Azithromycin 1.5g Over 5 Days Compared to 1g Single Dose in Urethral
            <i>Mycoplasma genitalium</i>
            : Impact on Treatment Outcome and Resistance

Read, Timothy Richard; Fairley, Christopher K.; Tabrizi, Sepehr N.; Bissessor, Melanie; Vodstrcil, Lenka A; Chow, Eric P F; Grant, M; Danielewski, Jennifer; Garland, Suzanne M.; Hocking, Jane S; Chen, Marcus Y; Bradshaw, Catriona

doi:10.1093/cid/ciw719

Cited by 66 publications

(85 citation statements)

References 21 publications

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“…This study provides only moderate evidence that fewer patients with MG urogenital infection will fail treatment and develop macrolide resistance with the extended 5-day regimen compared with azithromycin 1 g which conflicts with the recent findings of Read et al 30. Caution needs to be continued to be exercised when using the extended regimen as a replacement for azithromycin 1 g and all patients followed up to establish that they have been cured as some patients will still fail treatment either due to pre-existent macrolide resistance or to its emergence following treatment and may be asymptomatic 1–3 25.…”

Section: Discussioncontrasting

confidence: 99%

“…Finally, an alternative but not mutually exclusive explanation is that in populations with high level of resistance mixed infections, not detected with the current methodologies, would tend to contribute to apparent resistance development. Taken together, the conclusion of Read et al that the extended azithromycin 1.5 g was no more effective than a single 1 g dose should be viewed with caution and highlights the need for further high-quality prospective studies using this regimen 30. When the data from the Read study is added to this study and combined in a crude way, no difference is observed between azithromycin 1 g and the extended regimen in post-treatment macrolide mutations (p=0.09) but remains significantly different when patients with prior doxycycline are included (p=0.005).…”

Section: Discussionmentioning

confidence: 99%

“…However, these findings could be explained by the presence of macrolide-resistant micro-organisms in the population prior to treatment; the efficacy of both regimens is affected in macrolide-resistant isolates 1 28. Recently, Read et al in a retrospective observational study found that 4/34 (12%, 95% CI 3% to 27%) patients with wild-type infection had macrolide post-treatment mutations with the azithromycin-extended 5-day regimen 30. The duration of follow-up was median 36 days (14–100 days) with a loss to follow-up of 63 (37%) of 169 men.…”

Section: Discussionmentioning

confidence: 99%

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Which azithromycin regimen should be used for treating Mycoplasma genitalium? A meta-analysis

et al. 2017

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General rightsThis document is made available in accordance with publisher policies. Please cite only the published version using the reference above. Full terms of use are available: http://www.bristol.ac.uk/pure/about/ebr-terms  Azithromycin 1g treatment is associated with 13.9% (7.7-20.1%) rate of failure and 12.0%(7.1-16.9%) risk of macrolide antimicrobial resistance. There is moderate but conflicting evidence that the 5 day regimen may be more effective and less likely to cause resistance. The difference in failure and resistance rates is 9.7% (95% CI: 4.3-15.0%, p=0.012) and 8.5%(95% CI: 3.2-13.8%, p=0.027) respectively. 3 AbstractBackground: There is increasing evidence that azithromycin 1g is driving the emergence of

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Section: Discussioncontrasting

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Which azithromycin regimen should be used for treating Mycoplasma genitalium? A meta-analysis

et al. 2017

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“…genitalium and macrolide testing in asymptomatic patients. The data presented indicate that 63.1% of the specimens had macrolide resistance-associated mutations; however, these single nucleotide mutations confer high-level resistance to azithromycin and have been consistently associated with clinical failure of this drug (10, 24). Comparison to phenotypic resistance assay results was not possible in this study due to the well-established difficulty in culturing M.…”

Section: Resultsmentioning

confidence: 91%

Prospective Evaluation of ResistancePlus MG, a New Multiplex Quantitative PCR Assay for Detection of Mycoplasma genitalium and Macrolide Resistance

Tabrizi

Bradshaw

et al. 2017

J Clin Microbiol

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Mycoplasma genitalium is a significant pathogen for which first-line treatment is becoming less effective due to increased resistance to macrolides. As conventional culture and antimicrobial susceptibility testing is not feasible for routine detection of this pathogen, molecular markers such as detection of mutations in the 23S rRNA gene have been described to predict resistance. Recently, a novel multiplex quantitative PCR (qPCR) assay, ResistancePlus MG, has been described for the simultaneous detection of Mycoplasma genitalium and macrolide resistance. In the current study, the clinical performance of the assay was evaluated on 1,089 consecutive urine and anogenital swab samples in symptomatic and asymptomatic male and female patients. Overall, 6.0% were positive for M. genitalium, with 63.1% having macrolide resistance-associated mutations. Compared to the laboratory-validated qPCR method targeting the 16S rRNA gene and Sanger sequencing to determine 23S rRNA mutations, the sensitivity and specificity of M. genitalium detection were 98.5% and 100% and for detection of macrolide resistance mutations were 100.0% and 96.2%, respectively. This assay offers a considerable advantage in clinical settings for M. genitalium testing by making the results of macrolide resistance and mutation analyses simultaneously available, which is increasingly important with escalating macrolide resistance.

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“…The men carried a wild-type organism before treatment, but their post-treatment specimens contained mutations in the 23S rRNA gene that conferred macrolide resistance [18]. Since then, other investigators have also detected macrolide resistance mutations de novo (also known as acquired, induced or selected) in M. genitalium [7,10,[19][20][21][22].…”

Section: Introductionmentioning

confidence: 99%

De novo mutations drive the spread of macrolide-resistant Mycoplasma genitalium: a mathematical modelling study

Cadosch¹,

García²,

Althaus³

et al. 2018

Preprint

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The rapid spread of azithromycin resistance in sexually transmitted infections caused by Mycoplasma genitalium 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. We analysed epidemiological data and developed a compartmental model to investigate the contribution of de novo macrolide resistance mutations to the spread of antimicrobial resistant M.genitalium. We fitted the model to data from France, Sweden and Denmark and estimated treatment rates and the time point of azithromycin introduction. In a meta-analysis of six studies, we estimated that de novo resistance develops in 12% (95% CI 7 -17%, I 2 44%) of M. genitalium infections treated with 1g azithromycin.Our model shows that the high probability of de novo resistance is responsible for the observed rapid spread of antimicrobial resistant M. genitalium. The estimated per capita treatment rate in France was lower than in Denmark and Sweden but confidence intervals for the three estimates overlap. The estimated dates of introduction of azithromycin in each country are consistent with published reports.

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Azithromycin 1.5g Over 5 Days Compared to 1g Single Dose in Urethral Mycoplasma genitalium : Impact on Treatment Outcome and Resistance

Abstract: Extended azithromycin 1.5g was no more effective than a single 1g dose at achieving cure of M. genitalium urethritis and importantly did not reduce the selection of macrolide resistance. Nonmacrolide and new approaches for the treatment of M. genitalium urethritis are required.

Cited by 66 publications

References 21 publications

Which azithromycin regimen should be used for treating Mycoplasma genitalium? A meta-analysis

Which azithromycin regimen should be used for treating Mycoplasma genitalium? A meta-analysis

Prospective Evaluation of ResistancePlus MG, a New Multiplex Quantitative PCR Assay for Detection of Mycoplasma genitalium and Macrolide Resistance

De novo mutations drive the spread of macrolide-resistant Mycoplasma genitalium: a mathematical modelling study

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