Fifer H, et al. - Experts conducted a whole-genome sequencing to probe high-level azithromycin-resistant Neisseria gonorrhoeae outbreak to ascertain if the ongoing outbreak represented clonal spread of an HL-AziR N gonorrhoeae strain identified in Leeds. They also elucidated the molecular mechanisms of azithromycin resistance in N gonorrhoeae in the UK. Findings suggested sustained transmission of a successful HL-AziR clone across England. In isolates with lower azithromycin MICs, mutation 2059A-G was found. To recombine with wild-type copies, azithromycin exposure could have provided the selection pressure for 1 or 2 mutated copies of the 23S rRNA gene, leading to 3 or 4 mutated copies and the HL-AziR phenotype. As part of dual therapy for the treatment of gonorrhoea, HL-AziR could emerge in isolates with low azithromycin MICs and eliminate the effectiveness of azithromycin.

Methods

• In this observational study, authors did whole-genome sequencing on the HL-AziR N gonorrhoeaeisolates from England.
• They also sequenced 110 isolates from the UK and Ireland as comparators, with a range of azithromycin MICs , including 8 isolates from Scotland with azithromycin MICs ranging from 0·12 mg/L to 1·00 mg/L that were N gonorrhoeae multi-antigen sequence type 9768 (ST9768), which was the sequence type initially responsible for the outbreak.
• They also incestigated the presence of mutations or genes associated with azithromycin resistance.

Results

• As per data, 37 of the 60 HL-AziR isolates from England belonged to ST9768, and were genetically similar (mean 4·3 single-nucleotide polymorphisms).
• Results demonstrated that in 3 or all 4 alleles of the 23S rRNA gene, a 2059A-G mutation was detected.
• Data suggested that 5 susceptible ST9768 isolates had 1 mutated 23S rRNA allele and 1 low-level resistant ST9768 isolate had 2 mutated alleles.