Stably high azithromycin resistance and decreasing ceftriaxone susceptibility in Neisseria gonorrhoeae in 25 European countries, 2016

Participating laboratories from 25 EU/EEA countries (Table 1) collected N. gonorrhoeae isolates from consecutive patients (one isolate per patient) from September to November 2016 unless sufficient numbers could not be achieved during this time frame, in which case isolates were collected throughout the year. The United Kingdom (UK) collected isolates from July to September 2016 (to coincide with the collection in the national Gonococcal Resistance to Antimicrobials Surveillance Programme (GRASP) [10]) and isolates were selected from this collection to give full UK geographical representation. The isolate collection period was the same as 2015. Full details of the Euro-GASP N. gonorrhoeae isolate collection and selection criteria can be found in the Euro-GASP protocol [11]. Antimicrobial susceptibility testing was performed using MIC gradient strip tests or agar dilution methods (determination of minimum inhibitory concentration (MIC) or breakpoint technique) for ceftriaxone, cefixime, azithromycin, ciprofloxacin, spectinomycin and gentamicin as previously described [11]. Since 2014, spectinomycin and gentamicin are only tested every 3 years as they are not in routine use for treatment, susceptibility has appeared to be stably high, and spectinomycin is difficult to acquire. Isolates from eight (32%) countries (Table 1) were tested centrally at Public Health England or Örebro University Hospital, Sweden with the remaining 17 (68%) countries performing antimicrobial susceptibility testing in their own laboratories (these laboratories successfully fulfilled established quality criteria prior to commencing their own testing). All Euro-GASP laboratories participated in an annual external quality assessment (EQA) programme [12] to ensure comparability of antimicrobial susceptibility data. The antimicrobial susceptibility data were interpreted into susceptibility, intermediate susceptibility and resistance using EUCAST resistance breakpoints: cefixime/ceftriaxone resistance MICs > 0.125 mg/L, azithromycin resistance MIC > 0.5 mg/L, ciprofloxacin resistance MIC > 0.06 mg/L, and spectinomycin resistance MIC > 64 mg/L [13]. In addition to antimicrobial susceptibility data, patient epidemiological data were collected and categorised; age (< or ≥ 25 years); gender and sexual orientation (men who have sex with men (MSM), male heterosexual or female); anatomical site of collection (urogenital, rectal, pharyngeal, other); previous gonorrhoea (yes/no) and concurrent Chlamydia trachomatis infection (yes/no). The overall coverage of Euro-GASP was estimated by comparing the number of isolates tested in Euro-GASP to the number of cases reported as part of the enhanced epidemiological surveillance of STI in 2016 [14].

Statistical analysis was performed using Stata v13.1 (StataCorp LP, Texas, USA). The Z-test was used to determine differences between AMR and epidemiological data collected in 2016 versus 2015 and a Mann-Whitney test was used to test whether the differences in age distribution were statistically significant. Where datasets contained sufficient numbers, associations between patient epidemiological data and AMR were assessed using odds ratios (OR) and 95% confidence intervals (CI); the Pearson’s χ² test was used to measure if these odds ratios differed significantly from 1. For small cell numbers, Fisher’s exact test was performed. Statistical significance for all tests was assumed when p < 0.05.