D008911:Minocycline / Q000627:therapeutic use*; D011374:Progesterone / Q000494:pharmacology; D013997:Time Factors; D014621:Vagina / Q000382:microbiology
D002969:Clavulanic Acids; D011374:Progesterone; D019980:Amoxicillin-Potassium Clavulanate Combination; D000658:Amoxicillin; D017963:Azithromycin; D008911:Minocycline; D004318:Doxycycline