Cholangitis is one of the most serious infectious complications of ERCP. Current guidelines recommend antibiotic prophylaxis (AP) only for selected high-risk patients, yet most randomized controlled trials (RCT) informing these recommendations were performed more than two decades ago, before ERCP evolved into a predominantly therapeutic procedure. A recent study (Leem et al., 2024) reported reduced infectious complications in patients with biliary obstruction, suggesting that the effectiveness of AP may differ in contemporary practice. Our aim was to update the evidence by performing a comprehensive meta-analysis of all trials evaluating AP before ERCP.

A systematic search was conducted in five databases (Medline, Embase, CENTRAL, Scopus and Web of Science) on 19^th November 2024 to identify RCT’s comparing AP versus no prophylaxis before ERCP. Primary outcome was cholangitis; secondary outcomes included bacteremia, septicemia, pancreatitis and mortality. Random-effects models were used to calculate risk ratios (RR) with 95% confidence intervals (CI). Risk of bias was assessed with the ROB2 tool, and certainty of evidence was evaluated using GRADE.

In total 14 RCTs involving 2055 patients were included. Antibiotic prophylaxis showed a trend toward reducing cholangitis (RR=0.60, CI 0.29-1.26) although this did not reach statistical significance. In the subgroup of patients with biliary obstruction, AP again favored lower cholangitis risk (RR = 0.55, CI 0.12–2.40), but the effect was not statistically significant. Bacteremia was nearly significantly reduced (RR=0.46, CI 0.20-1.08). Estimates for septicemia (RR=0.56, CI 0.20-1.57), pancreatitis (RR=0.73, CI 0.41-1.30) also favored AP but remained non-significant. The mortality in both groups was low (RR 1.16, CI 0.73-1.84). Overall heterogeneity across outcomes was low to moderate.

Although not statistically significant, the evidence suggests a potential benefit of antibiotic prophylaxis for preventing post-ERCP infectious complications, particularly in patients with biliary obstruction. However, the certainty of this evidence is limited, and the true effect remains uncertain. Further modern RCTs are needed to identify patient groups who may benefit from prophylaxis.