Discussion

We evaluated the sensitivity and specificity of VRE colonization status to predict the presence of VRE bacteremia in patients with enterococcal bloodstream infection and calculated estimates of the NPVs and PPVs based on the proportion of VRE among all Enterococcus bacteremia. We demonstrated that, for a given VRE proportion less than 27%, the NPV of a VRE screening test for predicting VRE bacteremia exceeded 90% and increased to 95% when the VRE proportion was below 15%. In stable patients for whom a 5%–10% risk of delaying VRE therapy is clinically acceptable, a negative screening test can guide a decision to forego empiric linezolid or daptomycin. As expected, the 30-day criterion was less sensitive but more specific than other criteria. However, the overall diagnostic properties were similar for all criteria and older results remain helpful depending on the local VRE proportion. Our findings suggest that even if screening practices vary, even a dated VRE colonization status can be helpful in choosing antimicrobials in the absence of high levels of nosocomial VRE transmission. We have provided PPV/NPV at different VRE proportions (Figs. 1–3) to allow other institutions to evaluate the operating characteristics of VRE screening swabs in their local context.

One limitation of our study was our lack of access to individual patient-level data. Nevertheless, in general, colonization likely precedes infection, and we have previously shown that, for MRSA, colonization status is the single most important risk factor for infection.^{Reference Butler-Laporte, Cheng, McDonald and Lee19} There is no reason a priori to suspect that it might be different for VRE. Another limitation is our focus on bloodstream infections. We chose this subset of infections due to the relative ease and specificity of case finding and because it provides both the worst case for the NPV and the best case for the PPV. Using a negative VRE colonization status to withhold anti-VRE therapy seems justified in most patients, especially for infections in which Enterococcus is unlikely to be contributory. At the same time, using a positive colonization status to drive empiric anti-VRE therapy when an Enterococcus infection is unlikely would be unjustified. However, in situations in which an Enterococcus spp is justifiably suspected, such as hepatobiliary infections or when susceptibility data from a confirmed gram-positive cocci infection is pending, empiric VRE-directed therapy could be justified. Essentially, clinicians would need to refer to local microbiology and clinical data when using VRE colonization for treatment guidance. Additionally, because second-line antimicrobials for Enterococcus are usually not tested during first-line susceptibility testing, a positive VRE screen might be used to alert the microbiology laboratory that early second-line susceptibility testing could be warranted for presumed enterococci to avoid delays.^{Reference Rubinstein, Hirsch and Bandyopadhyay20}

Previously, most studies involving the use of VRE colonization status in predicting vancomycin resistance in clinical isolates have involved the role of VRE colonization as a risk factor for eventual VRE infection.^{Reference Bossaer, Hall and Garrett-Mayer21,Reference Ford, Lopansri and Haydoura22} To our knowledge, apart from Brasg et al^{Reference Brasg, Elligsen, MacFadden and Daneman13} and Webb et al,^{Reference Webb, Healy and Majers14} no other study has analyzed the predictive accuracy of VRE screening tests to guide empiric therapy when an enterococcal infection is known or suspected. Although the conclusions of other studies were similar, their study designs differed in multiple ways, which significantly limits their generalizability. First, we screened all patients on admission to medical, surgical, and critical care wards, regardless of medical comorbidities, although the other studies restricted their patient population either by limiting screening to specific patient groups at high risk of VRE colonization or by only including patients undergoing stem cell transplantation or leukemia induction chemotherapy. Second, the overall proportion of VRE in their institutions was much lower than ours. Third, their VRE screening protocols differed greatly. In Brasg et al,^{Reference Brasg, Elligsen, MacFadden and Daneman13} the protocol began with VRE specific agar with confirmation of vanA and/or vanB gene carriage by PCR. By performing PCR first, our protocol may have achieved higher sensitivity. In Webb et al,^{Reference Webb, Healy and Majers14} no PCR was used, and the screening agar also differed, which also most likely reduced their sensitivity. We suspect that these methodological differences contribute to any discordant results.

Although the retrospective nature of our study does not provide proof of clinical benefit, we contend that knowledge of previous VRE screening test results can help guide appropriate empiric antibiotic therapy. Our research adds to the growing number of studies reporting on the importance of a patient’s bacterial flora on subsequent resistance in infection. In addition to MRSA^{Reference Butler-Laporte, De L’Etoile-Morel, Cheng, McDonald and Lee12} and VRE, a similar predictive value has been observed in gram-negative bacterial infections.^{Reference MacFadden, Coburn and Shah23} We suggest that we are moving toward an era in which empiric therapy can be personalized based on an individual’s known colonization status and previous microbiology, local epidemiology, likely source of infection, and severity of the illness, to improve outcomes and reduce adverse events.