A single day of antibiotic treatment is noninferior to a standard 4- to 7-day course for acute cholangitis following adequate endoscopic biliary drainage, with fewer antibiotic-related adverse events, according to new research.

The findings indicate that “a 1-day course after adequate drainage is sufficient and can be the standard treatment duration for acute cholangitis with source control,” said first author Anouk G. Overdevest, MD, of Amsterdam UMC Locatie AMC, who presented the results at Digestive Disease Week (DDW) 2026.

Acute cholangitis, a serious infection of the bile ducts resulting from bile flow obstruction, typically from gallstones and bacterial overgrowth, is generally treated with endoscopic biliary drainage (ERCP) and antibiotics. Current international Tokyo Guidelines recommend initiating antibiotics promptly and continuing treatment for 4-7 days.

However, concerns about antimicrobial resistance and the need for antibiotic stewardship, particularly with common Gram-negative bacteria such as Escherichia coli and Klebsiella species, have prompted interest in shorter treatment durations. 

COBRA Trial Design

To evaluate whether shorter therapy compromises efficacy, Overdevest and colleagues conducted the COBRA trial, a multicenter, open-label trial enrolling 413 patients between 2023 and 2025 at 31 hospitals in the Netherlands.

Eligible patients had acute cholangitis due to distal biliary obstruction, achieved adequate drainage with ERCP, and had fever resolution within 24 hours after ERCP. Patients with concomitant infections or those receiving immunosuppressive therapy were excluded.

Participants were randomized 1:1 to receive antibiotics for either 1 day or 4-7 days following ERCP, with 205 patients in each group. 

Baseline characteristics were similar between groups. The median age was 74 years, 43.4% were female, 10.0% had malignant obstruction, 57.6% had moderate/severe cholangitis, and 35.6% had Gram-negative bacteremia at randomization. Adherence to the allocated antibiotic treatment duration was high (93.0%), with only three patients lost to follow-up.

Comparable Outcomes Across Groups

The primary endpoint of clinical cure, defined as being symptom-free by day 14 without relapse or death by day 30, was achieved in 95.1% of patients in the 1-day group vs 93.7% in the 4- to 7-day group. The absolute risk difference was 1.5% (one-sided 95% confidence limit, -2.4%), meeting criteria for noninferiority. 

A per-protocol analysis (n = 384) confirmed noninferiority, with an absolute risk difference of 0.6% (one-sided 95% confidence limit, -3.2%). Noninferiority was also maintained in a worst-case sensitivity analysis, in which those lost to follow-up were counted as treatment failures. 

All-cause 90-day mortality was 2.9% in the 1-day group vs 1.5% in the 4- to 7-day group (absolute risk difference, 1.5%; one-sided 95% confidence limit, 3.8%). Cholangitis-related mortality by day 90 was 1.0% in the 1-day antibiotic group and 0% in the 4- to 7-day group. Relapse occurred in approximately 10% of patients in both groups. 

The noninferior outcomes were similar across subgroups, including patients with malignant obstruction and those with Gram-negative bacteremia at baseline.

The average hospital stay through day 30 was shorter in the 1-day group (1 day vs 2 days).

Antibiotic-related adverse events occurred in 8.3% of patients in the 1-day group compared with 16.6% in the 4- to-7-day group, for an absolute risk difference of -8.3%.  

Based on the findings, Overdevest concluded that “we as a COBRA study group suggest and recommend that a 1-day course after adequate drainage is sufficient and can be the standard duration for acute cholangitis with source control.”

Results ‘Provide Confidence’ 

Commenting on the study, Elena Stoffel, MD, clinical professor of internal medicine at the University of Michigan, Ann Arbor, and session co-moderator, said the findings address long-standing concerns.

“Many of us were concerned that stopping antibiotics, especially in the setting of a malignant obstruction, may be associated with worse outcomes,” she said. 

“But this beautifully designed trial shows that there really does not appear to be any benefit [of 4- to 7-day antibiotics] for most patients who have biliary obstructions — once the obstruction is cleared and the fever comes down, there's no need to continue the antibiotics,” Stoffel told Medscape Medical News.

Overdevest and Stoffel reported no relevant disclosures.