eMedicine Specialties > Gastroenterology > Biliary
Cholangitis
Updated: Nov 16, 2009
Introduction
Background
Cholangitis is an infection of the biliary tract with the potential to cause significant morbidity and mortality. Many patients with acute cholangitis respond to antibiotic therapy; however, patients with severe or toxic cholangitis may not respond and may require emergency biliary drainage. Jean M. Charcot recognized this illness in 1877 when he described a triad of fever, jaundice, and right upper quadrant pain. In 1959, Reynolds and Dargon described a more severe form of the illness that included the additional components of septic shock and mental confusion, which is referred to as the Reynolds pentad.
Pathophysiology
Historically, choledocholithiasis was the most common cause of biliary tract obstruction resulting in cholangitis. Over the past 20 years, biliary tract manipulations/interventions and stents have reportedly become more common causes of cholangitis. Hepatobiliary malignancies are a less common cause of biliary tract obstruction and subsequent bile contamination.1
Mortality/Morbidity
The condition has significant potential for mortality and morbidity, especially if left untreated. Reported mortality rates vary from 13-88%.
Race
Cholangitis is reported in all races. One variant, Asian cholangitis (also referred to as recurrent pyogenic cholangitis), is observed with increased frequency in Southeast Asia.2
Sex
The condition is reported in both females and males and has no clear predominance in either.
Age
The condition mostly occurs in adults, with a reported median age at onset of 50-60 years.
Clinical
History
A history of choledocholithiasis or recent biliary tract manipulation associated with fever, abdominal (right upper quadrant) pain, and jaundice (the Charcot triad) is highly suggestive of cholangitis. Fever reportedly occurs in nearly 95% of patients with cholangitis. Approximately 90% of patients have right upper quadrant tenderness, and 80% have jaundice.
Physical
Physical examination may reveal fever, icterus, jaundice, and abdominal pain.
Causes
Two main causes of cholangitis are biliary tract manipulation and common bile duct stones.3 Other possible causes of biliary tract obstruction that may lead to infection include strictures, tumors, choledochal/biliary cysts, or sump syndrome. Hepatolithiasis is also a possible cause of cholangitis4 and is observed more frequently in East Asia. More than 90% of patients with hepatolithiasis have calcium bilirubinate stones, also referred to as brown pigment stones.
Differential Diagnoses
Primary Sclerosing Cholangitis
Other Problems to Be Considered
Consider variants such as Asian cholangitis, sclerosing cholangitis, and AIDS-related cholangitis.
Workup
Laboratory Studies
- Obtain CBC count, liver function tests, and blood cultures.
- Common laboratory findings include leukocytosis, hyperbilirubinemia (patients with a malignant obstruction generally have a significantly higher bilirubin level than those with a benign obstruction), and elevated alkaline phosphatase levels.
- Other possible laboratory findings include elevation of transaminases and serum amylase levels (due to possible concurrent pancreatitis from stone impaction at the ampulla of Vater).
- Blood culture findings are positive in nearly 50% of patients.
- Bile culture findings are positive in nearly all patients.
- Multiple organisms are identified in approximately 60% of patients. Commonly reported aerobic organisms include Escherichia coli and Klebsiella and Enterococcus species. The most commonly reported anaerobic organism is Bacteroides fragilis.
Imaging Studies
- Abdominal ultrasound
Procedures
- The following procedures may be used for diagnostic and therapeutic purposes:
- Endoscopic retrograde cholangiopancreatography (ERCP)
- Percutaneous transhepatic cholangiography (PTC)
Treatment
Medical Care
Administration of broad-spectrum intravenous antibiotics and correction of fluid and electrolyte imbalances constitute essential medical care for cholangitis.
- High biliary pressures caused by an obstruction may impair the biliary secretion of antibiotics; therefore, treatment may require decompression and drainage of the biliary system.
- For patients with severe cholangitis, endoscopic drainage has replaced emergency surgical common duct exploration and T-tube drainage as standard treatment.
- Percutaneous transhepatic biliary drainage (PTBD) is another possible nonsurgical method of biliary drainage.
