Impact of 16S rRNA Single Nucleotide Polymorphisms on Mycoplasma genitalium Organism Load with Doxycycline Treatment

Chua, Teck-Phui; Danielewski, Jennifer; Bodiyabadu, Kaveesha; Bradshaw, Catriona S; Machalek, Dorothy A; Garland, Suzanne M.; Plummer, Erica L; Vodstrcil, Lenka A; Murray, Gerald L

doi:10.1128/aac.00243-22

Cited by 7 publications

(3 citation statements)

References 47 publications

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“…While there are no large clinical studies using minocycline for the treatment of M genitalium , randomized trials largely conducted over a decade ago consistently found that the tetracycline doxycycline was inferior to azithromycin in eradicating M genitalium with proportion cured in the order of 20%–40% [ 4 ]. However, no molecular mechanisms of resistance in the 16S ribosomal RNA gene have been found to consistently explain the low efficacy of doxycycline [ 22 ], and no correlation between MICs and microbial cure has been demonstrated [ 20 ].…”

Section: Discussionmentioning

confidence: 99%

Efficacy of Minocycline for the Treatment ofMycoplasma genitalium

Clarke,

Vodstrcil,

Plummer

et al. 2023

Open Forum Infectious Diseases

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Background High levels of macrolide resistance and increasing fluoroquinolone resistance are making Mycoplasma genitalium increasingly difficult to treat. Minocycline is an alternative treatment for patients with macrolide-resistant M. genitalium infections that have failed moxifloxacin, or for those with fluoroquinolone contraindications or resistance. Published efficacy data for minocycline for M. genitalium are limited. Methods We evaluated minocycline 100 mg BD for 14 days at Melbourne Sexual Health Centre (MSHC). Microbial cure was defined as a negative test-of-cure within 14-90 days after completing minocycline. The proportion cured with 95% confidence intervals (CI) was calculated and logistic regression was used to explore factors associated with treatment failure. We pooled data from the current study with a prior adjacent case series of patients with M. genitalium who had received minocycline 100 mg BD for 14 days at MSHC. Results Minocycline cured 60 of 90 (67%, 95% confidence interval (CI) 56-76%) infections. Adherence was high (96%) and side-effects were mild and self-limiting. No demographic or clinical characteristics were associated with minocycline failure in regression analyses. In the pooled analyses of 123 patients, 83 (68%, 95% CI 58-76) were cured following minocycline. Conclusion Minocycline cured 68% of macrolide-resistant M. genitalium infections. These data provide tighter precision around the efficacy of minocycline for macrolide-resistant M. genitalium and show that it is a well- tolerated regimen. With high levels of macrolide-resistance, increasing fluoroquinolone resistance, and the high cost of moxifloxacin, access to non-quinolone options such as minocycline is increasingly important for the clinical management of M. genitalium.

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Section: Discussionmentioning

confidence: 99%

Efficacy of Minocycline for the Treatment ofMycoplasma genitalium

Clarke,

Vodstrcil,

Plummer

et al. 2023

Open Forum Infectious Diseases

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“…Despite the limited efficacy of doxycycline monotherapy for M. genitalium , with about one‐third of infections being cured, doxycycline is an important part of the current treatment regimen of resistance‐guided therapy and any reduction in efficacy of doxycycline for M. genitalium would have a substantial impact on the cure of an STI with already limited treatment options 30 . Although increases in doxycycline resistance have not been reported among small studies of M. genitalium , the molecular mechanisms of doxycycline resistance in this organism remain poorly understood, 31 precluding routine surveillance of doxycycline resistance in M. genitalium .…”

Section: Antimicrobial Stewardship Resistance and Microbiota Impactsmentioning

confidence: 99%

Response to the ASHM 2023 statement on the use of doxy‐PEP in Australia: considerations and recommendations

Bell,

Sweeney,

Kong

et al. 2024

Medical Journal of Australia

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Response to the ASHM 2023 statement on the use of doxy-PEP in Australia: considerations and recommendations I n September 2023, the Australasian Society for HIV, Viral Hepatitis and Sexual Health Medicine (ASHM) released the 2023 Consensus statement on doxycycline prophylaxis (doxy-PEP) for the prevention of syphilis, chlamydia and gonorrhoea among gay, bisexual, and other men who have sex with men in Australia, 1 which appears in this issue of the MJA. 2 The Statement addresses important considerations for the use of doxy-PEP to reduce acquisition, potential transmission, and negative sequalae primarily for syphilis, while noting its clinical benefit, albeit to a lesser extent, for chlamydial and gonococcal infection for gay and bisexual men who have sex with men (GBMSM). We commend ASHM on this timely and important statement, with people already requesting or using doxy-PEP, with or without clinical oversight. In response, we wish to further emphasise two important considerations for doxy-PEP implementation, notably, the potential threat of increasing antimicrobial resistance (AMR) and the urgent need to implement measures to effectively monitor doxy-PEP use and its impact.

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“…9,10 Similarly, M. genitalium has developed resistance to macrolide and fluoroquinolone antibiotics, with clinicians increasingly encountering infections that are difficult or impossible to treat. [11][12][13][14] To tackle the multifaceted problem of STI AMR, the Hub has four synergistic, cross-cutting research themes.…”

Section: The Exemplar Problem Of Sexually Transmitted Infections As P...mentioning

confidence: 99%

The AMR Hub: a public–private partnership to overcome barriers to commercialisation and deliver antimicrobial stewardship innovations

Bonello,

Applegate,

Badman

et al. 2024

Microbiol. Aust.

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Antimicrobial resistance (AMR) is recognised as one of the greatest scientific challenges of the 21st century, disproportionately affecting people living in low- and middle-income countries. With bacterial pathogens becoming increasingly resistant to antibiotics, there is an urgent need for innovative approaches to combat this growing threat. The World Health Organization has recognised this need and prioritised further research to enhance diagnostics, surveillance and our understanding the epidemiology and drivers of AMR. The Industrial Transformation Research Hub to Combat AMR, or the AMR Hub, is an Australian collaborative private–public research partnership involving over 20 organisations. It aims to foster multidisciplinary collaborations across sectors and develop wholistic solutions that address barriers to the commercialisation of tools to minimise the risks of AMR. The AMR Hub’s research is focusing on sexually transmitted infections, which are increasingly resistant to antibiotics and have few alternative candidates in the pipeline. Investigators are together developing novel diagnostics, optimising treatment, identifying tools to detect active bacterial infections, and engaging stakeholders to optimise AMR innovation. Through a multidisciplinary ecosystem across sectors, the AMR Hub seeks to fast-track the development of adaptable technologies, new antibiotics and stewardship innovations for prevention, while also addressing societal, economic and commercial aspects of AMR solutions.

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Impact of 16S rRNA Single Nucleotide Polymorphisms on Mycoplasma genitalium Organism Load with Doxycycline Treatment

Abstract: Doxycycline targets the 16S rRNA and is widely used for the treatment of sexually transmitted infections. While it is not highly effective at eradicating Mycoplasma genitalium infections, it can reduce organism load.

Cited by 7 publications

References 47 publications

Efficacy of Minocycline for the Treatment ofMycoplasma genitalium

Efficacy of Minocycline for the Treatment ofMycoplasma genitalium

Response to the ASHM 2023 statement on the use of doxy‐PEP in Australia: considerations and recommendations

The AMR Hub: a public–private partnership to overcome barriers to commercialisation and deliver antimicrobial stewardship innovations

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