eMedicine Specialties > Emergency Medicine > Gastrointestinal

Cholangitis

Adam J Rosh, MD, MS, Assistant Professor, Department of Emergency Medicine, Wayne State University/Detroit Receiving Hospital
Jeffrey A Manko, MD, Assistant Professor of Clinical Surgery/Emergency Medicine, Director, Emergency Medicine Residency Program, Consulting Staff, Emergency Medicine Services, New York University/Bellevue Medical Center; Sally Santen, MD, Program Director, Assistant Professor, Department of Emergency Medicine, Vanderbilt University

Updated: Sep 29, 2009

Introduction

Background

Acute cholangitis is a bacterial infection superimposed on an obstruction of the biliary tree most commonly from a gallstone, but it may be associated with neoplasm or stricture.

Pathophysiology

The main factors in the pathogenesis of acute cholangitis are biliary tract obstruction, elevated intraluminal pressure, and infection of bile. A biliary system that is colonized by bacteria but is unobstructed, typically does not result in cholangitis. It is believed that biliary obstruction diminishes host antibacterial defenses, causes immune dysfunction, and subsequently increases small bowel bacterial colonization. Although the exact mechanism is unclear, it is believed that bacteria gain access to the biliary tree by retrograde ascent from the duodenum or from portal venous blood. As a result, infection ascends into the hepatic ducts, causing serious infection. Increased biliary pressure pushes the infection into the biliary canaliculi, hepatic veins, and perihepatic lymphatics, leading to bacteremia (25-40%). The infection can be suppurative in the biliary tract.

The bile is normally sterile. In the presence of gallbladder or common duct stones (CBD), however, the incidence of bactibilia increases. The most common organisms isolated in bile are Escherichia coli (27%), Klebsiella species (16%), Enterococcus species (15%), Streptococcus species (8%), Enterobacter species (7%), and Pseudomonas aeruginosa (7%). Organisms isolated from blood cultures are similar to those found in the bile. The most common pathogens isolated in blood cultures are E coli (59%), Klebsiella species (16%), Pseudomonas aeruginosa (5%), and Enterococcus species (4%). In addition, polymicrobial infection is commonly found in bile cultures (30-87%) and less frequent in blood cultures (6-16%). For related pathophysiology, please see the Cholelithiasis and Cholecystitis and Biliary Colic articles.

Primary sclerosing cholangitis is a chronic liver disease that is thought to be due to an autoimmune mechanism.¹ It is characterized by inflammation and fibrosis of the intrahepatic and extrahepatic bile ducts. This condition ultimately leads to portal hypertension and cirrhosis of the liver with the only definitive treatment being a liver transplant.²  For more on this condition, please refer to the Primary Sclerosing Cholangitis article.

Frequency

United States

Cholangitis is relatively uncommon. It occurs in association with other diseases that cause biliary obstruction and bactibilia (eg, after endoscopic retrograde cholangiopancreatography [ERCP], 1-3% of patients develop cholangitis). Risk is increased if dye is injected retrograde.

International

Recurrent pyogenic cholangitis, sometimes referred to as Oriental cholangiohepatitis, is endemic to Southeast Asia. It is characterized by multiple occurrences of biliary tract infection, intrahepatic and extrahepatic biliary stone formation, hepatic abscesses, and dilatation and stricturing of the intrahepatic and extrahepatic bile duct.³ For more on this condition, please refer to the Recurrent Pyogenic Cholangitis article.

Mortality/Morbidity

• Mortality of cholangitis is high due to the predisposition in people with underlying disease. Historically, the mortality rate was 100%. With the advent of endoscopic retrograde cholangiography, therapeutic endoscopic sphincterotomy, stone extraction, and biliary stenting, the mortality rate has significantly declined to approximately 5-10%.
• The following patient characteristics are associated with higher morbidity and mortality rates:
  • Hypotension
  • Acute renal failure
  • Liver abscess
  • Cirrhosis
  • Inflammatory bowel disease
  • High malignant strictures
  • Radiologic cholangitis – Post percutaneous transhepatic cholangiography
  • Female gender
  • Age older than 50 years
  • Failure to respond to antibiotics and conservative therapy
• Advanced age, concurrent medical problems, and delay in decompression increase the emergent operative mortality rate (17-40%).
• The mortality rate of elective surgery after medical stabilization is significantly less (approximately 3%).
• In the past, suppurative cholangitis was thought to have increased morbidity; however, prospective studies have not found this to be true.

Race

• Cholangitis frequently occurs secondary to a gallstone obstructing the common bile duct. Therefore, it carries the same risk factors as that of cholelithiasis.
• Prevalence of gallstones is highest in fair-skinned people of Northern European descent as well as in Hispanic populations, Native Americans, and Pima Indians.
• In addition, certain Asian populations and inhabitants of countries where intestinal parasites are common are also at increased risk. Asians are more likely to have primary stones due to chronic biliary infections, parasites, bile stasis, and biliary strictures. Recurrent pyogenic cholangitis (Oriental cholangiohepatitis) rarely is observed in the United States
• African Americans with sickle cell disease are at increased risk.

Sex

• Although gallstones are more common in women than in men, the male-to-female ratio is equal in cholangitis.

