INTRODUCTION — Biliary drainage, usually by endoscopic retrograde cholangiopancreatography (ERCP), is essential in the management of patients with acute obstructive cholangitis. However, acute cholangitis is the most common infectious adverse event associated with ERCP. It is important to use preventive strategies to reduce the risk of cholangitis and other abdominal infections related to ERCP.
This topic will discuss pathogenesis, prevention, and an overview of management for infections related to ERCP. Other aspects of ERCP including indications, patient preparation, and noninfectious adverse events are discussed separately:
●(See "Overview of endoscopic retrograde cholangiopancreatography (ERCP) in adults".)
●(See "Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis".)
●(See "Post-endoscopic retrograde cholangiopancreatography (ERCP) bleeding".)
●(See "Post-ERCP perforation".)
The clinical features, diagnosis, and management of acute cholangitis and acute cholecystitis are discussed in detail separately. (See "Acute cholangitis: Clinical manifestations, diagnosis, and management" and "Acute calculous cholecystitis: Clinical features and diagnosis" and "Treatment of acute calculous cholecystitis".)
RATES OF BACTEREMIA AND INFECTION — Infections have been reported in up to 3 percent of patients undergoing ERCP [1-6]. As an example, in a summary of 21 studies involving 16,855 adult patients, the rate of infection related to ERCP was 1.4 percent and the periprocedural mortality rate was 0.1 percent [2].
Transient bacteremia that is not associated with sepsis may be common following ERCP. In patients with biliary obstruction, transient bacteremia rates of 18 percent have been reported, but the risk for subsequent sepsis is uncertain [7].
PATHOGENESIS — For patients undergoing ERCP, bacteremia may result from translocation of endogenous bacteria into the blood stream via mucosal trauma. In addition, injection of contrast during ERCP may also result in bacteria being introduced into a previously sterile space. Patients who have biliary obstruction and/or impaired host defenses are more susceptible to developing infection [8,9]. The mechanism by which biliary obstruction can lead to sepsis is presumed to be elevated biliary pressure causing biliary-venous reflux [8]. (See "Antibiotic prophylaxis for gastrointestinal endoscopic procedures", section on 'Pathogenesis'.)
The most frequent organisms responsible for ERCP-related infections are enteric, gram-negative bacteria [1,10,11]. Although polymicrobial enteric flora are often found in infected bile, single organisms are usually isolated from blood cultures in most patients with septic infection [8].
Gastrointestinal endoscopy-related transmission of infection occurs very rarely. However, duodenoscopes have been implicated in transmission of multidrug-resistant organisms such as carbapenem-resistant Enterobacteriaceae (CRE; including Escherichia coli, Klebsiella pneumoniae) [12-14]. Strategies for endoscope reprocessing have been developed to reduce the risk of transmitting infection, and such protocols are discussed separately. (See "Preventing infection transmitted by gastrointestinal endoscopy".)
PREVENTIVE STRATEGIES — For patients undergoing ERCP, the goal of a preventive strategy is to reduce the risk of post-ERCP infection, and these strategies include [15]:
●Antibiotic prophylaxis — Antibiotic prophylaxis is recommended in selected patients undergoing ERCP as outlined in the table (table 1). For example, antibiotic prophylaxis before ERCP is typically administered when incomplete biliary drainage is anticipated or when ERCP-guided cholangioscopy is planned. (See "Cholangioscopy and pancreatoscopy", section on 'Patient preparation'.)
Antibiotic prophylaxis and specific antibiotic regimens are discussed in more detail separately. (See "Antibiotic prophylaxis for gastrointestinal endoscopic procedures", section on 'Endoscopic retrograde cholangiopancreatography (ERCP)'.)
●General endoscopic techniques – Endoscopic techniques for reducing the risk of infection include [16]:
•Aspirating bile before injecting sterile contrast material to avoid using excessive hydrostatic pressure
•Using the minimum volume of contrast that is needed to obtain diagnostic fluoroscopic images (ie, biliary stones, biliary stricture)
●Establishing biliary drainage – For patients with biliary obstruction, the goal of endoscopic intervention is to establish complete, long-term biliary drainage. When complete drainage is not possible, the approach is informed by the cause of obstruction.
As an example, for patients with obstruction due to bile duct stones, a temporary plastic biliary stent is usually placed to establish drainage if the bile duct cannot be cleared during the initial endoscopic intervention. This is discussed in more detail separately. (See "Endoscopic management of bile duct stones", section on 'Patients with incomplete duct clearance'.)
The approach to drainage for patients with malignant biliary obstruction is discussed separately. (See "Endoscopic stenting for malignant biliary obstruction", section on 'ERCP with biliary stent placement'.)
