The increase in gonorrhoea in many developed countries and the occurrence of resistance to antimicrobial treatment constitute an important public health problem. Sequence-based genotyping methods have proven helpful to understand the transmission patterns of infection and to follow the emergence and spread of antibiotic resistance.
The 93 French isolates analyzed in this study revealed the same antibiotic phenotype trend observed in others parts of the world. All French isolates were susceptible to spectinomycin. In France, this antibiotic is only used in case of β-lactam allergy. Even though azithromycin was not tested, the probability that isolates were all susceptible to this agent is strong, since no resistance to erythromycin was observed for any isolate. In France, azithromycin is not used for N. gonorrhoeae
treatment. In contrast, N. gonorrhoeae
azithromycin resistance increased in Scotland (14
). It may have occurred as a response to exposure to sublethal levels of azithromycin resulting from the treatment of C. trachomatis
infections. Possibly another reason was azithromycin being prescribed alone in N. gonorrhoeae
infection, as suggested by Habib and Fernando (5
Reduction of susceptibility to ceftriaxone is worrying, especially in combination with ciprofloxacin resistance. As a consequence, since 2005, French guidelines have not recommended fluoroquinolones for N. gonorrhoeae
treatment, which could hopefully result in a steady state or a decrease of resistance over the next few years. Ceftriaxone became the recommended treatment, always associated with azithromycin for C. trachomatis
infections (Groupe de Travail sur les Antibiotiques, GTA no. 188, 6 June 2005; http://www.afsapps.sante.fr
This study presents the first molecular epidemiology analysis of N. gonorrhoeae strains that are currently circulating in France. As in previous studies, the NG-MAST method revealed numerous single STs, probably due to the lack of effective procedures for an exhaustive diagnosis in partners or in the community. In addition, high recombination rates in N. gonorrhoeae result in a rapid evolution of genotypes. Only six isolates from women were analyzed, and all had different STs, excluding any interpretation about genotype variability related to gender.
No geographic clustering was observed, and even though 88% of isolates (23/26) from group II were isolated from MSM from the same area (Paris), no predominant ST was identified in this group. A particular antibiotic-resistant phenotype (phenotype 6) was only found in this group, with chromosomal resistance to tetracycline, high-level resistance to ciprofloxacin, and high susceptibility to ceftriaxone.
ST225, one of the main STs identified in France (16 isolates), is characterized by 87.5% of isolates with resistance to tetracycline and ciprofloxacin and by slightly reduced susceptibility to ceftriaxone (0.016 to 0.032 mg/liter). This ST was previously found to be prevalent in Denmark (S. H. Hoffman, L. Lambertsen, L. Berthelsen, and S. Cowan, Presented at the International Society for Sexually Transmitted Disease Research 16th Meeting, Amsterdam, The Netherlands, 10 to 13 July 2005), Scotland (12
), and Australia (19
) and has been reported in Greece and Hong Kong (http://www.ng-mast.net
). In Scotland, ST225 was the most prevalent ST (with 85 out of 1,526 isolates), where it had the same predominant antibiotic phenotype as in France (except that ceftriaxone was not reported) (12
). In Australia, Todd et al. (19
) described 10 out of 14 isolates of ST225 that showed the same antibiotic resistance phenotype as that in the present study, including the increased MIC of ceftriaxone (0.03 mg/liter). The two prevalent STs ST880 and ST437, which are genetically closely related to ST225, presented the same antibiotic resistance phenotype in our study as well as in other countries (http://www.ng-mast.net
). These results are clearly indicative of the international spread of the antimicrobial-resistant clone that comprises ST225, ST880, and ST437. In contrast, French isolates from ST292, resistant to ciprofloxacin (phenotypes 4 and 6), did not share the same antibiotic resistance phenotype as ST292 isolates from Scotland (12
), suggesting a recent acquisition of resistance in France.
ST1479 comprised isolates resistant to ciprofloxacin, with plasmidic resistance to penicillin and tetracycline. This ST, exclusively identified in nine French isolates (including knee fluid sample), was characterized by the multiresistance phenotype 1 or 2. ST211, which was also associated with phenotype 1 in France (2 isolates), was previously found in Scotland (13
), London, Australia, Greece, and New Zealand (http://www.ng-mast.net
). However, the sequences of both genes (tbpB
) were distant between ST1479 and ST211. Therefore, it cannot be determined whether antimicrobial resistance phenotype 1 was acquired independently in these two genomic backgrounds or whether the genes tbpB
evolved from a common antimicrobial-resistant ancestor. Expectedly, the susceptible isolates (antibiotic phenotype 3) were diverse. Many STs of susceptible isolates (ST2, ST26, ST359, ST975, ST1813, and ST1986) were observed in other countries (14
). In contrast, some STs that were described as being frequent in other countries did not appear in this study (ST661, ST547, ST835, and ST338) or were represented only once (ST147) (11
). Thus, ST225 stands out as the only widespread international clone, probably selected by the widespread use of ciprofloxacin and oral cephalosporins.
In conclusion, this study provides a first overview of the characteristics of N. gonorrhoeae infections in France. Even though a large diversity of genotypes was found, few clones associated with particular antimicrobial resistance phenotypes were observed. Comparison with European and international data identifies ST225 as one international multiresistant clone, whereas ST1479 was prevalent in France but has not been described elsewhere so far. Our results show that the worrying increase in resistance is due to a combination of clonal spread and emergence of resistance in distinct genomic backgrounds.
Epidemiological studies based on antibiotic susceptibility testing remain a good phenotypic approach for the surveillance of N. gonorrhoeae infections. NG-MAST provides improved capacity for the detection of chains of transmission and helps in predicting antibiotic susceptibility trends, as the antibiotic resistance phenotype is generally conserved for a given ST.