Age

• Elderly patients are more likely to progress from asymptomatic gallstones to serious complications of gallstones and cholangitis.
• Suspect cholangitis in older patients presenting with sepsis and mental status changes. Elderly patients are more prone to gallstones and CBD stones and, therefore, cholangitis.
• The median age at presentation is between 50 and 60 years.

Clinical

History

In 1877, Charcot described cholangitis as a triad of findings of right upper quadrant (RUQ) pain, fever, and jaundice. The Reynolds pentad adds mental status changes and sepsis to the triad. A spectrum of cholangitis exists, ranging from mild symptoms to fulminant overwhelming sepsis. With septic shock, the diagnosis can be missed in up to 25% of patients. Consider cholangitis in any patient who appears septic, especially in patients who are elderly, jaundiced, or who have abdominal pain. A history of abdominal pain or symptoms of gallbladder colic may be a clue to the diagnosis.

• Charcot’s triad consists of fever, RUQ pain, and jaundice. It is reported in up to 50-70% of patients with cholangitis. However, recent studies believe it is more likely to be present in 15-20% of patients.
• Fever is present in approximately 90% of cases.
• Abdominal pain and jaundice is thought to occur in 70% and 60% of patients, respectively.
• Patients present with altered mental status 10-20% of the time and hypotension approximately 30% of the time. These signs, combined with Charcot’s triad, constitute Reynolds pentad.
• Consequently, many patients with ascending cholangitis do not present with the classic signs and symptoms.⁴
• Most patients complain of RUQ pain; however, some patients (ie, elderly persons) are too ill to localize the source of infection.
• Other symptoms include the following:
  • Jaundice
  • Fever, chills, and rigors
  • Abdominal pain
  • Pruritus
  • Acholic or hypocholic stools
  • Malaise
• The patient's medical history may be helpful. For example, a history of the following increases the risk of cholangitis:
  • Gallstones, CBD stones
  • Recent cholecystectomy
  • Endoscopic manipulation or ERCP, cholangiogram
  • History of cholangitis
  • History of HIV or AIDS: AIDS-related cholangitis is characterized by extrahepatic biliary edema, ulceration, and obstruction. The etiology is uncertain, but it may be related to cytomegalovirus or Cryptosporidium infections. The management of this condition is described below, although decompression is usually not necessary.

Physical

• In general, patients with cholangitis are quite ill and frequently present in septic shock without an apparent source of the infection.
• Physical examination may reveal the following:
  • Fever (90%), although elderly patients may have no fever
  • RUQ tenderness (65%)
  • Mild hepatomegaly
  • Jaundice (60%)
  • Mental status changes (10-20%)
  • Sepsis
  • Hypotension (30%)
  • Tachycardia
  • Peritonitis (uncommon, and should lead to a search for an alternative diagnosis)

Causes

In Western countries, choledocholithiasis is the most common cause of acute cholangitis, followed by ERCP and tumors.

Any condition that leads to stasis or obstruction of bile in the CBD, including benign or malignant stricture, parasitic infection, or extrinsic compression by the pancreas, can result in bacterial infection and cholangitis. Partial obstruction is associated with a higher rate of infection than complete obstruction.

• CBD stones predispose patients to cholangitis.
  • Approximately 10-15% of patients with cholecystitis have CBD stones.
  • Approximately 1% of patients post cholecystectomy have retained CBD stones. Most CBD stones are immediately symptomatic, while some remain asymptomatic for years.
  • Some CBD stones are formed primarily rather than secondarily to gallstones.
• Obstructive tumors cause cholangitis. Partial obstruction is associated with an increased rate of infection compared with that of complete neoplastic obstruction.
  • Pancreatic cancer
  • Cholangiocarcinoma⁵
  • Ampullary cancer
  • Porta hepatis tumors or metastasis
• Additional causes of cholangitis include the following:
  • Strictures or stenosis
  • Endoscopic manipulation of the CBD
  • Choledochocele
  • Sclerosing cholangitis (from biliary sclerosis)
  • AIDS cholangiopathy
  • Ascaris lumbricoides infections

Differential Diagnoses

Cholecystitis and Biliary Colic
Diverticular Disease
Hepatitis
Mesenteric Ischemia
Pancreatitis
Shock, Septic

Other Problems to Be Considered

Cirrhosis
Liver failure
Liver abscess
Acute appendicitis
Perforated peptic ulcer
Pyelonephritis
Right colon diverticulitis

Workup

Laboratory Studies

• CBC: Leukocytosis: In patients with cholangitis, 79% had a WBC greater than 10,000/mL, with a mean of 13.6. Septic patients may be leukopenic.
• Electrolyte panel with renal function may be performed.
• Calcium level is necessary to check if pancreatitis, which can lead to hypocalcemia, is a concern.
• Expect liver function test results to be consistent with cholestasis, hyperbilirubinemia (88-100%), and increased alkaline phosphatase level (78%).
• Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels are usually mildly elevated.
• Prothrombin time and activated partial thromboplastin time: Do not expect either to be elevated unless sepsis is associated with disseminated intravascular coagulation or underlying cirrhosis exists. A coagulation profile may be required if the patient needs operative intervention.
• C-reactive protein level and erythrocyte sedimentation rate are typically elevated.³
• Blood cultures (2 sets): Between 20% and 30% of blood cultures are positive. Many exhibit polymicrobial infections.
• Urinalysis result is usually normal.
• Blood type, screen, and crossmatch: With urgent operating room dispatch, patients need to have blood available.
• Lipase: Involvement of the lower CBD may cause pancreatitis and an elevated lipase level. One third of patients have a mildly elevated lipase level.
• Biliary cultures (not performed in the ED): Send biliary cultures if the patient has biliary drainage by interventional radiology or endoscopy.

