AUTHOR AND EDITOR INFORMATION

Section 1 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

INTRODUCTION

Section 2 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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.

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.

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

Section 3 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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. 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 cholangitis 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.

DIFFERENTIALS

Section 4 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Other Problems to be Considered

Consider variants such as Asian cholangitis, sclerosing cholangitis, and AIDS-related cholangitis.

WORKUP

Section 5 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Lab 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

Section 6 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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

Section 7 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

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.

Drug Category: Antibiotics

Initial empiric antimicrobial therapy must be comprehensive and should cover both aerobic and anaerobic gram-negative organisms.

Drug Name	Ceftazidime (Ceptaz, Fortaz, Tazidime)
Description	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.
Adult Dose	250 mg to 2 g IV/IM q8-12h
Pediatric Dose	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
Contraindications	Documented hypersensitivity
Interactions	Nephrotoxicity may increase with aminoglycosides, furosemide, and ethacrynic acid; probenecid may increase levels
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

Drug Name	Ampicillin (Marcillin, Omnipen, Polycillin, Principen)
Description	Bactericidal activity against susceptible organisms.
Adult Dose	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 Dose	50-100 mg/kg/d PO divided q4-6h 100-400 mg/kg/d IV/IM divided q4-6h
Contraindications	Documented hypersensitivity
Interactions	Probenecid and disulfiram elevate levels; allopurinol decreases effects and has additive effects on ampicillin rash; may decrease effects of oral contraceptives
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adjust dose in renal failure; evaluate rash, and differentiate from hypersensitivity reaction

Drug Name	Metronidazole (Flagyl)
Description	Imidazole ring-based antibiotic active against various anaerobic bacteria and protozoa.
Adult Dose	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 Dose	Administer as in adults using body weight
Contraindications	Documented hypersensitivity
Interactions	May increase toxicity of anticoagulants, lithium, and phenytoin; cimetidine may increase toxicity; disulfiram reaction may occur with orally ingested ethanol
Pregnancy	B - Usually safe but benefits must outweigh the risks.
Precautions	Adjust dose in hepatic disease; monitor for seizures and development of peripheral neuropathy

Drug Name	Ciprofloxacin (Cipro)
Description	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.
Adult Dose	250-500 mg PO bid for 7-14 d Alternatively, 200-400 mg IV q12h
Pediatric Dose	<18 years: Not recommended >18 years: Administer as in adults
Contraindications	Documented hypersensitivity
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)
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

Drug Name	Levofloxacin (Levaquin)
Description	For pseudomonal infections and infections due to multidrug-resistant gram-negative organisms.
Adult Dose	500 mg PO/IV qd for 7-14 d
Pediatric Dose	<18 years: Not recommended >18 years: Administer as in adults
Contraindications	Documented hypersensitivity
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)
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

Drug Category: Coagulants

Vitamin K or fresh frozen plasma (FFP) may be used for correction of coagulopathy when needed.

Drug Name	Fresh frozen plasma (FFP)
Description	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).
Adult Dose	IV as directed by protocol
Pediatric Dose	Administer as in adults
Contraindications	Documented hypersensitivity
Interactions	None reported
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

Section 8 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

In/Out Patient Meds:

• Consider maintenance therapy/antibiotics (ie, sulfamethoxazole and trimethoprim [SMZ-TMP] or a fluoroquinolone) for patients with recurrent cholangitis.

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

Section 9 of 10  

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

Medical/Legal Pitfalls

• Delay in diagnosis or treatment may result in a higher risk of death.

REFERENCES

Section 10 of 10

• Authors and Editors
• Introduction
• Clinical
• Differentials
• Workup
• Treatment
• Medication
• Follow-up
• Miscellaneous
• References

• 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].

Article Last Updated: Jun 4, 2006