High-level cefixime- and ceftriaxone-resistant N. gonorrhoeae in Europe (France): novel penA mosaic allele in a successful international clone causes treatment failure

Publié le 1 Mars 2012
Mis à jour le 09 septembre 2019

Recently, the first Neisseria gonorrhoeae strain (H041) highly resistant to the extended-spectrum cephalosporins (ESC) ceftriaxone and cefixime, which are the last remaining options for first-line gonorrhoea treatment, was isolated in Japan. Here, we confirm and characterize a second strain (F89) with high-level cefixime and ceftriaxone resistance, which was isolated in France and most likely caused a treatment failure with cefixime. F89 was examined using six species-confirmatory tests, antibiograms (33 antimicrobials), porB sequencing, N. gonorrhoeae multiantigen sequence typing (NG-MAST), multilocus sequence typing (MLST), and sequencing of known gonococcal resistance determinants (penA, mtrR, penB, ponA, and pilQ). F89 was assigned to MLST ST1901 and NG-MAST ST1407, which is a successful gonococcal clone that has spread globally. F89 has high-level resistance to cefixime (MIC=4 Œg/ml) and ceftriaxone (MIC=1-2 Œg/ml), and resistance to most other antimicrobials examined. A novel penA mosaic allele (penA-CI), which was penA-XXXIV with an additional A501P alteration in penicillin-binding protein 2, was the primary determinant for high-level ESC resistance as determined by transformation experiments into a set of recipient strains. N. gonorrhoeae appears to be emerging as a superbug, and in certain circumstances and settings, gonorrhea may become untreatable. Investigations of the biological fitness, and enhanced understanding and monitoring of the ESC-resistant clones and their international transmission are required. Enhanced disease control activities, antimicrobial resistance control and surveillance worldwide, and public health response plans for global (and national) perspectives are also crucial. Nevertheless, new treatment strategies and/or drugs, and ideally a vaccine, are essential to develop for efficacious gonorrhea management.

Auteur : Unemo M, Golparian D, Nicholas R, Ohnishi M, Gallay A, Sednaoui P
Antimicrobial Agents and Chemotherapy, 2012, vol. 56, n°. 3, p. 1273-80