INTRODUCTION — Biliary drainage, usually by urgent endoscopic retrograde cholangiopancreatography (ERCP), is essential in the management of patients with acute obstructive cholangitis, and delayed or failed ERCP is associated with worse outcomes [1]. On the other hand, infection is one of the most morbid complications of ERCP and among the most common causes of ERCP-related death. Septic complications of ERCP include ascending cholangitis, liver abscess, acute cholecystitis, infected pancreatic pseudocyst, infection following perforation of a viscus, and less commonly, endocarditis/endovasculitis [2].

The post-ERCP septic complications of acute cholangitis, acute cholecystitis, and pancreatic sepsis will be reviewed here. Post-ERCP perforation and general overviews of acute cholangitis and acute cholecystitis are discussed separately. (See "Post-ERCP perforation" and "Acute cholangitis: Clinical manifestations, diagnosis, and management" and "Acute calculous cholecystitis: Clinical features and diagnosis" and "Treatment of acute calculous cholecystitis".)

PATHOGENESIS — Bacteria can enter the biliary tract by either a hematogenous or, more frequently, a retrograde route. In patients with a normal biliary tract, anatomical barriers impede both these routes. In contrast, patients who are immunocompromised or who have obstruction of the biliary system have impaired bacterial defenses, making them more susceptible to these complications [3,4].

The most frequent organisms responsible for post-ERCP infections are enteric bacteria [5,6]. Although polymicrobial enteric flora are often found in infected bile, single organisms are isolated from blood cultures in the majority of patients [3]. In the 1980s, cross infection via contaminated endoscopes and ancillary ERCP equipment, such as cannulation catheters, was implicated in severe cases or outbreaks of septicemia from pseudomonas [7-9]. Improvements in the methods of disinfection have now made such nosocomial infections rare [10].

However, in recent years, outbreaks of multidrug-resistant pathogens (Klebsiella, Escherichia coli, Pseudomonas aeruginosa) associated with ERCP procedures have been reported [11-18]. The source of infection may be related to difficulty cleaning the elevator mechanism of duodenoscopes [11,19]. Therefore, when reprocessing duodenoscopes, the scientific societies and manufacturers recommend strict adherence to guidelines and reprocessing protocols. The risk of transmitting infection and protocols for disinfecting duodenoscopes are discussed in detail separately. (See "Preventing infection transmitted by gastrointestinal endoscopy", section on 'Overview of endoscope reprocessing'.)

PERIPROCEDURAL BACTEREMIA — Both diagnostic and therapeutic ERCP can lead to transient bacteremia that, in most cases, is not clinically significant. Variable rates of up to 15 percent have been reported for diagnostic procedures [20,21] and of up to 27 percent for therapeutic procedures [20,22-24]. Differences in specimen collection, timing of blood cultures, and culture techniques may explain the variable estimates [22].

Bacteria isolated from the blood following ERCP are commonly oropharyngeal flora, particularly alpha-hemolytic streptococci [20,22]. Entrance into the blood stream is presumably through minor trauma by the endoscope, similar to bacteremia that has been observed with tooth brushing or after diagnostic upper gastrointestinal endoscopy [25,26].

Asymptomatic periprocedural bacteremia rarely leads to clinical sepsis in immunocompetent patients [22]. As a result, bacteremic episodes occurring during ERCP do not appear to have clinically significant consequences. Antibiotic prophylaxis is not warranted in most patients. (See 'Antibiotic prophylaxis' below.)

ASCENDING CHOLANGITIS — Ascending cholangitis, while uncommon, is the most frequent infectious complication of ERCP. Clinical manifestations include fever, jaundice, and abdominal pain that result from stasis and infection in the biliary tract. In the setting of ERCP, it is most often due to incomplete drainage of an infected and obstructed biliary system.

Incidence — Estimates of the incidence of clinically significant cholangitis have ranged from 0.4 to more than 10 percent in various reports [3,5,27-30]. In a summary of 21 prospective studies involving 16,855 patients between 1987 and 2003, infection occurred in 1.4 percent (0.2 percent were severe), with a periprocedural mortality rate of 0.1 percent [27]. Similar rates of infection (1.0 to 2.2 percent) were reported in other large studies [5,28,29].

Risk factors for cholangitis — Failure to achieve drainage of an obstructed biliary system is the most important predictor of post-ERCP biliary sepsis. The mechanism by which obstruction leads to sepsis is presumed to be elevated biliary pressure causing biliary-venous reflux [3].

