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University of Washington San Francisco Department of Health St. James Hospital, Dublin, Ireland

Azithromycin resistance in Treponema pallidum in the United States and Ireland is associated with a mutation in the 23S rRNA gene. University of Washington San Francisco Department of Health St. James Hospital, Dublin, Ireland Johns Hopkins University. Major points.

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University of Washington San Francisco Department of Health St. James Hospital, Dublin, Ireland

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  1. Azithromycin resistance in Treponema pallidum in the United States and Ireland is associated with a mutation in the 23S rRNA gene University of Washington San Francisco Department of Health St. James Hospital, Dublin, Ireland Johns Hopkins University

  2. Major points • Observations of clinical failure • Searching for a resistance-associated mutation • Functional resistance in vivo—rabbit model • Development of a rapid screening method • Survey of samples from different geographical regions

  3. Benzathine penicillin G • Depot form of penicillin • Long half-life • Single dose for early syphilis • Painful intramuscular injection

  4. Azithromycin as an Alternative Therapy • Macrolide family • Long tissue half-life • Oral administration

  5. Published Studies of Azithromycin Treatment for Syphilis

  6. Case Report – July, 2003 • Day 0:33 yo HIV-infected man presented to ER with nontender penile ulcer x 1 week • Rx 2 g azithromycin PO • Day 1: Took additional 1 g azithromycin PO • Day 2: Presented SF STD Clinic for f/u • 1 cm indurated, nontender ulcer on glans penis • Left inguinal adenopathy • Serum VDRL NR; DF Neg

  7. Case Report – July, 2003 • Day 5: RTC with persistent ulcer • DF pos for T. pallidum • TP-PA Reactive • Rx 2.4 MU BPG • Day 19: RTC – resolution of lesion • 3 mo: VDRL Nonreactive

  8. Sequence Analysis of 23S rRNA Gene in Selected T. pallidum Strains

  9. Functional Evidence of Azithromycin Resistance – Rabbit Model • Intradermal infection 106Tp/site • Nichols or Street 14 strain • Treatment groups • Untreated • BPG • Erythromycin (2 g/day x 14 d) • Azithromycin (1 g/day x 14d)

  10. Outcome – Rabbit Study

  11. PCR amplify 23S rRNA gene fragment 628 bp Rapid screening method TAGACGGAAAGACCCC TAGACGGGAAGACCCC Mbo II Mutation Cut with Mbo II No 628 bp Yes 440 bp 188 bp

  12. 23S rRNA Gene Mutation in Treponema pallidum Samples

  13. Restriction Digestion of 23S rRNA Gene Amplicon

  14. Sequence Analysis of 23S rRNA Gene in Selected T. pallidum Strains

  15. Summary • A → G mutation in 23S rRNA gene confers azithromycin resistance in T. pallidum • Rapid restriction digestion method can detect mutation in swab specimens from ulcers • Mutation is found in multiple geographical locations

  16. Implications • The true prevalence of resistant strains is unknown, but worrisome. • If azithromycin is used for treatment of syphilis, close follow-up must be assured. • In geographical regions where resistance may be relatively high, the recommended treatment for syphilis should remain penicillin.

  17. University of Washington Sheila Lukehart, Ph.D. Christina Marra, M.D. Charmie Godornes Barbara Molini, M.S. Patricia Sonnet St. James Hospital, Dublin, Ireland Susan Hopkins, M.D. Fiona Mulcahy, M.D. San Francisco Department of Health Joseph Engelman, M.D. Samuel J. Mitchell, M.D., Ph.D. Jeffrey D. Klausner, M.D., M.P.H. Johns Hopkins University Anne Rompalo, M.D. Authors

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