Outcomes of Resistance-guided Sequential Treatment of<i>Mycoplasma genitalium</i>Infections: A Prospective Evaluation

Read, Timothy Richard; Fairley, Christopher K.; Murray, Gerald L; Jensen, Jørgen Skov; Danielewski, Jennifer; Worthington, Karen; Doyle, Martha; Mokany, Elisa; Tan, Litty; Chow, Eric P F; Garland, Suzanne M.; Bradshaw, Catriona

doi:10.1093/cid/ciy477

Cited by 161 publications

(150 citation statements)

References 27 publications

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“…Treatment strategies to maintain the use of existing antimicrobials are now being evaluated since resistance to second line treatment with moxifloxacin is already increasing (Murray et al, 2017). In an observational study, resistance-guided therapy for symptomatic M. genitalium, with initial treatment with doxycycline followed by 2.5 g azithromycin over three days for macrolide susceptible infections and sitafloxacin for resistant infections resulted in an incidence of de novo macrolide resistance of 2.6% (95% CI [0.3-9.2]%) (Read et al, 2019). Randomized controlled trials are now needed to evaluate different treatment algorithms and new antimicrobials or combination therapy that might have a lower propensity for the emergence of de novo resistance (Bradshaw, Jensen & Waites, 2017).…”

Section: Resultsmentioning

confidence: 99%

Understanding the spread of de novo and transmitted macrolide-resistance in Mycoplasma genitalium

Cadosch

García

Jensen

et al. 2020

PeerJ

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Background The rapid spread of azithromycin resistance in sexually transmitted Mycoplasma genitalium infections is a growing concern. It is not yet clear to what degree macrolide resistance in M. genitalium results from the emergence of de novo mutations or the transmission of resistant strains. Methods We developed a compartmental transmission model to investigate the contribution of de novo macrolide resistance mutations to the spread of antimicrobial-resistant M. genitalium. We fitted the model to resistance data from France, Denmark and Sweden, estimated the time point of azithromycin introduction and the rates at which infected individuals receive treatment, and projected the future spread of resistance. Results The high probability of de novo resistance in M. genitalium accelerates the early spread of antimicrobial resistance. The relative contribution of de novo resistance subsequently decreases, and the spread of resistant infections in France, Denmark and Sweden is now mainly driven by transmitted resistance. If treatment with single-dose azithromycin continues at current rates, macrolide-resistant M. genitalium infections will reach 25% (95% confidence interval, CI [9–30]%) in France, 84% (95% CI [36–98]%) in Denmark and 62% (95% CI [48–76]%) in Sweden by 2025. Conclusions Blind treatment of urethritis with single-dose azithromycin continues to select for the spread of macrolide resistant M. genitalium. Clinical management strategies for M. genitalium should limit the unnecessary use of macrolides.

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Section: Resultsmentioning

confidence: 99%

Understanding the spread of de novo and transmitted macrolide-resistance in Mycoplasma genitalium

Cadosch

García

Jensen

et al. 2020

PeerJ

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“…This strategy has been recommended [1,2] given the poor clinical response of M. genitalium to doxycycline (30-40%) [20][21][22], although this antibiotic has recently been recommended for the empirical treatment of non-gonococcal urethritis (of unknown aetiology) due to growing resistance to macrolides in M. genitalium, attributable to the widespread use of azithromycin 1 g for the treatment of C. trachomatis infection [23]. Recently, resistance-guided sequential treatment (doxycycline initially followed by azithromycin or sitafloxacin depending on the resistance test) has shown good efficacy, eradicating the infection and limiting the selection of antibiotic resistance [24]. This strategy could be a possibility in the context of high macrolide resistance rates and/or when guided therapy cannot be applied rapidly.…”

Section: Discussionmentioning

confidence: 99%

Molecular Typing of Mycoplasma genitalium-Positive Specimens Discriminates between Persistent and Recurrent Infections in Cases of Treatment Failure and Supports Contact Tracing

