TY - JOUR
T1 - Moxifloxacin and Sitafloxacin Treatment Failure in Mycoplasma genitalium Infection
T2 - Association with parC Mutation G248T (S83I) and Concurrent gyrA Mutations
AU - Murray, Gerald L.
AU - Bodiyabadu, Kaveesha
AU - Danielewski, Jennifer
AU - Garland, Suzanne M.
AU - Machalek, Dorothy A.
AU - Fairley, Christopher K.
AU - Jensen, Jørgen S.
AU - Williamson, Deborah A.
AU - Tan, Lit Y.
AU - Mokany, Elisa
AU - Durukan, Duygu
AU - Bradshaw, Catriona S.
PY - 2020/3/2
Y1 - 2020/3/2
N2 - 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.
AB - 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.
KW - Mycoplasma genitalium
KW - antibiotic resistance
KW - fluoroquinolone
KW - mutation
KW - treatment failure
UR - http://www.scopus.com/inward/record.url?scp=85079801378&partnerID=8YFLogxK
U2 - 10.1093/infdis/jiz550
DO - 10.1093/infdis/jiz550
M3 - Article
C2 - 32031634
AN - SCOPUS:85079801378
SN - 0022-1899
VL - 221
SP - 1017
EP - 1024
JO - The Journal of Infectious Diseases
JF - The Journal of Infectious Diseases
IS - 6
ER -