Shorter Antibiotic Course Noninferior for Gram-Negative Bacteremia

A 7-day antibiotic course has demonstrated noninferiority compared with a 14-day course in treating uncomplicated gram-negative bacteremia.

A 7-day antibiotic course has demonstrated noninferiority compared with a 14-day course in treating uncomplicated gram-negative bacteremia, according to a study published in Clinical Infectious Diseases. This shorter course has benefits that include fewer days on antibiotics and a shorter period to regaining of baseline functional capacity.

This open-label, multicenter, randomized controlled trial included 604 participants, 306 of whom received an interventional 7-day course of antibiotic therapy and 298 of whom constituted the control group with a 14-day course. Participants were randomly assigned 1:1 to either intervention or control group. Enterobacteriaceae comprised 89.9% of etiologic microbes, with 68% of participants experiencing a urinary tract-based infection. 

None of the participants included in the study had an uncontrolled focus of infection, infection with either Brucella or Salmonella, HIV or other immunosuppression, or polymicrobial growth. At 90 days, the primary outcome was a combination of treatment failure, re-admission, hospital stay >2 weeks, and all-cause mortality. Noninferiority was designated at a 10% margin. The Fisher’s exact test or chi-square test were used to compare categorical variables, whereas continuous variables were compared using the Mann-Whitney U test. The Wald method was utilized to calculate 95% confidence intervals.

The primary outcome was similar between the 7-day group and the 14-day group (45.8% vs 48.3%; risk difference, -2.6%; 95% CI, -10.5% to 5.3%), indicating noninferiority of the intervention. Weighting for inverse variance and stratifying by study center resulted in a similar risk difference of -2.7% (95% CI, -10.7% to 5.2%). The individual parts of the primary outcome did not vary significantly between groups, with similar all-cause mortality (11.8% in the 7-day group vs 10.7% in the 14-day group; risk difference, 1.0%; 95% CI, -4% to 6.1%). The 7-day group did exhibit a shorter return to baseline functioning capacity (median 2 weeks vs 3 weeks) and total antibiotic days within 3 months (median 10 days vs 16 days).

Limitations to this study included Enterobacteriaceae comprising a majority of causative pathogens, the inability to examine associations between lower antibiotic use and resistance, and the potential for re-admissions and >2-week hospital stays influencing noninferiority.

The study researchers concluded that “[in] hospitalized patients with [g]ram-negative bacteremia, hemodynamically stable and afebrile for at least 48 hours without an ongoing focus of infection, 7 days of antibiotic therapy were non-inferior to 14 days. Seven days of antibiotic therapy had the advantage of fewer cumulative antibiotic days within 3 months and more rapid regain of baseline functional capacity.”

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Yahav D, Franceschini E, Koppel F, et al. Seven versus fourteen days of antibiotic therapy for uncomplicated gram-negative bacteremia: a non-inferiority randomized controlled trial [published online December 11, 2018]. Clin Infect Dis. doi: 10.1093/cid/ciy1054