The risk of cholangitis varies depending upon the nature and site of the obstruction. Patients with malignant hilar obstructions and those with sclerosing cholangitis are at particularly increased risk of cholangitis due to difficulty in achieving complete drainage [8,31-37]. Cholangitis is also a frequent complication of occluded biliary stents [38].

The importance of incomplete drainage as a risk factor for cholangitis was illustrated in two retrospective series in which incomplete biliary drainage was present in 87 and 90 percent of patients who developed sepsis [7,8]. High rates of cholangitis in patients with incomplete biliary drainage were also found in a prospective study of 242 patients undergoing sphincterotomy for bile duct stones [39]. Cholangitis developed in 75 percent of patients with retained stones and failed biliary drainage and in 40 percent of those with a precut papillotomy and unsuccessful drainage. By comparison, cholangitis developed in only 3 percent of patients with successful drainage.

The risk of cholangitis in patients with bile duct stones treated with mechanical lithotripsy (which may result in retained stone fragments and/or require multiple sessions for duct clearance) is discussed elsewhere. (See "Endoscopic management of bile duct stones: Standard techniques and mechanical lithotripsy", section on 'Mechanical lithotripsy'.)

In addition to incomplete biliary drainage, other risk factors for cholangitis have been identified in prospective studies. These include jaundice, a small endoscopy center, combined percutaneous-endoscopic procedures, stenting of malignant strictures, and a delay in performing ERCP [40-42]. A retrospective analysis of 168 consecutive patients admitted for acute cholangitis found that a delay in performing ERCP, development of post-ERCP adverse events, and etiology of cholangitis not related to stones increased the risk of 30-day readmissions. The overall readmission rate was 22 percent and recurrence of cholangitis was the most common etiology for readmissions (37.8 percent) [42].

In two studies of patients who underwent ERCP with cholangioscopy, rates of post-procedure bacteremia ranged between 9 and 19 percent, and the rate of cholangitis was 7 percent [43,44]. In one study, 72 patients who underwent single-operator choledochoscopy were examined [43]. Of 14 patients (19 percent) with sustained bacteremia following ERCP or choledochoscopy, 10 patients (14 percent) had sustained bacteremia related to choledochoscopy. Despite the use of post-procedure intravenous antibiotic administration, seven patients (9.7 percent) required further antibiotic treatment for infectious complications, three of whom (4 percent) were hospitalized in order to receive intravenous antibiotic therapy.

Clinical presentation and diagnosis — Cholangitis typically develops within 24 to 72 hours after ERCP in patients with failed biliary drainage [7,39]. The classic triad of Charcot (fever, right upper quadrant pain, and jaundice) occurs in only 50 to 75 percent of patients with acute cholangitis. Confusion and hypotension can occur in patients with suppurative cholangitis, producing Reynolds pentad, which is associated with significant morbidity and mortality, including multiorgan failure due to septic shock. Hypotension may be the only presenting symptom in elderly patients. (See "Acute cholangitis: Clinical manifestations, diagnosis, and management".)

Severe cases may also be associated with the development of a hepatic abscess [7,9,40,45,46]. (See "Pyogenic liver abscess".)

Patients with suspected post-ERCP ascending cholangitis are diagnosed in the same manner as patients with ascending cholangitis due to other causes. (See "Acute cholangitis: Clinical manifestations, diagnosis, and management", section on 'Diagnostic approach'.)

Grading — Post-ERCP cholangitis can be graded as mild, moderate, or severe based upon a consensus definition [47]:

●Mild – Temperature >38ºC 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 surgery

Treatment of post-ERCP cholangitis — The mainstay of treatment is decompression of the obstructed duct while providing supportive care including antibiotics and exchanging biliary stents if they are obstructed (picture 1 and picture 2) (see "Acute cholangitis: Clinical manifestations, diagnosis, and management", section on 'Management').

ACUTE CHOLECYSTITIS — Acute cholecystitis following ERCP or percutaneous transhepatic biliary drainage may be more common than once appreciated, and must be distinguished from cholangitis [39-41,48-54].

