Antimicrobial susceptibility testing in two extremely fastidious bacterial sexually transmitted infections

Antimicrobial resistance is the biggest threat to modern medicine since the dawn of the antibiotic era. Detection and monitoring of antimicrobial resistance are mainstays of antibiotic stewardship. Where organisms can be propagated in vitro using standard culture techniques, such as growth on agar plates, susceptibility testing can be performed with relative ease. Where organisms are more fastidious, requiring complex culture systems such as tissue culture, susceptibility testing becomes more challenging. This thesis details investigations into antimicrobial resistance in two common, fastidious, sexually transmitted bacterial infections, Chlamydia trachomatis and Mycoplasma genitalium. The thesis presents some of the first susceptibility data for these organisms in England and discusses methodological developments for performing non-standardised susceptibility testing and whole-genome sequencing. Data is presented for different patient groups including those persistently infected with C. trachomatis and individuals infected with M. genitalium accessing sexual healthcare and in the general population. Whilst no genotypic evidence of antimicrobial resistance was detected in C. trachomatis, differences in susceptibility to doxycycline were noted when compared to isolates from successfully treated patients. Insight into the clinical relevance of decreased susceptibility to doxycycline in C. trachomatis is required. Extensive resistance to both first- and second-line treatment options for M. genitalium was reported in all patient groups tested. Dual drug resistance was also reported frequently. Initiation of national surveillance of antimicrobial resistance in M. genitalium was described in the first molecular surveillance programme. As alternative treatment options beyond the current first- and second-line therapies are extremely limited, continued monitoring of antimicrobial resistance in M. genitalium and improved understanding of genotypic markers of resistance and their effect on the organisms' susceptibility in vivo, is essential to retain it as a treatable infection. Data from these reports directly informed national treatment guidelines and public health strategy.