By Samuel Nadler, MD, PhD

Critical Care, Pulmonary Medicine, The Polyclinic Madison Center, Seattle; Clinical Instructor, University of Washington, Seattle

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

SYNOPSIS: In patients with gram-negative rod bacteremia, patients receiving seven days of antibiotics had similar 90-day mortality, readmission rates, and rates of recurrent bacteremia as patients receiving 14 days of antibiotic.

SOURCE: Yahav D, Franceschini E, Koppel, et al; Bacteremia Duration Study Group. Seven versus 14 days of antibiotic therapy for uncomplicated gram-negative bacteremia: A noninferiority randomized controlled trial. Clin Infect Dis 2019;69:1091-1098.

With the continuing emergence of resistant organisms, antibiotic stewardship is increasingly important. Meta-analyses of mostly nonrandomized trials have shown that a shorter duration of antibiotics for various infections can be equally effective compared to longer courses.1,2 However, many of these trials excluded bacteremia. This study reports a noninferiority trial of a shorter vs. longer course of antibiotics specifically for gram-negative rod (GNR) bacteremia.

The Bacteremia Duration Study Group conducted a randomized, multicenter, open-label noninferiority trial of seven vs. 14 days of antibiotics for GNR bacteremia. This trial enrolled 604 patients with aerobic GNR bacteremia who had already achieved hemodynamic stability by day 7 of antibiotic coverage. It included bacteremia from the urinary tract, intra-abdominal sources, respiratory tract, line infections, and unknown sources. Patients were excluded if they had uncontrolled sources of bacteremia, polymicrobial sepsis, HIV or hematopoietic stem cell transplantation, and specific pathogens such as Brucella and Salmonella. The study was designed to have an 80% power to detect noninferiority within a 10% margin, assuming a 35% rate of the primary outcome.

Patients receiving a seven-day course of antibiotics had similar rates of a composite primary outcome (45.8% vs. 48.3%; P = 0.527) compared with those receiving 14 days of antibiotics. Each component of the composite outcome was similar in the two groups, including 90-day all-cause mortality (11.8% vs. 10.7%; P = 0.527), hospital readmission rates (38.9% vs. 42.6%; P = 0.363), relapse of bacteremia (2.6% vs. 2.7%; P = 0.957), and extended hospitalizations beyond 14 days (4.9% vs. 6.4%; P = 0.483). Secondary endpoints including 14- and 28-day mortality also were similar. The only statistically significant differences between the two groups besides duration of antibiotic therapy were time to return of baseline activity (two vs. three weeks; P = 0.01) and functional capacity at 30 days, both favoring the shorter antibiotic arm.

COMMENTARY

This study adds to a growing body of evidence supporting a shorter duration of antibiotic therapy for various infections, specifically GNR bacteremia, in this publication. The study population was inclusive of patients with solid organ transplants, central venous catheters, endotracheal tubes, prosthetic valves, and implanted devices. The most common GNR was Escherichia coli, but the study also included patients with Klebsiella, Enterobacteriaceae, and, notably, Pseudomonas. Although not powered to look for these events, there did not seem to be an improvement in the rates of acute kidney injury, diarrhea, rash, or Clostridium difficile infections that might be benefits from a shorter duration of antibiotics.

It is important to consider the exclusion criteria in this trial to determine whether a patient could be treated with a shorter course of antibiotics. The most common reasons for exclusion from this trial were uncontrolled infection, recurrent bacteremia, hemodynamic instability after seven days of therapy, polymicrobial bacteremia, or immunosuppression from conditions such as HIV or stem cell transplantation. In patients with GNR bacteremia without these factors, a seven-day course of antibiotic is noninferior to 14 days and may lead to earlier functional recovery.

REFERENCES

  1. Royer S, DeMerle KM, Dickson RP, Prescott HC. Shorter versus longer courses of antibiotics for infection in hospitalized patients: A systematic review and meta-analysis. J Hosp Med 2018;13:336-342.
  2. Havey TC, Fowler RA, Daneman N. Duration of antibiotic therapy for bacteremia: A systematic review and meta-analysis. Crit Care 2011;15:R267.