The association between antimicrobial resistance mutations and treatment outcomes for Mycoplasma genitalium infections from 2018 to 2022: a cross-sectional study from Auckland, New Zealand
Shivani Fox-Lewis A # , Rose Forster
B C # * , Indira Basu A D , Matthew Blakiston A D and Gary McAuliffe E
A
B
C
D
E
Abstract
New Zealand has among the highest rates of antimicrobial resistance in Mycoplasma genitalium in the world. The aim of this study was to correlate treatment outcomes with 23S rRNA and parC mutations associated with macrolide and fluroquinolone resistance, respectively, in a cohort of sexual health clinic patients.
Laboratory and clinical data were collected for patients with M. genitalium infections attending Auckland Sexual Health Service between 1 January 2018 and 31 December 2022, who had a test-of-cure performed within 21–90 days of a treatment episode. Treatment outcomes were correlated with the presence or absence of resistance mutations and treatment regimen utilised.
A total of 95 infections from 93 patients met the study inclusion criteria. Eighty of 93 (86%) infections with available data were macrolide resistant, with 20 of 74 (27%) having both macrolide resistance and parC mutations. Sixteen of 20 (80%) of parC mutations were G248T (S83I), three of 20 (15%) G259T (D87Y) and one of 20 (5%) A247C (S83R). All macrolide-susceptible infections treated with doxycycline and azithromycin were cured (12/12), as were all macrolide-resistant infections without parC mutations treated with doxycycline and moxifloxacin (37/37). Cure rates for macrolide-resistant infections with parC mutations were lower, with variable and often multiple treatment courses; eight of 16 (50%) were cured using one course of sequential doxycycline and moxifloxacin, seven of nine (78%) with one course of minocycline, zero of two (0%) with pristinamycin and one of one (100%) with doxycycline and sitafloxacin.
Our findings highlight the differing treatment outcomes for infections with and without parC mutations, offering opportunities to refine management of M. genitalium infections.
Keywords: antimicrobial resistance, fluoroquinolone resistance, minocycline, moxifloxacin, Mycoplasma genitalium resistance, New Zealand, resistance-guided therapy, treatment outcomes, Western Pacific.
References
1 Jensen JS, Cusini M, Gomberg M, Moi H, Wilson J, Unemo M. 2021 European guideline on the management of Mycoplasma genitalium infections. J Eur Acad Dermatol Venereol 2022; 36(5): 641-650.
| Crossref | Google Scholar | PubMed |
2 Soni S, Horner P, Rayment M, Pinto-Sander N, Naous N, Parkhouse A, Bancroft D, Patterson C, Fifer H. British Association for Sexual Health and HIV national guideline for the management of infection with Mycoplasma genitalium (2018). Int J STD AIDS 2019; 30(10): 938-950.
| Crossref | Google Scholar | PubMed |
3 van der Schalk TE, Braam JF, Kusters JG. Molecular basis of antimicrobial resistance in Mycoplasma genitalium. Int J Antimicrob Agents 2020; 55(4): 105911.
| Crossref | Google Scholar | PubMed |
4 ASHM. Australian STI management guidelines for use in primary care; 2021. Available at https://ashm.org.au/resources/australian-sti-management-guidelines-for-use-in-primary-care/ [accessed 12 April 2024]
5 Aotearoa New Zealand STI management guidelines. Mycoplasma genitalium; 2021. Available at https://sti.guidelines.org.nz/infections/mycoplasma-genitalium/ [accessed 14 April 2024]
6 Machalek DA, Tao Y, Shilling H, Jensen JS, Unemo M, Murray G, Chow EPF, Low N, Garland SM, Vodstrcil LA, Fairley CK, Hocking JS, Zhang L, Bradshaw CS. Prevalence of mutations associated with resistance to macrolides and fluoroquinolones in Mycoplasma genitalium: a systematic review and meta-analysis. Lancet Infect Dis 2020; 20(11): 1302-1314.
| Crossref | Google Scholar | PubMed |
7 Murray GL, Bodiyabadu K, Danielewski J, Garland SM, Machalek DA, Fairley CK, Jensen JS, Williamson DA, Tan LY, Mokany E, Durukan D, Bradshaw CS. Moxifloxacin and sitafloxacin treatment failure in Mycoplasma genitalium infection: association with parC mutation G248T (S83I) and concurrent gyrA mutations. J Infect Dis 2020; 221(6): 1017-1024.
| Crossref | Google Scholar | PubMed |
8 Manhart LE, Jensen JS. Quinolone resistance–associated mutations in Mycoplasma genitalium: not ready for prime time. Sex Transm Dis 2020; 47(3): 199-201.
| Crossref | Google Scholar | PubMed |
9 Basu I, Roberts SA, Bower JE, Henderson G, Reid M. High macrolide resistance in Mycoplasma genitalium strains causing infection in Auckland, New Zealand. J Clin Microbiol 2017; 55(7): 2280-2282.
