Multiple Drug–ResistantChlamydia trachomatisAssociated with Clinical Treatment Failure

Abstract

In vitro susceptibility testing and genotyping were done on urogenital isolates of Chlamydia trachomatis from 3 patients, 2 of whom showed evidence of clinical treatment failure with azithromycin and one of whom was the wife of a patient. All 3 isolates demonstrated multidrug resistance to doxycycline, azithromycin, and ofloxacin at concentrations >4.0 microg/mL. Recurrent disease due to relapsing infection with the same resistant isolate was documented on the basis of identical genotypes of both organisms. This first report of clinically significant multidrug-resistant C. trachomatis causing relapsing or persistent infection may portend an emerging problem to clinicians and public health officials.

Intracellular pharmacodynamics of antibiotics

“…Indeed, whereas some organisms, like Chlamydia and Legionella, are quite sensitive, this may not be the case for others, such as S aureus. The importance of a concentration threshold in intracellular activity has been demonstrated recently by the description of clinical failures with Chlamydia showing resistance to concentrations of azithromycin of 4 mg/L or higher in the BGMK cell assay system [87]. Interestingly enough, an increase in azithromycin accumulation, as obtained by inhibiting its efflux from macrophages, has been shown to decrease the extracellular concentration needed to obtain a bacteriostatic affect in the S aureus/J774 macrophage model depicted in Fig.…”

Effect of the steroid receptor antagonist RU486 (mifepristone) on an IFNγ-induced persistent Chlamydophila pneumoniae infection model in epithelial HEp-2 cells

“…Bacterial growth modification was assessed by IFU assay, fluorescence microscopic analysis and RT-PCR as shown below. Because it is well known that ofloxacin (OFLX) or clarithromycin (CAM) are ineffective against bacteria in the persistent phase [12], these antibiotics were used as an indicator to confirm whether persistent infection occurred due to treatment with IFN.…”

“…The presence of C. pneumoniae in persistent infection is characterized by an absence of culturability [7], in addition to altered bacterial RNA and protein levels [8][9][10][11], morphologically altered chlamydial bodies [8] and increased resistance to antimicrobials, such as azithromycin or clarithromycin, frequently used for the treatment of C. pneumoniae infection [12]. The mechanisms leading to persistent C. pneumoniae infection remain unclear; however, infection in reported cases occurred during an uncompleted developmental cycle with a lack of maturation of the EB, and an absence of bacterial metabolic activity caused a decrease in sensitivity to the antibiotics used.…”

REVIEW ARTICLE: Chlamydia trachomatis, a Hidden Epidemic: Effects on Female Reproduction and Options for Treatment

“…61 There is emerging evidence that C. trachomatis is developing antibiotic resistance, with some clinical isolates having single and multidrug resistance when cultured in vitro. [62][63][64][65] Isolates have been individually resistant to tetracyclines, macrolides, fluoroquinolones, 64 or resistant to doxycycline, azithromycin, and ofloxacin. 65 In addition, a study of infected women, who completed antibiotic treatment, found that 10% of the cohort was re-infected within 1 month of treatment completion, and 13% by 3 months, even though abstinence or 100% condom use was reported.…”

“…[62][63][64][65] Isolates have been individually resistant to tetracyclines, macrolides, fluoroquinolones, 64 or resistant to doxycycline, azithromycin, and ofloxacin. 65 In addition, a study of infected women, who completed antibiotic treatment, found that 10% of the cohort was re-infected within 1 month of treatment completion, and 13% by 3 months, even though abstinence or 100% condom use was reported. 66 While the shortened duration of infections from early antibiotic treatment has reduced infection-associated reproductive sequelae, the number of case rates continues to increase.…”