WHEN TO TRAT ― Acute cholangitis is an inflammation of the biliary tree, most commonly caused by bacterial infection in the setting of biliary stasis or obstruction. Severity ranges from a self-limited to a potentially life-threatening disease requiring urgent management. The classic symptoms include the Charcot triad of fever, abdominal pain, and jaundice. Severe cases may have the Reynold pentad, which includes the Charcot triad plus septic shock and an altered mental status.
Infecting organisms are enteric in origin and may include gram-negative rods (such as Escherichia coli or Klebsiella), Enterococcus spp., and anaerobes. Suspect acute cholangitis in patients presenting with fever, shaking chills, jaundice, and/or abdominal pain, typically right-upper quadrant pain. The diagnosis is still only suspected in the presence of systemic inflammation plus either cholestasis or compatible imaging findings.
WHEN TO INVESTIGATE
Cholangitis can be diagnosed in the presence of systemic inflammation plus cholestasis plus compatible imaging findings. Systemic inflammation can be demonstrated by the presence of fever, elevated white blood cell count, or elevated C-reactive protein.
Cholestasis can be demonstrated by jaundice or total bilirubin ≥ 2 mg/dL (34.2 mcmol/L), or by alkaline phosphate or gamma-glutamyl transferase levels > 1.5 times the normal upper limit. Compatible imaging findings include intrahepatic biliary dilatation or visualization of stricture, stone, stent, or other cause of obstruction. Ultrasound is the recommended initial imaging choice in all patients. Magnetic resonance cholangiopancreatography is more sensitive and may be helpful in planning for endoscopic or surgical interventions.
After establishing the diagnosis, the immediate and accurate assessment of severity is critical to management (using diagnostic criteria and severity grading for acute cholangitis according to Tokyo Guidelines for Acute Cholangitis 2018). Use your mobile MD+CALC: (TG18), https://www.mdcalc.com/tokyo-guidelines-acute-cholangitis-2018. Perform severity assessment at diagnosis, within 24 hours from diagnosis, and 24 to 48 hours after diagnosis..
- Grade I (mild) - meeting diagnostic criteria for cholangitis but not Grade II/Grade III severity
- Grade II (moderate) - associated with any combination of ≥ 2 of the following conditions
- Abnormal white blood cell count < 4,000 cells/mcL or > 12,000 cells/mcL
- Fever ≥ 39 degrees C (102.2 degrees F)
- Age ≥ 75 years
- Hyperbilirubinemia (total bilirubin ≥ 5 mg/dL [85.5 mcmol/L])
- Hypoalbuminemia (< 0.7 times lower limit of normal)
- Grade III (severe) - associated with dysfunction of ≥ 1 of the following conditions
- Cardiovascular - hypotension requiring interventions with dopamine ≥ 5 mcg/kg/minute, or any dose of norepinephrine
- Neurologic - interruption of consciousness
- Respiratory - PaO2/FiO2 ratio < 300
- Renal - oliguria or serum creatinine ≥ 2 mg/dL (176.8 mcmol/L)
- Hepatic - prothrombin time-INR > 1.5
- Hematologic - platelet count < 100,000/mm3
Antibiotic Prescribing
Tokyo Guidelines 2018 (TG18) ― Empiric broad-spectrum antibiotics are indicated for all patients with definite or suspected cholangitis. For patients with mild-to-moderate community-acquired disease, recommended options include cefazolin, cefuroxime, or ceftriaxone. For patients with severe physiologic disturbance, advanced age, immunocompromise, or infection following bilioenteric anastomosis, recommended empiric regimens include a combination of metronidazole PLUS piperacillin-tazobactam, cefepime, ciprofloxacin, levofloxacin, imipenem-cilastatin, ertapenem, or meropenem. For patients with a healthcare-associated biliary infection, vancomycin should be added to the regimens.
Infectious Diseases Society of America (IDSA) 2010 guidelines ― Treat patients with suspected infection and acute cholecystitis or cholangitis with empiric antibiotics. Antimicrobial therapy should be directed at enteric pathogens (primarily gram-negative pathogens). Anaerobic therapy is not indicated unless biliary-enteric anastomosis is present. For patients with mild-to-moderate community-acquired disease, recommended empiric regimens including 1 of (1) Cefazolin 1-2 g IV every 8 hours, (2) Cefuroxime 1.5 g IV every 8 hours, (3) Ceftriaxone 1-2 g IV every 12-24 hours.
For patients with severe physiologic disturbance, advanced age, immunocompromise, or infection following bilioenteric anastomosis, recommended empiric regimens include metronidazole 0.5 g IV every 8-12 hours plus 1 of the following (1) Piperacillin-tazobactam 3.375 g IV every 6 hours, (2) Imipenem-cilastatin 0.5 g IV every 6 hours or 1 g IV every 8 hours, (3) Meropenem 1 g IV every 8 hours, (3) Cefepime 2 g IV every 8-12 hours, (4) Ciprofloxacin 0.4 g IV every 12 hours, (5) Levofloxacin 0.75 g IV every 24 hours.
- 4-7 days of therapy once source of infection is controlled and infection is uncomplicated.
- Minimum duration of antibiotics 2 weeks recommended if bacteremia (may be longer in some cases).
- Continuation of therapy until all anatomical issues are resolved (such as residual stones or obstruction).
- Can consider conversion to oral therapy in patients tolerating oral feeding depending on the susceptibility of infecting organism(s), bioavailability of oral antibiotic options, and nature of infection.
REFERENCES
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Solomkin, J.S., Mazuski, J.E., and others (2010). Diagnosis and Management of Complicated Intra‐abdominal Infection in Adults and Children: Guidelines by the Surgical Infection Society and the Infectious Diseases Society of America. Clinical Infectious Diseases, [online] 50(2), pp.133–164. Available at: https://academic.oup.com/cid/article/50/2/133/327316
Kimura, Y., Takada, T., Strasberg, S.M., and others (2013). TG13 current terminology, etiology, and epidemiology of acute cholangitis and cholecystitis. Journal of Hepato-Biliary-Pancreatic Sciences, [online] 20(1), pp.8–23. Available at: https://www.ncbi.nlm.nih.gov/pubmed/23307004
Kiriyama, S., Kozaka, K., and others (2018). Tokyo Guidelines 2018: diagnostic criteria and severity grading of acute cholangitis (with videos). Journal of Hepato-Biliary-Pancreatic Sciences, 25(1), pp.17–30. Available at: https://onlinelibrary.wiley.com/doi/full/10.1002/jhbp.512
Gomi, H., Solomkin, J.S., Schlossberg, and others (2018). Tokyo Guidelines 2018: antimicrobial therapy for acute cholangitis and cholecystitis. Journal of Hepato-Biliary-Pancreatic Sciences, [online] 25(1), pp.3–16. Available at: https://onlinelibrary.wiley.com/doi/full/10.1002/jhbp.518
