Rapid diagnostic tests (RDTs) have revolutionized the management of Gram-negative bacteremia by allowing antimicrobial stewardship teams the ability to escalate therapy and improve patient outcomes through timely organism identification and detection of certain resistance determinants. However, given the complex nature of Gram-negative resistance, stewardship teams are left without clear direction for how to respond when resistance determinants are absent as the safety of de-escalation in this setting is unknown. The primary purpose of this analysis was to determine the negative predictive values (NPV) of resistance marker absence to predict susceptibility in target bug/drug scenarios at two geographically distinct institutions. 1,046 Gram-negative bloodstream isolates that were analyzed with Verigene GN-BC were assessed. Outside of P. aeruginosa the absence of resistance determinants by the RDT largely predicted susceptibility to target antibiotics at both institutions. NPVs for ceftriaxone susceptibility in E. coli and K.pneumoniae in the absence of either CTX-M or a carbapenemase gene were 98% and 93-94%, respectively. Similar results were seen with other target bug/drug scenarios with NPVs of 94-100% demonstrated at both institutions, with the exception of P. aeruginosa, where NPVs were poor likely due to the more complex nature of resistance in this pathogen. The results of this study show that clinicians at both institutions should have confidence in de-escalation in the absence of resistance determinant detection by Verigene BC-GN, and the methodology described within this manuscript can serve as a blueprint for other stewardship programs to employ at their institutions to optimize management of Gram-negative bacteremia.
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