Prophylactic Antibiotics for Upper Gastrointestinal Bleeding in Patients With Cirrhosis

Importance: International guidelines recommend 5 to 7 days of antibiotic prophylaxis for patients with cirrhosis and upper gastrointestinal bleeding. However, the evidence for this recommendation has not been reassessed recently. Objective: To determine whether current evidence continues to support the recommended 5 to 7 days of antibiotic prophylaxis in patients with cirrhosis and upper gastrointestinal bleeding. Data Sources: Searches were performed of the Embase, MEDLINE, and CENTRAL databases for randomized clinical trials (RCTs) from inception to September 25, 2024. The search query included the keywords gastrointestinal bleeding and prophylactic antibiotics. Study Selection: Included RCTs compared longer durations of antibiotic prophylaxis to shorter durations (or 0 days) in patients with cirrhosis and upper gastrointestinal bleeding. Observational and pediatric studies, gray literature, comparisons of systemic antibiotics, studies not reporting mortality or early rebleed, and studies of nonsystemic antibiotics were excluded. Data Extraction and Synthesis: Data were extracted in duplicate by independent reviewers. Study quality was assessed in duplicate using the Cochrane Risk of Bias 2 tool. Data were pooled by random-effects bayesian meta-analyses using a noninformative prior for the effect and a weakly informative prior for heterogeneity. To account for therapeutic advancements, a post hoc subgroup analysis was performed for studies published after 2004. Main Outcomes and Measures: The primary outcome was all-cause mortality with a prespecified 5% noninferiority margin on the risk difference (RD) scale. Early rebleed and bacterial infections were secondary outcomes. Results: The analysis included 14 RCTs totaling 1322 participants (mean age range, 41.5 to 62.0 years; 981 male [74.2%] individuals), of whom 1202 (90.9%) had a variceal source of bleeding. Study quality was low to moderate, bacterial infections were heterogeneously defined, and no studies reported adverse events. Two RCTs compared longer (5-7 days) to shorter (2-3 days) durations and 12 RCTs compared any prophylaxis (1-10 days) to none. Shorter durations (including none) had a 97.3% probability of noninferiority for all-cause mortality (RD, 0.9%; 95% credible interval [95% CrI], -2.6 to 4.9). Shorter durations had a 73.8% probability of noninferiority for early rebleeding (RD, 2.9%; 95% CrI, -4.2 to 10.0) but were associated with more study-defined bacterial infections (RD, 15.2%; 95% CrI, 5.0 to 25.9). The probabilities of noninferiority of shorter durations for all 3 outcomes were higher in studies published after 2004. Conclusions and Relevance: The findings of this systematic review and bayesian meta-analysis do not support the purported mortality benefit driving guideline recommendations for antibiotic prophylaxis in patients with cirrhosis and upper gastrointestinal bleeds. Although prophylaxis reduced reported infections, methodological concerns regarding infection definitions introduced high risk of bias. Higher-quality RCTs are needed to determine the benefit and optimal duration of antibiotic prophylaxis in the modern era of advanced interventions. Until these studies are available, clinicians should be aware that the current guideline recommendations are not based on high-quality evidence.