| Crossref | Google Scholar | PubMed |
10 Vesty A, McAuliffe G, Roberts S, Henderson G, Basu I. Mycoplasma genitalium antimicrobial resistance in community and sexual health clinic patients, Auckland, New Zealand. Emerg Infect Dis 2020; 26(2): 332-335.
| Crossref | Google Scholar | PubMed |
11 Anderson T, Coughlan E, Werno A. Mycoplasma genitalium macrolide and fluoroquinolone resistance detection and clinical implications in a selected cohort in New Zealand. J Clin Microbiol 2017; 55(11): 3242-3248.
| Crossref | Google Scholar | PubMed |
12 Vodstrcil LA, Plummer EL, Doyle M, Murray GL, Bodiyabadu K, Jensen JS, Whiley D, Sweeney E, Williamson DA, Chow EPF, Fairley CK, Bradshaw CS. Combination therapy for Mycoplasma genitalium, and new insights into the utility of parC mutant detection to improve cure. Clin Infect Dis 2022; 75(5): 813-823.
| Crossref | Google Scholar | PubMed |
13 Durukan D, Read TRH, Murray G, Doyle M, Chow EPF, Vodstrcil LA, Fairley CK, Aguirre I, Mokany E, Tan LY, Chen MY, Bradshaw CS. Resistance-guided antimicrobial therapy using doxycycline–moxifloxacin and doxycycline−2.5 g azithromycin for the treatment of Mycoplasma genitalium infection: efficacy and tolerability. Clin Infect Dis 2020; 71(6): 1461-1468.
| Crossref | Google Scholar | PubMed |
14 Read TRH, Fairley CK, Murray GL, Jensen JS, Danielewski J, Worthington K, Doyle M, Mokany E, Tan L, Chow EPF, Garland SM, Bradshaw CS. Outcomes of resistance-guided sequential treatment of Mycoplasma genitalium infections: a prospective evaluation. Clin Infect Dis 2019; 68(4): 554-560.
| Crossref | Google Scholar | PubMed |
15 Conway RJH, Cook S, Malone C, Bone S, Hassan-Ibrahim MO, Soni S. Clearance of Mycoplasma genitalium infection with moxifloxacin in the presence of quinolone resistance–associated mutations. Sex Transm Dis 2020; 47(3): 197-198.
| Crossref | Google Scholar | PubMed |
16 Murray GL, Bodiyabadu K, Vodstrcil LA, Machalek DA, Danielewski J, Plummer EL, Garland SM, Whiley DM, Sweeney EL, Bradshaw CS. parC variants in Mycoplasma genitalium: trends over time and association with moxifloxacin failure. Antimicrob Agents Chemother 2022; 66(5): e0027822.
| Crossref | Google Scholar | PubMed |
17 Le Roy C, Bébéar C, Pereyre S. Performance of three commercial molecular diagnostic assays for the simultaneous detection of Mycoplasma genitalium and macrolide resistance. J Clin Microbiol 2021; 59(6): e00020–21.
| Crossref | Google Scholar | PubMed |
18 Shipitsyna E, Khusnutdinova T, Budilovskaya O, Shedko E, Goloveshkina E, Khayrullina G, Krysanova A, Shalepo K, Savicheva A, Unemo M. Performance of the first commercial dual resistance assay, AmpliSens Mycoplasma genitalium-ML/FQ-Resist-FL, for detection of potential macrolide and quinolone resistance-associated mutations and prevalence of M. genitalium resistance mutations in St. Petersburg, Russia. Sex Transm Infect 2023; 99(3): 191-194.
| Crossref | Google Scholar | PubMed |
19 Sweeney EL, Lowry K, Ebeyan S, Lundgren M, Whiley DM. Evaluation of the SpeeDx MG parC (Beta) PCR assay for rapid detection of Mycoplasma genitalium quinolone resistance-associated mutations. J Clin Microbiol 2020; 58(10): e01432–20.
| Crossref | Google Scholar | PubMed |
20 Gardette M, Hénin N, Le Roy C, Guiraud J, Touati A, Bébéar C, Pereyre S. clinical performance of three commercial molecular diagnostic assays for the detection of fluoroquinolone resistance-associated mutations in Mycoplasma genitalium. J Clin Microbiol 2022; 60(12): e0113522.
| Crossref | Google Scholar | PubMed |
21 Murray GL, Plummer EL, Bodiyabadu K, Vodstrcil LA, Huaman JL, Danielewski JA, Chua TP, Machalek DA, Garland S, Doyle M, Sweeney EL, Whiley DM, Bradshaw CS. gyrA mutations in Mycoplasma genitalium and their contribution to moxifloxacin failure: time for the next generation of resistance-guided therapy. Clin Infect Dis 2023; 76(12): 2187-2195.
| Crossref | Google Scholar | PubMed |
22 Vandepitte J, Weiss HA, Kyakuwa N, Nakubulwa S, Muller E, Buvé A, Van der Stuyft P, Hayes R, Grosskurth H. Natural history of Mycoplasma genitalium infection in a cohort of female sex workers in Kampala, Uganda. Sex Transm Dis 2013; 40(5): 422-427.
| Crossref | Google Scholar | PubMed |
