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RESEARCH ARTICLE (Open Access)

Individualised treatment of sexually transmitted infections by rapid molecular assays

Gerald L. Murray A B C * , Emma L. Sweeney D and Catriona S. Bradshaw E F G
+ Author Affiliations
- Author Affiliations

A The Department of Obstetrics and Gynaecology, The University of Melbourne, Parkville, Vic., Australia.

B Centre for Women’s Infectious Diseases, The Royal Women’s Hospital, Parkville, Vic., Australia.

C Molecular Microbiology Research Group, Murdoch Children’s Research Institute, Parkville, Vic., Australia.

D Centre for Clinical Research (UQCCR), Faculty of Medicine, The University of Queensland, Brisbane, Qld, Australia.

E Melbourne Sexual Health Centre, Alfred Hospital, Melbourne, Vic., Australia.

F School of Translational Medicine, Monash University, Melbourne, Vic., Australia.

G School of Population and Global Health, The University of Melbourne, Melbourne, Vic., Australia.




Gerald Murray is a senior research officer in the department of obstetrics, gynaecology and newborn health at The University of Melbourne, based at the Royal Women’s Hospital. His research interests include investigating mechanisms of antimicrobial resistance, studying the human microbiota in health and disease, and human papillomavirus (HPV).



Emma Sweeney is a senior research fellow at The University of Queensland Centre for Clinical Research. Her research interests include the development of novel molecular tools to detect and characterise pathogens of global health importance, with a particular focus on the sexually transmitted infection (STI) superbug Mycoplasma genitalium.



Catriona Bradshaw is a clinician researcher at Melbourne Sexual Health Centre, Monash University and Alfred Hospital. Her research interests include translational research to improve the treatment and control of drug resistant and refractory sexually transmitted infections.

* Correspondence to: gerald.murray@unimelb.edu.au

Microbiology Australia https://doi.org/10.1071/MA24035
Submitted: 7 June 2024  Accepted: 11 July 2024  Published: 30 July 2024

© 2024 The Author(s) (or their employer(s)). Published by CSIRO Publishing on behalf of the ASM. This is an open access article distributed under the Creative Commons Attribution 4.0 International License (CC BY).

Abstract

Antimicrobial resistance (AMR) is a major problem in the field of sexually transmitted infections (STIs), where escalating levels have coincided with a surge in infections. The individualised treatment of STIs by rapid molecular ‘resistance’ assays is a new approach to patient management that has developed through understanding of the mechanisms of resistance, combined with nucleic acid amplification diagnostics. Mycoplasma genitalium provides an excellent example of this approach because of a restricted repertoire of effective antibiotics, and resistance mediated by single nucleotide polymorphisms. Detection of one of five M. genitalium 23S rRNA gene mutations is highly predictive of treatment failure with macrolides; employing this diagnostically yields >95% cure with azithromycin. Detection of fluoroquinolone resistance mutations in parC (especially affecting serine 83) and gyrA is predicted to have a similar diagnostic value and is currently being evaluated. This work is underpinned by high quality resistance data, emphasising the importance of ongoing surveillance. Despite some limitations, individualised treatment has demonstrated value in antimicrobial stewardship, extending the use of current therapies despite substantial levels of resistance, reducing prescription of ineffective treatments and sparing last-resort antibiotics.

Keywords: antibiotic resistance, diagnostic tests, Mycoplasma genitalium, PCR, sexually transmitted infections, STIs.

Biographies

MA24035_B1.gif

Gerald Murray is a senior research officer in the department of obstetrics, gynaecology and newborn health at The University of Melbourne, based at the Royal Women’s Hospital. His research interests include investigating mechanisms of antimicrobial resistance, studying the human microbiota in health and disease, and human papillomavirus (HPV).

MA24035_B2.gif

Emma Sweeney is a senior research fellow at The University of Queensland Centre for Clinical Research. Her research interests include the development of novel molecular tools to detect and characterise pathogens of global health importance, with a particular focus on the sexually transmitted infection (STI) superbug Mycoplasma genitalium.

MA24035_B3.gif

Catriona Bradshaw is a clinician researcher at Melbourne Sexual Health Centre, Monash University and Alfred Hospital. Her research interests include translational research to improve the treatment and control of drug resistant and refractory sexually transmitted infections.

References

Wi T et al. (2017) Antimicrobial resistance in Neisseria gonorrhoeae: global surveillance and a call for international collaborative action. PLoS Med 14, e1002344.
| Crossref | Google Scholar | PubMed |

Machalek DA et al. (2020) Prevalence of mutations associated with resistance to macrolides and fluoroquinolones in Mycoplasma genitalium: a systematic review and meta-analysis. Lancet Infect Dis 20, 1302-1314.
| Crossref | Google Scholar | PubMed |

Murray GL et al. (2022) parC variants in Mycoplasma genitalium: trends over time and association with moxifloxacin failure. Antimicrob Agents Chemother 66, e0027822.
| Crossref | Google Scholar | PubMed |

Horner PJ, Martin DH (2017) Mycoplasma genitalium infection in men. J Infect Dis 216, S396-S405.
| Crossref | Google Scholar | PubMed |