2019

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Mycoplasma genitalium causes a sexually transmitted infection that sometimes persists or recurs despite adequate antibiotic treatment. Between 2014 and 2018, molecular typing was applied to 75 M. genitalium-positive samples from 48 patients with repeated infection and/or couples/groups of other infected sexual contacts. MG191 adhesin, MG309 lipoprotein, and the rRNA operon were amplified, sequenced, and typed using phylogenetic, variable number tandem repeat, and single-nucleotide polymorphism analysis, respectively. Amplicons were obtained in 74/75 samples, and the combination of locus patterns gave 44 different genetic profiles (discriminatory index of 0.987), with 43 considering only MG191 and MG309. Interestingly, 15/17 patients who presented a first sample sensitive and a second resistant to macrolides had the same genetic variant in the samples (persistence of the same strain). In 2/17 patients, discordant variants (one mixed infection and one recurrence due to incomplete contact tracing) were detected. In 31 additional not related and randomly distributed samples, MG191 typing obtained 23 different genotypes, with no appreciable clustering over time. The typing method allowed persistent and recurrent infections to be distinguished, indicating that macrolide resistance-associated mutations mostly developed during treatment. To detect these secondary resistant strains, prevent reinfections, and improve the control of M. genitalium infections, tests of cure and contact tracing of sexual partners should be mandatory.

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“…1A, data, including sex, age, sample type, and sample load (determined by retrospective analysis, as described in the following section) were extracted for samples (n ϭ 531; 319 urine samples, 63 anal/rectal swabs, 89 cervical/endocervical swabs, 54 vaginal swabs, and 6 urethral swabs) testing positive for M. genitalium between 16 June 2016 to 30 January 2017. Estimates of load were previously determined for a subset of 499 samples using a validated M. genitalium-specific 16S rRNA quantitative PCR method (not used for routine clinical care; published limit of detection, 6 copies of 16S rRNA gene) (2,11). These data were used for a comparison of quantitation methods and also for analysis of load by sample type.…”

Section: Methodsmentioning

confidence: 99%

Analysis of Infection Loads in Mycoplasma genitalium Clinical Specimens by Use of a Commercial Diagnostic Test

et al. 2019

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Mycoplasma genitalium is a common sexually transmitted infection with a propensity to acquire resistance to commonly used antimicrobial therapies. Bacterial load has been linked to patient symptoms and the success of treatment. In this study, we demonstrate methodology to estimate load from routine diagnostic assays using the ResistancePlus MG test (SpeeDx Pty Ltd., Australia). The method gave comparable quantitation to an M. genitalium-specific 16S rRNA quantitative PCR (qPCR; Spearman r = 0.94) for the samples analyzed (n = 499, including urine and swab types as detailed below) and was, therefore, employed to analyze typical load levels for samples in a diagnostic laboratory (total of 1,012 tests). When stratified by sample type, female urine (median, 826 genomes/ml) had the lowest load. This was significantly lower than median loads for all other sample types (male urine [6.91 × 103 genomes/ml], anal swabs [5.50 × 103], cervical swabs [8.15 × 103], endocervical swabs [3.97 × 103], and vaginal swabs [6.95 × 103]) (P < 0.0001). There were no significant differences in load estimates between the other sample types. Reproducibility of load estimates conducted on the same samples was high (r > 0.85). In conclusion, this methodology to provide load estimates for M. genitalium can be easily integrated into routine diagnostic laboratory workflow. Given the association between organism load, symptoms, and treatment success, load assessment has future diagnostic potential.

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Outcomes of Resistance-guided Sequential Treatment ofMycoplasma genitaliumInfections: A Prospective Evaluation

Abstract: In the context of high levels of antimicrobial resistance, switching from azithromycin to doxycycline for presumptive treatment of M. genitalium, followed by resistance-guided therapy, cured ≥92% of infections, with infrequent selection of macrolide resistance.

Cited by 161 publications

References 27 publications

Understanding the spread of de novo and transmitted macrolide-resistance in Mycoplasma genitalium

Understanding the spread of de novo and transmitted macrolide-resistance in Mycoplasma genitalium

Molecular Typing of Mycoplasma genitalium-Positive Specimens Discriminates between Persistent and Recurrent Infections in Cases of Treatment Failure and Supports Contact Tracing

Analysis of Infection Loads in Mycoplasma genitalium Clinical Specimens by Use of a Commercial Diagnostic Test

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