Evaluation of Azithromycin Resistance in Treponema pallidum Specimens From Madagascar

Damme, Kathleen Van; Behets, Frieda; Ravelomanana, N.; Godornes, Charmie; Khan, Maria R.; Randrianasolo, Bodo; Rabenja, Ny Lovaniaina; Lukehart, Sheila A.; Cohen, Myron S.; Hook, Edward W.

doi:10.1097/olq.0b013e3181bd11dd

Cited by 55 publications

(36 citation statements)

References 18 publications

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“…The overall prevalence of the A2058G mutation in Sydney remained at 84% across the study period. Again, this is in agreement with the high levels observed in the United States [15]), but the high prevalence is in sharp contrast to levels reported from studies in South Africa (1% [18]), Madagascar (0% [17]), and Taiwan (0% [19]). The reason for the large differences in resistance prevalence rates between countries is not clear but is likely to represent differences in exposure of the at-risk population to macrolide antibiotics.…”

Section: Discussioncontrasting

confidence: 53%

“…However, clinical treatment failures were soon reported, followed by the identification of rising rates of the 23S ribosomal mutation A2058G, which confers resistance to macrolide antibiotics. This mutation has now been identified in the United States (11,12), Ireland (13), the United Kingdom (14), China (15), and Canada (16), but it was not found at significant levels in Madagascar (17), South Africa (18), or Taiwan (19).…”

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confidence: 99%

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Azithromycin-Resistant Syphilis-Causing Strains in Sydney, Australia: Prevalence and Risk Factors

et al. 2014

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e Azithromycin has shown high efficacy in randomized trials when used for treating infectious syphilis in Africa. However, its use in clinical practice has been limited by the development of antimicrobial drug resistance. Resistance has not previously been reported from Australasia. The aim of this study was to determine the prevalence of and risk factors for azithromycin-resistant syphilis-causing strains in Sydney, Australia. We evaluated 409 samples that were PCR positive for Treponema pallidum DNA collected between 2004 and 2011 for the presence of the A2058G mutation, which confers resistance to macrolide antibiotics such as azithromycin. Overall, 84% of samples harbored the mutation. The prevalence of the mutation increased during the study period (P trend, 0.003). We also collected clinical and demographic data on 220 patients from whom these samples had been collected to determine factors associated with the A2058G mutation; 97% were from men who have sex with men. Reporting sex in countries other than Australia was associated with less macrolide resistance (adjusted odds ratio, 0.25; 95% confidence interval, 0.09 to 0.66; P ‫؍‬ 0.005), with other study factors showing no association (age, HIV status, recent macrolide use, stage of syphilis, or history of prior syphilis). Azithromycin cannot be recommended as an alternative treatment for syphilis in Sydney.

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Section: Discussioncontrasting

confidence: 53%

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confidence: 99%

Azithromycin-Resistant Syphilis-Causing Strains in Sydney, Australia: Prevalence and Risk Factors

et al. 2014

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“…Moreover, an increasing trend in macrolide resistance has also been described in studies by Grimes et al (19), Marra et al (27), and Mitchell et al (28). In contrast to these data, no macrolide resistance-causing mutations were found during analyses of the 23S rRNA gene locus in Madagascar (29) and Taiwan (21). As first predicted by Marra et al (27), macrolideresistant isolates appear in infected populations because of antibiotic pressure.…”

Section: Discussioncontrasting

confidence: 50%

Molecular Typing of Treponema pallidum in the Czech Republic during 2011 to 2013: Increased Prevalence of Identified Genotypes and of Isolates with Macrolide Resistance

et al. 2014

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“…The percentages of T. pallidum-positive clinical specimens containing the A2058G mutation have increased significantly over time in San Francisco and Seattle, from 4 and 9% in 2002 to 77 and 56% in 2005, respectively (8,(16)(17)(18). While the mutation has been shown to be prevalent among T. pallidum strains from primary syphilis cases in Shanghai, China (11), reports from other countries (such as Taiwan, Madagascar, Tanzania, Uganda, and southern Africa) have either not found the mutation or shown it to be relatively uncommon (16,(19)(20)(21)(22)(23). However, an increasing prevalence of macrolide-resistant T. pallidum can be expected because of the spread of these resistant strains and the increasing use of macrolides for the treatment of sexually transmitted and other, unrelated, infections.…”

Section: Detection Of the A2058g And A2059g 23s Rrna Gene Point Mutatmentioning

confidence: 93%

Detection of the A2058G and A2059G 23S rRNA Gene Point Mutations Associated with Azithromycin Resistance in Treponema pallidum by Use of a TaqMan Real-Time Multiplex PCR Assay

et al. 2013

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Macrolide treatment failure in syphilis patients is associated with a single point mutation (either A2058G or A2059G) in both copies of the 23S rRNA gene in Treponema pallidum strains. The conventional method for the detection of both point mutations uses nested PCR combined with restriction enzyme digestions, which is laborious and time-consuming. We initially developed a TaqMan-based real-time duplex PCR assay for detection of the A2058G mutation, and upon discovery of the A2059G mutation, we modified the assay into a triplex format to simultaneously detect both mutations. The point mutations detected by the realtime triplex PCR were confirmed by pyrosequencing. A total of 129 specimens PCR positive for T. pallidum that were obtained from an azithromycin resistance surveillance study conducted in the United States were analyzed. Sixty-six (51.2%) of the 129 samples with the A2058G mutation were identified by both real-time PCR assays. Of the remaining 63 samples that were identified as having a macrolide-susceptible genotype by the duplex PCR assay, 17 (27%) were found to contain the A2059G mutation by the triplex PCR. The proportions of macrolide-susceptible versus -resistant genotypes harboring either the A2058G or the A2059G mutation among the T. pallidum strains were 35.6, 51.2, and 13.2%, respectively. None of the T. pallidum strains examined had both point mutations. The TaqMan-based real-time triplex PCR assay offers an alternative to conventional nested PCR and restriction fragment length polymorphism analyses for the rapid detection of both point mutations associated with macrolide resistance in T. pallidum.

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Evaluation of Azithromycin Resistance in Treponema pallidum Specimens From Madagascar

Cited by 55 publications

References 18 publications

Azithromycin-Resistant Syphilis-Causing Strains in Sydney, Australia: Prevalence and Risk Factors

Azithromycin-Resistant Syphilis-Causing Strains in Sydney, Australia: Prevalence and Risk Factors

Molecular Typing of Treponema pallidum in the Czech Republic during 2011 to 2013: Increased Prevalence of Identified Genotypes and of Isolates with Macrolide Resistance

Detection of the A2058G and A2059G 23S rRNA Gene Point Mutations Associated with Azithromycin Resistance in Treponema pallidum by Use of a TaqMan Real-Time Multiplex PCR Assay

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