Abstract
Rectal chlamydia is a common sexually transmissible infection (STI) in men who have sex with men (MSM) that is predominantly asymptomatic. The recommended treatment of azithromycin 1 g as a single oral dose has not been subject to randomized trials and so its efficacy is unknown. We conducted a retrospective case-note review of all MSM diagnosed at the Sydney Sexual Health Centre with asymptomatic rectal chlamydia in 2009. We identified 116 MSM who received azithromycin; 85 (73%) attended for the recommended re-test at varying times (median 78 days, range 21–372 days). Of the men who returned, 11 (13%) had a persistently positive result; we reviewed behavioural data to classify these men as probable re-infections (6/11) or possible treatment failures (5/11), suggesting an efficacy of 94%. Until a randomized controlled trial (RCT) is conducted, patients with rectal chlamydia should be encouraged to attend for a re-test at 6–12 weeks.
INTRODUCTION
Chlamydia trachomatis infection (chlamydia) is transmitted sexually, and can occur in the genitourinary tract, rectum and oropharynx in men who have sex with men (MSM). Rectal chlamydia is more common than urethral infection, with the incidence of rectal infection in a Sydney cohort of HIV-negative MSM being 7.4 per 100 person-years compared with 5.0 per 100 person-years for urethral infection. 1 Chlamydia has public health importance in MSM because of its potential to increase the risk of transmission of HIV. 2
Regular testing and treatment is a key public health control strategy for chlamydia, as infection is mostly asymptomatic. 3 Like many other countries, Australian guidelines recommend a single dose of azithromycin (1 g) for treatment of rectal chlamydia. 4 As there have been no randomized controlled trials (RCTs) of treatment of rectal chlamydia, the efficacy of azithromycin is unknown.
A recent report suggested that azithromycin might not be an ideal antibiotic for the treatment of rectal chlamydia, with a 13% treatment failure rate reported in a Scottish study, with nearly half of the failures being among HIV-infected MSM. 5 However, this study did not differentiate re-infections from treatment failures.
The present paper describes a retrospective case-note review of the outcomes of a single 1 g dose of azithromycin as treatment for asymptomatic rectal C. trachomatis infection in MSM.
METHODS
In late 2008, Sydney Sexual Health Centre (SSHC) implemented a six-week test-of-cure policy for all men diagnosed with rectal chlamydia who were treated with azithromycin. Chlamydia testing was performed with the Roche Amplicor PCR assay (Roche Molecular Systems Inc., Branchburg, NJ, USA).
We carried out a retrospective case-note review of all MSM diagnosed with rectal chlamydia at SSHC in 2009. The following data were extracted from each patient file: demographic information, HIV status and current CD4 count, sexual behaviour, ano-genital symptoms, other sexually transmissible infections (STIs), chlamydia testing dates and outcomes, treatment given, side-effects related to the antibiotics, and self-reported contact tracing outcomes. These data were recorded in Microsoft Excel.
MSM with anal symptoms were excluded from this analysis, due to the possibility of lymphogranuloma venereum (LGV) infection. LGV is an invasive inflammatory form of rectal disease caused by L-serovars of C. trachomatis, which is routinely treated with three weeks of doxycycline.
A chi-square test was used to assess whether there was any difference in baseline characteristics (age group, HIV status, condom use, partner numbers, concurrent STIs and STIs in the past 12 months) between (i) men re-tested and not re-tested, and (ii) men re-tested less than and greater than 12 weeks after treatment.
Of men re-tested and found to have a persistent positive test, we used behavioural data routinely collected at the clinic to group these men into those with untreated ongoing known sexual partners (probable re-infection) and those who did not have any obvious ongoing exposure, either because they did not report any further anal sex or because condoms were used consistently (possible treatment failure).
Stata 10.0 statistical software (Stata Corp, College Station, TX, USA) was used to conduct all analyses. A cut-off of P < 0.05 was used for all statistical tests. The project was approved by the South Eastern Sydney Illawarra (Northern Hospital Network) Area Health Service and University of New South Wales Human Research Ethics Committees.