Surgical Care
Endoscopic biliary drainage and decompression have usually replaced surgery as the initial treatment of severe cholangitis. Surgical decompression is appropriate for patients in whom endoscopic or transhepatic drainage is unsuccessful or unavailable.
Consultations
- Gastroenterologists
- Surgeons
- Radiologists
Diet
Patients should take nothing by mouth in the acute stage of cholangitis. Accomplish hydration with intravenous fluids.
Medication
Possible antibiotic treatments include penicillin derivatives (eg, piperacillin) or a second- or third-generation cephalosporin (eg, ceftazidime) for gram-negative coverage, ampicillin for gram-positive coverage, and metronidazole for anaerobic coverage. Some researchers have reported use of fluoroquinolones (eg, ciprofloxacin, levofloxacin) as effective therapy.
The selection and dosing of appropriate antibiotics and other medications listed below or from another source must be performed by the patient's primary physician and gastroenterologist based on history and clinical presentation.
Antibiotics
Initial empiric antimicrobial therapy must be comprehensive and should cover both aerobic and anaerobic gram-negative organisms.
Piperacillin (Pipracil)
Inhibits biosynthesis of cell wall mucopeptides and the stage of active multiplication; has antipseudomonal activity.
Dosing
Adult
2-3 g/dose IV/IM q6-12h; not to exceed 2 g with IM injection
Serious infection: 3-4 g/dose IV/IM q4-6h; not to exceed 24 g/d
Pediatric
200-300 mg/kg/d IV/IM divided q4-6h
Interactions
Tetracyclines may decrease effects; high concentrations may physically inactivate aminoglycosides; probenecid may increase levels; coadministration with aminoglycosides has synergistic effects
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
B - Usually safe but benefits must outweigh the risks.
Precautions
Caution in renal impairment and in history of seizures
Ceftazidime (Ceptaz, Fortaz, Tazidime)
Third-generation cephalosporin with broad-spectrum, gram-negative activity; lower efficacy against gram-positive organisms; higher efficacy against resistant organisms. Arrests bacterial growth by binding to one or more penicillin-binding proteins.
Dosing
Adult
250 mg to 2 g IV/IM q8-12h
Pediatric
Neonates: 30 mg/kg IV q12h
Infants and children: 30-50 mg/kg/dose IV q8h; not to exceed 6 g/d
Adolescents: Administer as in adults
Interactions
Nephrotoxicity may increase with aminoglycosides, furosemide, and ethacrynic acid; probenecid may increase levels
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
B - Usually safe but benefits must outweigh the risks.
Precautions
Adjust dose in severe renal insufficiency (high doses may cause CNS toxicity); superinfections and promotion of nonsusceptible organisms may occur with prolonged use or repeated therapy
Ampicillin (Marcillin, Omnipen, Polycillin, Principen)
Bactericidal activity against susceptible organisms.
Dosing
Adult
250-500 mg PO q6h
500 mg to 1.5 g IM q4-6h
500 mg to 3 g IV q4-6h; not to exceed 12 g/d
Pediatric
50-100 mg/kg/d PO divided q4-6h
100-400 mg/kg/d IV/IM divided q4-6h
Interactions
Probenecid and disulfiram elevate levels; allopurinol decreases effects and has additive effects on ampicillin rash; may decrease effects of oral contraceptives
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
B - Usually safe but benefits must outweigh the risks.
Precautions
Adjust dose in renal failure; evaluate rash, and differentiate from hypersensitivity reaction
Metronidazole (Flagyl)
Imidazole ring-based antibiotic active against various anaerobic bacteria and protozoa.
Dosing
Adult
Loading dose: 15 mg/kg or 1 g for 70-kg adult IV over 1 h
Maintenance dose: 6 h following loading dose; infuse 7.5 mg/kg or 500 mg IV for 70-kg adult over 1 h q6-8h; not to exceed 4 g/d
Pediatric
Administer as in adults using body weight
Interactions
May increase toxicity of anticoagulants, lithium, and phenytoin; cimetidine may increase toxicity; disulfiram reaction may occur with orally ingested ethanol
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
B - Usually safe but benefits must outweigh the risks.
