Susceptibility Categories Should Be Agreed Upon

LETTER

I thank the editor in chief very much for his comic strip beautifully describing the differences and similarities in susceptibility (“S”) categories as defined by the Clinical and Laboratory Standards Institute (CLSI) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) (1). Judging from my experience as a clinical microbiologist, antimicrobials assigned to the intermediate susceptibility (“I”) category in antibiograms reported according to CLSI or former EUCAST rules are hardly ever used. Resistance (“R”) to antimicrobial agents is growing relentlessly; concomitantly, the number of cases in which clinicians, facing limited treatment options, have to consider antimicrobials categorized as “I” increases. Antimicrobials must be used based on the best available evidence, balancing the needs of the individual patients and the selective pressure caused; concise, clear, and unambiguous communication of laboratory results to clinicians is of paramount importance. Therefore, I very much applaud the decision of the EUCAST steering committee to change the definition of “I” so as to remove the uncertainty this category has been tainted with historically (2). Under current EUCAST rules, results which are fraught with substantial uncertainty are tagged with a warning message (“Area of Technical Uncertainty” [ATU]), which must be dealt with by the laboratory. For results marked as ATU, an alternative test may be used, or the susceptibility categories that apply may be flagged as uncertain, suppressed from reporting, or stepped up (i.e., the marked result may be reported as resistant). Disadvantageously, EUCAST still has failed to change the susceptibility categories for yeasts. Hopefully, this inconsistency, which could cause substantial confusion, will be remedied soon. The principle of sticking to the traditional S, I, and R shorthand symbols and yet changing the definitions of the susceptibility categories comes at a price: intense and ongoing education is urgently needed to avoid misunderstandings and misinterpretations.

Sadly, despite impressive efforts, CLSI and EUCAST have not yet unified their rules for reporting qualitative susceptibility results. The CLSI committee on antimicrobial susceptibility testing has discussed the matter extensively (see p. 21 to 24 in reference 3) and came to conclusions different from EUCAST’s.

EUCAST’s new definition of the category “I” (“susceptible, increased exposure”) is quite similar to CLSI’s definition of “Susceptible Dose Dependent” (SDD) (see p. 242 in reference 4). For bacteria, CLSI introduced this susceptibility category in 2014 (see p. 18 in reference 5); at that time, EUCAST did not adopt the change. In CLSI M100, SDD is used increasingly, but still rarely, even in the current edition (4): SDD is listed only for cefepime in Enterobacteriaceae (Enterobacterales), ceftaroline in Staphylococcus aureus, and daptomycin in Enterococcus faecium (see p. 35, 63, and 70 in reference 4). For Pseudomonas aeruginosa, for instance, most antimicrobial agents effective in strains with wild-type susceptibility depend on application of high dosages for their efficacy, with meropenem the most notable exception to this rule. The current CLSI documents include comments to convey this need. For P. aeruginosa, as well as for many other bacterial species where using this category would be prudent, SDD is not used in the CLSI standard (see p. 42 to 45 in reference 4). In my view, it would be advantageous to use SDD or “I” as defined by EUCAST instead of adding lengthy comments that might not always enjoy the attention of the clinicians to whom the results are being reported. The recipients’ attention to the change must be caught by proper legends to the antibiogram, a link to the dosage table used for determination of the breakpoints, and continuing education. General use of “I” to convey the need for a high exposure of the microbes to the antimicrobial in question where appropriate is expected to be agreed upon by EUCAST in 2020 and may be used beforehand, which our laboratory chose to do. Creating new susceptibility categories might attract the recipients’ attention for the change in definitions to be noted. Susceptibility categories that are rarely used, however, will not spread the news effectively and may be misunderstood. CLSI and EUCAST will have to fulfill the need for education about both the new terminology and changes in the definition of existing terms.

To make sure the recipients of our susceptibility reports note the changes that the definitions of the categories “S” and “I” have been subjected to by EUCAST (6), we introduced the following colors on our reports: susceptible and resistant assignments have been printed with a white “S” or “I” on a green background and a white “R” on a red background, respectively, since 1 January 2019 (anonymized examples of our reports are available as supplemental material). Until EUCAST extends the new definition of the category “I” to yeasts, our laboratory will continue to display a black “I” on an orange background to indicate “intermediate” results. The definitions of the white “I” on a green background and the black “I” on an orange background are included in the legends of antibiograms which contain these shorthand symbols. Admittedly, the colors our laboratory has chosen suffer from the major disadvantage of being hard to discern by persons stricken with color blindness; the advantages of the analogy to traffic lights, however, in our opinion, overruled this concern. With our laboratory information software (LIS), based on open source software, the changes to our reports were achieved quickly and easily and at no cost.

EUCAST decided to stick with a mere three categories for reporting susceptibility results to clinicians and to change the definition of “I” in a way that removes the ambiguities previously included in this category. While CLSI has introduced the SDD category, in my opinion, they still use this category very restrictively. In addition, as Albert Einstein has pointed out, “everything should be as simple as it can be, but not simpler.” Three susceptibility categories, wisely defined, are completely sufficient and allow for lengthy comments on laboratory reports to be restricted to cases where they are both useful and unavoidable. In my humble opinion, the guidelines should be unified with regard to the categories susceptibility results are assigned to; three unambiguous, clear-cut categories offer comprehensive and yet detailed categorical reporting of susceptibility results.