Gerald L Murray1,2,3,4, Kaveesha Bodiyabadu2,3,5, Jennifer Danielewski2,3, Suzanne M Garland1,2,3, Dorothy A Machalek2,3,6, Christopher K Fairley7,8, Jørgen S Jensen9, Deborah A Williamson4, Lit Y Tan5, Elisa Mokany5, Duygu Durukan7,8, Catriona S Bradshaw7,8. 1. The Department of Obstetrics and Gynaecology, The University of Melbourne, Parkville, Victoria, Australia. 2. Centre for Women's Infectious Diseases, The Royal Women's Hospital, Parkville, Victoria, Australia. 3. Molecular Microbiology Research Group, Murdoch Children's Research Institute, Parkville, Victoria, Australia. 4. Microbiological Diagnostic Unit Public Health Laboratory, The University of Melbourne, The Peter Doherty Institute for Infection and Immunity, Melbourne, Victoria, Australia. 5. SpeeDx, Sydney, Australia. 6. Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health, The University of Melbourne, Parkville, Victoria, Australia. 7. Melbourne Sexual Health Centre, Alfred Health, Carlton, Victoria, Australia. 8. Central Clinical School, Monash University, Melbourne, Victoria, Australia. 9. Statens Serum Institut, Copenhagen, Denmark.
Abstract
BACKGROUND: The basis of fluoroquinolone treatment failure for Mycoplasma genitalium is poorly understood. METHODS: To identify mutations associated with failure we sequenced key regions of the M. genitalium parC and gyrA genes for patients undergoing sequential therapy with doxycycline-moxifloxacin (201 patients, including 21 with failure) or doxycycline-sitafloxacin (126 patients, including 13 with failure). RESULTS: The parC G248T/S83I mutation was more common among patients with failed sequential doxycycline-moxifloxacin (present in 76.2% of failures vs 7.8% cures, P < .001) or doxycycline-sitafloxacin (50% vs 16.8%, respectively; P = .01) treatment. Doxycycline-sitafloxacin was more efficacious than doxycycline-moxifloxacin against infections carrying the parC mutation conferring S83I amino acid change. Treatment was more likely to fail in these infections if they had a concurrent gyrA mutation (M95I or D99N) (P = .07 for doxycycline-moxifloxacin group and P = .009 for doxycycline-sitafloxacin group), suggesting an additive effect. CONCLUSIONS: This study indicates that parC G248T/S83I mutations contribute to failure of moxifloxacin and sitafloxacin, and the findings will inform the development of quinolone resistance assays needed to ensure optimal selection of antimicrobials for M. genitalium.
BACKGROUND: The basis of fluoroquinolone treatment failure for Mycoplasma genitalium is poorly understood. METHODS: To identify mutations associated with failure we sequenced key regions of the M. genitaliumparC and gyrA genes for patients undergoing sequential therapy with doxycycline-moxifloxacin (201 patients, including 21 with failure) or doxycycline-sitafloxacin (126 patients, including 13 with failure). RESULTS: The parCG248T/S83I mutation was more common among patients with failed sequential doxycycline-moxifloxacin (present in 76.2% of failures vs 7.8% cures, P < .001) or doxycycline-sitafloxacin (50% vs 16.8%, respectively; P = .01) treatment. Doxycycline-sitafloxacin was more efficacious than doxycycline-moxifloxacin against infections carrying the parC mutation conferring S83I amino acid change. Treatment was more likely to fail in these infections if they had a concurrent gyrA mutation (M95I or D99N) (P = .07 for doxycycline-moxifloxacin group and P = .009 for doxycycline-sitafloxacin group), suggesting an additive effect. CONCLUSIONS: This study indicates that parCG248T/S83I mutations contribute to failure of moxifloxacin and sitafloxacin, and the findings will inform the development of quinolone resistance assays needed to ensure optimal selection of antimicrobials for M. genitalium.
Authors: Alexander Ring; Suraj Balakrishna; Frank Imkamp; Sara Burkard; Flurina Triet; Flurina Brunschweiler; Christina Grube; Rebecca Bodmer; Roger D Kouyos; Huldrych F Günthard; Dominique L Braun Journal: Open Forum Infect Dis Date: 2022-04-27 Impact factor: 4.423
Authors: Gerald L Murray; Kaveesha Bodiyabadu; Lenka A Vodstrcil; Dorothy A Machalek; Jennifer Danielewski; Erica L Plummer; Suzanne M Garland; David M Whiley; Emma L Sweeney; Catriona S Bradshaw Journal: Antimicrob Agents Chemother Date: 2022-04-27 Impact factor: 5.938
Authors: Duygu Durukan; Michelle Doyle; Gerald Murray; Kaveesha Bodiyabadu; Lenka Vodstrcil; Eric P F Chow; Jorgen S Jensen; Christopher K Fairley; Ivette Aguirre; Catriona S Bradshaw Journal: Emerg Infect Dis Date: 2020-08 Impact factor: 6.883
Authors: Teck-Phui Chua; Kaveesha Bodiyabadu; Dorothy A Machalek; Suzanne M Garland; Catriona S Bradshaw; Erica L Plummer; Jennifer Danielewski; Lenka A Vodstrcil; Michelle L Doyle; Gerald L Murray Journal: J Med Microbiol Date: 2021-09 Impact factor: 2.472
Authors: Lisa E Manhart; William M Geisler; Catriona S Bradshaw; Jørgen S Jensen; David H Martin Journal: Emerg Infect Dis Date: 2022-08 Impact factor: 16.126