Association of 30-Day Mortality With Oral Step-Down vs Continued Intravenous Therapy in Patients Hospitalized With Enterobacteriaceae Bacteremia

Abstract

IMPORTANCE Conversion to oral therapy for Enterobacteriaceae bacteremia has the potential to improve the quality of life of patients by improving mobility, eliminating catheterassociated discomfort, decreasing the risk for noninfectious and infectious catheterassociated adverse events, and decreasing health care costs. OBJECTIVE To compare the association of 30-day mortality with early oral step-down therapy vs continued parenteral therapy for the treatment of Enterobacteriaceae bloodstream infections. DESIGN, SETTING, AND PARTICIPANTS This retrospective multicenter cohort study included a 1:1 propensity score-matched cohort of 4967 unique patients hospitalized with monomicrobial Enterobacteriaceae bloodstream infection at 3 academic medical centers from January 1, 2008, through December 31, 2014. Eligibility criteria included appropriate source control measures, appropriate clinical response by day 5, active antibiotic therapy from day 1 until discontinuation of therapy, availability of an active oral antibiotic option, and ability to consume other oral medications or feeding. Statistical analysis was performed from March 2, 2018, to June 2, 2018. EXPOSURES Oral step-down therapy within the first 5 days of treatment of Enterobacteriaceae bacteremia. MAIN OUTCOMES AND MEASURES The main outcome was 30-day all-cause mortality. RESULTS Of the 2161 eligible patients, 1185 (54.8%) were male and 1075 (49.7%) were white; the median (interquartile range [IQR]) age was 59 (48-68) years. One-to-one propensity-score matching yielded 1478 patients, with 739 in each study arm. Sources of bacteremia included urine (594 patients [40.2%]), gastrointestinal tract (297 [20.1%]), central line-associated (272 [18.4%]), pulmonary (58 [3.9%]), and skin and soft tissue (41 [2.8%]). There were 97 (13.1%) deaths in the oral step-down group and 99 (13.4%) in the intravenous (IV) group within 30 days (hazard ratio [HR], 1.03; 95% CI, 0.82-1.30). There were no differences in recurrence of bacteremia within 30 days between the groups (IV, 6 [0.8%]; oral, 4 [0.5%]; HR, 0.82 [0.33-2.01]). Patients transitioned to oral step-down therapy were discharged from the hospital an average of 2 days (IQR, 1-6) sooner than patients who continued to receive IV therapy (5 days [IQR, 3-8 days] vs 7 days [IQR, 4-14 days]; P < .001). CONCLUSIONS AND RELEVANCE In this study, 30-day mortality was not different among hospitalized patients who received oral step-down vs continued parenteral therapy for the treatment of Enterobacteriaceae bloodstream infections. The findings suggest that transitioning to oral step-down therapy may be an effective treatment approach for patients with Enterobacteriaceae bacteremia who have received source control and demonstrated an appropriate clinical response. Early transition to oral step-down therapy may be associated with a decrease in the duration of hospital stay for patients with Enterobacteriaceae bloodstream infections.

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“…A recent observational study by Tamma et al showed similar 30-day mortality in a cohort of hospitalized patients with Enterobacteriacea bacteremia who received oral step down therapy compared to ongoing intravenous therapy [19]. Nearly half the patients in their study were male.…”

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“…The literature for gram-negative BSI has significantly changed treatment recommendations by supporting shorter treatment durations [ 28 ], early switch to oral antibiotics [ 29 ], and demonstrating lack of benefit of repeat blood cultures [ 30 ]. Using an approach that is well described in gram-positive infections, Erickson and colleagues conducted a single-center, retrospective cohort evaluation of an antimicrobial stewardship bundle coupled with rapid diagnostic tests (RDTs) for uncomplicated gram-negative bacteremia [ 13 ].…”

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“…They found that both oral step-down therapy and early de-escalation of therapy were not associated with higher 30-day mortality rates and clinical fail-ure rates in BSIs with Enterobacteriaceae. Furthermore, switch to oral therapy shortened the duration of hospitalization significantly (65,66).…”