Imaging Studies

• Imaging studies are important to confirm the presence and cause of biliary obstruction and to rule out other conditions. Ultrasonography and CT scanning are the most commonly used first-line imaging modalities.
• Ultrasonography is excellent for gallstones and cholecystitis. It is highly sensitive and specific for examining the gallbladder and assessing bile duct dilatation. However, it often misses stones in the distal bile duct.⁶

Sonogram of dilated intrahepatic ducts.

• Transabdominal ultrasonography is the initial imaging study of choice.
• Ultrasonography can differentiate intrahepatic obstruction from extrahepatic obstruction and image dilated ducts.
• In one study of cholangitis, only 13% of CBD stones were observed on ultrasonography, but dilated CBD was found in 64%.
• Advantages to sonography include the ability to be performed rapidly at the bedside by the ED physician, capacity to image other structures (eg, aorta, pancreas, liver), identification of complications (eg, perforation, empyema, abscess), and lack of radiation.
• Disadvantages to sonography include operator and patient dependence, cannot image the cystic duct, and decreased sensitivity for distal CBD stones.
• A normal sonogram does not rule out acute cholangitis.
• Endoscopic retrograde cholangiopancreatography (ERCP) is both diagnostic and therapeutic and is considered the criterion standard for imaging the biliary system.
  • ERCP should be reserved for patients who may require therapeutic intervention.
  • Patients with a high clinical suspicion for cholangitis should proceed directly to ERCP.
  • ERCP has a high success rate (98%) and is considered safer than surgical and percutaneous intervention.
  • Diagnostic use of ERCP carries a complication rate of approximately 1.38% and a mortality rate of 0.21%. The major complication rate of therapeutic ERCP is 5.4%, and it has a mortality rate of 0.49%.
  • Complications include pancreatitis, bleeding, and perforation.
• CT is adjunctive to and may replace ultrasonography. Spiral or helical CT improves imaging of the biliary tree. CT cholangiography uses a contrast agent that is taken up by the hepatocytes and secreted into the biliary system. This enhances the ability to visualize radiolucent stones and increases detection of other biliary pathology.

CT scan of dilated intrahepatic bile ducts. Image courtesy of David Schwartz, MD, New York University Hospital.

• Dilated intrahepatic and extrahepatic ducts and inflammation of the biliary tree are imaged.
• Gallstones are poorly visualized with traditional CT scan.
• Advantages of CT include the following:
  • Other pathologies that are causes or complications of cholangitis (eg, ampullary tumors, pericholecystic fluid, liver abscesses) can be imaged.
  • Pathology that must be distinguished from cholangitis also can be observed (eg, right-sided diverticulitis, papillary necrosis, some evidence of pyelonephritis, mesenteric ischemia, ruptured appendix).
  • Detection of biliary pathology with CT cholangiography approaches that of ERCP.
• Disadvantages of CT include poor imaging of gallstones, allergic reaction to contrast, exposure to ionizing radiation, and diminished ability to visualize the biliary tree with elevated serum bilirubin level.
• Magnetic resonance cholangiopancreatography (MRCP) is a noninvasive imaging modality that is increasingly being used in the diagnosis of biliary stones and other biliary pathology.
  • MRCP is accurate for detecting choledocholithiasis, neoplasms, strictures, and dilations within the biliary system.
  • Limitations of MRCP include the inability for invasive diagnostic tests such as bile sampling, cytologic testing, stone removal, or stenting.
  • It has limited sensitivity for small stones (<6 mm in diameter).
  • Absolute contraindications are the same as for a traditional MRI, which include the presence of a cardiac pacemaker, cerebral aneurysm clips, ocular or cochlear implants, and ocular foreign bodies. Relative contraindications include the presence of cardiac prosthetic valves, neurostimulators, metal prostheses, and penile implants.
  • The risk of MRCP during pregnancy is not known.
• In general, abdominal films aid little in the diagnosis of acute cholangitis.
  • An ileus may be observed.
  • Between 10% and 30% of gallstones have a ring of calcium and, as a result, are radiopaque.
  • Films may show air in the biliary tree after endoscopic manipulation or if the patient has emphysematous cholecystitis, cholangitis, or a cholecystic-enteric fistula.
  • Air in the gallbladder wall indicates emphysematous cholecystitis.

Other Tests

• Biliary scintigraphy (hepatic 2,6-dimethyliminodiacetic acid [HIDA] and diisopropyl iminodiacetic acid [DISIDA])
  • HIDA and DISIDA scans are functional studies of the gallbladder.
  • Obstruction of the CBD causes nonvisualization of the small intestine. A HIDA scan with complete biliary obstruction does not visualize the biliary tree.
  • Advantages include its ability to assess function and positive results may appear before the ducts are enlarged sonographically.
  • One disadvantage is that high bilirubin levels (>4.4) may decrease the sensitivity of the study. Recent eating or no food in 24 hours also may affect the study. In addition, anatomic imaging for other structures is lacking. The study takes several hours, so it is not recommended in critically ill or unstable patients.

