30-day readmission, antibiotics costs and costs of delay to adequate treatment of Enterobacteriaceae UTI, pneumonia, and sepsis: a retrospective cohort study

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.

Keywords: Costs; Enterobacteriaceae; Pneumonia; Readmission; Sepsis; UTI.

Conflict of interest statement

Ethics approval and consent to participate

This study utilized an already existing HIPAA-compliant fully de-identified data, and, therefore, it was exempt from ethics review.

Consent for publication

Not applicable.

Competing interests

Dr. Zilberberg is a consultant to The Medicines Company. Her employer, EviMed Research Group, LLC, has received research grant support from The Medicines Company.

Dr. Nathanson is an employee of OptiStatim, LLC, who received grant support from EviMed Research Group, LLC, for conducting the analyses.

Ms. Fan and Ms. Sulham are employees of and stockholders in The Medicines Company.

Dr. Shorr is a consultant to and has received research grant support from The Medicines Company.

Drs. Zilberberg and Shorr have received grant support and/or have served as consultants to Merck, Tetraphase, Pfizer, Astellas, Shionogi and Theravance.

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