Prevalence of mutations associated with resistance to macrolides and fluoroquinolones in Mycoplasma genitalium: a systematic review and meta-analysis

Machalek, Dorothy A; Tao, Yusha; Shilling, Hannah; Jensen, Jørgen Skov; Unemo, Magnus; Murray, Gerald L; Chow, Eric P F; Low, Nicola; Garland, Suzanne M.; Vodstrcil, Lenka A; Fairley, Christopher K; Hocking, Jane; Zhang, Lei; Bradshaw, Catriona S

doi:10.1016/s1473-3099(20)30154-7

Cited by 189 publications

(230 citation statements)

References 81 publications

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“…The mutations in 23S rRNA and parC have been identi ed as the cause of failure of macrolide and quinolone in the treatment of M. genitalium [53,54]. In our study, 66.4% (101/152) and 77.7% (108/139) of samples manifested mutations in 23S rRNA and parC genes, and A2072G (59/101, 58.4%) and S83I (79/108, 73.1%) were highly predominating in 23S rRNA and parC genes, respectively.…”

Section: Discussionmentioning

confidence: 99%

Macrolide and fluoroquinolone associated mutations in Mycoplasma genitalium in a retrospective study of male and female patients seeking care at a STI Clinic in Guangzhou, China, 2016-2018.

Tso

et al. 2020

Preprint

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Background Antimicrobial resistance in M. genitalium is a growing clinical problem. We investigated the mutations associated with macrolide and fluoroquinolone resistance, two commonly used medical regimens for treatment in China. Our aim is to analyze the prevalence and diversity of mutations among M. genitalium-positive clinical specimens in Guangzhou, south China.Methods A total of 154 stored M. genitalium positive specimens from men and women attending a STI clinic were tested for macrolide and fluoroquinolone mutations. M. genitalium was detected via TaqMan MGB real-time PCR. Mutations associated with macrolide resistance were detected using primers targeting region V of the 23S rRNA gene. Fluoroquinolone resistant mutations were screened via primers targeting topoisomerase IV (parC) and DNA gyrase (gyrA).Results 98.7% (152/154), 95.5% (147/154) and 90.3% (139/154) of M. genitalium positive samples produced sufficient amplicon for detecting resistance mutations in 23S rRNA, gyrA and parC genes, respectively. 66.4% (101/152), 0.7% (1/147) and 77.7% (108/139) samples manifested mutations in 23S rRNA, gyrA and parC genes, respectively. A2072G (59/101, 58.4%) and S83I (79/108, 73.1%) were highly predominating in 23S rRNA and parC genes, respectively. Two samples had amino acid substitutions in gyrA (M95I and A96T, respectively). Two samples had two amino acid substitutions in parC (S83I + D87Y). 48.6% (67/138) of samples harbored both macrolide and fluoroquinolone resistance-associated mutations. The most common combination of mutations was A2072G (23S rRNA) and S83I (parC) (40/67, 59.7%). One sample had three amino acid changes in 23S rRNA, gyrA and parC genes (A2072G + A96T + S83I).Conclusions The high antimicrobial resistance rate of M. genitalium in Guangzhou is a very worrying problem and suggests that antimicrobial resistance testing and the development of new antibiotic regimens are crucially needed.

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Section: Discussionmentioning

confidence: 99%

Macrolide and fluoroquinolone associated mutations in Mycoplasma genitalium in a retrospective study of male and female patients seeking care at a STI Clinic in Guangzhou, China, 2016-2018.

Tso

et al. 2020

Preprint

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“…The univariable analysis showed that women who were younger, in their first pregnancy, employed, single or separated, had never used a modern method of contraception, or had abnormal vaginal discharge at any time in their current pregnancy were at increased risk for certain STIs, to varying degrees of statistical significance. In the multivariable analysis, primigravida women and those 16 16; p = 0.02).…”

Section: Factors Associated With Curable Stismentioning

confidence: 93%

“…In pregnant women, estimates range from 0.7% in the United Kingdom (14) to 11.9% in the Solomon Islands (15). During 2010-2019, global macrolide resistance to M. genitalium increased from 10% to >50% (16). In many regions, the prevalence of M. genitalium and its susceptibility to antimicrobial drugs is unknown.…”

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confidence: 99%

Mycoplasma genitalium and Other Reproductive Tract Infections in Pregnant Women, Papua New Guinea, 2015–2017

Scoullar¹,

Boeuf²,

Peach³

et al. 2021

Emerg. Infect. Dis.

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Much about the range of pathogens, frequency of coinfection, and clinical effects of reproductive tract infections (RTIs) among pregnant women remains unknown. We report on RTIs ( Mycoplasma genitalium , Chlamydia trachomatis , Neisseria gonorrhoeae , Trichomonas vaginalis , Treponema pallidum subspecies pallidum , bacterial vaginosis, and vulvovaginal candidiasis) and other reproductive health indicators in 699 pregnant women in Papua New Guinea during 2015–2017. We found M. genitalium , an emerging pathogen in Papua New Guinea, in 12.5% of participants. These infections showed no evidence of macrolide resistance. In total, 74.1% of pregnant women had > 1 RTI; most of these infections were treatable. We detected sexually transmitted infections (excluding syphilis) in 37.7% of women. Our findings showed that syndromic management of infections is greatly inadequate. In total, 98.4% of women had never used barrier contraception. These findings will inform efforts to improve reproductive healthcare in Papua New Guinea.