Procedures

• ED physicians generally do not perform procedures for cholangitis (eg, ERCP and transhepatic decompression).
• If an obstruction is observed, ERCP provides direct visualization and potential treatment. It is best performed after 72 hours of antibiotics or after resolution of fever.
• In unstable patients, a reasonable option for decompression of the biliary tract is percutaneous transhepatic cholangiogram and biliary drain. The biliary ducts are observed, even when no ductal dilatation is present.

Treatment

Prehospital Care

• Diagnosis of cholangitis is not a prehospital diagnosis. Mild cholangitis may present with abdominal pain, jaundice, and fever. When transporting these patients to the hospital, place the patient on a monitor and insert an intravenous (IV) line.
• In unstable patients with cholangitis, prehospital care should include the following:
  • Immediate assessment of ABCs
  • Monitoring (eg, pulse oximetry, cardiac monitor, frequent blood pressure measurements, blood glucose measurement)
  • Stabilization (eg, oxygen, placement of 2 large-bore IVs, administration of IV fluids to unstable patients)
  • Rapid transport

Emergency Department Care

• Suspect mild cholangitis in patients with jaundice and a fever; consider cholangitis in all patients with sepsis.
• Degree of urgency of treatment depends on severity of illness. Important points are resuscitation, diagnosis, and treatment.
• After assessment of the ABCs, place the patient on a monitor with pulse oximetry, provide oxygen via nasal canula, and obtain an ECG. Draw and send laboratory studies (including blood cultures) when the intravenous line is placed.
• Provide fluid resuscitation with IV crystalloid solution (eg, 0.9% normal saline).
• Administer parenteral antibiotics empirically after blood cultures are drawn. Do not delay administration of antibiotics if blood cultures cannot be drawn.
• Correct any electrolyte abnormalities or coagulopathies.
• For management of patients in septic shock, see Shock, Septic.
• Standard therapy for cholangitis consists of broad-spectrum antibiotics with close observation to determine the need for emergency decompression of the biliary tree.
• A nasogastric tube may be helpful for patients who are vomiting.
• Patients should be nothing by mouth (NPO). Place a Foley catheter in ill patients to monitor urine output.
• The surgical literature states that, in patients with mild cholangitis, 80-90% respond to medical therapy.³ Approximately 15% do not respond and subsequently require immediate surgical or endoscopic decompression. Mortality rates approach 100% for patients who fail medical therapy and do not have surgical decompression.
• In severely ill patients, treatment is immediate biliary decompression. The method depends on the degree of illness. In the past, drainage was performed surgically. Today, options of percutaneous or endoscopic drainage exist in addition to medical management with antibiotics. Endoscopic drainage has been shown to decrease mortality rates from 30% to 10%.
• Medical therapy can be complementary to surgical or endoscopic treatments. In less ill patients, medical treatment may be all that is necessary.
• Maintain medical therapy and consider elective surgery with patients who show improvement. Patients who are being medically managed and do not improve or who deteriorate should rapidly be referred to undergo either ERCP, sphincterotomy, or percutaneous drainage.
• The mainstay of therapy is drainage. ERCP is the best method to accomplish biliary drainage.
• A novel technique that is being used in Asia in the surgical management of acute cholangitis is endoscopic nasobiliary drainage.⁷

Consultations

• Immediately consult a surgeon and a gastroenterologist.
• While most patients respond to antibiotics and conservative care, a subset requires emergent procedures (eg, ERCP, percutaneous drainage). In deciding to drain, consult with a gastroenterologist and a surgeon.
• Increased mortality is observed in patients with hypotension, acute renal failure, liver abscess, cirrhosis, high malignant strictures, female gender, and advanced age. Therefore, consider decompression earlier for these patients. Patients with malignant obstruction usually do not respond to antibiotics (59% compared to 85%).
• Unstable septic patients require clinical judgment to determine if they will survive until medical therapy has a chance to work or if they require emergency decompression with its associated high mortality rate.

Medication

The goal of antimicrobial therapy is to resolve the infection. Debate exists as to whether the most effective antibiotics must have high biliary concentrations. When high intrabiliary pressures exist due to biliary obstruction, whether any antibiotic is excreted effectively into the bile is doubtful, thus making biliary levels irrelevant. The choice of antibiotics should be guided by local sensitivity patterns.

It is critical that antibiotics are administered early in the management of cholangitis. In the ED, empiric antibiotic therapy should cover against gram-negative aerobic enteric organisms (eg, E coli, Klebsiella species, Enterobacter species), gram-positive organisms (eg, Enterococcus and Streptococcus species), and anaerobes (eg, Bacteroides fragilis, Clostridium perfringens). There is an increase of up to 85% in infectious complications when biliary cultures are not susceptible to the empiric antibiotics. Therefore, traditional therapy with ampicillin and an aminoglycoside is now a less ideal regimen secondary to weakened activity of ampicillin against both aerobic and anaerobic gram-negative bacilli, and is concern for nephrotoxicity of aminoglycosides.

Many newer combinations have been shown to be effective as either a single agent or combination therapy. Combinations include extended-spectrum cephalosporin, metronidazole, and ampicillin. Single-agent regimens include piperacillin and tazobactam; mezlocillin; imipenem; meropenem; ticarcillin and clavulanate; or ampicillin and sulbactam, which can also be combined with metronidazole.

