The results of this study establish an ecological link between linezolid consumption and increasing incidence of enterococci with decreased susceptibility to linezolid. Previous studies have identified exposure to linezolid as a risk factor for linezolid resistance among enterococci (4
). However, these studies used phenotypic testing methods to detect linezolid resistance, and as such, the rates of nonsusceptibility and the relationship between linezolid use and resistance reported in these studies may not be an accurate reflection of the incidence of genotypically confirmed resistance (4
). This is the first report to assess the incidence of G2576T mutants in the setting of increasing linezolid consumption and demonstrate a correlation between linezolid consumption and genotypically proven linezolid resistance among VREF strains.
At our institution, linezolid use has increased since the introduction of the drug in 2000. For several years, persistent use of this agent did not appear to translate into the emergence of resistant organisms; however, since 2002 an increase in LIRVREF isolates possessing the G2576T mutation has been observed. We standardized our resistance data for increasing patient numbers in recent years and verified an increasing rate of LIRVREF incidence despite these increases in patient census. Additionally, we confirmed that our VRE burden did not increase over the study period. The results shown in Fig. demonstrate a stable rate of clinical VRE isolation. We previously demonstrated that commonly utilized phenotypic tests, such as E-test and disk diffusion, do not accurately reflect the true incidence of linezolid resistance compared to the rate of isolation of G2576T mutants (9
). These findings were further corroborated through the work of Tenover and colleagues, who also described significant error rates for the detection of linezolid resistance among enterococci when phenotypic methods were utilized, with very major errors reaching rates between 20% and 40% for some automated systems (9
). Additionally, disk diffusion tests and E-tests have shown 7% major error rates (13
). Only agar dilution and broth microdilution methods appear to have a high correlation with the incidence of genotypic resistance (9
). Data such as these highlight the attractiveness of genetic confirmation for resistance. It is especially convenient when only a single mutation is associated with resistance, such as with the G2576T mutation for linezolid resistance among clinical enterococci. A reliable means of identifying linezolid resistance is critical, since false reporting of resistance may lead to unnecessary increases in resource utilization and subsequent patient morbidity (12
Clinical VRE rate (one isolate per patient per year per 1,000 patient days).
Potential limitations of our analysis follow. First, this study used antibiotic purchase data as a method of quantifying antimicrobial usage; however, since each compartmentalized time period (1 year) was relatively long and the period analyzed (fiscal year) remained constant throughout the study, the purchase data are thought to correlate well with actual antimicrobial consumption. Second, horizontal spread of resistant isolates may potentially be implicated in outbreaks of LIRVREF (2
). This is unlikely to have accounted for the increase in resistance at our institution, since only genetically distinct isolates were used for the calculations. As such, it appears that the increasing isolation of genotypically confirmed isolates of LIRVREF has followed an increase in linezolid usage at our institution. Third, these data are ecological and do not establish causality; however, we suggest that increased linezolid consumption leads to an increase in the incidence of LIRVREF. This presumption is strengthened by the facts that the data are biologically plausible, such an association is concordant with results of in vitro experiments, and linezolid use and resistance are temporally linked.