TY - JOUR
T1 - Seven Versus 14 Days of Antibiotic Therapy for Uncomplicated Gram-negative Bacteremia
T2 - A Noninferiority Randomized Controlled Trial
AU - Yahav, Dafna
AU - Franceschini, Erica
AU - Koppel, Fidi
AU - Turjeman, Adi
AU - Babich, Tanya
AU - Bitterman, Roni
AU - Neuberger, Ami
AU - Ghanem-Zoubi, Nesrin
AU - Santoro, Antonella
AU - Eliakim-Raz, Noa
AU - Pertzov, Barak
AU - Steinmetz, Tali
AU - Stern, Anat
AU - Dickstein, Yaakov
AU - Maroun, Elias
AU - Zayyad, Hiba
AU - Bishara, Jihad
AU - Alon, Danny
AU - Edel, Yonatan
AU - Goldberg, Elad
AU - Venturelli, Claudia
AU - Mussini, Cristina
AU - Leibovici, Leonard
AU - Paul, Mical
N1 - Publisher Copyright:
© 2018 The Author(s).
PY - 2019/9/13
Y1 - 2019/9/13
N2 - 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: This was a randomized, multicenter, open-label, noninferiority trial. Inpatients with gram-negative bacteremia, who were afebrile and hemodynamically stable for at least 48 hours, were randomized to receive 7 days (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 readmission or extended hospitalization (>14 days). The noninferiority margin was set at 10%. Results: We included 604 patients (306 intervention, 298 control) between January 2013 and August 2017 in 3 centers in Israel and Italy. The source of the infection was urinary in 411 of 604 patients (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 of 306 patients (45.8%) in the 7-day group vs 144 of 298 (48.3%) in the 14-day group (risk difference,-2.6% [95% confidence interval,-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-course therapy arm. Conclusions: In patients hospitalized with gram-negative bacteremia achieving clinical stability before day 7, an antibiotic course of 7 days was noninferior to 14 days. Reducing antibiotic treatment for uncomplicated gram-negative bacteremia to 7 days is an important antibiotic stewardship intervention. Clinical Trials Registration: NCT01737320.
AB - 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: This was a randomized, multicenter, open-label, noninferiority trial. Inpatients with gram-negative bacteremia, who were afebrile and hemodynamically stable for at least 48 hours, were randomized to receive 7 days (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 readmission or extended hospitalization (>14 days). The noninferiority margin was set at 10%. Results: We included 604 patients (306 intervention, 298 control) between January 2013 and August 2017 in 3 centers in Israel and Italy. The source of the infection was urinary in 411 of 604 patients (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 of 306 patients (45.8%) in the 7-day group vs 144 of 298 (48.3%) in the 14-day group (risk difference,-2.6% [95% confidence interval,-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-course therapy arm. Conclusions: In patients hospitalized with gram-negative bacteremia achieving clinical stability before day 7, an antibiotic course of 7 days was noninferior to 14 days. Reducing antibiotic treatment for uncomplicated gram-negative bacteremia to 7 days is an important antibiotic stewardship intervention. Clinical Trials Registration: NCT01737320.
KW - antibiotics
KW - bacteremia
KW - duration
KW - gram-negative
UR - http://www.scopus.com/inward/record.url?scp=85072141021&partnerID=8YFLogxK
U2 - 10.1093/cid/ciy1054
DO - 10.1093/cid/ciy1054
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C2 - 30535100
AN - SCOPUS:85072141021
SN - 1058-4838
VL - 69
SP - 1091
EP - 1098
JO - Clinical Infectious Diseases
JF - Clinical Infectious Diseases
IS - 7
ER -