Vancomycin Minimum Inhibitory Concentration as a Predictor of Mortality in Methicillin‐ResistantStaphylococcus aureusBacteremia: A Second Look

To the Editor—We read with interest the article by Soriano et al. [1] that described vancomycin MIC as a predictor of mortality in patients with methicillin-resistant Staphylococcus aureus bacteremia. The issue of MIC “creep” was documented elsewhere [2], and the conclusion that a higher MIC is associated with an increased risk of mortality is not surprising. In addition, the presence of shock associated with methicillin-resistant Staphylococcus aureus bacteremia was documented elsewhere as a risk factor for mortality [3]. However, the negative association between the development of shock and vancomycin MIC is extremely intriguing. Soriano et al. [1] hypothesize that this relationship could be attributed to a decrease in pathogenicity as resistance increases through a variety of mechanisms. We offer an alternative explanation of the data and address some concerns with the study by Soriano et al. [1]. After examination of the absolute incidence of patient characteristics, it is clear that the development of shock is negatively associated with vancomycin MIC without adjustment for confounding variables (for 1 µg/mL, 28.4%; for 1.5 µg/mL, 20.2%; for 2 µg/mL, 10.9%; P=.007). It is also clear that heart failure occurred in a significantly higher percentage of patients in the 2 µg/mL cohort (7.6%), compared with patients in comparator cohorts (3.7% in the 1 µg/mL cohort and 1.4% in the 1.5 µg/mL cohort; P=.01). Neither all-cause mortality nor infection-related mortality is significantly different among groups analyzed without statistical adjustment. Although the presence of heart failure was not found to be a predictor of mortality, we would argue that such a diagnosis would weigh into the category of “prognosis of underlying disease,” which was determined to be a significant factor in mortality. Through a series of statistical steps, Soriano et al. [1] determined that a vancomycin MIC of 2 µg/mL, compared with an MIC of 1 µg/mL, was independently associated with all-cause mortality. They also stated that this relationship remains when infection-related mortality is substituted as the dependent variable, although they did not provide data to support this claim. Additionally, there is a typographical error in the last paragraph of the Results section that made interpretation of this study difficult at best: “This was entirely because of the fact...had isolates with a vancomycin MIC of 1 µg/mL...than among those who had isolates with a vancomycin MIC of 1 µg/mL...” [1, p. 197]. Although the sample size appears to be adequate, no power analysis was reported. Additionally, Soriano et al. [1] note that all patients receiving vancomycin were treated to a goal trough level of ⩾10 µg/mL. Soriano et al. [1] did not report what percentage of patients actually achieved this target trough at first measurement, nor do they report mean time to target trough attainment. The study by Soriano et al. [1] is also confounded by indication [4]. In other words, the fact that the patients had methicillin-resistant Staphylococcus aureus bacteremia made them more likely to die. In the end, we were left with more questions than answers and would like to see further evidence to support the findings of the study by Soriano et al. [1]. Potential conflicts of interest. A.D.P. and G.D.B.: no conflicts.