●Adhering to endoscope reprocessing protocols – Gastrointestinal endoscopes are devices that contact the mucous membranes, and such devices require high-level disinfection (HLD) to destroy microorganisms and prevent transmission of endoscopy-related infection. Protocols for endoscope disinfection and reprocessing are informed by regulatory agencies, manufacturers, and professional societies, and these issues are discussed separately. (See "Preventing infection transmitted by gastrointestinal endoscopy", section on 'Overview of endoscope reprocessing'.)
Disposable duodenoscopes may reduce the risk of endoscopy-related infection, especially for patients with risk factors (eg, those who are immunosuppressed). Studies suggest that the technical performance of disposable duodenoscopes is similar to reusable duodenoscopes [17]; however, routine use of disposable equipment may be limited by cost. (See "Preventing infection transmitted by gastrointestinal endoscopy", section on 'Duodenoscopes with disposable designs'.)
APPROACH TO THE PATIENT WITH SUSPECTED INFECTION
When to suspect an ERCP-related infection — An infection should be suspected in patients who develop fever (temperature >38⁰C; frequently with chills) and/or abdominal pain within 72 hours after ERCP.
Initial testing — For patients with a suspected ERCP-related infection based on symptoms and timing of presentation, the evaluation begins with the following:
●Laboratory testing – We obtain complete blood count, electrolytes, liver biochemical and function tests, amylase, and lipase. In patients with fever, blood cultures are obtained to guide antibiotic therapy.
●Imaging – The approach to initial diagnostic imaging is informed by patient presentation and clinician preference. For example, the authors of this topic typically obtain abdominal ultrasound to confirm the presence of pneumobilia (a sign that the sphincterotomy and/or biliary stent is patent) and to exclude acute cholecystitis, whereas other contributors begin the evaluation with cross-sectional imaging (eg, computed tomography scan or magnetic resonance imaging with cholangiopancreatography) [18]. (See 'Specific post-ERCP infections' below.)
The initial evaluation is also informed by clinical suspicion for other healthcare-associated infections (eg, pneumonia, catheter-related infection), and these conditions are discussed separately:
●(See "Intravascular non-hemodialysis catheter-related infection: Clinical manifestations and diagnosis".)
●(See "Clostridioides difficile infection in adults: Clinical manifestations and diagnosis".)
Initial management — Patients with suspected infection are ideally given empiric antibiotic therapy after blood samples have been obtained for culture. In general, the empiric regimens for post-ERCP intra-abdominal infections include antimicrobial activity against biliary flora, and this is discussed separately (table 2). (See "Acute cholangitis: Clinical manifestations, diagnosis, and management", section on 'Antibiotics' and "Antimicrobial approach to intra-abdominal infections in adults".)
The duration of antibiotic therapy is individualized and is informed by blood culture results, imaging results, and source of infection. For patients in whom symptoms resolve but an infectious source is not identified, we typically discontinue antibiotics after three to five days. For patients with positive blood cultures and/or with a slower response to antibiotic therapy (ie, symptomatic improvement after five days of antibiotic therapy), we continue antibiotics for a total of 7 to 14 days.
For patients in whom a diagnosis of intra-abdominal infection is established, further management is discussed below. (See 'Specific post-ERCP infections' below.)
DIFFERENTIAL DIAGNOSIS — The differential diagnosis of an ERCP-related infection includes other etiologies of post-ERCP fever and abdominal pain:
●Post-ERCP perforation – Duodenal perforation related to ERCP may be recognized during the procedure based on fluoroscopic imaging, or the patient may present hours after the procedure with abdominal pain, fever, and leukocytosis. Thus, the diagnosis of duodenal perforation may be established during ERCP and/or with computed tomography scan. (See "Post-ERCP perforation".)
●Acute post-ERCP pancreatitis – The diagnosis of post-ERCP pancreatitis is established in patients with abdominal pain who have elevated amylase and/or lipase by >3 times the upper limit of normal at more than 24 hours after ERCP and who require hospital admission or prolongation of a planned postprocedure admission [19-21]. Fever may be present but is typically uncommon in patients with acute pancreatitis. The diagnosis and management of post-ERCP pancreatitis is discussed separately. (See "Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis".)
SPECIFIC POST-ERCP INFECTIONS
Acute cholangitis
Incidence and risk factors — Cholangitis is one of the most common infectious events related to ERCP with a reported incidence that ranges from 1 to 3 percent [2,5,22].
Risk factors for post-ERCP cholangitis include [15]:
●Incomplete biliary drainage – Patients with an obstructed biliary system for whom biliary drainage is not established are at risk for cholangitis. Such patients include those with the following conditions:
•Malignant biliary obstruction and/or stent occlusion – For patients with a biliary malignancy, hilar obstruction is a risk factor for incomplete biliary drainage. In addition, biliary stents may become occluded due to tumor ingrowth and/or overgrowth, retained stones or sludge, or bacterial biofilm [23]. The evaluation and management of patients with suspected stent occlusion is discussed in detail separately. (See "Endoscopic stenting for malignant biliary obstruction".)
