Resistance-Guided Antimicrobial Therapy for Mycoplasma genitalium Infection

For infections with Mycoplasma genitalium, resistance-guided therapy using doxycycline followed by azithromycin or moxifloxacin led to high levels of microbiologic cure and low levels of de novo resistance, according to data published in Clinical Infectious Diseases.

A total of 383 patients who attended Melbourne Sexual Health Centre in Australia between 2017 and 2018 with sexually transmitted infection-related syndromes were included in the study cohort. Patients were treated empirically with doxycycline for 7 days and recalled if testing returned positive for M genitalium. If recalled, patients with macrolide-susceptible infection received 2.5g azithromycin (1g, then 500 mg daily for 3 days) and patients with resistant infections received moxifloxacin (400 mg daily for 7 days). Patients were recommended to return to the health center for test of cure at 14 to 28 days after completion of antibiotic therapy; adherence and adverse events were recorded.

The results demonstrated that 71.5% of patients had a macrolide-resistant infection with M genitalium; the infection rate was highest among men who have sex with men (83.7%).

In patients with macrolide-resistant infections, microbiologic cure was demonstrated in 95.4% of patients treated with doxycycline-azithromycin compared with 92.0% of patients who received doxycycline-moxifloxacin treatment; there were 5 and 22 cases of treatment failure, respectively. In 4.6% of cases, researchers detected a de novo macrolide-resistant infection. Investigators also combined doxycycline-azithromycin data with a prior resistance-guided therapy study of 186 patients, which yielded a pooled cure of 95.7% (95% CI, 91.6-97.8). In 15% to 22% of macrolide-resistant cases at baseline, parC mutations implicated in moxifloxacin non-response were present.

Adherence to treatment was documented in 77.8% of patients who received doxycycline, 74.3% of patients who were recalled and received azithromycin, and 78.5% of patients who were recalled and received moxifloxacin. However, data from patients’ reporting demonstrated that 100%, 97.2%, and 94% of patients receiving azithromycin, moxifloxacin, and doxycycline, respectively, reported adherence to treatment regimens.

Despite a high-level of retention and completion of adherence, reinfection risk, and adverse effect data at the Melbourne Sexual Health Centre, the largest sexual health service in Australia, the data is still self-reported; therefore, recall bias may have occurred. The health center is also a specialized clinic; thus, results may not be generalizable to the broader public. Roughly one-quarter of patients did not return for test of cure and it is possible that this may represent patients achieving symptom resolution, leading to an overestimation of failure. Investigators were also unable to disentangle the relative contribution of doxycycline vs 2.5g azithromycin to the high cure and low level of de novo resistance. They also could not comment on whether the high cure following moxifloxacin in the context of high levels of circulating parC mutations was affected by preceding doxycycline. A final study limitation was the allocation of patients to the treatment arm based on ResistancePlus assay results. However, the resistance component of this assay is slightly less than the gold standard of Sanger sequencing.

Investigators did conclude that this work provides evidence that “[resistance-guided therapy] for [M genitalium] using doxycycline followed by 2.5g azithromycin for macrolide-susceptible strains or moxifloxacin for macrolide-resistant strains achieves microbial cure of 95% and 92%, respectively, and low levels of de novo resistance.” Also, this regime is easily implemented within high case load services and was associated with high adherence. They also believe that resistance-guided therapy is an essential strategy for the preservation of current antimicrobials while waiting for the next generations of resistance assays, classes of antimicrobials, and combination therapies.

Reference

Durukan D, Read TRH, Murray G, et al. Resistance-guided antimicrobial therapy using doxycycline-moxifloxacin and doxycycline-2.5g azithromycin for the treatment of Mycoplasma genitalium infection: efficacy and tolerability [published online October 20 2019). Clin Infect Dis. doi:10.1093/cid/ciz1031