The clinical use of quinolones.

enoxacin and norfloxacin on inclusion development and infectivity. The MICs and MLCs of these drugs are compared in Table 1. There was considerable variation in the sensitivity of C. trachomatis to these quinolones, which may reflect their varying ability to penetrate eukaryotic cells. However, at effective concentrations, the action of each drug was lethal, i.e. infectivity was not affected by further incubation after withdrawal of the drug, so there was little or no difference between the MIC and MLC. Additional tests in vitro, summarized in Table 2, were carried out on ofloxacin, the most active of the quinolones tested against chlamydia. Exposure of infected monolayers for the first 24h of the cycle (when RB replication predominantly occurs) (schedule D) was almost as effective as exposure throughout one cycle (48h) or longer (96h) (schedules A and B), and little recovery occurred when monolayers were reincubated in drug-free medium for a further 72h (schedule E). AS might have been predicted, exposure of monolayers to ofloxacin for the second 24 h of the cycle (when maturation rather than replication of RBs occurs) had little effect (schedules F and G). An unexpected finding, however, was the dramatic reduction in infectivity which occurred after prolonged (72 h) exposure to ofloxacin after the majority of RB replication had taken place (schedule H). This suggested that ofloxacin was acting against some enzyme function which was essential for survival of non-replicating intracellular chlamydia. Such action may be particularly relevant for treatment of naturally occurring infections, which are frequently characterized by persistent quiescent infection (Oriel & Ridgway, 1982). These studies in vitro suggest that a quinolone active at concentrations which can be achieved in serum would act quickly against chlamydia, so that only a short course of treatment would be required (< 7 days). Of the drugs tested, ofloxacin (MLC 1 mg/l) appeared to have most therapeutic potential. This coincides with the findings of Table 2. Schedules in vitro used to investigate the effect of ojloxacin on infectivity of chlamydia-infected monolayers