Ceftriaxone-resistant, multidrug-resistant Neisseria gonorrhoeae with a novel mosaic penA-237.001 gene, France, June 2022

Abstract

We report a ceftriaxone-resistant, multidrug-resistant urogenital gonorrhoea case in a heterosexual woman in France, June 2022. The woman was successfully treated with azithromycin 2 g. She had unprotected sex with her regular partner, who developed urethritis following travel to Vietnam and Switzerland. Whole genome sequencing of the gonococcal isolate (F92) identified MLST ST1901, NG-STAR CC-199, and the novel mosaic penA-237.001, which caused ceftriaxone resistance. penA-237.001 is 98.7% identical to penA-60.001, reported in various ceftriaxone-resistant strains, including the internationally spreading FC428 clone.

Multidrug-resistant Neisseria gonorrhoeae isolate SE690: mosaic penA-60.001 gene causing ceftriaxone resistance internationally has spread to the more antimicrobial-susceptible genomic lineage, Sweden, September 2022

“…Publicly available gonococcal genomes (n = 38,370) were downloaded from the European Nucleotide Archive using the search term 'Taxon:485' (12 December, 2022) and analysed as described [4,6]. All genomes were characterised based on a core genome MLST (cgMLST) scheme defined by the 2016 WHO gonococcal reference strains [17], WHO Q [15] and FC428 [8] using Ridom Seqsphere+ (v.8.4.1).…”

“…The isolate was resistant to ceftriaxone, cefixime, cefotaxime, ciprofloxacin, tetracycline and benzylpenicillin but susceptible to azithromycin and spectinomycin. The MIC of gentamicin, ertapenem and the new antimicrobials zoliflodacin [1,2] and lefamulin [3][4][5] were considered wild-type according to previous publications and because no known antimicrobial resistance (AMR) determinants for these antimicrobials were detected (Table ).…”

“…Bacterial DNA was isolated using QIAsymphony (QIAGEN, Hilden, Germany) with the DSP DNA Midi Kit (QIAGEN). Next-generation sequencing (NGS) using Illumina (San Diego, US) and Oxford Nanopore Technologies (Oxford, United Kingdom (UK)), and bioinformatic analysis were performed as previously described [4,6,7].…”

“…Phylogenomic analysis including publicly available NG genomes (n = 38,370) showed that SE690 differs greatly from previously reported ceftriaxone-resistant, multidrug-resistant (MDR) NG strains (Figure 1A). For example, mosaic penA-60.001-containing ones such as the internationally spreading FC428 clone [8][9][10][11][12][13][14], AT159 [6,7] and WHO Q [15], but also WHO X [17], WHO Y [17] and F92 [4], are located in genomic lineage A and very distant to SE690 (> 4,000 single nucleotide polymorphisms (SNP)) in genomic lineage B (Figure 1A).…”

Development and validation of a high throughputNeisseria gonorrhoeaegenotyping method

“…This is not surprising because although NG-MAST has a higher discrimination power than MLST, it makes primer design difficult to amplify all alleles. Recently, a novel AMR N. gonorrhoeae was reported without NG-MAST analysis 29 , suggesting that NG-MAST may no longer be necessary in typing N. gonorrhoeae . We believe that WGS, not NG-MAST, is required for high resolution gonococcal transmission analysis 30 .…”