Abstract
BACKGROUND: Enterobacteriaceae are common pathogens in pneumonia, sepsis and urinary tract infection (UTI). Though rare, carbapenem resistance (CRE) among these organisms complicates efforts to ensure adequate empiric antimicrobial therapy. In turn this negatively impacts such outcomes as mortality and hospital costs. We explored proportion of total costs represented by antibiotics, 30-day readmission rates, and per-day costs of inadequate antimicrobial coverage among patients with Enterobacteriaceae pneumonia, sepsis and/or UTI in the context of inappropriate (IET) vs. appropriate empiric (non-IET) therapy and carbapenem resistance (CRE) vs. susceptibility (CSE). METHODS: We conducted a retrospective cohort study in the Premier Research database (2009-2013) of 175 US hospitals. We included all adult patients admitted with a culture-confirmed UTI, pneumonia, or sepsis as principal diagnosis, or as a secondary diagnosis in the setting of respiratory failure. Patients with hospital acquired infections or transfers from other acute facilities were excluded. IET was defined as failure to administer an antibiotic therapy in vitro active against the culture-confirmed pathogen within 2 days of admission. RESULTS: Among 40,137 patients with Enterobacteriaceae infections (54.2% UTI), 4984 (13.2%) received IET. CRE (3.1%) was more frequent in patients given IET (13.0%) than non-IET (1.6%, p < 0.001). The proportions of total costs represented by antibiotics were similar in IET and non-IET (3.3% vs. 3.4%, p = 0.01), and higher among the group with CRE than CSE (4.2% vs. 3.4%, p < 0.001). The 30-day readmission rates were higher in both IET than non-IET (25.6% vs. 21.1%, p < 0.001) and CRE than CSE (29.7% vs. 21.5%, p < 0.001) groups. Each additional day of inadequate therapy cost an additional $766 (95% CI $661, $870, p < 0.001) relative to adequate treatment. CONCLUSIONS: In this large US cohort of Enterobacteriaceae infections, the cost of antibiotics was a small component of total costs, irrespective of whether empiric treatment was appropriate or whether a CRE was isolated. In contrast, each extra day of inadequate treatment added >$750 to hospital costs. Both CRE and IET were associated with an increased risk of readmission within 30 days.