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Seven versus fourteen Days of Antibiotic Therapy for uncomplicated Gram-negative Bacteremia: a Non-inferiority Randomized Controlled Trial.
Clin Infect Dis. 2018 Dec 11;:
Authors: Yahav D, Franceschini E, Koppel F, Turjeman A, Babich T, Bitterman R, Neuberger A, Ghanem-Zoubi N, Santoro A, Eliakim-Raz N, Pertzov B, Steinmetz T, Stern A, Dickstein Y, Maroun E, Zayyad H, Bishara J, Alon D, Edel Y, Goldberg E, Venturelli C, Mussini C, Leibovici L, Paul M, Bacteremia Duration Study Group
Abstract
Background: Gram-negative bacteremia is a major cause of morbidity and mortality in hospitalized patients. Data to guide the duration of antibiotic therapy are limited.
Methods: Randomized, multicenter, open-label, non-inferiority trial. Inpatients with Gram-negative bacteremia, afebrile and hemodynamically stable for at least 48 hours, were randomized to receive 7 (intervention) or 14 days (control) of covering antibiotic therapy. Patients with uncontrolled focus of infection were excluded. The primary outcome at 90 days was a composite of all-cause mortality; relapse, suppurative or distant complications; and re-admission or extended hospitalization (>14 days). The non-inferiority margin was set at 10%.
Results: We included 604 patients (306 intervention, 298 control) between January 2013 and August 2017 in three centers in Israel and Italy. The source of the infection was urinary in 411/604 (68%); causative pathogens were mainly Enterobacteriaceae (543/604, 90%). A 7-day difference in the median duration of covering antibiotics was achieved. The primary outcome occurred in 140/306 (45.8%) patients in the 7 days group versus 144/298 (48.3%) in the 14 days group (risk difference [RD] -2.6%, 95% confidence interval [CI] -10.5% to 5.3%). No significant differences were observed in all other outcomes and adverse events, except for a shorter time to return to baseline functional status in the short therapy arm.
Conclusions: In patients hospitalized with Gram-negative bacteremia achieving clinical stability before day 7, an antibiotic course of 7 days was non-inferior to 14 days. Reducing antibiotic treatment for uncomplicated Gram-negative bacteremia to 7 days is an important antibiotic stewardship intervention. (ClinicalTrials.gov number, NCT01737320).
PMID: 30535100 [PubMed - as supplied by publisher]