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%, I2 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. Since de novo resistance is the main driver of azithromycin resistance in M. genitalium, enhanced surveillance is needed and clinical management strategies for M. genitalium should seek to limit the unnecessary use of macrolides.
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