Post-ERCP infection and its epidemiological and clinical characteristics in a large Chinese tertiary hospital: a 4-year surveillance study

China has a large number of patients with biliary or pancreatic diseases, especially bile duct stones. Currently, endoscopic retrograde cholangiopancreatography (ERCP) plays a major role in the treatment of biliary and pancreatic diseases. The use of ERCP has increased considerably in China in recent years. From 2006 to 2012, the total of ERCP surgeries performed increased from 63,787 to 195,643 in China, of which more than 95% were therapeutic [1]. Post-ERCP infections have been studied extensively in the USA and European countries, for example, surveillance of post-ERCP bacteremia showed infection rates of 5% in England [2] and 27.8% in the USA [3]. However, another retrospective observational study carried out in the USA over an 11-year period indicated that the post-ERCP infection rate was as low as 0.28% [4].

The variations in surveillance results for post-ERCP infections mainly result from different case definitions, varied surveillance durations and the different data collection methods used in previous studies [5]. To date, few studies have been conducted in China. One multicenter cross-sectional questionnaire study that aimed to determine the status of ERCP services in China, reported a cholangitis prevalence of 0.66% post-ERCP [1]. More research on understanding the incidence of adverse events following ERCP services is required in China.

This study aimed to describe the overall incidence of post-ERCP infection and characterize the infected patients after different ERCP operations. In addition, to improve our knowledge regarding the risk factors for post-ERCP infections and the effectiveness of prevention and treatment methods, our work determined the type of ERCP surgery associated with the highest incidence of healthcare-associated infections (HAI), and investigated the pathogenic spectrum and antibiotic resistance of the infecting bacteria. Our study involved surveillance in one of the largest tertiary hospitals in China from 2012 to 2015.

To our knowledge, this is the first report on post-ERCP infections in Chinese tertiary hospitals. Previous studies have indicated that therapeutic ERCP endoscopic procedures are associated with the highest rates of bacteremia and other infectious complications [3, 12]. Our study had a clear definition for HAIs post-ERCP operations, which excluded all infections that occurred before the ERCP. Using this definition, the overall prevalence of post-ERCP was 7.57%. However, it must be considered that, for example, if cholangitis occurred post-ERCP whether it was a complication of ERCP or just a natural history of gallbladder stones. The prevalence of bacteremia post-ERCP was 3.56% (62/1743) in our study, which was far lower than in other studies from other countries. Both Thosani et al. [3] in the USA and Kullman et al. [11] in Sweden reported the incidence of bacteremia associated with ERCP to be as high as 27%. The major reason for the high incidence might be that in these studies, two or three blood samples were obtained from each patient immediately before and after ERCP, to test the pathogenic spectrum. This active surveillance might increase the positive detection rate of bacteremia. In addition, these studies did not distinguish between primary and secondary bacteremia. Our study was based on daily medical work and only 17.73% (309/1743) of inpatients with suspected bacteremia provided samples for blood cultures.

In our study, the most prevalent infection post-ERCP was cholangitis (4.02%; 70/1743). Ertugrul et al. [13] reported a similar result, that 3.3% (17/503) of patients developed cholangitis after ERCP. In addition, the risk of cholangitis was significantly higher in patients with biliary dilatation and biliary stent insertion. Our study indicated that surgery for biliary tract disease was associated with the highest risk of infection. Surgery on the biliary tract frequently uses a basket or balloon lithotomy and biliary stent implantation is difficult and exposes patients to a high risk of bile duct injury. Bacterial colonization in the gallbladder or bile duct increases the risk of biliary tract infection post-surgery.

Our analysis showed the predominance of gram-negative organisms (60.34%) in the blood cultures, compared with gram-positive organisms (37.93%). The most prevalent isolates were E. faecium and E. coli. Rerknimitr et al. [14] reported similar findings in patients undergoing ERCP, which indicated that Enterococcus spp. and E. coli were the most prevalent organisms isolated from bile cultures. In addition, Thosani et al. [3] reported that E. coli and Enterococcus spp. were the most prevalent causes of bacteremia post-ERCP.

Park et al. [15] confirmed that E. coli and Enterococcus spp. were the most prevalent organisms isolated from the blood cultures of biliary tract-infected patients. According to patient outcomes, prophylactic antibiotics are thought to be the most effective prevention against infections from gram-negative bacteria and Enterococcus spp. Several guidelines [16‐19] have been published about antibiotic prophylaxis prior to ERCP. Most guidelines [17, 18], such as the American Society for Gastrointestinal Endoscopy and the British Society of Gastroenterology Endoscopy, advocate prophylaxis for patients with biliary obstruction, whereas the European Society of Gastrointestinal Endoscopy [19] recommends prophylaxis for every type of therapeutic ERCP. Antibiotic prophylaxis involves administering an antibiotic to combat biliary microorganisms, such as E. coli, Klebsiella pneumoniae and Enterococcus spp. Oral ciprofloxacin, intravenous piperacillin-tazobactam or gentamicin is recommended in the USA [20].

In China, the excessive long-term use of antibiotics by hospitals and the widespread addition of quinolones to animal feed has led to the emergence of significant levels of bacterial resistance to many antimicrobials [21, 22]. For example, bacteria of the Enterobacteriaceae (especially E. coli) are resistant to fluoroquinolones and Xiao et al. reported that about 65% of E. coli strains were resistant to fluoroquinolones between 2004 and 2005 [21]. In our study, only 27% of E. coli isolates were found to be susceptible to ciprofloxacin. This limits the use of fluoroquinolones as prophylactic drugs in China. The 2015 Chinese Clinical Application of Antibacterial Drugs guidelines [23] recommended second generation cephalosporin or ceftriaxone as the antibiotics of choice for prophylaxis for the pathogenic bacteria that can cause skin incision infections after ERCP. However, all gram-negative organisms in our study were resistant to cefazolin. Nearly 90% of inpatients were treated with metronidazole and ceftriaxone prophylactic antibiotics in the study hospital; however, the drug susceptibility results revealed that only 38% of E. coli isolates were susceptible to ceftriaxone. The high infection rate after ERCP and the prevalence of drug-resistant pathogens indicate that further studies are important. A cost benefit analysis is also necessary to determine whether the recommended guidelines should be modified.

This study has several limitations. The rate of bacteremia may have been underestimated, because Chinese doctors in general less frequently submit blood specimens for bacterial culture [24]. Some cases of bacteremia would have therefore gone undetected because of a lack of blood culture results. Another issue is that our study monitored all ERCP cases during hospitalization but post-discharge surveillance was not carried out at 30 days post-ERCP procedure. Post-discharge surveillance could be performed to identify HAIs that were not been reported and documented in our research.

Compared with HAIs in the whole hospital [24], post-ERCP infections generally exhibited a higher incidence (7.6% vs. 4.1%) and different types of infections (cholangitis vs. respiratory tract infections). The detailed epidemiological data for HAIs after ERCP in China may improve our understanding of the severity of post-ERCP infections and potential prevention and treatment measures. Our study indicates that the incidence of post-ERCP infection is high and that drug resistance among the causative bacteria is common; thus, we suggest that the use of second generation cephalosporin or ceftriaxone as the antibiotic of choice for prophylaxis before ERCP may not be effective. Therefore, we recommend administering a high-grade antibiotic (i.e. piperacillin-tazobactam), which would target most biliary organisms, before ERCP.