In patients with few comorbidities and who are well-appearing, using a single agent such as cefoxitin (second-generation cephalosporin) may be appropriate. However, cefoxitin’s anaerobic coverage is poor. Newer-generation fluoroquinolones (eg, moxifloxacin) also have broad gram-positive and gram-negative coverage and better anaerobic activity, but they are poorly effective against Pseudomonas species. In patients with multiple comorbidities or who are ill-appearing, broad-spectrum antimicrobials with pseudomonal and enterococcal coverage is recommended. Once blood cultures results are available, the antibiotic regimen can be narrowed based on the culture results.

The following dosages are general recommendations. Please check current sources prior to administration.

Antibiotics

Ampicillin (Omnipen, Marcillin)

Interferes with bacterial cell wall synthesis during active multiplication, causing bactericidal activity against susceptible organisms. Must be used in combination.

Dosing

Adult

2 g IV q6h

Pediatric

50 mg/kg IV q6h

Interactions

Probenecid and disulfiram elevate ampicillin levels; allopurinol decreases ampicillin effects and has additive effects on ampicillin rash; may decrease effects of oral contraceptives

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

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. Usually used in combination with other antimicrobial agents.

Dosing

Adult

1 g IV loading dose, followed by 500 mg IV q6h or 1 g IV q12h

Pediatric

7.5-15 mg/kg/d IV divided bid

Interactions

May increase toxicity of anticoagulants, lithium, and phenytoin; cimetidine may increase toxicity of metronidazole; disulfiram reaction may occur with orally ingested ethanol

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in hepatic disease; monitor for seizures and development of peripheral neuropathy

Gentamicin (Gentacidin, Garamycin)

Aminoglycoside antibiotic for gram-negative coverage. Used in combination with both an agent against gram-positive organisms and one that covers anaerobes.
Not DOC. Consider if penicillins or other less toxic drugs are contraindicated, when clinically indicated, and in mixed infections caused by susceptible staphylococci and gram-negative organisms.
Dosing regimens are numerous; adjust dose based on CrCl and changes in volume of distribution. May be given IV/IM.
Follow each regimen by at least a trough level drawn on the third or fourth dose (0.5 h before dosing); may draw a peak level 0.5 h after 30-min infusion.

Dosing

Adult

3-5 mg/kg/d IV divided tid

Pediatric

5-7 mg/kg/d IV divided tid

Interactions

Coadministration with other aminoglycosides, cephalosporins, penicillins, and amphotericin B may increase nephrotoxicity; aminoglycosides enhance effects of neuromuscular blocking agents, thus prolonged respiratory depression may occur
Coadministration with loop diuretics may increase auditory toxicity of aminoglycosides; possible irreversible hearing loss of varying degrees may occur (monitor regularly)

Contraindications

Documented hypersensitivity; non–dialysis-dependent renal insufficiency

Precautions

Pregnancy

D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus

Precautions

Monitor gentamicin levels to prevent ototoxicity; narrow therapeutic index (not intended for long-term therapy); caution in patients with renal failure who are not on dialysis, myasthenia gravis, hypocalcemia, and conditions that depress neuromuscular transmission; adjust dose in renal impairment

Cefoxitin (Mefoxin)

A second-generation cephalosporin that has broad gram-negative coverage, while retaining efficacy against gram-positive organisms. It also has activity against anaerobes.
However, it lacks pseudomonal and enterococcal coverage.

Dosing

Adult

1-2 g IV q6-8h

Pediatric

80-160 mg/kg divided q4-6h; administer higher dose for severe infection

Interactions

Warfarin anticoagulation effect may be enhanced, and INR should be monitored

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in renal failure; can lower seizure threshold; can cause phlebitis at the infusion site

Piperacillin/tazobactam (Zosyn)

Antipseudomonal penicillin plus beta-lactamase inhibitor. Inhibits biosynthesis of cell wall mucopeptide and is effective during stage of active multiplication. Used in combination therapy.

Dosing

Adult

3.375 g IV q6h

Pediatric

75 mg/kg IV q6h

Interactions

Tetracyclines may decrease effects of ticarcillin; high concentrations of ticarcillin may physically inactivate aminoglycosides if administered in same IV line; effects when administered concurrently with aminoglycosides are synergistic; probenecid may increase penicillin levels

Contraindications

Documented hypersensitivity; do not treat severe pneumonia, bacteremia, pericarditis, emphysema, meningitis, and purulent or septic arthritis with oral penicillin during acute stage

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Tetracyclines may decrease effects of ticarcillin; high concentrations of ticarcillin may physically inactivate aminoglycosides if administered in same IV line; effects when administered concurrently with aminoglycosides are synergistic; probenecid may increase penicillin levels

Cefotaxime (Claforan)

Third-generation cephalosporin that has broad gram-negative spectrum, lower efficacy against gram-positive organisms, and higher efficacy against resistant organisms.
Arrests bacterial cell wall synthesis and inhibits bacterial growth by binding to one or more of the penicillin-binding proteins.
Can be used in combination with metronidazole or clindamycin.

