In-vitro activity of azithromycin, erythromycin, ciprofloxacin and norfloxacin against Neisseria gonorrhoeae, Haemophilus ducreyi, and Chlamydia trachomatis

113

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 steadystate 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.Chlamydia trachomatis is an obligate intracellular bacterial parasite whose life cycle involves alternation between the infectious extracellular, metabolically inactive elementary body (EB) form and the intracellular, metabolically active reticulate body form; the latter is the vegetative growth stage of the organism. Depending on the specific serovar involved, human infection with C. trachomatis causes a variety of ocular, pulmonary, and genital diseases. Genital infection with chlamydial serovars D to K is considered to be of major public health importance, since C. trachomatis is the most common sexually transmitted bacterium worldwide (54). Further, acute urogenital infections can progress to persistent infection, which in turn may initiate a pathogenic process leading to chronic diseases, including pelvic inflammatory disease, ectopic pregnancy, tubal factor infertility, and chlamydia-induced arthritis (12, 53). Importantly, C. trachomatis has been shown to be fully viable and metabolically active in both the acute and chronic, persistent infection state. In acute infections, the bacterium can be recovered usually by standard laboratory culture. Chronic chlamydial infections are often characterized by culture negativity, although viability has...

Section: Discussionsupporting

confidence: 91%

“…For C. trachomatis, such in vitro susceptibility testing indicated good activity for ciprofloxacin (22,38,45,46,49). However, in clinical trials a high rate of treatment failure has been observed with this drug.…”

mentioning

confidence: 99%

Persistence ofChlamydia trachomatisIs Induced by Ciprofloxacin and Ofloxacin In Vitro

Dreses-Werringloer

Padubrin

Jürgens‐Saathoff

et al. 2000

113

“…2A). These results suggest that the MIC of AZI for 90% of chlamydia grown in cultured HeLa cells is 100 ng/ml and that AZI is about threefold less active than ERY, a finding that agrees well with previous estimates of chlamydial sensitivity to AZI (14,17 Figure 2B demonstrates that de novo protein synthesis in chlamydia was not inhibited if the inoculating EBs had been exposed previously to AZI (lanes 1 and 2). In contrast, when chlamydia were treated with AZI for 15 min at 18 hpi (at which time they are predominantly intracellular RBs), complete inhibition of de novo protein synthesis was observed (lane 3).…”

Section: Concentration Of Azi That Inhibitssupporting

confidence: 89%

Azithromycin-induced block of elementary body formation in Chlamydia trachomatis

Engel

1992

The mechanism of action of azithromycin on the murine strain of Chlamydia trachomatis grown in tissue culture epithelial cells is addressed. Azithromycin at a concentration of 100 ng/ml inhibits chlamydial growth in tissue culture, a value that agrees well with prior in vitro data from human strains of C. trachomatis grown in tissue culture. By morphological criteria, the block to chlamydial growth appears to occur early in its life cycle. Azithromycin is not directly toxic to chlamydial elementary bodies but does inhibit chlamydial protein synthesis in chlamydia-infected cells. This inhibition appears quite general in nature and is rapid. It is further shown that azithromycin does not directly inhibit mRNA synthesis. Azithromycin blocks chlamydial protein synthesis in host cell-free chlamydial reticulate bodies in a manner similar to its inhibition in infected cells, albeit at slightly higher concentrations. The inhibition of chlamydial protein synthesis following a brief exposure to azithromycin is more long lasting than that following a brief exposure to erythromycin.

“…Tetracyclines have been used frequently for chlamydial infections for many years, although they have some undesirable side effects. Recently, some new quinolones have been reported to have antichlamydial activity in vitro (1,7,9,16), and some of them have successfully been applied to chlamydial infections in humans (2,3). Sparfloxacin has been reported to have potent antichlamydial activity (10), but its position in antichlamydial chemotherapy remains uncertain because of the relatively few comparative data available.…”

mentioning

confidence: 99%

In vitro and in vivo activities of sparfloxacin, other quinolones, and tetracyclines against Chlamydia trachomatis

Nakata

Maeda

Fujii

et al. 1992