Distal malignant biliary obstruction (DMBO) frequently requires ERCP with biliary stenting. Early post-procedural infectious complications—mainly cholangitis and cholecystitis—remain clinically relevant despite advances in technique. Current guidelines recommend prophylactic antibiotics only in selected high-risk situations, and data specific to DMBO are scarce. This study aimed to evaluate the effect of prophylactic antibiotics on early infectious complications following ERCP in a DMBO-only population.

We conducted a prospective, monocentric study at CHU Mohammed VI Marrakech, including 165 consecutive patients who underwent initial ERCP with stent placement for DMBO between 2022 and 2024. Patients were categorized according to the administration or not of prophylactic antibiotics before ERCP. The primary outcome was the incidence of infectious complications (cholangitis or cholecystitis) within 5 days. A multivariable logistic regression model was used to identify independent predictors.

Early infectious complications occurred in 3.6% of patients receiving prophylactic antibiotics versus 10.3% in those without prophylaxis, corresponding to an absolute risk reduction of 6.7% (p = 0.029) and a number needed to treat (NNT) of 15. Rates of post-ERCP pancreatitis showed no significant difference between groups (approximately 6–10%, p> 0.3). In multivariable analysis, absence of prophylactic antibiotics remained independently associated with infectious complications (OR 2.45, 95% CI 1.22–4.92). Compared with previous literature—mostly small retrospective DMBO series showing no clear benefit—this prospective study provides stronger evidence supporting prophylaxis. Results also align with data from hilar obstruction studies and meta-analyses reporting reduced bacteremia after antibiotic prophylaxis.

In this prospective Moroccan cohort, prophylactic antibiotics significantly reduced early infectious complications after ERCP for DMBO without increasing post-procedure pancreatitis. These findings support the systematic use of prophylactic antibiotics in patients undergoing ERCP for DMBO, even when complete drainage is anticipated. Larger multicenter prospective trials are warranted to refine prophylactic strategies and update guideline recommendations.