To determine the frequency and cause of inadequate initial antibiotic therapy with vancomycin and piperacillin-tazobactam in patients with severe sepsis and septic shock in the emergency department (ED), characterize its impact on patient outcomes, and identify patients who would benefit from an alternative initial empiric regimen.

Retrospective cohort study conducted between 2012 and 2015 in which 342 patients with culture-positive severe sepsis or septic shock who received initial vancomycin and piperacillin-tazobactam were reviewed to determine appropriateness of antimicrobial therapy, risk factors for inappropriate use, and outcome data. Univariate and multivariate regression analyses were determined to identify associations between inappropriate antibiotic use and outcomes and to identify risk factors that may predict which patients would benefit from an alternative initial regimen.

Vancomycin and piperacillin-tazobactam were inappropriate for 24% of patients with severe sepsis or septic shock, largely due to non-susceptible infections, particularly ESBL organisms and Clostridium difficile. Risk factors included multiple sources of infection (OR 4.383), admission from a skilled nursing facility (OR 3.763), a history of chronic obstructive pulmonary disease (COPD) (OR 3.175), intra-abdominal infection (OR 2.890), and immunosuppression (OR 1.930). We did not find a mortality impact.

Vancomycin and piperacillin-tazobactam were an inappropriate antibiotic combination for approximately 24% of patients with either severe sepsis or septic shock in the ED. Patients with known COPD, residence at a skilled nursing facility, a history concerning for Clostridium difficile, and immunosuppression would benefit from an alternative regimen. Future prospective studies are needed to validate these findings.