Background The first Neisseria gonorrhoeae strain (H041) worldwide that is highly resistant to the extended-spectrum cephalosporin (ESC) ceftriaxone, which is the last remaining option for empirical treatment of gonorrhoea, has now been identified! This is a large public health problem and the era of untreatable gonorrhoea may now have been initiated. The present study completely characterised H041, phenotypically and genetically, to confirm the finding, comprehensively examine its antimicrobial resistance (AMR) and in detail elucidate the resistance mechanisms. Finally, public health actions for preventing and/or detaining global spread of ceftriaxone-resistant and untreatable gonorrhoea will be discussed.

Methods H041 was examined using seven species-confirmatory tests, antibiograms (30 antimicrobials) with Etest and agar dilution (only for ESCs), porB sequencing, N gonorrhoeae multi-antigen sequence typing (NG-MAST), multilocus sequence typing (MLST) and sequencing of ESC resistance determinants (penA, mtrR, penB, ponA and pilQ). Transformation, using appropriate recipient strains, was performed to confirm the ESC resistance determinants.

Results H041 was assigned serovar Bpyust, MLST ST7363 and the new NG-MAST ST4220. H041 proved highly resistant to ceftriaxone (2–4 mg/l, which is 4-8-fold higher than any previously described isolate) and all other cephalosporins, as well as most other antimicrobials tested. A new penA mosaic allele, containing only four not previously described amino acid alterations, caused the ceftriaxone resistance, which was all proven using several transformation experiments.

Conclusions The new superbug N gonorrhoeae has now developed also ceftriaxone resistance and an era of untreatable gonorrhoea may have been initiated. A reduction in global gonorrhoea burden by enhanced disease control activities combined with wider strategies for general AMR control and enhanced understanding of mechanisms of emergence and spread of AMR, which need to be monitored globally, is crucial. Furthermore, a public health response plan (including sustainable clinical, microbiological and epidemiological components) for a global perspective is essential. Ultimately, new drugs are essential to develop for efficacious gonorrhoea treatment.