•Incomplete stone clearance (eg, retained stone fragments following mechanical lithotripsy). (See "Endoscopic management of bile duct stones", section on 'Mechanical lithotripsy'.)
●History of primary sclerosing cholangitis – Patients with primary sclerosing cholangitis who undergo ERCP are at increased risk for developing cholangitis, and this is discussed separately. (See "Primary sclerosing cholangitis in adults: Management", section on 'Endoscopic therapy'.)
●Cholangioscopy – Miniature endoscopes and catheters have been developed for direct visualization of the bile duct, and this examination is referred to as cholangioscopy. Such instrumentation of the bile duct has been associated with risk of bacteremia and subsequent cholangitis [24,25]. In an observational study of 57 patients who underwent ERCP with cholangioscopy, five patients had post-procedure bacteremia (9 percent), and four patients developed cholangitis requiring hospital admission (7 percent) [25]. Biopsy sampling during cholangioscopy was associated with higher rates of bacteremia compared with no biopsy sampling (29 versus 5 percent).
●History of liver transplantation – Liver transplant recipients are at increased risk for infection because of immunosuppression and because of increased likelihood for incomplete biliary drainage. These issues are discussed in detail separately. (See "Liver transplantation in adults: Endoscopic management of biliary complications".)
●Other factors – Other risk factors include delay in performing ERCP (ie, >48 hours after presentation) [26].
Clinical features and diagnosis — Cholangitis typically develops within 72 hours after ERCP, and the most common symptoms are fever with chills, right upper quadrant pain, and jaundice (Charcot's triad) [15]. Mental status changes and hypotension may occur in patients with suppurative (severe) cholangitis (Reynold's pentad), whereas hypotension may be the only presenting symptom in older patients. Patients with acute cholangitis can also present with complications related to bacteremia, including liver abscess, sepsis, and multiple organ system dysfunction [27].
Patients with suspected post-ERCP cholangitis are diagnosed in the same manner as patients with acute cholangitis due to other causes (ie, temperature >38⁰C combined with cholestasis as demonstrated by elevated liver tests and imaging). (See "Acute cholangitis: Clinical manifestations, diagnosis, and management".)
Cultures should also be obtained from bile that is aspirated during repeat ERCP because bile cultures have been associated with higher diagnostic yield than blood cultures [28,29]. In a study including 93 patients with acute cholangitis who underwent ERCP, bile culture was associated with higher rates of a positive culture result compared with blood culture (97 versus 32 percent) [28].
Post-ERCP cholangitis can be graded as mild, moderate, or severe based upon a consensus definition [19,30]:
●Mild – Temperature >38⁰C for 24 to 48 hours
●Moderate – Febrile or septic illness requiring more than three days of hospital treatment or endoscopic or percutaneous intervention
●Severe – Septic shock or requiring procedural intervention
Management — The cornerstone of treatment for cholangitis is decompression of the obstructed biliary ducts and supportive care with antibiotic therapy. For patients with biliary obstruction related to an occluded biliary stent, an ERCP-guided stent exchange is typically performed (picture 1 and picture 2). (See "Endoscopic stenting for malignant biliary obstruction", section on 'Stent occlusion'.)
The management of acute cholangitis is discussed in detail separately. (See "Acute cholangitis: Clinical manifestations, diagnosis, and management", section on 'Management'.).
Acute cholecystitis — For patients with an intact gallbladder who develop common bile duct stones, most centers perform cholecystectomy after ERCP with biliary sphincterotomy and stone removal. (See "Endoscopic management of bile duct stones".)
Timing of cholecystectomy in patients who are treated for choledocholithiasis is discussed separately. (See "Choledocholithiasis: Clinical manifestations, diagnosis, and management", section on 'Subsequent evaluation and management'.)
Incidence and pathogenesis — The incidence of post-ERCP acute cholecystitis has ranged from less than 0.5 to nearly 9 percent in various reports; however, most large series report an incidence of ≤0.5 percent [20,31-33]. The pathogenesis may be related to the introduction of nonsterile contrast material into a poorly emptying gallbladder and/or obstruction of the cystic duct from malignancy, gallstone, or a biliary stent [33].
For patients with an intact gallbladder, cholecystitis may occur if a self-expandable metal stent (SEMS) is placed across the origin of the cystic duct, resulting in a functional gallbladder obstruction [34,35]. The risk of acute cholecystitis related to SEMS placement is discussed separately. (See "Endoscopic stenting for malignant biliary obstruction", section on 'Cholecystitis'.)
Clinical features and diagnosis — Acute cholecystitis following ERCP should be suspected in patients who present with fever, abdominal pain, abdominal tenderness localized in the right upper quadrant, and leukocytosis. The diagnosis is confirmed with imaging (typically, ultrasonography or computed tomography) that shows thickening of the gallbladder wall and pericholecystic fluid. (See "Acute calculous cholecystitis: Clinical features and diagnosis".)
