Euro-GASP external quality assessment scheme for Neisseria gonorrhoeae antimicrobial susceptibility testing 2021
External quality assessment (EQA) is an essential part of any laboratory-based surveillance system, allowing for the monitoring of performance and comparability of results from participating laboratories, identification of potential issues and deployment of resources and training where necessary. An EQA scheme for antimicrobial susceptibility testing in Neisseria gonorrhoeae has been available to laboratories participating in ECDC’s European Sexually Transmitted Infections (STI) surveillance network since 2010. This EQA scheme has so far shown high levels of inter-laboratory comparability, even when using differing methodologies.
Materials and methods
The EQA specimen panel of 10 gonococcal isolates was selected by UK Health Security Agency (UKHSA) (formerly Public Health England) and distributed by the United Kingdom National External Quality Assessment Service (UK NEQAS). Of the 10 gonococcal isolates provided, one strain was in triplicate and two strains were in duplicate to test intralaboratory concordance. The remaining isolates were all provided as singular isolates, meaning that the N. gonorrhoeae antimicrobial susceptibility EQA panel comprised of six different strains in total. The isolates were representative of a range of different antimicrobial susceptibility profiles and consisted of the four WHO reference strains, WHO G, O, V and X, and two clinical isolates obtained in the UK in 2020. Participating laboratories were requested to test the EQA panel using their local methodology (i.e. MIC gradient strip test, agar dilution, or disc diffusion) and relevant international breakpoints (i.e. EUCAST, CLSI, etc.) against a range of antimicrobial agents. Results were submitted directly to UK NEQAS, who issued individual laboratory reports. The results were then supplied to UKHSA, who decoded and analysed the results based on the categories of susceptibility assigned. Susceptibility category concordance (categorical agreement) was assessed using the consensus category (the category most often reported) of susceptibility for each tested strain. MIC concordance was assessed by examining MIC results within one (essential agreement) and two doubling dilutions of the modal MIC. Intralaboratory concordance was examined using the triplicate and the two duplicate strains.
In July 2021, 28 laboratories in 28 European Union/European Economic Area countries were dispatched 10 gonococcal isolates for antimicrobial susceptibility testing. Only 26 of the 28 participating laboratories (one laboratory was unable to retrieve N. gonorrhoeae from the freeze-dried cultures and one did not receive the isolates) returned EQA results to UK NEQAS. Most (96.4%) laboratories used MIC gradient strip tests and all used EUCAST breakpoints. The highest level of categorical agreement was seen with spectinomycin and ceftriaxone (both 100%), while the lowest was seen with ciprofloxacin (92.9%). Compared to the previous distribution, except for ciprofloxacin (92.9% in 2021, 99.3% in 2020), categorical agreement increased for all antibiotics with the largest increase observed for azithromycin (96.4% in 2021, 90.4% in 2020).
Overall, 91.5% and 96.0% of the reported minimum inhibitory concentrations (MICs) were within one (essential agreement) and two doubling dilutions of the modal MIC, demonstrating that the level of essential agreement has decreased since 2020 (93.8%). However, this decrease may also be due to the fact that there were different laboratories participating in the analysis for each year (76% were decentralised testing laboratories in the 2020 report, 67% were decentralised testing laboratories in this report). When comparing the 2021 and 2020 EQA schemes, the level of essential agreement for individual antimicrobials decreased for ciprofloxacin, ceftriaxone, azithromycin, and gentamicin and increased for cefixime and spectinomycin. Of the 26 laboratories, 19 (73%) achieved an intralaboratory MIC concordance percentage score of 95% or higher, with nine laboratories obtaining a score of 100%.
Discussion and conclusion
The harmonisation of susceptibility testing methodologies and breakpoints used by participating laboratories was maintained in 2021, with most laboratories using MIC gradient strip tests and all applying EUCAST breakpoints for interpretation of MIC results. Overall, most laboratories participating in the 2021 EQA scheme performed well and showed good levels of competency in testing N. gonorrhoeae isolates of unknown phenotype. When compared with 2020, the level of categorical agreement increased for all tested antibiotics, except ciprofloxacin, with the largest increase for azithromycin. In most cases, the inter- and intralaboratory concordance was high, demonstrating comparability between different testing methodologies and promoting confidence in decentralised testing for surveillance purposes. Most susceptibility category discrepancies were attributable to strains with MICs on or close to a breakpoint, which highlights the need to consider the actual MIC as well as susceptibility category when interpreting susceptibility results. Analysis of the individual results submitted by the participating laboratories highlighted five centres in need of further guidance to help bring them in line with the European Gonococcal Antimicrobial Surveillance Programme (Euro-GASP) recommended target (95% of MICs within two doubling-dilutions of the modal MICs and beta-lactamase assessment).