Original Investigation
Infectious Diseases
March 21, 2025
Seven vs Fourteen Days of Antibiotics for Gram-Negative Bloodstream Infection: A Systematic Review and Noninferiority Meta-Analysis
Todd C. Lee, Connor J. Prosty, Michael Fralick, et al
JAMA Netw Open. 2025;8(3):e251421. doi:10.1001/jamanetworkopen.2025.1421
Question Are 7 days of antibiotic therapy adequate for the treatment of most Gram-negative bloodstream infections?
Findings In this systematic review and meta-analysis of 4 randomized clinical trials including 3729 patients, 7 days of antibiotics had a 97.8% probability of being noninferior to 14 days for the outcome of 90-day mortality.
Meaning These findings suggest that most Gram-negative bloodstream infections can be treated with 7 days of antibiotics unless there is a concern for inadequate source control.
Abstract
Importance Gram-negative bloodstream infections are a common cause of hospitalization. A 2-week duration of antibiotic therapy has been commonly used, but shorter durations may have similar outcomes.
Objectives To assess whether 7 days of antibiotic therapy was noninferior to 14 days.
Data Sources Starting with a 2022 individual patient data meta-analysis, PubMed, Cochrane Central Register of Controlled Trials, and Web of Science were searched to identify additional eligible randomized clinical trials (RCTs) conducted from May 1, 2022, until November 30, 2024.
Study Selection RCTs involving primarily adults who were hospitalized at the time of Gram-negative bloodstream infection and were allocated to 7 or 14 days of antibiotic therapy. Studies were independently reviewed by 2 investigators.
Data Extraction and Synthesis PRISMA guidelines were followed. Data were extracted by 2 investigators. Any unpublished data were obtained directly from study authors. Risk of bias and certainty of the evidence were assessed in duplicate using the Cochrane Risk of Bias Tool, version 2, and the Grading of Recommendations Assessment, Development and Evaluation approach. Data were pooled by separate random-effects meta-analyses for the intention-to-treat (ITT) and per-protocol (PP) populations. A noninformative prior probability was used for the effect, and an evidence-based weakly informative prior probability was used for heterogeneity. Risk ratios (RRs), 95% credible intervals (CrIs), and probability of noninferiority were calculated using a prespecified upper bound of 1.25 or less.
Main Outcomes and Measures Ninety-day all-cause mortality.
Results Four eligible RCTs contributed 3729 patients in the ITT population (1912 women [51.3%]; median age range, 67-79 years) and 3126 in the PP population. In the ITT analysis, within 90 days, 226 patients (12.8%) receiving 7 days of antibiotics died compared with 253 (13.7%) receiving 14 days, corresponding to an RR for 90-day mortality of 0.91 (95% CrI, 0.69-1.22) and a 97.8% probability of noninferiority. In the PP analysis, the RR was 0.93 (95% CrI, 0.68-1.32), corresponding to a 95.1% probability of noninferiority.
Conclusions and Relevance In this systematic review and meta-analysis of patients with Gram-negative bloodstream infections and adequate source control, 7 days of antibiotic therapy had a high probability of being noninferior to 14 days. These findings support a shorter duration of antibiotic therapy for appropriately selected patients like those in the included RCTs.
