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Macrolide Resistance in Treponema pallidum Correlates With 23S rDNA Mutations in Recently Isolated Clinical Strains

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 caus...

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Autores principales: Molini, Barbara J., Tantalo, Lauren C., Sahi, Sharon K., Rodriguez, Veronica I., Brandt, Stephanie L., Fernandez, Mark C., Godornes, Charmie B., Marra, Christina M., Lukehart, Sheila A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Lippincott Williams & Wilkins 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4982755/
https://www.ncbi.nlm.nih.gov/pubmed/27513385
http://dx.doi.org/10.1097/OLQ.0000000000000486
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author Molini, Barbara J.
Tantalo, Lauren C.
Sahi, Sharon K.
Rodriguez, Veronica I.
Brandt, Stephanie L.
Fernandez, Mark C.
Godornes, Charmie B.
Marra, Christina M.
Lukehart, Sheila A.
author_facet Molini, Barbara J.
Tantalo, Lauren C.
Sahi, Sharon K.
Rodriguez, Veronica I.
Brandt, Stephanie L.
Fernandez, Mark C.
Godornes, Charmie B.
Marra, Christina M.
Lukehart, Sheila A.
author_sort Molini, Barbara J.
collection PubMed
description 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.
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spelling pubmed-49827552016-08-26 Macrolide Resistance in Treponema pallidum Correlates With 23S rDNA Mutations in Recently Isolated Clinical Strains Molini, Barbara J. Tantalo, Lauren C. Sahi, Sharon K. Rodriguez, Veronica I. Brandt, Stephanie L. Fernandez, Mark C. Godornes, Charmie B. Marra, Christina M. Lukehart, Sheila A. Sex Transm Dis Original Studies 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. Lippincott Williams & Wilkins 2016-09 2016-08-12 /pmc/articles/PMC4982755/ /pubmed/27513385 http://dx.doi.org/10.1097/OLQ.0000000000000486 Text en Copyright © 2016 American Sexually Transmitted Diseases Association All rights reserved. This is an open-access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND) (http://creativecommons.org/licenses/by-nc-nd/4.0/) , where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially.
spellingShingle Original Studies
Molini, Barbara J.
Tantalo, Lauren C.
Sahi, Sharon K.
Rodriguez, Veronica I.
Brandt, Stephanie L.
Fernandez, Mark C.
Godornes, Charmie B.
Marra, Christina M.
Lukehart, Sheila A.
Macrolide Resistance in Treponema pallidum Correlates With 23S rDNA Mutations in Recently Isolated Clinical Strains
title Macrolide Resistance in Treponema pallidum Correlates With 23S rDNA Mutations in Recently Isolated Clinical Strains
title_full Macrolide Resistance in Treponema pallidum Correlates With 23S rDNA Mutations in Recently Isolated Clinical Strains
title_fullStr Macrolide Resistance in Treponema pallidum Correlates With 23S rDNA Mutations in Recently Isolated Clinical Strains
title_full_unstemmed Macrolide Resistance in Treponema pallidum Correlates With 23S rDNA Mutations in Recently Isolated Clinical Strains
title_short Macrolide Resistance in Treponema pallidum Correlates With 23S rDNA Mutations in Recently Isolated Clinical Strains
title_sort macrolide resistance in treponema pallidum correlates with 23s rdna mutations in recently isolated clinical strains
topic Original Studies
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4982755/
https://www.ncbi.nlm.nih.gov/pubmed/27513385
http://dx.doi.org/10.1097/OLQ.0000000000000486
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