Infections caused by the obligate intracellular bacteriumChlamydia trachomatis are among the most prevalent causes of ocular and urogenital diseases worldwide. Clinical manifestations of acute infections related to C. trachomatis serovars A to C or serovars D to K are trachoma or cervicitis and urethritis, respectively. These infections can progress to persistent infections, which may initiate a pathogenic process that leads to chronic diseases including blindness or pelvic inflammatory disease, ectopic pregnancy, tubal factor infertility, and chlamydia-induced arthritis, including Reiter's syndrome.Standard therapy for acute urogenital tract infections is a 7-day course of doxycycline or a single dose of azithomycin. Both regimens have been shown to result in satisfactory cure rates in clinical trials (20,21,32,34,40,43,49).Relapsing chlamydial infections are, however, a common problem, even though patients are often treated appropriately (6, 24, 56). Usually, recurrent infections are supposed to be a consequence of reinfection. Most of the clinical trials that have addressed relapsing chlamydial infections did not distinguish between reinfection and relapse and thus did not define the role of persistence. There are, however, recent reports of recurrent infections after appropriate antibiotic treatment which appeared to be a result of the persistence of chlamydia (15,25,38).This observation presents an apparent contradiction to results of determination of the MIC and the minimum bactericidal concentration (MBC), which clearly indicated successful suppression of chlamydial growth by clinically used antibiotics. The experimental setting involved with this kind of in vitro testing is, however, not truly reflective of the situation in vivo for chlamydial infection. In natural infections, chlamydia are usually exposed to antimicrobials long after an infection has been well established. In contrast, the conventional in vitro systems used for susceptibility testing represent a quite different condition, in that antibiotics are added usually 48 h after the infectious agent is added or are sometimes added simultaneously with the infectious agent. Recently, we could demonstrate that ciprofloxacin and ofloxacin not only failed to eradicate chlamydia from host cells but induced a persistent infection, although both antibiotics are efficient in susceptibility testing (16). Using this in vitro model, we investigated the efficacies of azithromycin, rifampin, and the combination of azithromycin and rifampin for the elimination of chlamydia from epithelial cells.
MATERIALS AND METHODSCells. Cells of the HEp-2 cells line, a human laryngeal epidermoid cell line, were maintained at 37°C with 5% CO 2 in RPMI 1640 medium supplemented with 10% fetal calf serum (Seromed, Berlin, Germany), 1% L-glutamine, and 100 g of gentamicin (Seromed) per ml.Growth, purification, and titration of chlamydia. C. trachomatis serovar K/UW-31/Cx (obtained from the Washington Research Foundation, Seattle) was cultured in HEp-2 cells, as described recentl...