Abstract
BackgroundEnterobacteriaceae 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).MethodsWe 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.ResultsAmong 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.ConclusionsIn 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.
Highlights
Enterobacteriaceae are common pathogens in pneumonia, sepsis and urinary tract infection (UTI)
Both carbapenem resistance (CRE) and inappropriate empiric therapy (IET) were associated with an increased risk of readmission within 30 days
In a representative cohort of patients, on balance, does each day of exposure to inadequate antimicrobial treatment cost more than the potential savings from using less active but cheaper medications, which are more likely to be inadequate? Or what proportion of the overall hospital bill is attributable to antimicrobials and how, if at all, does it differ between patients given appropriate and inappropriate empiric treatment? Answering these questions may lend a broader perspective to the debate of risks and benefits of broad-spectrum treatment when warranted than focusing on acquisition costs
Summary
Enterobacteriaceae are common pathogens in pneumonia, sepsis and urinary tract infection (UTI). 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). Despite the link between inappropriate therapy and worsened outcomes, multiple obstacles preclude clinicians from effectively targeting these resistant organisms These challenges include difficulty with risk stratification, concern about promoting further resistance through prescribing unnecessarily broad empiric coverage, and the acquisition costs of potentially active, newer antimicrobials. In a representative cohort of patients, on balance, does each day of exposure to inadequate antimicrobial treatment cost more than the potential savings from using less active but cheaper medications, which are more likely to be inadequate? Or what proportion of the overall hospital bill is attributable to antimicrobials and how, if at all, does it differ between patients given appropriate and inappropriate empiric treatment? Answering these questions may lend a broader perspective to the debate of risks and benefits of broad-spectrum treatment when warranted than focusing on acquisition costs
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