Gonococcal antimicrobial susceptibility surveillance in the European Union/European Economic Area, 2019
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.
During 2019, 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 (mostly Etest) or agar dilution) for the following antimicrobials (where available): ceftriaxone, cefixime, azithromycin, ciprofloxacin, spectinomycin, and gentamicin, as well as testing for β-lactamase production for detection of high-level penicillin resistance. Decentralised testing took place on the premise of participating laboratories fulfilling set quality criteria.
In 2019, 26 EU/EEA Member States participated in Euro-GASP, 19 via decentralised testing. In total, 4 166 isolates were tested; the majority of specimens were from male patients (83.0%), with patient age ranging from under one year to 85 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 mainly genital (68.1%), followed by rectal (19.6%), and pharyngeal (9.7%). In 2019, for the first time data were captured on samples specifically from blood (0.03%), eye (0.08%), and joint fluid (0.11%) infection sites. Among cases with information on previous diagnosis of gonorrhoea, 24.7% had previously been diagnosed with the infection and 21.8% of the patients were concurrently diagnosed with Chlamydia trachomatis infection. Among cases with known sexual orientation and sex (56.6%), 54.4% were heterosexual men or women, and 45.6% were men who have sex with men (MSM). Among all cases, 14.1% were HIV-positive and 84.9% of those were MSM.
In 2019, three isolates with resistance to ceftriaxone (MIC=0.25 mg/L, n=2, and MIC=0.5 mg/L) were detected, in Norway, Portugal and Belgium. All isolates had an azithromycin MIC at or below the azithromycin epidemiological cut-off value (ECOFF) of 1 mg/L (MIC=0.25 mg/L, MIC=1 mg/L and MIC=0.5 mg/L) and all were ciprofloxacin-resistant (MIC>32 mg/L, MIC=4 mg/L and MIC>32 mg/L). The 2019 Euro-GASP results revealed a total of 0.9% of gonococcal isolates with resistance to cefixime (MIC>0.125 mg/L), which has previously displayed stable level of 1.4% to 2.1% from 2014 to 2018 (1.4% in 2018 and 1.9% in 2017) with a stable number of countries reporting any resistant isolates (n=14).
Since January 2019, the European Committee on Antimicrobial Susceptibility Testing (EUCAST) clinical resistance breakpoint for azithromycin of MIC>0.5 mg/L has been replaced with an ECOFF value of MIC>1 mg/L. As observed in 2018, there was again a significant increase in the proportion of isolates above azithromycin ECOFF, with 10.1% observed in 2019 compared to 7.6% in 2018 and 3.7% observed in 2017 (p<0.01). In 2019, 24 countries recorded at least one isolate with azithromycin above ECOFF (MICs >1 mg/L) compared to 25 countries in 2018, 21 in 2017 and 20 countries in 2016, respectively. The proportion of isolates showing ciprofloxacin resistance continued the trend of significant increase from 50.3% in 2018 to 57.3% in 2019 (p<0.01) compared to 46.5% in 2017.
The decreasing azithromycin susceptibility combined with the continued detection of ceftriaxone resistance is a major concern and threatens the effectiveness of the currently highly effective dual-therapy regimen (ceftriaxone plus azithromycin) and high-dose ceftriaxone monotherapy recently adopted by some European countries. 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 ensuring that gonorrhoea remains a treatable inf