RESULTS
Patient characteristics
During 2009, 2688 MSM attended the clinic and 125 (5%) were diagnosed with rectal chlamydia. Of these 125 men, nine had symptoms or signs of proctitis and were excluded, leaving 116 asymptomatic MSM all of whom had received the recommended therapy of azithromycin 1 g as a single oral dose. The 116 men had a median age of 33 years (range 20–64 years) and 14 (12%) were HIV infected.
Only 85 of the 116 men (73%) had a later re-test. There were no significant differences in baseline characteristics between those who re-tested and those who did not (Table 1).
Characteristics of MSM diagnosed with rectal chlamydia, by repeat testing history and by time to re-test, Sydney Sexual Health Centre, 2009
MSM = men who have sex with men; STI = sexually transmissible infection
*Chi-square test
†Thirty-three years used as this was the median age
‡STI diagnoses were HIV, urethral chlamydia, urethral, rectal and pharyngeal gonorrhoea, infectious syphilis, first-episode anogenital herpes, non-gonococcal urethritis and anogenital warts
Of those who re-tested, 55% re-tested within 12 weeks, with the median re-test time being 78 days (range 21–372 days). Only 12 men (14%) re-tested within six weeks. There were no significant differences in baseline characteristics between those who re-tested in less than 12 weeks and those who re-tested after 12 weeks (Table 1).
Persistent positive tests
Eleven of the 85 (13%) men had a persistent positive result (Table 2) at re-test and none reported any adverse experiences that could have reduced absorption of azithromycin.
Characteristics of patients with a positive rectal chlamydia at repeat testing, Sydney Sexual Health Centre, 2009
STI = sexually transmissible infection; ART = antiretroviral therapy; RMP = regular male partner; Rx = treatment; NGU = non-gonococcal urethritis
Six of the 11 positive tests were classified as ‘probable re-infection’ with the infections detected between 47 and 209 days after treatment; all these men had documented ongoing sexual contact with untreated partners. One of the probable re-infections was in a newly diagnosed HIV-infected man whose regular partner had untreated chlamydia. The other five positive tests were classified as ‘possible treatment failures’, with the infections detected between 48 and 165 days; all men in this group had documentation that ongoing partners had received treatment and that condoms had been used with any new partners. None of these possible treatment failures were in HIV-infected men. Excluding the probable re-infections the apparent treatment efficacy was 94% (95% confidence intervals 87–98%).
DISCUSSION
This review has shown that a single dose of 1 g azithromycin may be an effective first-line treatment for asymptomatic rectal chlamydia. The 94% apparent efficacy in our study is comparable with the cure rate for urethral and cervical chlamydia of 96.5%. 6 Our efficacy estimate is slightly higher than the Edinburgh study, possibly because we collected additional behavioural data to be able to differentiate probable re-infections from possible treatment failures. By including the total 11 persistent positive results in the treatment efficacy estimate, we get an estimate similar to the Edinburgh study of 87%.
There are some limitations to our study. The time for re-testing varied considerably. Only 14% of men re-tested around the recommended six weeks. Although we have shown that there was no difference in baseline variables between those who returned early, late or did not return, it is possible that this impacted on our results. We cannot rule out spontaneous resolution of infections 7 that may have resulted in an over-estimation of the apparent efficacy. Nor can we exclude additional exposure to antibiotics, either as treatment for concurrent STIs – although the antibiotics prescribed for the other STIs (penicillin and ceftriaxone) have limited effect against chlamydia – or those prescribed by general practitioners for other medical conditions that were not documented in the case-notes.
While patient self-reported sexual behaviour is subject to various forms of bias, the fact that the assessment of re-infection/treatment failure was based on ongoing contact with untreated known contacts minimizes the risk of unreported behaviours affecting our assessment. Although all possible treatment failures reported condom use with new partners, we cannot rule out transmission by other activities – genotyping would be required to confirm treatment failures in these cases.
Due to the limited data on how quickly C. trachomatis clears from rectal specimens it is difficult to know how early to recommend men attend for a re-test to minimize the chance of re-infection. It is important to define this time before a larger randomized comparison is undertaken.
Although our paper suggests a reasonable treatment efficacy, the only way to definitively answer the question of whether azithromycin or doxycycline is effective as first-line treatment for asymptomatic rectal chlamydia is by a RCT. In the meantime, we advise men who receive either azithromycin or doxycycline for rectal chlamydia to attend for a repeat test.