By Stan Deresinski, MD, FACP, FIDSA

Clinical Professor of Medicine, Stanford University

Dr. Deresinski reports no financial relationships relevant to this field of study.

SYNOPSIS: Antibiotic administration for seven days is sufficient in stable patients with Gram-negative bacteremia.

SOURCE: Yahav D, Franceschini E, Koppel F, et al; Bacteremia Duration Study Group. Seven versus fourteen days of antibiotic therapy for uncomplicated Gram-negative bacteremia: A non-inferiority randomized controlled trial. Clin Infect Dis 2018; doi: 10.1093/cid/ciy1054. [Epub ahead of print].

Yahav and colleagues examined the question of the necessary duration of antibiotic therapy in 604 patients with bacteremia due to aerobic Gram-negative bacilli in a randomized, open-label, noninferiority trial. Ninety percent of infections were due to Enterobacteriaceae, mostly Escherichia coli, while Pseudomonas was isolated in 7.5% of cases. The urinary tract was the source of infection in two-thirds of cases. Patients who were hemodynamically stable and afebrile for at least 48 hours were randomized to receive a total antibiotic therapy course of either seven or 14 days.

The noninferiority margin was set at 10%. The primary composite outcome, including mortality, clinical failure, and readmissions or extended hospitalization at 90 days, occurred in 140/306 (45.8%) of those who received seven days of therapy and in 144/298 (48.3%) of those who received 14 days of therapy (difference, -2.6%; 95% confidence interval [CI], -10.5% to 5.3%).

Researchers found no significant differences for any of the individual components of the composite outcome, including all-cause 90-day mortality, which was 11.8% and 10.7% in the short- and long-duration therapy groups, respectively. The duration of appropriate antibiotic therapy was seven days fewer in the short-duration group. Investigators observed no significant difference in the frequency of adverse events between the treatment groups.

COMMENTARY

The results of this trial indicate that a seven-day course of antibiotic therapy was noninferior to treatment for 14 days in patients with Gram-negative bacteremia, the majority of whom were infected with E. coli and for whom the source of bloodstream infection was the urinary tract.

These results are consistent with those of several mostly retrospective studies, which were briefly reviewed by the authors. Therefore, they are totally unsurprising. However, it could be argued that the results are biased by the large proportion of patients with a urinary source, which often may be cleared more readily.

Clinicians have long given overly prolonged courses of antibiotics for various infections. This practice often includes infectious disease specialists, whose contribution to the problem is likely disproportionate because of their influence over other clinicians. Fortunately, we are beginning to develop the necessary data that allow us to turn back the tide of overly prolonged antibiotic therapy and its attendant adverse consequences regarding microbiome alteration, selection of resistance, superinfection, allergic reactions, and direct drug toxicity.