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Antimicrobial Agents and Chemotherapy, December 2000, p. 3288-3297, Vol. 44, No. 12
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.

Persistence of Chlamydia trachomatis Is Induced by Ciprofloxacin and Ofloxacin In Vitro

Ute Dreses-Werringloer,1 Ingrid Padubrin,1 Barbara Jürgens-Saathoff,1 Alan P. Hudson,2 H. Zeidler,1 and L. Köhler1,*

Department of Rheumatology, Hannover Medical School, Hannover, Germany,1 and Department of Immunology and Microbiology, Wayne State University School of Medicine, Detroit, Michigan 492012

Received 29 November 1999/Returned for modification 18 June 2000/Accepted 28 August 2000

An in vitro cell culture model was used to investigate the long-term effect of ciprofloxacin and ofloxacin on infection with Chlamydia trachomatis. Standard in vitro susceptibility testing clearly indicated successful suppression of chlamydial growth. To mimic better in vivo infection conditions, extended treatment with the drugs was started after infection in vitro had been well established. Incubation of such established chlamydial cultures with ciprofloxacin and ofloxacin not only failed to eradicate the organism from host cells, but rather induced a state of chlamydial persistence. This state was characterized by the presence of nonculturable, but fully viable, bacteria and the development of aberrant inclusions. In addition chlamydia exhibited altered steady-state levels of key chlamydial antigens, with significantly reduced major outer membrane protein and near constant hsp60 levels. Resumption of overt chlamydial growth occurred after withdrawal of ciprofloxacin, confirming the viability of persisting chlamydia. In vitro ciprofloxacin results are consistent with clinical data, thereby providing an explanation for treatment failures of ciprofloxacin. Parallel in vitro studies with ofloxacin suggest a better correlation between clinical and laboratory-defined efficacy, although the clinical studies on which this assessment is based did not include monitoring of chlamydial persistence. The data presented here clearly demonstrate that under at least some circumstances, standard determination of MICs and minimal bactericidal concentrations for C. trachomatis allows no more than a simple definition of whether an antibiotic has some anti chlamydial activity; however, such testing is not always sufficient to verify that the antibiotic will eliminate the organism in vivo.

* Corresponding author. Mailing address: Department of Rheumatology, Medical School Hannover, Carl-Neuberg-Strasse 1, 30625 Hannover, Germany. Phone: 49/511-5322319. Fax: 49/511-5325841. E-mail: Koehler.Lars{at}mh-hannover.de.

Antimicrobial Agents and Chemotherapy, December 2000, p. 3288-3297, Vol. 44, No. 12
0066-4804/00/$04.00+0
Copyright © 2000, American Society for Microbiology. All rights reserved.


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