Assumed versus Approved Breakpoints

In our opinion, recent articles by Jacobs et al. (1) and Zhanel et al. (4) disseminated misleading information. Our first objection is that the authors failed to abide by the journal's policy of not assigning interpretive MIC breakpoints in the absence of approved breakpoints. The Instructions to Authors are explicit on this point: “The percentage of strains susceptible and/or resistant to an antibiotic at its breakpoint concentration may be given only if an appropriate breakpoint has been approved, as by the National Committee for Clinical Laboratory Standards, 940 W. Valley Rd., Suite 1400, Wayne, PA 19087-1898. In the absence of approved breakpoints, authors cannot assign breakpoints, use breakpoints from related antibiotics, or use a range of concentrations to report a cumulative display of percent susceptible/resistant strains. ” Jacobs et al. and Zhanel et al. reported percent susceptibility of Streptococcus pneumoniae to cefaclor using assumed breakpoints. Zhanel et al. assumed breakpoints that are approved for cefuroxime, and Jacobs et al. used breakpoints derived by application of pharmacodynamic (PD) principles. The use of an assigned breakpoint for susceptibility (≤0.5 μg/ml) resulted in fewer than a quarter and just over half of the penicillin-susceptible S. pneumoniae (PSSP) strains being classified as susceptible to cefaclor, respectively, in the two papers. Those findings are inconsistent with long-standing clinical experience and with NCCLS recommendations. Since its registration, cefaclor has proven itself, time and time again, effective in treatment of infections caused by PSSP. Since the early 1990s, NCCLS has recommended reporting all PSSP strains as susceptible to cefaclor (2). That recommendation remains in the most recent iteration of NCCLS interpretive standards (3), which also includes the recently adopted cefaclor-specific pneumococcal MIC breakpoint for susceptibility, ≤1 μg/ml. Our second objection concerns the lack of attention to detail that Jacobs et al. used in abstracting their manuscript. Within the body of the article, they compared their PD breakpoint with the NCCLS established breakpoint for Haemophilus influenzae. Even though there is considerable explanation of this comparison within the text, this information was not included in the abstract. Unfortunately, the abstract includes only the susceptibility rate (2%) derived using the PD breakpoint, without mentioning the result determined using the NCCLS breakpoint (79%). It is well accepted that the majority of individuals screening articles, through either literature searches or personal reading, review only the abstracts of published manuscripts. Therefore, neglecting to include the percent susceptible by the NCCLS breakpoint only serves to allow the casual reader to misinterpret the published work. We are troubled by these irregularities since they represent both a disregard for your journal's Instructions to Authors and a breakdown in the refereeing process that was designed to ensure the scientific rigor of the journal. Occurrences such as these only serve to misinform the reader and to tarnish the reputation of this journal in the eyes of the scientific community.