Overall Low Extended-Spectrum Cephalosporin Resistance but high Azithromycin Resistance in Neisseria gonorrhoeae in 24 European Countries, 2015

Abstract

BackgroundSurveillance of Neisseria gonorrhoeae antimicrobial susceptibility in Europe is performed through the European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP), which additionally provides data to inform the European gonorrhoea treatment guideline; currently recommending ceftriaxone 500 mg plus azithromycin 2 g as first-line therapy. We present antimicrobial susceptibility data from 24 European countries in 2015, linked to epidemiological data of patients, and compare the results to Euro-GASP data from previous years.MethodsAntimicrobial susceptibility testing by MIC gradient strips or agar dilution methodology was performed on 2134 N. gonorrhoeae isolates and interpreted using EUCAST breakpoints. Patient variables associated with resistance were established using logistic regression to estimate odds ratios (ORs).ResultsIn 2015, 1.7% of isolates were cefixime resistant compared to 2.0% in 2014. Ceftriaxone resistance was detected in only one (0.05%) isolate in 2015, compared with five (0.2%) in 2014. Azithromycin resistance was detected in 7.1% of isolates in 2015 (7.9% in 2014), and five (0.2%) isolates displayed high-level azithromycin resistance (MIC ≥ 256 mg/L) compared with one (0.05%) in 2014. Ciprofloxacin resistance remained high (49.4%, vs. 50.7% in 2014). Cefixime resistance significantly increased among heterosexual males (4.1% vs. 1.7% in 2014), which was mainly attributable to data from two countries with high cefixime resistance (~11%), however rates among men-who-have-sex-with-men (MSM) and females continued to decline to 0.5% and 1%, respectively. Azithromycin resistance in MSM and heterosexual males was higher (both 8.1%) than in females (4.9% vs. 2.2% in 2014). The association between azithromycin resistance and previous gonorrhoea infection, observed in 2014, continued in 2015 (OR 2.1, CI 1.2–3.5, p < 0.01).ConclusionsThe 2015 Euro-GASP sentinel system revealed high, but stable azithromycin resistance and low overall resistance to ceftriaxone and cefixime. The low cephalosporin resistance may be attributable to the effectiveness of the currently recommended first-line dual antimicrobial therapy; however the high azithromycin resistance threatens the effectiveness of this therapeutic regimen. Whether the global use of azithromycin in mono- or dual antimicrobial therapy of gonorrhoea is contributing to the global increases in azithromycin resistance remains to be elucidated. The increasing cefixime resistance in heterosexual males also needs close monitoring.

Applications of genomics to slow the spread of multidrug‐resistant Neisseria gonorrhoeae

“…In Southeast Asia and the Western Pacific, rates of ciprofloxacin resistance remain extremely high (>90% in 2014) . Even as first‐line antibiotic therapies have changed, resistance to older therapies remains high in N. gonorrhoeae populations across the globe . For example, 44.1% of isolates collected by the Gonococcal Isolate Surveillance Project (GISP) in 2016 were resistant to penicillin, tetracycline, and/or ciprofloxacin .…”

“…67 Even as first-line antibiotic therapies have changed, resistance to older therapies remains high in N. gonorrhoeae populations across the globe. [68][69][70][71][72] For example, 44.1% of isolates collected by the Gonococcal Isolate Surveillance Project (GISP) in 2016 were resistant to penicillin, tetracycline, and/or ciprofloxacin. 1 With the idea that dual therapy would be helpful to halt the development of resistance to the remaining effective antibiotics, the CDC currently recommends ceftriaxone and azithromycin dual therapy.…”

Epidemiology, molecular characterisation and antimicrobial susceptibility ofNeisseria gonorrhoeaeisolates in Madrid, Spain, in 2016

“…In this way, monitoring of strain populations by molecular techniques and determination of antimicrobial susceptibility of N. gonorrhoeae isolates became imperative, as well as gathering of data on clinical and social risk factors associated with AMR in order to identify at-risk patient groups and provide evidence-based data for the implementation of public health control programmes [16]. …”

Association between intensity of STI screening and development of antimicrobial resistance in N. gonorrhoeae in 12 cities in the USA: An ecological study

“…The proportion testing for bacterial STIs was associated with an increase of MIC for cefixime and azithromycin but not ceftriaxone. A plausible reason for the lack of association between ceftriaxone and MIC change is that ceftriaxone has been used almost exclusively in combination with azithromycin 3, 15 and even on its own may be less susceptible to the develop of resistance than cefixime and azithromycin 16 . These findings are compatible with the theory that screening intensity plays a role in the selection of antimicrobial resistance in N. gonorrhoeae in MSM.…”