A 1-day course of antibiotics is noninferior to the standard 4–7-day regimen in achieving clinical cure for patients with acute cholangitis who have undergone adequate biliary drainage, according to the COBRA trial presented at ESCMID 2026.
The 2018 Tokyo Guidelines recommend 4–7 days of antibiotic treatment after source control through adequate biliary drainage, although some observational evidence indicates shorter treatment periods may be sufficient, said study author Anouk Overdevest, a PhD candidate from the Department of Gastroenterology & Hepatology at Amsterdam University Medical Centre, Amsterdam, The Netherlands.
A multicentre, open-label, noninferiority trial involving 413 patients (median age 72 years, 43.4 percent female) with acute cholangitis, all of whom achieved adequate biliary drainage with ERCP*, was conducted at 31 centres in the Netherlands. Participants were randomly assigned in a 1:1 ratio to receive antibiotics for either 1 day or 4–7 days (n=205 in each group) following ERCP and were followed up for 90 days.
In an intention-to-treat analysis, 95 percent of patients in the 1-day course group and 94 percent in the 4–7-day course group achieved clinical cure, defined as being symptom-free by day 14 with no relapse or death by day 30. The absolute risk difference between the treatment groups was 1.5 percent (one-sided 95 percent confidence limit, –2.4 percent), which falls within the noninferiority margin of –7.5 percent. [ESCMID 2026, abstract L0043]
The per-protocol analysis confirmed these findings, with both treatment groups achieving clinical cure rates of 95.3 percent (one-day group) and 94.8 percent (4–7-day group), and an absolute risk difference of 0.6 percent (one-sided 95 percent confidence limit, –3.2 percent), which remains within the inferiority margin.
Overdevest noted that subgroup analysis, including patients with malignant obstruction and gram-negative bacteraemia, also supported the noninferiority of the shorter regimen over the longer regimen.
At day 90, the 1-day course demonstrated noninferiority over the 4–7-day course in the rates of all-cause mortality (2.9 percent vs 1.5 percent), cholangitis-related mortality (1 percent vs 0 percent), and relapse (8 percent vs 10.4 percent), with a comparable duration of hospital stay (2 days).
However, the longer course was associated with a higher incidence of antibiotic-related adverse events compared with the shorter course (16.6 percent vs 8.3 percent).
“Overall, this study confirms that 1 day of antibiotic treatment after adequate biliary drainage was noninferior to 4–7 days in adults with acute cholangitis,” said Overdevest.
“We recommend that a 1-day course after adequate drainage is sufficient and can be the standard treatment duration for acute cholangitis with source control,” she added.