From genotype to clinical outcome Antimicrobial resistance and treatment response in Mycoplasma genitalum

Mycoplasma genitalium is a sexually transmitted bacterium and an established cause of non-gonococcal urethritis in men, while also being associated with reproductive tract disease in women. Its clinical management is increasingly complicated by resistance to the main antibiotics used for treatment. This thesis explores the relationship between genetic markers of antimicrobial resistance, phenotypic susceptibility, and clinical treatment outcomes in M. genitalium, while also addressing diagnostics, molecular epidemiology, and associated disease.
The studies demonstrate the high prevalence and ongoing emergence of macrolide- and fluoroquinolone resistance-associated mutations. By combining molecular typing, in vitro susceptibility testing, longitudinal clinical follow-up, and sequencing, the thesis shows that resistance-associated mutations do not always directly predict treatment outcome. In particular, microbiological persistence may occur despite clinical improvement, while mutations associated with fluoroquinolone resistance are not consistently linked to treatment failure. These findings highlight the complexity of translating bacterial genotype into clinically relevant resistance.

The thesis additionally investigates pelvic inflammatory disease (PID) and tubo-ovarian abscess (TOA) in women. Most cases could not be attributed to M. genitalium, Chlamydia trachomatis, or Neisseria gonorrhoeae, supporting a polymicrobial etiology. Further investigation of the vaginal microbiome showed that bacterial vaginosis was common among women with PID and TOA and that antibiotic treatment induced a temporary shift towards a more Lactobacillus-dominant, less dysbiotic vaginal microbiome. Standard antibiotic treatment generally resulted in substantial clinical improvement and microbiological cure.
Overall, this thesis emphasizes the need for improved resistance-guided diagnostics, sensible antibiotic use, and greater consideration of clinical outcomes alongside microbiological cure.