EUCAST began harmonising the European clinical breakpoints over 10 years ago using an evidence based approach to setting breakpoints for many commonly used agents. They continue to review existing breakpoints using new pharmacokinetic/pharmacodynamics data or clinical therapeutic efficacy evidence and set clinical breakpoints for new agents, publishing updates every year. The EUCAST disc method was developed in 2009, evaluating the accuracy of the susceptibility test for each organism/agent combination. The method continues to be updated to improve accuracy of existing tests and to include more antimicrobial agents and bacterial species.
The areas where UK laboratory practice and EUCAST methods, guidelines and breakpoints do not align are discussed in detail below.
No nitrofurantoin or mecillinam clinical breakpoints for Enterobacteriales other than E. coli (nitrofurantoin) or E. coli, Klebsiella species and P. mirabilis (mecillinam).
There are currently EUCAST clinical breakpoints for nitrofurantoin and mecillinam, however these breakpoints can only be used to interpret tests performed on E. coli (nitrofurantoin) or E. coli, Klebsiella species and P. mirabilis (mecillinam) from uncomplicated UTI. These restricted interpretation criteria were present in all previous versions of the BSAC guidelines and so UK laboratories should not have been interpreting the results of these agents against Enterobacteriales other than those specified.
EUCAST review these breakpoints regularly, and as yet there is little evidence to support clinical breakpoints for species other than those stated.
Some UK Laboratories extrapolate the nitrofurantoin and mecillinam clinical breakpoints to interpret all Enterobacteriales, however, this is not recommended.
Nitrofurantoin susceptibility in Enterobacteriales varies, with E. coli particularly susceptible and Proteae (e.g. Proteus, Morganella and Providencia spp), some Klebsiella species and Pseudomonas species carrying intrinsic resistance. Infections with Enterobacteriales other than E. coli or staphylococci other than S. saprophyticus are commonly associated with upper urinary tract or complicated infections. EUCAST clinical breakpoints are based upon pharmacokinetic data, microbiological data and clinical experience. Most nitrofurantoin and mecillinam clinical data is derived from acute UTI studies, mostly comprising of E. coli (Hüttner et al., 2015). For these reasons, EUCAST considers Enterobacteriales other than E. coli, P. aeruginosa, Acinetobacter species, staphylococci other than S. saprophyticus, streptococci other than group B, H. influenzae, Moraxella catarrhalis, Neisseria species and anaerobes as poor targets for nitrofurantoin or inappropriate for nitrofurantoin therapy. For mecillinam, P. aeruginosa, Acinetobacter species, Staphylococcus species, Enterococcus species, streptococci, H. influenzae, M. catarrhalis, Neisseria species and anaerobes were considered poor targets or inappropriate for mecillinam therapy.
Data collection to support a EUCAST discussion on an extension of mecillinam breakpoints to other Enterobacterales is ongoing, but a resolution will probably not be before 2019. BSAC are currently collating zone diameter data for both agents on the species not covered by the breakpoints with the aim of establishing UK ECOFFs. In the interim:
BSAC CURRENTLY RECOMMENDS: DO NOT REPORT nitrofurantoin or mecillinam results for those species without breakpoints
No EUCAST disc diffusion method for Neisseria species
There is currently NO EUCAST disc diffusion method for susceptibility testing Neisseria species. MIC determination is recommended using EUCAST clinical breakpoints.
It is important for UK laboratories to continue susceptibility testing N. gonorrhoeae as resistance to azithromycin and ceftriaxone is increasing in this country. However, there is considerable uncertainty as to the validity of the disc method for and clinical significance of resistance in N. meningitidis.
As UK laboratories transferred to the EUCAST disc diffusion test for general testing, we advised to continue using the BSAC disc test for Neisseria species. BSAC are in collaboration with UK and European laboratories to develop both EUCAST MIC and disc diffusion methods for Neisseria species. These studies will take some time to complete and so the use of an unsupported method in UK laboratories would be untenable. We are therefore recommending the following interim advice:
BSAC CURRENTLY RECOMMENDS: Perform MIC testing for all clinically relevant <em>N. gonorrhoeae</em> and <em>N. meningitidis</em> as per EUCAST guidance.
BSAC RECOMMENDS: Two control organisms to be tested for N. gonorrhoeae: N. gonorrhoeae ATCC 49226 plus N. gonorrhoeae WHO X (Ceftriaxone & Azithromycin R; click here for reference)
Most laboratories use gradient strips for MIC testing, with manufacturer’s recommended media. The recommended media for use with gradient strips is available in a pre-poured state, albeit not universally, as is 3mL Mueller Hinton broth for inoculum preparation. Positive responses were received from media manufacturers regarding the availability of the recommended pre-poured media in future.
No EUCAST disc diffusion method for Anaerobic bacteria
EUCAST currently have NO disc diffusion test for anaerobic bacteria. MIC determination is recommended using EUCAST clinical breakpoints. EUCAST have recently set up a sub-committee to focus on disc susceptibility testing of anaerobic bacteria. Some work has already been performed and a disc diffusion method for Bacteroides species is near completion, being published this year (2018). Disc diffusion methods for other anaerobic bacterial species will be developed in the future. Until disc diffusion methods and criteria are published BSAC is recommending the following advice:
BSAC RECOMMENDS: Perform MIC testing for all clinically relevant anaerobic bacterial species as per EUCAST guidance
The anaerobe specific recommended media and inoculum preparation broths for gradient strips is not readily available in the UK. Positive responses were received from media manufacturers regarding the availability of the recommended pre-poured media in future.