Lis R et al. (2015) Mycoplasma genitalium infection and female reproductive tract disease: a meta-analysis. Clin Infect Dis 61, 418-426.
| Crossref | Google Scholar | PubMed |

Htaik K et al. (2024) Systematic review and meta analysis of the association between Mycoplasma genitalium and pelvic inflammatory disease. Clin Infect Dis: ciae295.
| Crossref | Google Scholar | PubMed |

Fookes MC et al. (2017) Mycoplasma genitalium: whole genome sequence analysis, recombination and population structure. BMC Genomics 18, 993.
| Crossref | Google Scholar | PubMed |

Hamasuna R et al. (2005) Antibiotic susceptibility testing of Mycoplasma genitalium by TaqMan 5’ nuclease real-time PCR. Antimicrob Agents Chemother 49, 4993-4998.
| Crossref | Google Scholar | PubMed |

Pitt R et al. (2022) Challenges of in vitro propagation and antimicrobial susceptibility testing of Mycoplasma genitalium. J Antimicrob Chemother 77, 2901-2907.
| Crossref | Google Scholar | PubMed |

10  Bradshaw CS et al. (2017) New horizons in Mycoplasma genitalium treatment. J Infect Dis 216, S412-S419.
| Crossref | Google Scholar | PubMed |

11  Hamasuna R et al. (2009) Antimicrobial susceptibilities of Mycoplasma genitalium strains examined by broth dilution and quantitative PCR. Antimicrob Agents Chemother 53, 4938-4939.
| Crossref | Google Scholar | PubMed |

12  Hamasuna R et al. (2018) Mutations in ParC and GyrA of moxifloxacin-resistant and susceptible Mycoplasma genitalium strains. PLoS ONE 13, e0198355.
| Crossref | Google Scholar | PubMed |

13  Jensen JS et al. (2008) Azithromycin treatment failure in Mycoplasma genitalium-positive patients with nongonococcal urethritis is associated with induced macrolide resistance. Clin Infect Dis 47, 1546-1553.
| Crossref | Google Scholar | PubMed |

14  Hamasuna R et al. (2022) Analysis of fluoroquinolone-resistance using MIC determination and homology modelling of ParC of contemporary Mycoplasma genitalium strains. J Infect Chemother 28, 377-383.
| Crossref | Google Scholar | PubMed |

15  Chua T-P et al. (2024) Evolving patterns of macrolide and fluoroquinolone resistance in Mycoplasma genitalium: an updated global systematic review and metaanalysis. SSRN 2024, 4764790 [Preprint, posted 21 March 2024] .
| Crossref | Google Scholar |

16  Murray GL et al. (2023) gyrA mutations in Mycoplasma genitalium and their contribution to moxifloxacin failure: time for the next generation of resistance-guided therapy. Clin Infect Dis 76, 2187-2195.
| Crossref | Google Scholar | PubMed |

17  Ando N et al. (2023) Effectiveness of sitafloxacin monotherapy for quinolone-resistant rectal and urogenital Mycoplasma genitalium infections: a prospective cohort study. J Antimicrob Chemother 78, 2070-2079.
| Crossref | Google Scholar | PubMed |

18  Clarke EJ et al. (2023) Efficacy of minocycline for the treatment of Mycoplasma genitalium. Open Forum Infect Dis 10, ofad427.
| Crossref | Google Scholar | PubMed |

19  Read TRH et al. (2019) Outcomes of resistance-guided sequential treatment of Mycoplasma genitalium infections: a prospective evaluation. Clin Infect Dis 68, 554-560.
| Crossref | Google Scholar | PubMed |

20  Chua TP et al. (2022) Impact of 16S rRNA single nucleotide polymorphisms on Mycoplasma genitalium organism load with doxycycline treatment. Antimicrob Agents Chemother 66, e0024322.
| Crossref | Google Scholar | PubMed |

21  Vodstrcil LA et al. (2022) Combination therapy for Mycoplasma genitalium, and new insights into the utility of parC mutant detection to improve cure. Clin Infect Dis 75, 813-823.
| Crossref | Google Scholar | PubMed |

22  Lahra MM et al. (2023) Australian Gonococcal Surveillance Programme Annual Report, 2022. Australian Government Department of Health and Aged Care.

23  Unemo M et al. (2021) WHO global antimicrobial resistance surveillance for Neisseria gonorrhoeae 2017–18: a retrospective observational study. Lancet Microbe 2, e627-e636.
| Crossref | Google Scholar | PubMed |

24  Trembizki E et al. (2016) Further evidence to support the individualised treatment of gonorrhoea with ciprofloxacin. Lancet Infect Dis 16, 1005-1006.
| Crossref | Google Scholar | PubMed |

25  Bell SFE et al. (2023) Antimicrobial susceptibility assays for Neisseria gonorrhoeae: a proof-of-principle population-based retrospective analysis. Lancet Microbe 4, e544-e551.
| Crossref | Google Scholar | PubMed |

26  Adawiyah RA et al. (2024) Cost effectiveness of resistance-guided therapy for Mycoplasma genitalium in Australia. Sci Rep 14(1), 12856.
| Crossref | Google Scholar | PubMed |