Relationship between the high frequency of 23S rRNA point mutations in Treponema pallidum and low serological response rate to azithromycin treatment in China

Abstract

Objective Although azithromycin is effective against Treponema pallidum (T. pallidum), the causative agent of syphilis, recent reports indicate that the prevalence of azithromycin resistance in China is very high, which may result in the failure of treatment. In this study, we aimed to investigate the association between azithromycin resistance and therapeutic outcomes in early syphilis patients. Methods Between February 2010 and December 2014, patients aged 18-65 years with early syphilis were enrolled. T. pallidum DNA were extracted to test the presence of A2058G and A2059G mutations. Then, eligible patients were randomly assigned to receive oral azithromycin (0.5 g, once daily for 15 days) or intramuscular BPG (2.4 million units, once weekly for 3 weeks). All patients were followed up in 2 weeks and 3, 6, 9, and 12 months after treatment to collect demographic and clinical characteristics and laboratory results. The differences on serological response, serological failure and serofast rate were compared between the two groups by Chi-square test. Results Among the 187 T. pallidum-infected patients enrolled, 172 (92.0%) cases had a mutation associated with azithromycin resistance (A2058G, 153 cases; A2059G, 19 cases). During the 5-year study period, the percentage of cases enrolled with these mutations steadily increased, from 90.9% in 2010 to 95.3% in 2014. Of the 172 patients presenting with these mutations, only 78 (45.3%; all benzathine penicillin G [BPG]-treated) obtained a serological response to treatment; 32.6% and 22.1% of patients presented with serological failure and serofast results, respectively. For azithromycin-treated cases, 66.3% and 33.7% had serological failure and serofast results, respectively, in contrast with 1.1% and 11.3% of BPG-treated cases. However, among the A2058G-and A2059G-negative patients, the serological response rates between the two treatment groups were similar. In multivariate analyses, patients with lower rapid plasma reagin (RPR) titers (RPR, ≤ 1:8; odds ratio[OR], 0.23; 95% confidence interval [CI], 0.09-0.37) or who received azithromycin treatment (OR, 121.50; 95% CI, 35.38-386.17) were more likely to display serological failure and serofast results. Conclusion This prospective study found that the 23S rRNA A2058G and A2059G point mutations in T. pallidum are currently circulating with high frequency in China, suggesting a correlation between the high prevalence of macrolide resistance and a lower serolo gical response rate to azithromycin treatment. Key words: Syphilis; Azithromycin; Mutation; Serological response; Treponema pallidum