Precautions
Adjust dose in hepatic disease; monitor for seizures and development of peripheral neuropathy
Ciprofloxacin (Cipro)
Fluoroquinolone with activity against Pseudomonas species, streptococci, MRSA, Staphylococcus epidermidis, and most gram-negative organisms but no activity against anaerobes. Inhibits bacterial DNA synthesis and, consequently, growth.
Dosing
Adult
250-500 mg PO bid for 7-14 d
Alternatively, 200-400 mg IV q12h
Pediatric
<18 years: Not recommended
>18 years: Administer as in adults
Interactions
Antacids, iron salts, and zinc salts may reduce serum levels; administer antacids 2-4 h before or after taking fluoroquinolones; cimetidine may interfere with metabolism of fluoroquinolones; reduces therapeutic effects of phenytoin; probenecid may increase ciprofloxacin serum concentrations; may increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT)
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
In prolonged therapy, perform periodic evaluations of organ system functions (eg, renal, hepatic, hematopoietic); adjust dose in renal function impairment; superinfections may occur with prolonged or repeated antibiotic therapy
Levofloxacin (Levaquin)
For pseudomonal infections and infections due to multidrug-resistant gram-negative organisms.
Dosing
Adult
500 mg PO/IV qd for 7-14 d
Pediatric
<18 years: Not recommended
>18 years: Administer as in adults
Interactions
Antacids, iron salts, and zinc salts may reduce serum levels; administer antacids 2-4 h before or after taking fluoroquinolones; cimetidine may interfere with metabolism of fluoroquinolones; reduces therapeutic effects of phenytoin; probenecid may increase levofloxacin serum concentrations; may increase toxicity of theophylline, caffeine, cyclosporine, and digoxin (monitor digoxin levels); may increase effects of anticoagulants (monitor PT)
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
In prolonged therapy, perform periodic evaluations of organ system functions (eg, renal, hepatic, hematopoietic); adjust dose in renal function impairment; superinfections may occur with prolonged or repeated antibiotic therapy
Coagulants
Vitamin K or fresh frozen plasma (FFP) may be used for correction of coagulopathy when needed.
Phytonadione (AquaMEPHYTON, Konakion, Mephyton)
Promotes liver synthesis of clotting factors that in turn inhibit warfarin effects.
Dosing
Adult
5-25 mg/d PO; alternatively, 10 mg IV/IM/SC
Pediatric
2.5-5 mg/d PO; alternatively, 1-2 mg/dose as single dose
Interactions
Effects of warfarin sodium and dicumarol are antagonized by phytonadione
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
C - Safety for use during pregnancy has not been established.
Precautions
Ineffective in hereditary hypoprothrombinemia
Fresh frozen plasma (FFP)
Plasma is the fluid compartment of blood containing the soluble clotting factors. Indications for using FFP include bleeding in patients with congenital coagulation defects and multiple coagulation factor deficiencies (severe liver disease).
Dosing
Adult
IV as directed by protocol
Pediatric
Administer as in adults
Interactions
None reported
Contraindications
Documented hypersensitivity
Precautions
Pregnancy
A - Safe in pregnancy
Precautions
Viral contamination and infection are possible but unlikely because of prescreening; ineffective in patients with factor IX inhibitors; may induce an anamnestic response
Follow-up
Inpatient & Outpatient Medications
Consider maintenance therapy/antibiotics (ie, sulfamethoxazole and trimethoprim [SMZ-TMP] or a fluoroquinolone) for patients with recurrent cholangitis.
Deterrence/Prevention
It has been reported that prophylactic antibiotics do not prevent ERCP-induced cholangitis significantly in unselected patients, and these agents should not be routinely recommended for this reason.5
Complications
- Pyogenic liver abscess
- Acute renal failure
Prognosis
The prognosis is usually guarded, although it improves with early antibiotic treatment and appropriate drainage and decompression of biliary tract as needed. Factors reportedly associated with a poor prognosis include old age, female sex, acute renal failure, preexisting cirrhosis, and malignant biliary obstruction.
Miscellaneous
Medicolegal Pitfalls
- Delay in diagnosis or treatment may result in a higher risk of death.
