Issue: May 2015
May 03, 2015
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Azithromycin ineffectively treats macrolide-resistant M. genitalium

Issue: May 2015
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Azithromycin appeared to have a high rate of failure among patients infected with Mycoplasma genitalium who demonstrated pretreatment macrolide resistance, according to recent findings.

Researchers evaluated 155 adult patients treated for M. genitalium infection between July 2012 and June 2013 at the Melbourne Sexual Health Centre in Victoria, Australia. Patients had their infection diagnosed through quantitative PCR and were treated with first-line azithromycin. All were instructed to forgo sexual activity for 14 days and to return for repeat testing between 14 and 28 days after therapy.

Patients completed questionnaires of their antibiotic use, sexually transmitted infection symptoms and interim sexual activity on days 14 and 28. Cases in which azithromycin failed were treated with moxifloxacin; if that failed, they were assigned pristinamycin. High-resolution melt analysis was used to test pretreatment and posttreatment samples for macrolide resistance mutation (MRMs). Cases that did not respond to moxifloxacin were tested for fluoroquinolone resistance mutations.

The researchers defined azithromycin cure as a negative test of cure (TOC) 28 days after 1 g azithromycin. Failure was defined either as one positive TOC 28 with no reinfection risk (moxifloxacin administered at day 28), or persistent symptoms before day 28 with no reinfection risk (moxifloxacin administered before day 28). The researchers used multivariable logistic regression analysis to evaluate factors related to treatment failure.

Data indicated that 61% of patients achieved azithromycin cure. Pretreatment MRM was identified in 36% of patients and was strongly correlated with treatment failure (87%; 95% CI, 76%-94%; adjusted OR = 47; 95% CI, 17.1-129). Among the remaining 99 participants in whom pretreatment MRMs were not detected, 11 had MRMs identified only in posttreatment samples All of these patients failed to respond to azithromycin.

Of the 60 participants who failed azithromycin, 88% were PCR negative at day 28 after moxifloxacin, and 12% remained PCR positive without risk for reinfection. In six cases, samples sequenced for quinolone resistance had pretreatment mutations in gyrA and parC genes. Six of the seven cases that failed moxifloxacin were treated with pristinamycin; all were PCR negative 28 days after initiation.

“These data provide further evidence that macrolide resistance is now highly prevalent in M. genitalium, and 1 g azithromycin is becoming ineffective,” the researchers wrote. “New strategies to improve treatment outcomes and curb the spread of resistant M. genitalium are required.” – by Jen Byrne

Disclosure: The researchers report no relevant financial disclosures.