Dosing

Adult

1 g IV q8-12h

Pediatric

80-180 mg/kg/d IV divided tid/qid

Interactions

Probenecid may increase cefotaxime levels; coadministration with furosemide and aminoglycosides may increase nephrotoxicity

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in severe renal impairment; has been associated with severe colitis

Clindamycin (Cleocin)

Lincosamide for treatment of serious skin and soft tissue staphylococcal infections. Also effective against aerobic and anaerobic streptococci (except enterococci). Inhibits bacterial growth, possibly by blocking dissociation of peptidyl tRNA from ribosomes, causing RNA-dependent protein synthesis to arrest.

Dosing

Adult

600 mg IV q6-8h

Pediatric

15-40 mg/kg IV divided tid/qid

Interactions

Increases duration of neuromuscular blockade induced by tubocurarine and pancuronium; erythromycin may antagonize effects of clindamycin; antidiarrheals may delay absorption of clindamycin

Contraindications

Documented hypersensitivity; regional enteritis; ulcerative colitis; hepatic impairment; antibiotic-associated colitis

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in severe hepatic dysfunction; no adjustment necessary in renal insufficiency; associated with severe and possibly fatal colitis

Mezlocillin (Mezlin)

During growth phase, interferes with bacterial cell wall synthesis, causing death in susceptible microorganisms. Has antipseudomonal activity. Use in combination therapies.

Dosing

Adult

3 g IV q4h

Pediatric

300 mg/kg/d IV/IM divided q4-6h; not to exceed 24 g/d

Interactions

Administered concomitantly with aminoglycosides, has synergistic effects; probenecid increases mezlocillin blood levels; administered concurrently with vecuronium, duration of neuromuscular blockade increases; enhances anticoagulant effects of heparin; may decrease effectiveness of oral contraceptives; bacteriostatic effects of tetracyclines may decrease effectiveness of penicillins

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Caution in preexisting sinus node dysfunction and renal impairment, bradycardias, antiarrhythmic agents, thrombocytopenia, electrolyte disturbances, or congestive heart failure

Imipenem and cilastatin (Primaxin)

A carbapenem; may be used alone or in combination. Used for treatment of multiple-organism infections for which other agents do not have wide-spectrum coverage or are contraindicated due to potential for toxicity.

Dosing

Adult

0.5 g IV q6h

Pediatric

<12 years: Not established; 15-25 mg/kg/dose IV q6h suggested for >3 mo
Fully susceptible organisms: Not to exceed 2 g/d
Moderately susceptible organisms: Not to exceed 4 g/d
>12 years: Administer as in adults

Interactions

Coadministration with cyclosporine may increase CNS adverse effects of both agents; coadministration with ganciclovir may result in generalized seizures

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

C - Fetal risk revealed in studies in animals but not established or not studied in humans; may use if benefits outweigh risk to fetus

Precautions

Adjust dose in renal insufficiency; avoid use in children <12 y

Meropenem (Merrem)

A carbapenem; may be used alone or in combination. Broad-spectrum carbapenem antibiotic that inhibits cell-wall synthesis and has bactericidal activity. Effective against most gram-positive and gram-negative bacteria.
Has slightly increased activity against gram-negative organisms and slightly decreased activity against staphylococci and streptococci compared to imipenem.

Dosing

Adult

0.5-1 g IV q6h

Pediatric

40 mg/kg IV q8h

Interactions

Probenecid may inhibit renal excretion of meropenem, increasing meropenem levels

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Pseudomembranous colitis and thrombocytopenia may occur, requiring immediate discontinuation of medication

Ticarcillin and clavulanate potassium (Timentin)

Inhibits biosynthesis of cell wall mucopeptide and is effective during stage of active growth.
Antipseudomonal penicillin plus a beta-lactamase inhibitor that provides coverage against most gram-positive and gram-negative organisms and most anaerobes.

Dosing

Adult

3.1 g IV q4-6h

Pediatric

75 mg/kg IV q6h

Interactions

Tetracyclines may decrease effects of ticarcillin; high concentrations of ticarcillin may physically inactivate aminoglycosides if administered in same IV line; effects when administered concurrently with aminoglycosides are synergistic; probenecid may increase penicillin levels

Contraindications

Documented hypersensitivity; severe pneumonia, bacteremia, pericarditis, emphysema, meningitis, and purulent or septic arthritis should not be treated with oral penicillin during acute stage

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Perform CBCs prior to initiation of therapy and at least weekly during therapy; monitor for liver function abnormalities by measuring AST and ALT during therapy; exercise caution in patients diagnosed with hepatic insufficiencies; perform urinalysis and BUN and creatinine determinations during therapy and adjust dose if values become elevated; monitor blood levels to avoid possible neurotoxic reactions

Ampicillin and sulbactam sodium (Unasyn)

Combination antimicrobial agent that uses a beta-lactamase inhibitor with ampicillin. Covers skin, enteric flora, and anaerobes. Not ideal for nosocomial pathogens.

