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Two Mutations Associated With Macrolide Resistance in Treponema pallidum: Increasing Prevalence and Correlation With Molecular Strain Type in Seattle, Washington

Grimes, Matthew BS*; Sahi, Sharon K. BS; Godornes, B. Charmie BS; Tantalo, Lauren C. BS; Roberts, Neal BS§; Bostick, David BS MPH§; Marra, Christina M. MD; Lukehart, Sheila A. PhD‡¶

doi: 10.1097/OLQ.0b013e31826ae7a8
Original Study

Background Although azithromycin promised to be a safe and effective single-dose oral treatment of early syphilis, azithromycin treatment failure has been documented and is associated with mutations in the 23S rDNA of corresponding Treponema pallidum strains. The prevalence of strains harboring these mutations varies throughout the United States and the world. We examined T. pallidum strains circulating in Seattle, Washington, from 2001 to 2010 to determine the prevalence of 2 mutations associated with macrolide resistance and to determine whether these mutations were associated with certain T. pallidum strain types.

Methods Subjects were enrolled in a separate ongoing study of cerebrospinal fluid abnormalities in patients with syphilis. T. pallidum DNA purified from blood and T. pallidum strains isolated from blood or cerebrospinal fluid were analyzed for two 23S rDNA mutations and for the molecular targets used in an enhanced molecular stain typing system.

Results Nine molecular strain types of T. pallidum were identified in Seattle from 2001 to 2010. Both macrolide resistance mutations were identified in Seattle strains, and the prevalence of resistant T. pallidum exceeded 80% in 2005 and increased through 2010. Resistance mutations were associated with discrete molecular strain types of T. pallidum.

Conclusions Macrolide-resistant T. pallidum strains are highly prevalent in Seattle, and each mutation is associated with discrete strain types. Macrolides should not be considered for treatment of syphilis in regions where prevalence of the mutations is high. Combining the resistance mutations with molecular strain typing permits a finer analysis of the epidemiology of syphilis in a community.

A study of persons with syphilis in Seattle, Washington, from 2001 to 2010 identifies the presence of 2 mutations associated with macrolide resistance, each associated with different molecular strain types of Treponema pallidum. The prevalence of strains with these mutations has been more than 80% since 2005.

From the *School of Medicine,Departments of †Neurology, and ‡Medicine, University of Washington, Seattle, WA; §School of Medicine, Howard University, Washington, DC; and ¶Department of Global Health, Schools of Medicine and Public Health, University of Washington, Seattle, WA

Supported by National Institutes of Health grants AI063940, AI42143, and AI094122 (to S.A.L.) and by NS034235 (to C.M.M.).

S.A.L., B.C.G., L.C.T., and C.M.M. are conducting research sponsored by Cempra Pharmaceuticals. For the remaining authors, no conflict was declared.

Correspondence: Sheila A. Lukehart, PhD, Department of Medicine, Box 359779, Harborview Medical Center 325 9th Ave, Seattle, WA 98104. E-mail: lukehart@u.washington.edu.

Received for publication April 20, 2012, and accepted July 20, 2012.

© Copyright 2012 American Sexually Transmitted Diseases Association