Neisseria gonorrhoeae: testing, typing and treatment in an era of increased antimicrobial resistance

This thesis discusses the management of Neisseria gonorrhoeae infections while under threat of emerging antimicrobial resistance. It focuses on improved diagnostics, and antimicrobial resistance to current and future therapies. We describe a new method of targeted deferred culture, using nucleic acid amplification test (NAAT) and ESwab medium samples. This method resulted in successful cultures after storage up to 3 days. We used RNA- and DNA-based NAATs as a test of cure to demonstrate that N. gonorrhoeae is cleared after 7 and 14 days, respectively. To limit the spread of antimicrobial resistance, international guidelines recommend dual therapy consisting of azithromycin and ceftriaxone. We showed that there is no evidence for a synergistic effect of this combination, or any of 65 other dual combinations, in vitro. In addition, we reported a rise of decreased susceptibility to azithromycin and ceftriaxone in Amsterdam since 2012. Moreover, we presented the first evidence that exposure to azithromycin shortly before a gonorrhoea infection is significantly associated with lower susceptibility to azithromycin, possibly induced by A39T or G45D mutations of mtrR. Finally, a genetic analysis of N. gonorrhoeae isolates from Amsterdam showed that although azithromycin resistance was significantly associated with 23S rRNA mutations and three NG-MAST genogroups, it has developed independently from the ‘background genome’.