EFFICACY OF PRISTINAMYCIN FOR TREATMENT RESISTANT MYCOPLASMA GENITALIUM.

Tim Read1,2, Jorgen Jensen3, Meiken Grant 2, Christopher Fairley1,2, Jennifer Danielewski 4,5, Jenny Su4,5, Lenka Vodstrcil 2, Karen Worthington2, Suzanne Garland4,5,6, Sepehr Tabrizi 4,5,6, Catriona Bradshaw 1,2

1Central Clinical School, Monash University, 2Melbourne Sexual Health, Centre, Alfred Health, 3Statens Serum Institute, Copenhagen, Denmark 4Murdoch Childrens Research Institute, Parkville, Victoria, 3052, Australia 5Department of Microbiology and Infectious Diseases, The Royal Women’s Hospital, Melbourne, Australi,6Department of Obstetrics and Gynaecology, University of Melbourne, Melbourne, Victoria, Australia.

Background: Macrolide resistance is becoming more prevalent in Mycoplasma genitalium and azithromycin failure now occurs in up to 50% of infections in Melbourne. The suitability of fluoroquinolones as alternatives is lessened by the emergence of resistance and by uncommon but serious side- effects. Safe alternative antimicrobials, including new classes, are urgently needed. Melbourne Sexual Health Centre has evaluated varying doses and combinations of pristinamycin, a streptogramin, for macrolide-resistant M. genitalium since August 2013.

Methods: We report proportions of patients cured, by dosage regimen and site of infection. Microbiologic cure was determined by polymerase chain reaction (PCR) ≥14 days after the initiation of treatment. Treatment failures had a positive PCR or symptoms requiring treatment. Macrolide resistance mutations were detected by sequencing of the 23S rRNA gene spanning two single nucleotide positions on stored pre- and post-treatment samples.

Results: Outcomes are reported for 130 macrolide-resistant M. genitalium infections treated with pristinamycin from August 2013 to January 2016. Of these 94 (72%) were urine or urethral samples, 30 (23%) were anal swabs and 6 (5%) were cervical swabs. Proportions cured by each regimen were: pristinamycin 1g bd 8/15 [53% (95% confidence interval (CI) 27, 79)], pristinamycin 1g tds with doxycycline 100mg bd 45/60 [75% (95%CI 62, 85)], pristinamycin 1g qid 38/55 69% (95%CI 55, 81)]. There was no significant difference in outcomes by site of infection or with increasing dose, p trend 0.92. Preliminary analyses indicate specific macrolide mutations in position 2058 of the 23S rRNA gene may be associated with pristinamycin failure; full macrolide and ribosomal protein gene resistance analyses will be presented.

Conclusion: Pristinamycin is not a highly effective alternative for macrolide- resistant M. genitalium, achieving cure at maximal dose or with doxycycline in 70-75% of macrolide-resistance infections, but may be the only currently available option for patients in whom fluoroquinolones are contraindicated.

Conflict of Interest: The authors declare no competing interests. Tim Read is funded by NHMRC early career fellowship 1091536.