Incidence and pathogenesis — The incidence of acute cholecystitis ranged from 0.1 to 8.6 percent in various reports [48], with most large series having an incidence ≤0.5 percent [40,41,55,56]. The pathogenesis may be related to the introduction of nonsterile contrast media into a poorly emptying gallbladder and/or mechanical or inflammatory obstruction of the cystic duct by an endoprosthesis, malignancy, or gallstone [49-53,56]. Two meta-analyses showed no difference in rates of cholecystitis between covered and uncovered metal stents for the treatment of distal malignant biliary disease [57,58]. Additionally, in a small case series including four patients with malignant biliary obstruction, acute cholecystitis following covered stent placement was successfully managed with stent removal and placement of an uncovered or plastic stent [59].  

Diagnosis — 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 on ultrasonography or computed tomography. The risk may be increased in patients with diabetes mellitus and in those with obstruction in whom stenting was unsuccessful [53]. (See "Acute calculous cholecystitis: Clinical features and diagnosis".)

Prevention — Most centers perform early cholecystectomy after ERCP and biliary sphincterotomy for common bile duct stones, a practice that would eliminate the most likely cause of cholecystitis in patients with gallstones; however, a selective wait-and-see has been advocated for high-risk patients [60]. (See "Endoscopic management of bile duct stones: Standard techniques and mechanical lithotripsy".)

Treatment of cholecystitis — The treatment of acute cholecystitis following ERCP is the same as the treatment for acute cholecystitis from other causes. (See "Treatment of acute calculous cholecystitis".)

PANCREATIC INFECTION — Infection of the pancreas following ERCP is uncommon and can have a variety of manifestations. These include:

●An infected pseudocyst due to contamination following pancreatic duct injection or stone removal [23,55,61].

●Post-ERCP pancreatitis may be due to iatrogenic bacterial seeding of the pancreas from contaminated equipment. However, microorganisms do not appear to have a significant role in the majority of such patients [62]. (See "Post-endoscopic retrograde cholangiopancreatography (ERCP) pancreatitis".)

Effective endoscopic drainage has been reported in rare cases of acute suppurative pancreatic ductitis associated with pancreatic duct obstruction [63,64]. Acute obstructive suppurative pancreatic ductitis occurred after ERCP in a patient with carcinoma of the pancreatic head and successful pancreatic drainage was achieved by pancreatic stent placement [65].

BACTERIAL PERITONITIS IN PATIENTS WITH CIRRHOSIS — A retrospective study of the National Inpatient Sample (United States) looked at adverse events in 1930 patients with cirrhosis who underwent endoscopic retrograde cholangiopancreatography (ERCP) with a matched control group of patients with cirrhosis who underwent other endoscopic procedures [66]. Patients who underwent ERCP were more likely to develop bacterial peritonitis than patients who underwent non-pancreaticobiliary endoscopy (2.2 versus 1.1 percent; p<0.005).

PREVENTION OF POST-ERCP SEPTIC COMPLICATIONS

Endoscopic technique — Proper ERCP technique and skill in drainage procedures are of paramount importance for minimizing the risk of infection. Guidelines to avoid septic complications following ERCP can be suggested based upon the available data and consensus opinion. The following recommendations are consistent with basic principles of endoscopy and with a statement from the American Society for Gastrointestinal Endoscopy [2,67]:

●Endoscopes must be properly cleaned and disinfected before each procedure (see "Preventing infection transmitted by gastrointestinal endoscopy").

●Radiographic contrast solutions must be sterile. The addition of antibiotics to contrast solutions appears to be unnecessary, but remains controversial [68-72].

●The volume of contrast injected should be the minimum necessary to obtain adequate radiographs in patients with known obstruction or cholangitis. Bile should be aspirated before injection to avoid injecting with excessive hydrostatic pressure.

●Every effort should be made to achieve prompt endoscopic decompression when biliary and/or pancreatic duct obstruction has been demonstrated. Thus, diagnostic ERCP should never be attempted in obstructed patients if drainage cannot be provided during the same procedure.

●When definitive endoscopic drainage cannot be achieved, temporary drainage with a nasobiliary tube or a stent is mandatory until a definitive procedure can be performed.

●If bile flow cannot be restored endoscopically, a percutaneous or surgical procedure should be undertaken without excessive delay.

