IMPORTANCEEstimates of the incidence of overall antibiotic-associated adverse drug events (ADEs) in hospitalized patients are generally unavailable.OBJECTIVE To describe the incidence of antibiotic-associated ADEs for adult inpatients receiving systemic antibiotic therapy. DESIGN, SETTING, AND PARTICIPANTSRetrospective cohort of adult inpatients admitted to general medicine wards at an academic medical center.EXPOSURES At least 24 hours of any parenteral or oral antibiotic therapy.MAIN OUTCOMES AND MEASURES Medical records of 1488 patients were examined for 30 days after antibiotic initiation for the development of the following antibiotic-associated ADEs: gastrointestinal, dermatologic, musculoskeletal, hematologic, hepatobiliary, renal, cardiac, and neurologic; and 90 days for the development of Clostridium difficile infection or incident multidrug-resistant organism infection, based on adjudication by 2 infectious diseases trained clinicians. RESULTSIn 1488 patients, the median age was 59 years (interquartile range, 49-69 years), and 758 (51%) participants were female. A total of 298 (20%) patients experienced at least 1 antibiotic-associated ADE. Furthermore, 56 (20%) non-clinically indicated antibiotic regimens were associated with an ADE, including 7 cases of C difficile infection. Every additional 10 days of antibiotic therapy conferred a 3% increased risk of an ADE. The most common ADEs were gastrointestinal, renal, and hematologic abnormalities, accounting for 78 (42%), 45 (24%), and 28 (15%) 30-day ADEs, respectively. Notable differences were identified between the incidence of ADEs associated with specific antibiotics.CONCLUSIONS AND RELEVANCE Although antibiotics may play a critical role when used appropriately, our findings underscore the importance of judicious antibiotic prescribing to reduce the harm that can result from antibiotic-associated ADEs.

PTZ appears inferior to carbapenems for the treatment of ESBL bacteremia. For patients at high risk of invasive ESBL infections, early carbapenem therapy should be considered. Our findings should not be extended to β-lactam/β-lactamase inhibitor combinations in development, as limited clinical data are available for these agents.

PPRF may have more of an impact on decreasing antibiotic DOTs compared with PPA. This information may be useful for institutions without sufficient resources to incorporate both stewardship approaches.

The duration of therapy for CAP was excessive at our institution and was decreased with a stewardship intervention. Confirmatory studies at other institutions are needed; efforts to assess and reduce duration of therapy for CAP should be strongly considered.

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.