Background/Objectives: The increasing prevalence of Mycoplasma genitalium infections with macrolide-resistance, causing high azithromycin failure rates, is a major concern internationally. In response to this challenge, diagnostics that simultaneously detect M. genitalium and genetic markers for macrolide-resistance enable the therapy to be individually tailored, i.e., to implement resistance-guided therapy (RGT). This study aimed to evaluate patient treatment outcomes of M. genitalium therapy, guided by a macrolide-resistance assay in Bulgaria. Methods: Consecutively referred M. genitalium infection cases (n = 17) were analyzed for macrolide-resistance mutations (MRMs) and specific antimicrobial treatment was recommended accordingly (MRMs-negative infections received azithromycin and MRMs-positive infections received moxifloxacin). The treatment outcome based on test-of-cure was recorded, and the treatment failure rates and time to achieve a microbiological cure were compared to treatment outcomes in patients treated before the implementation of RGT. Results: Among patients given RGT (n = 17), the overall treatment failure rate was 1/17 (5.9%). This was significantly lower than the rate (47.6%) observed in patients treated pre-RGT (p = 0.002). The time to achieve a microbiological cure was 29.4 days (CI 24.5–34.3), compared to 45.2 days (CI 36.5–53.7) pre-RGT (p = 0.001). Conclusions: The implementation of M. genitalium diagnostics with macrolide-resistance detection improved treatment outcomes in Bulgaria, with significantly lower treatment failure rates and reduced time to achieve a microbiological cure. In light of the limited treatment options and concerns about their decreasing efficacy in response to misuse and overuse, a diagnostic macrolide-resistance assay is critical to direct the appropriate first-line treatment, to maintain the efficacy of antimicrobial treatment (antibiotic stewardship) and to minimize the spread of antimicrobial resistance.

Background: The increasing prevalence of Mycoplasma genitalium infections with macrolide resistance causing high azithromycin failure rates is a major concern internationally. In response to this challenge, diagnostics that simultaneously detect M. genitalium and genetic markers for macrolide resistance enable the therapy to be individually tailored, i.e. to implement resistance-guided therapy (RGT). Objectives: This study aimed to evaluate patient treatment outcomes of M. genitalium therapy guided by a macrolide-resistance assay in Bulgaria; Methods: Consecutively referred M. genitalium infection cases (n=17) were analyzed for macrolide-resistance mutations (MRMs) and specific antimicrobial treatment was recommended accordingly (MRMs-negative infections received azithromycin and MRMs-positive received moxifloxacin). Treatment outcome based on test-of-cure was recorded and treatment failure rates and time to microbiological cure were compared with treatment outcomes in patients treated before the implementation of RGT; Results: Among patients given RGT (n=17), the overall treatment failure rate was 1/17 (5.9%). This was significantly lower than the rate (47.6%) observed in patients treated pre-RGT (p=0.002). The time to microbiological cure was 29.4 days (CI 24.5 – 34.3) compared to 45.2 days (CI 36.5 – 53.7) pre-RGT (p=0.001); Conclusions: Implementation of M. genitalium diagnostics with macrolide-resistance detection improved treatment outcomes in Bulgaria with significantly lower treatment failure rates and reduced time to microbiological cure. In light of limited treatment options and concerns about their decreasing efficacy in response to misuse and overuse, diagnostic macrolide-resistance assay is critical to direct appropriate first-line treatment, to maintain the efficacy of antimicrobial treatment (antibiotic stewardship) and to minimize the spread of antimicrobial resistance.