Management — Management of acute cholecystitis following ERCP is the same as the management for acute cholecystitis from other causes and generally includes antibiotic therapy and cholecystectomy (or nonsurgical gallbladder drainage). The management of acute cholecystitis is discussed separately. (See "Treatment of acute calculous cholecystitis".)
Other infections — Other post-ERCP abdominal infections that have been reported include:
●Bacterial peritonitis – For patients with cirrhosis complicated by ascites, bacterial peritonitis has been associated with ERCP. In a cohort study including 1930 patients with cirrhosis who underwent ERCP and a control group of patients with cirrhosis who underwent non-pancreaticobiliary endoscopy, ERCP was associated with higher rates of postprocedure bacterial peritonitis compared with other endoscopic procedures (2.2 versus 1.1 percent) [36].
●Acute pancreatic ductitis – Acute pancreatic ductitis associated with pancreatic duct obstruction has been rarely reported following ERCP [37,38]. As an example, acute suppurative pancreatic ductitis occurred after ERCP in a patient with cancer of the pancreatic head, and successful pancreatic drainage was achieved with pancreatic stent placement [39].
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Endoscopic retrograde cholangiopancreatography (ERCP)" and "Society guideline links: Biliary infection and obstruction".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Beyond the Basics topics (see "Patient education: ERCP (endoscopic retrograde cholangiopancreatography) (Beyond the Basics)")
SUMMARY AND RECOMMENDATIONS
●General principles – Biliary drainage, usually by endoscopic retrograde cholangiopancreatography (ERCP), is essential for treating patients with acute obstructive cholangitis. However, cholangitis is the most common infectious adverse event associated with ERCP. (See 'Introduction' above.)
Patients with biliary obstruction and/or impaired host defenses are more susceptible to developing infection. Bacteremia may result from translocation of endogenous bacteria into the blood stream via mucosal trauma. In addition, injection of contrast material during ERCP may also result in bacteria being introduced into a previously sterile space. (See 'Pathogenesis' above.)
●Preventive strategies – Strategies to reduce the risk of post-ERCP infection include (see 'Preventive strategies' above):
•Antibiotic prophylaxis – Antibiotic prophylaxis is recommended in selected patients undergoing ERCP who are at higher risk for infection (table 1). Specific antibiotic regimens are discussed separately. (See "Antibiotic prophylaxis for gastrointestinal endoscopic procedures", section on 'Endoscopic retrograde cholangiopancreatography (ERCP)'.)
•General endoscopic techniques – ERCP-related techniques include aspirating bile before injecting contrast material and using the minimum volume of contrast that is needed to obtain diagnostic fluoroscopic images.
•Establishing biliary drainage – For patients with biliary obstruction, the goal of endoscopic intervention is to establish complete, long-term biliary drainage during the initial endoscopic session.
•Adhering to protocols for endoscope reprocessing – Protocols for endoscope disinfection and reprocessing are informed by regulatory agencies, manufacturers, and professional societies, and these issues are discussed separately. (See "Preventing infection transmitted by gastrointestinal endoscopy".).
●Approach to the patient with suspected infection – ERCP-related infection should be suspected in patients who develop fever (frequently with chills) and/or abdominal pain within 72 hours after ERCP. Initial evaluation and management includes laboratory testing, diagnostic imaging to exclude biliary obstruction and cholecystitis, and empiric antibiotic therapy (table 2). (See 'Approach to the patient with suspected infection' above and "Antimicrobial approach to intra-abdominal infections in adults".)
●Specific infectious adverse events
•Acute cholangitis – Signs and symptoms of cholangitis include fever, right upper quadrant pain, and jaundice. Mental status changes and hypotension can occur in patients with suppurative (severe) cholangitis, whereas hypotension may be the only presenting symptom in older patients. (See 'Acute cholangitis' above.)
The cornerstone of treatment for cholangitis is decompression of the obstructed biliary ducts and supportive care with antibiotic therapy. (See "Acute cholangitis: Clinical manifestations, diagnosis, and management", section on 'Management'.)
•Acute cholecystitis – The diagnosis of acute cholecystitis following ERCP should be suspected in patients who develop tenderness localized in the right upper quadrant and have thickening of the gallbladder wall and pericholecystic fluid seen on ultrasound or computed tomography. (See 'Acute cholecystitis' above.)
Management of acute cholecystitis following ERCP is the same as the management for acute cholecystitis from other causes and generally includes antibiotic therapy and cholecystectomy (or nonsurgical gallbladder drainage). (See "Treatment of acute calculous cholecystitis".)
ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges Francesco Ferrara, MD, who contributed to earlier versions of this topic review.