References
Lee JG. Diagnosis and management of acute cholangitis. Nat Rev Gastroenterol Hepatol. Aug 4 2009;[Medline].
Lee KF, Chong CN, Ng D, et al. Outcome of surgical treatment for recurrent pyogenic cholangitis: a single-centre study. HPB (Oxford). 2009;11(1):75-80. [Medline]. [Full Text].
Shojaiefard A, Esmaeilzadeh M, Ghafouri A, Mehrabi A. Various techniques for the surgical treatment of common bile duct stones: a meta review. Gastroenterol Res Pract. 2009;2009:840208. [Medline].
Li FY, Cheng NS, Mao H, Jiang LS, et al. Significance of controlling chronic proliferative cholangitis in the treatment of hepatolithiasis. World J Surg. Jul 30 2009;epub ahead of print. [Medline].
Bai Y, Gao F, Gao J, Zou DW, Li ZS. Prophylactic antibiotics cannot prevent endoscopic retrograde cholangiopancreatography-induced cholangitis: a meta-analysis. Pancreas. Mar 2009;38(2):126-30. [Medline].
Bilhartz LE, Horton JD. Gallstone disease and its complications. In: Sleisenger and Fordtran's Gastrointestinal and Liver Disease. 6th ed. 1998:948-972.
Hanau LH, Steigbigel NH. Acute (ascending) cholangitis. Infect Dis Clin North Am. Sep 2000;14(3):521-46. [Medline].
Kadakia SC. Biliary tract emergencies. Acute cholecystitis, acute cholangitis, and acute pancreatitis. Med Clin North Am. Sep 1993;77(5):1015-36. [Medline].
Lai EC, Mok FP, Tan ES, et al. Endoscopic biliary drainage for severe acute cholangitis. N Engl J Med. Jun 11 1992;326(24):1582-6. [Medline].
Lameris JS, Overhagen HV. Imaging and intervention in patients with acute right upper quadrant disease. In: Bailliere's Clinical Gastroenterology. Vol 9. Harcourt Brace & Co;1995:21-36.
Lee DW, Chung SC. Biliary infection. In: Bailliere's Clinical Gastroenterology. Vol 11. Harcourt Brace & Co;1997:707-724.
Leung JW, Yu AS. Hepatolithiasis and biliary parasites. Bailliere's Clinical Gastroenterology. 1997;11:681-706.
Lillemoe KD. Surgical treatment of biliary tract infections. Am Surg. Feb 2000;66(2):138-44. [Medline].
Lipsett PA, Pitt HA. Acute cholangitis. Surg Clin North Am. Dec 1990;70(6):1297-312. [Medline].
Raraty MG, Finch M, Neoptolemos JP. Acute cholangitis and pancreatitis secondary to common duct stones: management update. World J Surg. Nov 1998;22(11):1155-61. [Medline].
van den Hazel SJ, Speelman P, Tytgat GN, et al. Role of antibiotics in the treatment and prevention of acute and recurrent cholangitis. Clin Infect Dis. Aug 1994;19(2):279-86. [Medline].
Keywords
cholangitis, acute cholangitis, ascending cholangitis, choledocholithiasis, biliary tract obstruction, angiocholitis, cholangeitis, hepatolithiasis, sump syndrome, pyogenic liver abscess, acute renal failure, liver disease, Escherichia coli, E coli, Klebsiella species, Enterococcus species, Bacteroides fragilis, B fragilis
Contributor Information and Disclosures
Author
Homayoun Shojamanesh, MD, Former Fellow, Digestive Diseases Branch, National Institutes of Health
Homayoun Shojamanesh, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, and American Society for Gastrointestinal Endoscopy
Disclosure: Nothing to disclose.
Coauthor(s)
Praveen K Roy, MD,, Comments and Criticisms Editor, Cochrane Colorectal Cancer Group; Adjunct Associate Research Scientist, Lovelace Respiratory Research Institute, Albuquerque
Praveen K Roy, MD, is a member of the following medical societies: American College of Gastroenterology and American Gastroenterological Association
Disclosure: Nothing to disclose.
