A snapshot of Chlamydia trachomatis genetic diversity using multilocus sequence type analysis in an Australian metropolitan setting.

High-resolution screening methodologies which enable the differentiation of Chlamydia trachomatis at the strain level, directly from clinical samples, can provide the detailed information required for epidemiological questions such as the dynamics of treatment failure. In addition, they give a detailed snapshot of circulating C. trachomatis genetic variation, data which are currently lacking for the Australian population. In the context of two Australian clinical trials, we assessed the genetic diversity of C. trachomatis and compared these to strains circulating globally. We used high-resolution multilocus sequence typing (MLST) of five highly variable genetic regions of C. trachomatis to examine variation in Australia. Samples with established genovars were drawn from a pool of 880 C. trachomatis-positive samples from two clinical studies, whereby 76 sample pairs which remained C. trachomatis-positive for the same genovar after treatment underwent MLST analysis to distinguish between treatment failure and reinfection. MLST analysis revealed a total of 25 sequence types (STs), six new allele variants and seven new STs not described anywhere else in the world, when compared to those in the international C. trachomatis MLST database. Of the eight most common global STs, seven were found in Australia (four derived from men who have sex with men (MSM) and three from heterosexuals). Newly identified STs were predominantly found in samples from the MSM population. In conclusion, MLST provided a diverse C. trachomatis strain profile, with novel circulating STs, and could be used to identify local sexual networks to focus on interventions such as testing and partner notification to prevent reinfection.

Higher organism load associated with failure of azithromycin to treat rectal chlamydia.

Repeat rectal chlamydia infection is common in men who have sex with men (MSM) following treatment with 1 g azithromycin. This study describes the association between organism load and repeat rectal chlamydia infection, genovar distribution, and efficacy of azithromycin in asymptomatic MSM. Stored rectal chlamydia-positive samples from MSM were analysed for organism load and genotyped to assist differentiation between reinfection and treatment failure. Included men had follow-up tests within 100 days of index infection. Lymphogranuloma venereum and proctitis diagnosed symptomatically were excluded. Factors associated with repeat infection, treatment failure and reinfection were investigated. In total, 227 MSM were included - 64 with repeat infections [28·2%, 95% confidence interval (CI) 22·4-34·5]. Repeat positivity was associated with increased pre-treatment organism load [odds ratio (OR) 1·7, 95% CI 1·4-2·2]. Of 64 repeat infections, 29 (12·8%, 95% CI 8·7-17·8) were treatment failures and 35 (15·4%, 95% CI 11·0-20·8) were reinfections, 11 (17·2%, 95% CI 8·9-28·7) of which were definite reinfections. Treatment failure and reinfection were both associated with increased load (OR 2·0, 95% CI 1·4-2·7 and 1·6, 95% CI 1·2-2·2, respectively). The most prevalent genovars were G, D and J. Treatment efficacy for 1 g azithromycin was 83·6% (95% CI 77·2-88·8). Repeat positivity was associated with high pre-treatment organism load. Randomized controlled trials are urgently needed to evaluate azithromycin's efficacy and whether extended doses can overcome rectal infections with high organism load.

Azithromycin versus doxycycline for the treatment of genital chlamydia infection: a meta-analysis of randomized controlled trials.

BACKGROUND: There has been recent debate questioning the efficacy of azithromycin for the treatment of urogenital chlamydia infection. We conducted a meta-analysis to compare the efficacy of 1 g azithromycin with 100 mg doxycycline twice daily (7 days) for the treatment of urogenital chlamydia infection. METHODS: Medline, PubMed, Embase, Cochrane Controlled Trials Register, Cochrane reviews, and Cumulative Index to Nursing and Allied Health Literature were searched until 31 December 2013. Randomized controlled trials comparing azithromycin with doxycycline for the treatment of genital chlamydia with evaluation of microbiological cure within 3 months of treatment were included. Sex, diagnostic test, follow-up time, attrition, patient symptomatic status, and microbiological cure were extracted. The primary outcome was the difference in efficacy at final follow-up. Study bias was quantitatively and qualitatively summarized. RESULTS: Twenty-three studies were included evaluating 1147 and 912 patients for azithromycin and doxycycline, respectively. We found a pooled efficacy difference in favor of doxycycline of 1.5% (95% confidence interval [CI], -.1% to 3.1%; I(2) = 1.9%; P = .435; random effects) to 2.6% (95% CI, .5%-4.7%; fixed effects). Subgroup analyses showed that the fixed effects pooled efficacy difference for symptomatic men was 7.4% (95% CI, 2.0%-12.9%), and the random effects was 5.5% (95% CI, -1.4% to 12.4%). CONCLUSIONS: There may be a small increased efficacy of up to 3% for doxycycline compared with azithromycin for the treatment of urogenital chlamydia and about 7% increased efficacy for doxycycline for the treatment of symptomatic urethral infection in men. However, the quality of the evidence varies considerably, with few double-blind placebo-controlled trials conducted. Given increasing concern about potential azithromycin failure, further well-designed and statistically powered double-blind, placebo-controlled trials are needed.