“Tolerance” of Misused Terminology? Enforcing Standardized Phenotypic Definitions

The recent paper by Haaber and colleagues entitled “Reversible Antibiotic Tolerance Induced in Staphylococcus aureus by Concurrent Drug Exposure” (1) revealed a possible alternative mechanism by which pathogens become less susceptible to standard therapy by screening for inducible antibiotic resistance in Staphylococcus aureus USA300 strain FP3757. We agree with the sentiments expressed by Bean and Wigmore (2) about the timeliness of this article and the need to examine antibiotic combinations, especially with increasing multidrug-resistant pathogens. Furthermore, this article highlighted some of the potential pitfalls of combination therapy and stressed the need for further research in this area. However, we have some concerns regarding the terminology and methods used in this study. First, the term “antibiotic tolerance” is used extensively throughout the article with no consideration of its official definition. The Clinical and Laboratory Standards Institute (CLSI) defines a vancomycin-tolerant strain as one for which the minimum bactericidal concentration (MBC)-to-MIC ratio is 32 after 24 h of incubation (3–7). The MIC, used as a measure of susceptibility, is the minimum concentration of an antibiotic that inhibits growth. In contrast, the MBC indicates the effectiveness of a bactericidal antibiotic, as it is the minimum concentration needed to kill an organism. Thus, although S. aureus FPR3757 showed an increased vancomycin MIC after pre-exposure to colistin, it did not display