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“…The macrolide azithromycin is the currently recommended first-line treatment, but macrolide resistance mutations (MRMs) arising from single nucleotide changes to the 23S rRNA gene confer resistance to treatment. These mutations are becoming increasingly common, with a recent meta-analysis finding an increase in prevalence from 10.0% [95% confidence interval (CI) 2.6-20.1%] prior to 2010, to 51.4% (40.3-62.4%) in 2016-17 [3]. The prevalence of resistance in some specific populations is even higher, with MRM levels of 84.2% reported in asymptomatic men who have sex with men in Australia [4].…”

Section: Introductionmentioning

confidence: 99%

“…The second-line therapy in many guidelines is the fluoroquinolone moxifloxacin, to which resistance is also increasing [3]. In the context of high levels of resistance, the use of diagnostic tests that also detect resistance mutations has shown promise for directing clinicians towards prescribing the most efficacious treatment (known as 'resistance-guided therapy'), with corresponding increases in overall levels of cure [5,6].…”

Section: Introductionmentioning

confidence: 99%

Evaluation of ResistancePlus MG FleXible, a ‘near-patient’ test for the detection of Mycoplasma genitalium and macrolide resistance mutations, using freshly collected clinical samples

Murray

Doyle

Bodiyabadu

et al. 2021

Journal of Medical Microbiology

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Introduction. Mycoplasma genitalium is a sexually transmitted pathogen with increasing resistance to first- and second-line antimicrobials. The ‘near-patient test’ ResistancePlus MG FleXible (SpeeDx) detects M. genitalium plus four macrolide resistance mutations (MRMs), facilitating same-day patient follow up. Hypothesis/Gap Statement. This assay has not been assessed on freshly collected samples. Aim. Our goal was to evaluate the performance of the ResistancePlus MG FleXible test against the standard of care open platform test. Methods. ResistancePlus MG FleXible (analysed on the Cepheid GeneXpert platform) was evaluated on freshly collected samples and compared to the standard of care open platform test ResistancePlus MG (SpeeDx) analysed on the LightCycler 480 II (Roche). Results. For 270 valid tests, ResistancePlus MG FleXible yielded a high positive per cent agreement (PPA) of 94.1% [96/102; 95 % confidence interval (CI): 87.6–97.8 %] and negative per cent agreement (NPA) of 95.2% (160/168; 95 % CI: 90.8–97.9%) for M. genitalium detection compared to the reference assay (kappa for test concordance of 0.89; 95 % CI: 0.83–0.95). Performance was similar across different sample types. For the detection of MRMs, ResistancePlus MG FleXible had a PPA of 97.1% (66/68; 95% CI: 89.8–99.6) and NPA of 78.6% (22/28; 95 % CI: 59.0–91.7), with test comparison kappa of 0.79 (95 % CI: 0.65–0.93). Notably, of six discordant results (i.e. determined to be wild type by the reference assay), five were positive for MRMs by Sanger sequencing, indicating that the ResistancePlus MG FleXible assay has an improved performance for mutation detection. Conclusion. ResistancePlus MG FleXible had comparable test performance for M. genitalium detection as the open platform assay, with improved detection of MRMs. The ResistancePlus MG FleXible ‘near-patient’ assay can deliver a rapid result to expedite appropriate treatment.

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Prevalence of mutations associated with resistance to macrolides and fluoroquinolones in Mycoplasma genitalium: a systematic review and meta-analysis

Abstract: Background: We summarised data from studies reporting on macrolide and fluoroquinolone resistanceassociated mutations in Mycoplasma genitalium, examined temporal trends, and associations with geographical location, sex and population.

Cited by 189 publications

References 81 publications

Macrolide and fluoroquinolone associated mutations in Mycoplasma genitalium in a retrospective study of male and female patients seeking care at a STI Clinic in Guangzhou, China, 2016-2018.

Macrolide and fluoroquinolone associated mutations in Mycoplasma genitalium in a retrospective study of male and female patients seeking care at a STI Clinic in Guangzhou, China, 2016-2018.

Mycoplasma genitalium and Other Reproductive Tract Infections in Pregnant Women, Papua New Guinea, 2015–2017

Evaluation of ResistancePlus MG FleXible, a ‘near-patient’ test for the detection of Mycoplasma genitalium and macrolide resistance mutations, using freshly collected clinical samples

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Prevalence of mutations associated with resistance to macrolides and fluoroquinolones in Mycoplasma genitalium: a systematic review and meta-analysis

Abstract: Background: We summarised data from studies reporting on macrolide and fluoroquinolone resistanceassociated mutations in Mycoplasma genitalium, examined temporal trends, and associations with geographical location, sex and population.

Cited by 189 publications

References 81 publications

Macrolide and fluoroquinolone associated mutations in Mycoplasma genitalium in a retrospective study of male and female patients seeking care at a&nbsp;STI Clinic in Guangzhou, China, 2016-2018.

Macrolide and fluoroquinolone associated mutations in Mycoplasma genitalium in a retrospective study of male and female patients seeking care at a&nbsp;STI Clinic in Guangzhou, China, 2016-2018.

Mycoplasma genitalium and Other Reproductive Tract Infections in Pregnant Women, Papua New Guinea, 2015–2017

Evaluation of ResistancePlus MG FleXible, a ‘near-patient’ test for the detection of Mycoplasma genitalium and macrolide resistance mutations, using freshly collected clinical samples

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Macrolide and fluoroquinolone associated mutations in Mycoplasma genitalium in a retrospective study of male and female patients seeking care at a STI Clinic in Guangzhou, China, 2016-2018.

Macrolide and fluoroquinolone associated mutations in Mycoplasma genitalium in a retrospective study of male and female patients seeking care at a STI Clinic in Guangzhou, China, 2016-2018.