Dosing

Adult

1.5 (1 g ampicillin + 0.5 g sulbactam) to 3 g (2 g ampicillin + 1 g sulbactam) IV/IM q6-8h; not to exceed 4 g/d sulbactam or 8 g/d ampicillin

Pediatric

<3 months: Not established
3 months to 12 years: 100-200 mg ampicillin/kg/d (150-300 mg Unasyn) IV divided q6h
>12 years: Administer as in adults; not to exceed 4 g/d sulbactam or 8 g/d ampicillin

Interactions

Probenecid and disulfiram elevate ampicillin levels; allopurinol decreases ampicillin effects and has additive effects on ampicillin rash; may decrease effects of oral contraceptives

Contraindications

Documented hypersensitivity

Precautions

Pregnancy

B - Fetal risk not confirmed in studies in humans but has been shown in some studies in animals

Precautions

Adjust dose in renal failure; evaluate rash and differentiate from hypersensitivity reaction

Follow-up

Further Inpatient Care

• Admission to ICU for ill patients is appropriate.
• Continue intravenous antibiotics.
  • Monitor the blood cultures so that the antibiotics can be narrowed to the appropriate pathogen.
  • Administer intravenous antibiotics 12-24 hours prior to nonemergent ERCP.
• Refer worsening patients to emergent ERCP for sphincterotomy or percutaneous drainage.
• Traditionally, antibiotics were administered for 7-10 days to treat cholangitis. However, it now appears that a 3-day course may be sufficient in patients who undergo adequate biliary drainage.

Transfer

• Transfer is appropriate in hospitals unable to manage significantly ill patients with intensive medical care, surgery, and endoscopic consultation.
• Optimize patient stabilization prior to transfer.
• Minimum initial stabilization includes the following:
  • Appropriate diagnostics
  • ABCs (including volume resuscitation)
  • Administration of broad-spectrum antibiotics
  • Critical care transport

Deterrence/Prevention

• Prophylactic antibiotics prior to ERCP may decrease risk of cholangitis.
• Prompt recognition and treatment of symptomatic cholelithiasis in patients at higher risk for complications (eg, those with diabetes) decrease risk of cholangitis.
• Aggressive search for CBD stones during diagnosis and treatment of cholecystitis may be necessary to prevent cholangitis.

Complications

• Patients are increasingly likely to have complications with greater degrees of illness, as follows:
  • Liver failure, hepatic abscesses, and microabscesses
  • Bacteremia (25-40%); gram-negative sepsis
  • Acute renal failure
  • Catheter-related problems in patients treated with percutaneous or endoscopic drainage
    • Bleeding (intra-abdominally or percutaneously)
    • Catheter-related sepsis
    • Fistulae
    • Bile leak (intraperitoneally or percutaneously)

Prognosis

• Prognosis depends on several factors.⁸
  • Early recognition and treatment of cholangitis
  • Response to therapy
  • Underlying medical conditions of the patient
• Mortality rate ranges from 5-10%, with a higher mortality rate in patients who require emergency decompression or surgery.
• In patients responding to antibiotic therapy, the prognosis is good.

Miscellaneous

Special Concerns

• Because pregnant women are prone to symptomatic gallstones, consider cholangitis in pregnant, febrile, or jaundiced patients. Differentiate cholangitis from HELLP syndrome (hemolysis, elevated liver enzymes, low platelet count) of preeclampsia, which also can cause abdominal pain and elevated LFTs. Blood pressure is elevated in preeclampsia and may be hypotensive in cholangitis.
• Cholelithiasis and cholangitis are uncommon in children, except in those with underlying hemolytic disorders or biliary anomalies.
• The incidence of cholangitis is higher in elderly persons, most likely due to the increased prevalence of common bile duct stones with age. As in other infections and abdominal processes, elderly patients frequently do not manifest pathology in a classic pattern. Consider cholangitis in febrile or hypotensive elderly patients.

Multimedia

Media file 1: Sonogram of dilated intrahepatic ducts.

Media file 2: CT scan of common bile duct occluded by stone. Image courtesy of David Schwartz, MD, New York University Hospital.

Media file 3: CT scan of 1-cm dilated common bile duct at portal triad. Image courtesy of David Schwartz, MD, New York University Hospital.

Media file 4: CT scan of dilated intrahepatic bile ducts. Image courtesy of David Schwartz, MD, New York University Hospital.

References

1. Aron JH, Bowlus CL. The immunobiology of primary sclerosing cholangitis. Semin Immunopathol. May 26 2009;[Medline].

2. Kashyap R, Mantry P, Sharma R, Maloo MK, Safadjou S, Qi Y, et al. Comparative Analysis of Outcomes in Living and Deceased Donor Liver Transplants for Primary Sclerosing Cholangitis. J Gastrointest Surg. May 9 2009;[Medline].

3. van Erpecum KJ. Gallstone disease. Complications of bile-duct stones: Acute cholangitis and pancreatitis. Best Pract Res Clin Gastroenterol. 2006;20(6):1139-52. [Medline].

4. Kinney TP. Management of ascending cholangitis. Gastrointest Endosc Clin N Am. Apr 2007;17(2):289-306, vi. [Medline].

5. Jabara B, Fargen KM, Beech S, Slakey DR. Diagnosis of cholangiocarcinoma: a case series and literature review. J La State Med Soc. Mar-Apr 2009;161(2):89-94. [Medline].

6. Rustemovic N, Cukovic-Cavka S, Opacic M, Petrovecki M, Hrstic I, Radic D, et al. Endoscopic ultrasound elastography as a method for screening the patients with suspected primary sclerosing cholangitis. Eur J Gastroenterol Hepatol. Jun 2 2009;[Medline].

7. Itoi T, Kawai T, Sofuni A, Itokawa F, Tsuchiya T, Kurihara T, et al. Efficacy and safety of 1-step transnasal endoscopic nasobiliary drainage for the treatment of acute cholangitis in patients with previous endoscopic sphincterotomy (with videos). Gastrointest Endosc. Jul 2008;68(1):84-90. [Medline].