●In patients with malignant hilar strictures, drainage should be selective, preferably based upon the results of magnetic resonance cholangiopancreatography (MRCP) [73-76], thereby avoiding unnecessary invasive imaging. In patients with unresectable complex hilar cholangiocarcinoma and predicted survival of longer than three months, drainage with a metallic stent is preferable to drainage with a plastic stent [77]. The use of air cholangiography or CO₂ cholangiography might reduce the rate of cholangitis in patients with Klatskin tumors compared with cholangiography using iodinated contrast, but the safety and efficacy of these techniques deserve confirmation [78-81].

●Patients with biliary stents need surveillance for early detection of stent occlusion and prevention of related infectious complications; however, a consensus has not been reached on optimal surveillance strategies. In a prospective controlled trial, elective replacement of plastic stents in patients with malignant biliary strictures did not significantly improve survival compared with stent exchange only when symptoms developed [82]. It is reasonable to monitor liver biochemical tests on a monthly basis following drainage, since plastic and metal stents generally remain patent for no more than three and six months, respectively.

Antibiotic prophylaxis — Antibiotic prophylaxis is recommended in selected patients undergoing ERCP (table 1). The general approach to antibiotic prophylaxis in patients undergoing ERCP is discussed separately. (See "Antibiotic prophylaxis for gastrointestinal endoscopic procedures", section on 'Endoscopic retrograde cholangiopancreatography (ERCP)'.)

We also suggest antibiotic prophylaxis for patients undergoing ERCP in high-risk settings, including hilar obstruction, sclerosing cholangitis, pancreatic pseudocysts, cholangioscopy (especially if tissue acquisition with biopsy sampling is planned), intraductal stone lithotripsy, and for patients who are immunocompromised [43,44,83,84].

Prophylactic antibiotics were once widely used [20,31], but the benefit of using them has been difficult to establish in controlled clinical trials. Two meta-analyses published in 1999 [85] and in 2009 [86] failed to show the effectiveness of antibiotics routinely administered before ERCP. A meta-analysis that included nine randomized clinical trials and 1573 patients concluded that prophylactic antibiotics reduced bacteriemia and seemed to prevent cholangitis and septicemia in patients undergoing elective ERCP; however, in the subgroup of patients with uncomplicated ERCP, the effect of antibiotics was less evident [87]. In a retrospective analysis of 11,484 ERCPs over 11 years from 1994 through 2006, the infection rate after ERCP decreased with time from 0.48 to 0.25 percent, despite a marked reduction in the proportion of patients given antibiotics, from 95 to 25 percent [88]. In a single center, between 2009 and 2011, infection rates were compared between a group of 301 antibiotic-treated patients and a subsequent group of 304 patients who did not receive antibiotic prophylaxis [89]. The rates of both post-ERCP pancreatitis (4.3 versus 4.9 percent) and cholangitis (1.7 versus 2.0 percent) were similar [89].

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 5^th to 6^th 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 10^th to 12^th 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

●Septic complications of endoscopic retrograde cholangiopancreatography (ERCP) include cholangitis, cholecystitis, and pancreatic sepsis. (See 'Introduction' above.)

●Signs and symptoms of cholangitis include fever with chills, right upper quadrant pain, and jaundice. Some patients will also develop confusion, which is associated with significant morbidity and mortality. (See 'Ascending cholangitis' above.)

●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.)

●Antibiotic prophylaxis is not generally recommended for ERCPs in the absence of cholangitis in patients with biliary obstruction (Grade 1C). However, we suggest antibiotic prophylaxis in some high-risk settings, including hilar obstruction, sclerosing cholangitis, pancreatic pseudocysts, and for procedures in immunocompromised patients (Grade 2C). (See 'Antibiotic prophylaxis' above and "Antibiotic prophylaxis for gastrointestinal endoscopic procedures".)

●Failed endoscopic drainage is the most important risk factor for post-ERCP cholangitis. (See 'Risk factors for cholangitis' above.)

●We suggest that postprocedure antibiotics be given to patients with incomplete biliary drainage following ERCP (Grade 2C). (See 'Risk factors for cholangitis' above and 'Antibiotic prophylaxis' above.)

●Percutaneous or surgical decompressive procedures should be promptly performed when adequate drainage cannot be achieved endoscopically (Grade 1C). (See 'Risk factors for cholangitis' above.)

●In patients with biliary or pancreatic stents, surveillance for early detection of stent occlusion is suggested (Grade 2C). (See 'Endoscopic technique' above.)

ACKNOWLEDGMENT — The UpToDate editorial staff thank Dr. Francesco Ferrara, MD for his contributions as author to prior versions of this topic review.