Persistence of Chlamydia trachomatis is induced by ciprofloxacin and ofloxacin in vitro

An in vitro cell culture model was used to investigate the long-term effect of ciprofloxacin and ofloxacin on infection with Chlamydia trachomatis. St andard in vitro susceptibility testing clearly indicated successful suppres sion of chlamydial growth. To mimic better in vivo infection conditions, ex tended treatment with the drugs was started after infection in vitro had be en well established. Incubation of such established chlamydial cultures wit h ciprofloxacin and ofloxacin not only failed to eradicate the organism fro m host cells, but rather induced a state of chlamydial persistence. This st ate was characterized by the presence of nonculturable, but fully viable, b acteria and the development of aberrant inclusions. In addition chlamydia e xhibited altered steady-state levels of key chlamydial antigens, with signi ficantly reduced major outer membrane protein and near constant hsp60 level s. Resumption of overt chlamydial growth occurred after withdrawal of cipro floxacin, confirming the viability of persisting chlamydia. In vitro ciprof loxacin results are consistent with clinical data, thereby providing an exp lanation for treatment failures of ciprofloxacin. Parallel in vitro studies with ofloxacin suggest a better correlation between clinical and laborator y-defined efficacy, although the clinical studies on which this assessment is based did not include monitoring of chlamydial persistence. The data pre sented here clearly demonstrate that under at least some circumstances, sta ndard determination of MICs and minimal bactericidal concentrations for C. trachomatis allows no more than a simple definition of whether an antibioti c has some anti chlamydial activity; however, such testing is not always su fficient to verify that the antibiotic will eliminate the organism in vivo.