Gonococcal antimicrobial susceptibility surveillance in the EU/ EEA
The surveillance of Neisseria gonorrhoeae antimicrobial susceptibility in the European Union/European Economic Area (EU/EEA) is essential for detecting emerging and increasing antimicrobial resistance. Since 2009, this surveillance has been co-ordinated by the European Centre for Disease Prevention and Control (ECDC). The quality-assured data produced can be used to inform treatment guidelines.
Executive Summary
During 2022, as in previous years, the European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) followed an annual decentralised and centralised testing model, requesting participating laboratories to collect gonococcal isolates during the period September–November. Susceptibility testing was performed on all isolates (MIC gradient strip test or agar dilution) for the following antimicrobials (where available): ceftriaxone, cefixime, azithromycin, ciprofloxacin, as well as testing for β-lactamase production for detection of high-level penicillin resistance. Gentamicin and spectinomycin were also tested in 2022 because these are tested every three years. Decentralised testing took place on the premise of participating laboratories fulfilling set quality criteria.
In 2022, 23 EU/EEA countries participated in Euro-GASP, 18 via decentralised testing. In total, 4396 isolates were tested, the majority of specimens were from male patients (80.9%) with patient age ranging from under one year to 75 years, with a median age of 30 years. Overall, 28.4% of patients were under 25 years, and males were significantly older than females. The anatomical site of specimen collection was reported for 99.6% of cases, mainly genital (69.0%), followed by rectal (17.8%) and pharyngeal (12.0%). In 2022, data were also captured on samples specifically from blood (0.1%), eye (0.6%) and joint fluid (0.1%) infection sites. Among cases with known sexual orientation and gender reported (56.0%), 54.0% were heterosexual men or women, and 46.0% were men who have sex with men (MSM). Among cases with information on previous diagnosis of gonorrhoea, 27.8% had previously been diagnosed with the infection and among all cases, 8.8% were HIV-positive and 96.0% of those were MSM.
In 2022, two isolates with resistance to ceftriaxone (MIC=0.25 mg/L) were detected, in Austria and Germany, respectively. One was extensively drug-resistant (XDR) and one multidrug-resistant (MDR). Both isolates displayed in addition to resistance to ceftriaxone also resistance to cefixime (MIC of 1 mg/L), had an azithromycin MIC of >256 mg/L and 0.032 mg/L, respectively, and both were ciprofloxacin-resistant (MIC of 8 and 4 mg/L). The 2022 Euro-GASP results revealed a total of 0.3% of gonococcal isolates with resistance to cefixime (MIC>0.125 mg/L), collected from eight countries.
In January 2019, the European Committee on Antimicrobial Susceptibility Testing (EUCAST) clinical resistance breakpoint for azithromycin of MIC>0.5 mg/L was replaced with an epidemiological cut-off (ECOFF) value of MIC>1 mg/L. After a significant increase in the proportion of isolates above azithromycin ECOFF in 2018 (7.6%) and 2019 (10.1%), the proportion remained stable in 2020 at 11.0% to significantly increase again in 2021 (14.2%) and to reach 25.6% in 2022. At least one isolate with azithromycin MIC above ECOFF (MIC>1 mg/L) was recorded in all the 23 participating countries. The proportion of isolates showing resistance to ciprofloxacin substantially increased: 65.9% in 2022 compared to that observed in 2021 (62.8%) and 2020 (57.7%).
Although dual ceftriaxone and azithromycin resistance is exceedingly rare in the EU/EEA, the rapidly decreasing azithromycin susceptibility combined with the continued detection of occasional ceftriaxone resistance is still of concern and threatens the effectiveness of treatment and control of gonorrhoea. Due to this, the European treatment guideline was updated in 2020 to recommend high-dose ceftriaxone plus azithromycin dual therapy or ceftriaxone high-dose monotherapy, which is now most frequently used, as shown in this report. Even though the level of resistance to cefixime has significantly decreased, cefixime resistance needs to be monitored closely, particularly because gonococcal strains with resistance to both cefixime and ceftriaxone continue to spread internationally. The continuation of quality-assured antimicrobial susceptibility surveillance activities, along with the development of alternative gonococcal regimens, is essential to ensure gonorrhoea remains a treatable infection.