Short-course Antibiotics vs Standard Course Antibiotics in Patients With Cholangitis

Very Short-course Versus Standard Course Antibiotic Therapy in Patients With Acute ChOlangitis After Adequate Endoscopic BiliaRy drAinage

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).

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