short-course antibiotics vs standard course antibiotics in patients with cholangitis

Conditions: Cholangitis

Summary: the goal of this multicentre randomized controlled trial is to investigate if a very short-course of antibiotics (1 day) for cholangitis after adequate drainage is non-inferior with respect to clinical cure in comparison with a standard course of antibiotics (4 to 7 days). secondary objectives include: * will a one-day course of antibiotics for cholangitis after adequate drainage be non-inferior with respect to relapse of cholangitis and mortality in comparison with a standard course of antibiotics? * will a one-day course of antibiotics for cholangitis after adequate drainage result in less adverse drug events in comparison with a standard course of antibiotics? * will a one-day course of antibiotics for cholangitis after adequate drainage reduce length of hospital stay? * will a one-day course of antibiotics for cholangitis after adequate drainage improve quality of life? * will a one-day course of antibiotics for cholangitis after adequate drainage be cost-effective?

acute cholangitis is an infection of the biliary tract which is managed with biliary drainage and antibiotic therapy (abt). currently the international tokyo guidelines 2018 (tg18) recommend 4 to 7 days of abt after source control. the national swab guideline of 2020 suggests a course of one to 3 days after biliary drainage. there are no randomized studies to guide the duration of abt for acute cholangitis. our recent retrospective study in the netherlands showed that a short course of abt seems safe and more evidence is available showing that other bacterial infections, including abdominal and bloodstream infections, can be treated with a short antibiotic course than previously assumed. hence, the hypothesis is that a very short-course of abt for acute cholangitis is non-inferior to a course of 4 to 7 days after adequate biliary drainage. this study is designed as a multicenter non-inferiority randomized controlled trial. patients will be randomly assigned to the intervention group (one day of antibiotic therapy after ercp) or the comparator group (4 to 7 days of antibiotic therapy after ercp).

Eligibility criteria:
inclusion criteria: * patients with acute cholangitis due to common bile duct stones, benign or malignant distal biliary obstruction or distal biliary stent dysfunction (only stents in situ for a minimum of 30 days) * ercp with adequate biliary drainage (all common bile duct stones are removed and/or there is adequate flow of clear bile with or without a biliary stent(s)) * absence of fever (temperature \<38.5°c) or a decrease of body temperature of at least 1°c has occurred within 24 hours after ercp * age ≥ 18 years * written informed consent (ic) exclusion criteria: * other aetiologies of acute cholangitis (e.g. primary sclerosing cholangitis, (sub)hilar and/or intrahepatic strictures or hilar stents) * a recurrent cholangitis (within 3 months) * patients with surgically altered anatomy (leading to biliary-enteric anastomosis) * concomitant pancreatitis, according to international association of pancreatology/american pancreatic association guidelines.\[18\] acute pancreatitis is diagnosed in case of fulfilment of 2 out of 3 of the following criteria: * upper abdominal pain * serum amylase or lipase \>3x uln * signs of acute pancreatitis on imaging * concomitant cholecystitis, according to tg18 criteria.\[19\] acute cholecystitis is suspected in case one item in a is met and one item in b and c. a. local signs of inflammation * a1: murphy's sign * a2: right upper quadrant mass/pain/tenderness b. systemic signs of inflammation * b1: fever * b2: elevated c-reactive protein * b3: elevated wbc count c. imaging findings characteristic of acute cholecystitis * concomitant liver abscess * another additional infectious diagnosis * admission on an intensive care unit (icu) at time of randomisation * use of maintenance antimicrobial therapy * use of immunosuppressants * neutropenia

Keywords: antibiotics randomized controlled trial