December 2019 brings changes to the Bacteriology schemes, with Paul Chadwick stepping down from his part time role as the interim Scheme Organiser and the full time appointment of Jennifer Henderson as the new Scheme Organiser for Bacteriology and Mycology. Paul will continue as Scheme Organiser for Interpretive Comments. We hope and expect that these changes will continue to allow UK NEQAS Microbiology to promote and develop all of these schemes moving forward.
In this section of the newsletter we will focus on the Antimicrobial Susceptibility scheme, where many changes have now started to take place. Twelve distributions are prepared and dispatched each year to over 600 UK and non-UK clinical diagnostic laboratories. For each distribution, two isolates are prepared and distributed and participants undertake AST (antimicrobial susceptibility testing) and reporting. The specimens contain potential pathogens that are fully characterised, with antimicrobial susceptibilities, and correspond to those likely to be found in clinical practice. Following the close of the distribution, a report is written to summarise the guidelines (EUCAST, CLSI) used by participants and the results obtained, so that participants can assess their individual performance and compare this to results obtained by aggregated participants. More than 80% of our participants tell us that they now use EUCAST methods to determine AST results. Expert comments accompany the reports with additional comments on methods used and findings in relation to the resistance genes present in the isolates. We are aware that participants find these expert comments very useful and we apologise that there is currently a long delay in adding these to the reports. This will be remedied in the near future and expert comments will be added to the 2019 reports.
Participants will be pleased to hear that a stringent series of quality control checks is undertaken, from the preparation of specimens to the dispatch of the distributions. In order to assess effects of transportation, panels are dispatched to five national centres, who return them to the UK NEQAS laboratory for us to check the viability and homogeneity of the organisms. Two reference laboratories provide MIC data obtained by broth microdilution and one reference laboratory provides whole genome sequencing (WGS) data to characterise all known resistance genes within isolates.
We receive many queries about scoring of this scheme. Note that EQA is an educational process which challenges the total quality system. Within this, trends are more important than individual results, and so while it is important to review and investigate all results where a full score is not achieved, it is the overall performance in the scheme that is most important. Scoring is based on a straight 80% consensus of participants (and must be in agreement with reference laboratories’ MIC results). The current version of EUCAST/CLSI is used. Scoring rules are published on the UK NEQAS website, and include scenarios where results differ between EUCAST and CLSI guidelines, or where only one of these committees provides an interpretation. Unfortunately we cannot determine why an individual participant/laboratory has been unsuccessful in obtaining the intended results by their stated guideline/method (although we are regularly asked to do so!). Following an incorrect result, participants should review all aspects of their AST in terms of media, inoculum, incubation time and temperatures, and storage conditions (both reagents and specimens) etc.
Clinical sites other than blood have now been introduced , which allows new antimicrobial agents to be tested by participants, for example AST for oral agents. Identification of organisms is now provided, as other schemes (such as the general bacteriology scheme) test characterisation of organisms.
Area of technical uncertainty (ATU) is new for 2019 from EUCAST and is potentially an issue for EUCAST users. However, the scoring depends upon MIC results from reference laboratories (not individual participants’ results). So far, ATU has not been applicable to the scheme, and when reference laboratory results do fall into the ATU, the results will probably not be scored. Another area that we have received queries about is the clinical interpretation of results that fall into the ‘intermediate’ category. This issue is also new in 2019 for EUCAST users. In effect, the clinical interpretation may change, so that the ‘I’ (intermediate) category is now susceptible, rather than resistant. Although participants may suppress or change interpretations, the ‘S’ (susceptible) , ‘I’ (intermediate) and ‘R’ (resistant) AST categories will continue to be requested of participants as test results in accordance with EUCAST/CLSI methods and so far this issue has not affected scheme results or scoring decisions.
The following organism/agent combinations have recently caused difficulties for participants:
Distribution 4270 (April 2018)
- Specimen 4347 was an Escherichia coli resistant to amoxicillin and ampicillin, and with reduced susceptibility to amoxicillin-clavulanate. WGS showed the presence of the blaTEM-1 gene encoding the TEM1 beta-lactamase. Typically, this enzyme confers resistance to aminopenicillins and is inhibited by clavulanate. However, this organism had reduced susceptibility to amoxicillin-clavulanate. The MIC for amoxicillin-clavulanate was 16 mg/L, which was resistant by EUCAST (S≤8, R>8) and intermediate by CLSI criteria (S≤8, R≥32). Performance was poor with only 42.5% of EUCAST users and 17.9% of CLSI users reporting reduced susceptibility. There was little difference in performance across different testing methods. Poor performance was probably due to the closeness of the organism MIC to the breakpoints, and the inherent difficulties in testing beta-lactam/beta-lactamase combinations.