Background There is no UK guidance specifically for the management of rectal Chlamydia trachomatis yet there is documented treatment failure with single-dose azithromycin suggesting that test of cure (TOC) and alternative treatment may be needed.
Objectives To evaluate the efficacy of single-dose azithromycin compared with 1 week of doxycycline in the treatment of rectal C trachomatis.
Methods Data were collected prospectively on all patients diagnosed with rectal C trachomatis who received azithromycin 1 g stat between 1 January and 30 June 2010 and between 1 October 2010 and 31 March 2011 following a local change in treatment protocol to 1 week of doxycycline 100 mg twice a day. Information was collected on gender, concurrent sexually transmitted infections, treatment received, re-infection risk, re-treatment and TOC at 6 weeks.
Results 11 patients (26.2%) had a positive TOC following treatment with stat azithromycin. The risk of re-infection was excluded in two, identifying nine of the 11 (81.8%) as treatment failures. Two patients had a positive TOC following treatment with 1 week of doxycycline, both were found to have a risk of re-infection. There was a significantly higher treatment failure rate in patients receiving azithromycin (p=0.0025).
Conclusions A higher treatment failure rate was found following azithromycin for rectal C trachomatis than previously published. If azithromycin is used for treatment of rectal C trachomatis, TOC may be required or alternative treatment with doxycycline may be preferable, but further data are required.
- Chlamydia trachomatis
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A meta-analysis of randomised control trials comparing azithromycin with doxycycline for urethral and cervical Chlamydia trachomatis infections concluded that they were equally efficacious in achieving microbial cure.1 There have been no randomised controlled trials comparing antibiotic therapy for rectal C trachomatis infection, yet screening of men who have sex with men (MSM) is now common practice. Data are conflicting on the rate of treatment failure following a single dose of azithromycin (6–13%)2 ,3 with a higher clearance rate of 98.8% reported following 1 week of doxycycline.4 These studies looked at treatment response in MSM; there are no data on antibiotic efficacy in women with rectal C trachomatis.
We aimed to evaluate the efficacy of single-dose azithromycin compared with 1 week of doxycycline in the treatment of rectal chlamydia in men and women attending a large genitourinary medicine clinic in Birmingham, UK.
Rectal chlamydia testing using the geneprobe Aptima Combo nucleic acid amplification test is routinely offered at Whittall Street Clinic (University Hospitals Birmingham NHS Foundation Trust) to all men and women who report receptive anal intercourse. Patients with positive tests are recalled for treatment and contact tracing. Positive rectal nucleic acid amplification test samples from MSM are sent to Colindale for the exclusion of Lymphogranuloma venereum in line with current British Association of Sexual Health and HIV guidance.
A test of cure (TOC) at 6 weeks after the start of therapy was introduced after reports of azithromycin failure.4 A prospective observational study was performed for 6 months between 1 January 2010 and 30 June 2010, of all patients diagnosed with rectal C trachomatis who received azithromycin 1 g stat as first-line treatment (phase 1). The study was repeated between 1 October 2010 and 31 March 2011 when first-line treatment was switched to 7 days of doxycycline 100 mg twice a day (phase 2). Antibiotic therapy was the only change made to clinic protocol during the study periods. Both treatment regimens are first-line recommendations in the British Association of Sexual Health and HIV uncomplicated C trachomatis infection guidelines.
Data were gathered on gender, concurrent sexually transmitted infections, treatment received, TOC result, risk of re-infection, re-treatment and result of repeat TOC.
Treatment failure was defined as positive TOC with a risk of re-infection and non-compliance with treatment was excluded. This was assessed by the completion of a telephone questionnaire at 2 weeks post-treatment and a repeat full sexual history at attendance for TOC. Risk of re-infection was defined as any sexual contact (even with a condom) with a new partner or before their regular partner received epidemiological treatment or a negative test result.
Patients who did not receive antibiotics as per treatment protocol were excluded from the final analysis. This included patients diagnosed with L venereum. Statistical analysis was performed using the Fisher's exact test (two-tailed).
Table 1 shows the baseline characteristics for the study population. Women accounted for 43.7% of rectal C trachomatis infection and were more likely to isolate C trachomatis at a concurrent genital site (58.9% women vs 5.3% men). No women reported rectal symptoms at presentation; however, 68.5% described non-rectal genital symptoms. MSM accounted for 56.3% of study patients. Five presented with rectal symptoms of which L venereum was confirmed in one case. Only 10 men presented with non-rectal genital symptoms.
Figure 1 summarises the results. Forty-two patients who received azithromycin in phase 1 attended for TOC (47.2%), of which 11 were positive (26.2%). Two were excluded due to the risk of re-infection identifying nine of the 11 (81.8%) as treatment failures. Of the 78 patients who received doxycycline in phase 2, 40 attended for TOC (51.3%) of which two (5%) were positive. No treatment failure was identified following doxycycline as both patients had a risk of re-infection. The treatment failure rate identified following azithromycin was statistically significant (p=0.0025).
This study identified a significantly higher treatment failure rate with azithromycin compared with doxycycline for rectal C trachomatis. In line with recent studies, the majority of rectal C trachomatis infections in men occurred without concurrent genital infection and would have been missed without the provision of asymptomatic rectal screening. In contrast, however, 43.7% of rectal infections treated in this study were in women. Although a larger proportion of women had C trachomatis isolated from other sites, the rectum could be a potential reservoir for infection despite treatment with azithromycin, supporting the routine screening of women reporting receptive anal intercourse.
The failure rate observed following azithromycin is higher than reported elsewhere.2 ,3 This may be partly due to the inclusion of symptomatic patients and differences in defining and assessing re-infection risk. The strength of this study is that it is prospective and includes a comparator group treated with doxycycline. It is likely that if patients had underreported sexual activity and the possible risk of re-infection before TOC, the rate of misreporting would be similar in both groups.
There are some limitations to this study. Although an attempt was made to compare the failure rate following azithromycin versus doxycycline, this is not a randomised controlled trial and the allocation of antibiotics followed an open change in local protocol. The number of patients who received antibiotics in line with local protocol was small, particularly in phase 2 when a large number of patients was predominantly excluded due to receiving epidemiological treatment with azithromycin on the day of presentation. The number of patients included in the analysis was further restricted by the high rate of non-attendance for TOC, which is greater than reported elsewhere.2 ,3 Attendance was not associated with patient gender or clinic location and was consistent across both phases of the study.
There are a number of possible explanations for the increased number of treatment failures identified following azithromycin. First, antibiotic sensitivity testing is not routinely available and antimicrobial resistance may explain chlamydia persistence following antibiotic therapy. Second, the concentration of azithromycin in rectal tissue following a single oral dose is not known, and extrapolating data from studies of urethral and cervical infection may be inappropriate.1
This study suggests that doxycycline may be more effective in the management of rectal C trachomatis in men and women. A larger, randomised controlled trial of azithromycin versus doxycycline is needed to inform the development of treatment guidelines, and further research is required to explore reasons for treatment failure.
Our data suggest a higher rate of chlamydia persistence following azithromycin than doxycycline in the treatment of rectal C trachomatis infection.
A TOC may be considered in patients treated with azithromycin.
One week doxycycline may be a preferable option for the treatment of rectal chlamydia.
Competing interests None.
Provenance and peer review Not commissioned; externally peer reviewed.
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