Effects of quinolone analog CI-960 in a monkey model of Chlamydia trachomatis salpingitis

Several quinolones have been shown to have antichlamydial activity in vitro and in vivo. We evaluated the effects of the quinolone CI-960 (Parke-Davis) on primary or repeated chlamydial infection in the monkey salpinx pocket model. The antichlamydial effect was evaluated in the tissues, and we tested for the presence of the organism by culture, immunocytochemical stains, in situ hybridization, and histopathology. An intravenous dosage of 5 mg/kg of body weight produced therapeutic concentrations in plasma (blood sera and pocket fluids) of at least 0.25 microgram/ml at 2 h posttreatment. In monkeys with primary infections, treatment was started 2 days after inoculation and was continued for 7 days. After CI-960 treatment, all animals became culture negative. One of two control animals was culture positive through day 10 postinoculation. In monkeys with repeated infections five inoculations were given within 2 weeks. A 7-day intravenous treatment was started on day 2 postinoculation following the last inoculation. Isolation of Chlamydia trachomatis prior to treatment was positive intermittently for all monkeys. After treatment, isolation of C. trachomatis was negative for all monkeys. In monkeys with both primary and repeated infections, no significant differences were noted in the inflammatory responses in the tissues of treated and untreated animals. All tissues tested were positive by immunoperoxidase staining and/or in situ hybridization. After CI-960 therapy, C. trachomatis organisms were no longer recoverable by cell culture. The persistent finding of chlamydial DNA throughout the observation periods following drug therapy may indicate the presence of dead organisms or viable organisms in an unculturable state.