Evaluation of Antimicrobial Resistance and Treatment Failures forChlamydiatrachomatis: A Meeting Report

Abstract

Each year, Chlamydia trachomatis causes ~3 million new infections and results in more than 1 billion dollars in medical costs in the United States. Repeat or persistent infection occurs in 10%-15% of women who are treated for C. trachomatis infection. However, the role played by antimicrobial resistance in C. trachomatis treatment failures or persistent infection is unclear. With researchers in the field, we reviewed current knowledge and available approaches for evaluating antimicrobial resistance and potential clinical treatment failures for C. trachomatis. We identified key research questions that require further investigation. To date, there have been no reports of clinical C. trachomatis isolates displaying in vitro homotypic resistance to antimicrobials, but in vitro heterotypic resistance in C. trachomatis has been described. Correlation between the results of existing in vitro antimicrobial susceptibility tests and clinical outcome after treatment for C. trachomatis infection is unknown. Animal models may provide insight into chlamydial persistence, since homotypic resistance against tetracycline has been described for Chlamydia suis in pigs. Evaluating C. trachomatis clinical treatment failures, interpreting laboratory findings, and correlating the 2 clearly remain extremely challenging undertakings.

Chlamydia trachomatisSerovar L2 Can Utilize Exogenous Lipoic Acid through the Action of the Lipoic Acid Ligase LplA1

“…Although antibiotic therapies are currently available for the treatment of ocular and genital tract infections caused by chlamydiae, reports of treatment failure and demonstration of in vitro resistance to antibiotics suggest that development of resistance to commonly used antibiotics against chlamydiae is possible (7,43). Given the importance of lipoic acid and its role in the growth and virulence of other intracellular pathogens, genes involved in lipoic acid biosynthesis and utilization make attractive candidates for the development of novel therapeutics (25).…”

Fitness Cost Due to Mutations in the 16S rRNA Associated with Spectinomycin Resistance in Chlamydia psittaci 6BC

“…At present, treatment failures following the appearance of mutations that confer antibiotic resistance have not been of great concern for chlamydial infections (43,47). However, the acquisition of drug resistance in chlamydia by horizontal gene transfer has been suggested by the identification and characterization of a tetracycline-resistant strain of C. suis (13).…”

“…Chlamydial infections are characterized by a high recurrence rate, despite appropriate drug therapy, yet clinical failures linked to real genotypic resistance due to chromosomal mutations have rarely been reported (43,47). This suggests that mutations that confer antibiotic resistance in chlamydiae are not selected in vivo.…”

Type I IFNs Enhance Susceptibility toChlamydia muridarumLung Infection by Enhancing Apoptosis of Local Macrophages

“…C. trachomatis can cause trachoma and sexually transmitted diseases, sometimes with serious sequelae, including blindness, pelvic inflammatory diseases, and infertility (22)(23)(24). Type II IFN (IFN-␥) has been shown to be the most important cytokine for host resistance to chlamydial infection (24 -28).…”