8. Rosing DK, De Virgilio C, Nguyen AT, et al. Cholangitis: analysis of admission prognostic indicators and outcomes. Am Surg. Oct 2007;73(10):949-54. [Medline].

9. Bornman PC, van Beljon JI, Krige JE. Management of cholangitis. J Hepatobiliary Pancreat Surg. 2003;10(6):406-14. [Medline].

10. Hanau LH, Steigbigel NH. Acute (ascending) cholangitis. Infect Dis Clin North Am. Sep 2000;14(3):521-46. [Medline].

11. Jain MK, Jain R. Acute bacterial cholangitis. Curr Treat Options Gastroenterol. Apr 2006;9(2):113-21. [Medline].

12. Lai EC. Management of severe acute cholangitis. Br J Surg. Jun 1990;77(6):604-5. [Medline].

13. Lipsett PA, Pitt HA. Acute cholangitis. Surg Clin North Am. Dec 1990;70(6):1297-312. [Medline].

14. Muir CA. Acute ascending cholangitis. Clin J Oncol Nurs. Apr 2004;8(2):157-60. [Medline].

15. Qureshi WA. Approach to the patient who has suspected acute bacterial cholangitis. Gastroenterol Clin North Am. Jun 2006;35(2):409-23. [Medline].

16. Romagnuolo J, Bardou M, Rahme E, et al. Magnetic resonance cholangiopancreatography: a meta-analysis of test performance in suspected biliary disease. Ann Intern Med. Oct 7 2003;139(7):547-57.

17. Sievert W, Vakil NB. Emergencies of the biliary tract. Gastroenterol Clin North Am. Jun 1988;17(2):245-64. [Medline].

18. Sinanan MN. Acute cholangitis. Infect Dis Clin North Am. Sep 1992;6(3):571-99. [Medline].

19. 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].

20. Yusoff IF, Barkun JS, Barkun AN. Diagnosis and management of cholecystitis and cholangitis. Gastroenterol Clin North Am. Dec 2003;32(4):1145-68. [Medline].

Keywords

cholangitis, gallstone, gall stone, gallbladder, biliary tract obstruction, common bile duct obstruction, primary sclerosing cholangitis, cholecystitis, biliary colic, cholelithiasis, cholangitis treatment, cholangitis symptoms, CBD, CBD stones

Contributor Information and Disclosures

Author

Adam J Rosh, MD, MS, Assistant Professor, Department of Emergency Medicine, Wayne State University/Detroit Receiving Hospital
Adam J Rosh, MD, MS is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Coauthor(s)

Jeffrey A Manko, MD, Assistant Professor of Clinical Surgery/Emergency Medicine, Director, Emergency Medicine Residency Program, Consulting Staff, Emergency Medicine Services, New York University/Bellevue Medical Center
Jeffrey A Manko, MD is a member of the following medical societies: American College of Emergency Physicians, Council of Emergency Medicine Residency Directors, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Sally Santen, MD, Program Director, Assistant Professor, Department of Emergency Medicine, Vanderbilt University
Sally Santen, MD is a member of the following medical societies: American College of Emergency Physicians and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Medical Editor

David FM Brown, MD, Assistant Professor, Division of Emergency Medicine, Harvard Medical School; Vice Chair, Department of Emergency Medicine, Massachusetts General Hospital
David FM Brown, MD is a member of the following medical societies: American College of Emergency Physicians and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

Eugene Hardin, MD, FAAEM, FACEP, Former Chair and Associate Professor, Department of Emergency Medicine, Charles Drew University of Medicine and Science; Former Chair, Department of Emergency Medicine, Martin Luther King Jr/Drew Medical Center
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Barry E Brenner, MD, PhD, FACEP, Professor of Emergency Medicine, Professor of Internal Medicine, Program Director, Emergency Medicine, University Hospitals, Case Medical Center
Barry E Brenner, MD, PhD, FACEP is a member of the following medical societies: Alpha Omega Alpha, American Academy of Emergency Medicine, American College of Chest Physicians, American College of Emergency Physicians, American College of Physicians, American Heart Association, American Thoracic Society, Arkansas Medical Society, New York Academy of Medicine, New York Academy of Sciences, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Clinical guidelines

ACR Appropriateness Criteria® right upper quadrant pain.
American College of Radiology - Medical Specialty Society.  1996 (revised 2005).  5 pages.  [NGC Update Pending] NGC:004781

AASLD practice guidelines: evaluation of the patient for liver transplantation.
American Association for the Study of Liver Diseases - Private Nonprofit Research Organization.  2000 Jan (revised 2005 Jun).  26 pages.  NGC:004333


Clinical trials

Compare Conventional Colonosocpy to Endoscopic AFI, NBI for Dysplasia Detection for Ulcerative Colitis & Cholangitis

Probiotics in Patients With Primary Sclerosing Cholangitis

Differential Gene Expression of Liver Tissue and Blood From Individuals With Chronic Viral Hepatitis

Related eMedicine topics

Cholangitis (Emergency Medicine)

Cholangitis, Primary Sclerosing (Radiology)

Primary Sclerosing Cholangitis (Gastroenterology)

Primary Sclerosing Cholangitis (Pediatrics: General Medicine)

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