Victor Nwakakwa, MD, MRCP (UK), Clinical Instructor, Department of Internal Medicine, Division of Gastroenterology, University of Virginia Health System
Disclosure: Nothing to disclose.
Medical Editor
Anil Minocha, MD, FACP, FACG, Clinical Professor, School of Pharmacy, Professor of Medicine, Director of Digestive Diseases, Medical Director of Nutrition Support, Medical Director of Gastrointestinal Endoscopy, Internal Medicine Department, University of Mississippi Medical Center
Anil Minocha, MD, FACP, FACG is a member of the following medical societies: American Academy of Clinical Toxicology, American Association for the Study of Liver Diseases, American College of Forensic Examiners, American College of Gastroenterology, American College of Physicians, American Federation for Clinical Research, American Gastroenterological Association, and American Society of Gastrointestinal Endoscopy
Disclosure: Nothing to disclose.
Pharmacy Editor
Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment
Managing Editor
James L Achord, MD, Professor Emeritus, Department of Medicine, Division of Digestive Diseases, University of Mississippi School of Medicine
James L Achord, MD is a member of the following medical societies: American Association for the Study of Liver Diseases, American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Medical Association, American Society for Gastrointestinal Endoscopy, Mississippi State Medical Association, New York Academy of Sciences, Sigma Xi, and Southern Medical Association
Disclosure: Nothing to disclose.
CME Editor
Alex J Mechaber, MD, FACP, Associate Dean for Undergraduate Medical Education, Associate Professor of Medicine, University of Miami Miller School of Medicine
Alex J Mechaber, MD, FACP is a member of the following medical societies: Alpha Omega Alpha, American College of Physicians-American Society of Internal Medicine, and Society of General Internal Medicine
Disclosure: Nothing to disclose.
Chief Editor
Julian Katz, MD, Clinical Professor of Medicine, Drexel University College of Medicine; Consulting Staff, Department of Medicine, Section of Gastroenterology and Hepatology, Hospital of the Medical College of Pennsylvania
Julian Katz, MD is a member of the following medical societies: American College of Gastroenterology, American College of Physicians, American Gastroenterological Association, American Geriatrics Society, American Medical Association, American Society for Gastrointestinal Endoscopy, American Society of Law Medicine and Ethics, American Trauma Society, Association of American Medical Colleges, and Physicians for Social Responsibility
Disclosure: Nothing to disclose.
Related eMedicine Topics
- Cholangitis [in the Emergency Medicine section]
- Cholangitis, Primary Sclerosing [in the Radiology section]
- Cholangitis, Recurrent Pyogenic [in the Radiology section]
- Cholelithiasis
- Primary Sclerosing Cholangitis
- Recurrent Pyogenic Cholangitis
- Cholangioscopy Using Narrow Band Imaging (NBI) in Patients With Primary Sclerosing Cholangitis (PSC) Undergoing Endoscopic Retrograde Cholangiopancreatogram (ERCP)
- Erlotinib for Chemoprevention in Trisomy 7 Positive Primary Sclerosing Cholangitis (PSC)
- Laparoendoscopic Rendez Vous Versus Standard Two Stage Approach for the Management of Cholelithiasis/Choledocholithiasis
- Use of Probiotics to Prevent Cholangitis in Children With Biliary Atresia After the Kasai Portoenterostomy
- ACR Appropriateness Criteria® acute abdominal pain and fever or suspected abdominal abscess. American College of Radiology - Medical Specialty Society. 1996 (revised 2006). 7 pages. NGC:005138
- ASGE guideline: the role of ERCP in diseases of the biliary tract and the pancreas. American Society for Gastrointestinal Endoscopy - Medical Specialty Society. 2005 Jul. 8 pages. NGC:00448
- Quality indicators for endoscopic retrograde cholangiopancreatography. American College of Gastroenterology - Medical Specialty Society; American Society for Gastrointestinal Endoscopy - Medical Specialty Society. 2006 Apr. 6 pages. NGC:004967
© 1994-
by Medscape.
All Rights Reserved
(http://www.medscape.com/public/copyright)