Emergence and dissemination of three mild outbreaks ofNeisseria gonorrhoeaewith high-level resistance to azithromycin in Barcelona, 2016–18

Abstract

Background Neisseria gonorrhoeae (NG) isolates with high-level azithromycin resistance (HL-AziR) have emerged worldwide in recent decades, threatening the sustainability of current dual-antimicrobial therapy. Objectives This study aimed to characterize the first 16 NG isolates with HL-AziR in Barcelona between 2016 and 2018. Methods WGS was used to identify the mechanisms of antimicrobial resistance, to establish the MLST ST, NG multiantigen sequence typing (NG-MAST) ST and NG sequence typing for antimicrobial resistance (NG-STAR) ST and to identify the clonal relatedness of the isolates with other closely related NG previously described in other countries based on a whole-genome SNP analysis approach. The sociodemographic characteristics of the patients included in the study were collected by comprehensive review of their medical records. Results Twelve out of 16 HL-AziR isolates belonged to the MLST ST7823/NG-MAST ST5309 genotype and 4 to MLST ST9363/NG-MAST ST3935. All presented the A2059G mutation in all four alleles of the 23S rRNA gene. MLST ST7823/NG-MAST ST5309 isolates were only identified in men who have sex with women and MLST ST9363/NG-MAST ST3935 were found in MSM. Phylogenomic analysis revealed the presence of three transmission clusters of three different NG strains independently associated with sexual behaviour. Conclusions Our findings support the first appearance of three mild outbreaks of NG with HL-AziR in Spain. These results highlight the continuous capacity of NG to develop antimicrobial resistance and spread among sexual networks. The enhanced resolution of WGS provides valuable information for outbreak investigation, complementing the implementation of public health measures focused on the prevention and dissemination of MDR NG.

Molecular Epidemiology, Antimicrobial Surveillance, and PK/PD Analysis to Guide the Treatment of Neisseria gonorrhoeae Infections

“…In this region of the north of Spain, the percentage of resistance was of the same order as recent data obtained from Madrid [20] and Barcelona [21,22], and also of those reported in other European countries [23]. As expected, the highest percentage of resistance was detected for ciprofloxacin (>45%).…”

“…Unlike the other antibiotics, all isolates resistant to azithromycin were collected in 2019 (n = 11). These data are consistent with the recent increase in the resistance of N. gonorrhoeae to azithromycin in Spain and worldwide [22,23]. Some studies support the notion that the selection/induction of azithromycin resistance in N. gonorrhoeae may be associated with the general use of azithromycin for the treatment of respiratory infections or non-gonococcal urethritis [24].…”

“…The majority of genotyped azithromycin-resistant isolates were MLST ST-9363. In a recent study carried out in Barcelona (Spain) [22], this genotype was associated with outbreaks of N. gonorrhoeae with high-level azithromycin resistance (MIC ≥ 256 mg/L) between 2016 and 2018. In that study, this genotype was found mainly in men who have sex with men.…”

Markedly decreasing azithromycin susceptibility of Neisseria gonorrhoeae, Germany, 2014 to 2021

“…NG with high-level azithromycin resistance (> 256 mg/L) have been reported from several European countries and worldwide, and sustained transmission of these isolates has been described [4,10,[12][13][14][15][16]. Interestingly, these isolates remain rare in Germany.…”

The postal code as a “bar code” of antimicrobial resistance

“…Esto podría hacernos concluir que de momento el uso de ceftriaxona como tratamiento de la infección por N. gonorrhoeae es el adecuado en nuestro medio. Cabe resaltar que en el estudio de las ITS la biología molecular y la utilización de técnicas de secuenciación para identificar cepas es cada vez más frecuente [ 12 , 17 ], especialmente en grandes ciudades y a nivel hospitalario, es decir, a gran escala. Además, hay que sumar a esto que el control de las ITS es sumamente complejo por múltiples factores, entre los que intervienen el estigma, desconocimiento, movilidad a otros centros sanitarios y la dificultad de realizar estudios de contacto óptimos.…”