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Macrolide Resistance in Treponema pallidum Correlates With 23S rDNA Mutations in Recently Isolated Clinical Strains.
Sex Transm Dis. 2016 09; 43(9):579-83.ST

Abstract

BACKGROUND

High rates of 23S rDNA mutations implicated in macrolide resistance have been identified in Treponema pallidum samples from syphilis patients in many countries. Nonetheless, some clinicians have been reluctant to abandon azithromycin as a treatment for syphilis, citing the lack of a causal association between these mutations and clinical evidence of drug resistance. Although azithromycin resistance has been demonstrated in vivo for the historical Street 14 strain, no recent T. pallidum isolates have been tested. We used the well-established rabbit model of syphilis to determine the in vivo efficacy of azithromycin against 23S rDNA mutant strains collected in 2004 to 2005 from patients with syphilis in Seattle, Wash.

METHODS

Groups of 9 rabbits were each infected with a strain containing 23S rDNA mutation A2058G (strains UW074B, UW189B, UW391B) or A2059G (strains UW228B, UW254B, and UW330B), or with 1 wild type strain (Chicago, Bal 3, and Mexico A). After documentation of infection, 3 animals per strain were treated with azithromycin, 3 were treated with benzathine penicillin G, and 3 served as untreated control groups. Treatment efficacy was documented by darkfield microscopic evidence of T. pallidum, serological response, and rabbit infectivity test.

RESULTS

Azithromycin uniformly failed to cure rabbits infected with strains harboring either 23S rDNA mutation, although benzathine penicillin G was effective. Infections caused by wild type strains were successfully treated by either azithromycin or benzathine penicillin G.

CONCLUSIONS

A macrolide resistant phenotype was demonstrated for all strains harboring a 23S rDNA mutation, demonstrating that either A2058G or A2059G mutation confers in vivo drug resistance.

Authors+Show Affiliations

From the *Department of Medicine, †Department of Neurology, and ‡Department of Global Health, University of Washington, Seattle, WA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural

Language

eng

PubMed ID

27513385

Citation

Molini, Barbara J., et al. "Macrolide Resistance in Treponema Pallidum Correlates With 23S rDNA Mutations in Recently Isolated Clinical Strains." Sexually Transmitted Diseases, vol. 43, no. 9, 2016, pp. 579-83.
Molini BJ, Tantalo LC, Sahi SK, et al. Macrolide Resistance in Treponema pallidum Correlates With 23S rDNA Mutations in Recently Isolated Clinical Strains. Sex Transm Dis. 2016;43(9):579-83.
Molini, B. J., Tantalo, L. C., Sahi, S. K., Rodriguez, V. I., Brandt, S. L., Fernandez, M. C., Godornes, C. B., Marra, C. M., & Lukehart, S. A. (2016). Macrolide Resistance in Treponema pallidum Correlates With 23S rDNA Mutations in Recently Isolated Clinical Strains. Sexually Transmitted Diseases, 43(9), 579-83. https://doi.org/10.1097/OLQ.0000000000000486
Molini BJ, et al. Macrolide Resistance in Treponema Pallidum Correlates With 23S rDNA Mutations in Recently Isolated Clinical Strains. Sex Transm Dis. 2016;43(9):579-83. PubMed PMID: 27513385.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Macrolide Resistance in Treponema pallidum Correlates With 23S rDNA Mutations in Recently Isolated Clinical Strains. AU - Molini,Barbara J, AU - Tantalo,Lauren C, AU - Sahi,Sharon K, AU - Rodriguez,Veronica I, AU - Brandt,Stephanie L, AU - Fernandez,Mark C, AU - Godornes,Charmie B, AU - Marra,Christina M, AU - Lukehart,Sheila A, PY - 2016/8/12/entrez PY - 2016/8/12/pubmed PY - 2017/12/12/medline SP - 579 EP - 83 JF - Sexually transmitted diseases JO - Sex Transm Dis VL - 43 IS - 9 N2 - BACKGROUND: High rates of 23S rDNA mutations implicated in macrolide resistance have been identified in Treponema pallidum samples from syphilis patients in many countries. Nonetheless, some clinicians have been reluctant to abandon azithromycin as a treatment for syphilis, citing the lack of a causal association between these mutations and clinical evidence of drug resistance. Although azithromycin resistance has been demonstrated in vivo for the historical Street 14 strain, no recent T. pallidum isolates have been tested. We used the well-established rabbit model of syphilis to determine the in vivo efficacy of azithromycin against 23S rDNA mutant strains collected in 2004 to 2005 from patients with syphilis in Seattle, Wash. METHODS: Groups of 9 rabbits were each infected with a strain containing 23S rDNA mutation A2058G (strains UW074B, UW189B, UW391B) or A2059G (strains UW228B, UW254B, and UW330B), or with 1 wild type strain (Chicago, Bal 3, and Mexico A). After documentation of infection, 3 animals per strain were treated with azithromycin, 3 were treated with benzathine penicillin G, and 3 served as untreated control groups. Treatment efficacy was documented by darkfield microscopic evidence of T. pallidum, serological response, and rabbit infectivity test. RESULTS: Azithromycin uniformly failed to cure rabbits infected with strains harboring either 23S rDNA mutation, although benzathine penicillin G was effective. Infections caused by wild type strains were successfully treated by either azithromycin or benzathine penicillin G. CONCLUSIONS: A macrolide resistant phenotype was demonstrated for all strains harboring a 23S rDNA mutation, demonstrating that either A2058G or A2059G mutation confers in vivo drug resistance. SN - 1537-4521 UR - https://www.unboundmedicine.com/medline/citation/27513385/Macrolide_Resistance_in_Treponema_pallidum_Correlates_With_23S_rDNA_Mutations_in_Recently_Isolated_Clinical_Strains_ L2 - https://doi.org/10.1097/OLQ.0000000000000486 DB - PRIME DP - Unbound Medicine ER -