Macrolides for treatment of Haemophilus ducreyi infection in sexually active adults

Laura Romero, Cesar Huerfano, Carlos F Grillo‐Ardila

Chancroid is a genital ulcerative disease caused by Haemophilus ducreyi. This microorganism is endemic in Africa, where it can cause up to 10% of genital ulcers. Macrolides may be an effective alternative to treat chancroid and, based on their oral administration and duration of therapy, could be considered as first line therapy. To assess the effectiveness and safety of macrolides for treatment of H ducreyi infection in sexually active adults. We searched the Cochrane STI Group Specialized Register, CENTRAL, MEDLINE, Embase, LILACS, WHO ICTRP, ClinicalTrials.gov and Web of Science to 30 October 2017. We also handsearched conference proceedings and reference lists of retrieved studies. Randomized controlled trials (RCTs) comparing macrolides in different regimens or with other therapeutic alternatives for chancroid. Two review authors independently assessed trials for inclusion, extracted data and assessed risk of bias. We resolved disagreements through consensus. We used the GRADE approach to assess the quality of the evidence. Seven RCTs (875 participants) met our inclusion criteria, of which four were funded by industry. Five studies (664 participants) compared macrolides with ceftriaxone, ciprofloxacin, spectinomycin or thiamphenicol. Low quality evidence suggested there was no difference between the groups after treatment in terms of clinical cure (risk ratio (RR) 1.09, 95% confidence interval (CI) 0.97 to 1.21; 2 studies, 340 participants with syndromic approach and RR 1.06, 95% CI 0.98 to 1.15; 5 studies, 348 participants with aetiological diagnosis) or improvement (RR 0.89, 95% CI 0.52 to 1.52; 2 studies, 340 participants with syndromic approach and RR 0.80, 95% CI 0.42 to 1.51; 3 studies, 187 participants with aetiological diagnosis). Based on low and very low quality evidence, there was no difference between macrolides and any other antibiotic treatments for microbiological cure (RR 0.93, 95% CI 0.74 to 1.16; 1 study, 45 participants) and minor adverse effects (RR 1.34, 95% CI 0.24 to 7.51; 3 studies, 412 participants).Two trials (269 participants) compared erythromycin with any other macrolide type. Low quality evidence suggested that, compared with azithromycin or rosaramicin, long courses of erythromycin did not increase clinical cure (RR 1.00, 95% CI 0.91 to 1.10; 2 studies, 269 participants with syndromic approach and RR 1.04, 95% CI 0.93 to 1.16; 2 studies, 211 participants with aetiological diagnosis), with a similar frequency of minor adverse effects between the groups (RR 1.14, 95% CI 0.63 to 2.06; 1 trial, 101 participants). For this comparison, subgroup analysis found no difference between HIV-positive participants (RR 1.02, 95% CI 0.73 to 1.43; 1 study, 38 participants) and HIV-negative participants (RR 1.04, 95% CI 0.94 to 1.14; 1 study, 89 participants). We downgraded the quality of evidence to low, because of imprecision, some limitations on risk of bias and heterogeneity.None of the trials reported serious adverse events, cost effectiveness and participant satisfaction. At present, the quality of the evidence on the effectiveness and safety of macrolides for treatment of H ducreyi infection in sexually active adults is low, implying that we are uncertain about the estimated treatment effect. There is no statistically significant difference between the available therapeutic alternatives for the treatment of sexually active adults with genital ulcers compatible with chancroid. Low quality evidence suggests that azithromycin could be considered as the first therapeutic alternative, based on their mono-dose oral administration, with a similar safety and effectiveness profile, when it is compared with long-term erythromycin use.Due to sparse available evidence about the safety and effectiveness of macrolides to treat H ducreyi infection in people with HIV, these results should be taken with caution.