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

Recently, the first Neisseria gonorrhoeae strain (H041) highly resistant to the expanded-spectrum cephalosporins (ESCs) ceftriaxone and cefixime, which are the last remaining options for first-line gonorrhea 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 sequence type 1901 (ST1901) and NG-MAST ST1407, which is a successful gonococcal clone that has spread globally. F89 has high-level resistance to cefixime (MIC = 4 µg/ml) and ceftriaxone (MIC = 1 to 2 µg/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 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.

Neisseria gonorrhoeae antibiotic resistance in Paris, 2005 to 2007: implications for treatment guidelines.

Quinolone-resistant Neisseria gonorrhoeae rates have increased worldwide since 1994. The objective of this study was to appraise: (i) the antimicrobial susceptibility of Neisseria gonorrhoeae in a venereology clinic in Paris, between 2005 and 2007; and (ii) the factors associated with quinolone-resistant N. gonorrhoeae. A prospective study of consecutive cases was performed for the period 2005 to 2007. Susceptibility of N. gonorrhoeae to five antibiotics (ciprofloxacin, ceftriaxone, spectinomycin, penicillin G and tetracycline) was tested systematically. Clinical and epidemiological data were collected using a standardized form. Male-to-female sex ratio was 22.0. Median age was 30.0 years. Of 115 cases, 84 occurred in men having sex with men (72.6%) and 22 involved the anorectal area (19.1%). The rate of quinolone-resistant N. gonorrhoeae was 37.4% (43/115), without significant association with gender, age, sexual behaviour, past history of sexually transmitted diseases and susceptibility to other antibiotics. All N. gonorrhoeae were susceptible to ceftriaxone and spectinomycin. The rate of quinolone-resistant N. gonorrhoeae in Paris has been increasing since 2004. Ceftriaxone remains the gold standard treatment.