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 Table of Contents  
ORIGINAL ARTICLE
Year : 2020  |  Volume : 4  |  Issue : 3  |  Page : 408-414

Role of intraductal antibiotic in preventing cholangitis in post-endoscopic retrograde cholangiopancreatography patients


1 Nephrology Unit, Dekernes General Hospital, Egyptian Ministry of Health, Egypt
2 Department of Internal Medicine, Faculty of Medicine for Girls, Al Azhar University, Egypt
3 Department of Internal Medicine, Military Medical Academy, Cairo, Egypt

Date of Submission07-Jun-2020
Date of Decision22-Jun-2020
Date of Acceptance23-Jun-2020
Date of Web Publication2-Oct-2020

Correspondence Address:
MD Sally S Abd Elhamed
Department of Internal Medicine, Lecturer of Internal Medicine Al-Azhar University, Faculty of Medicine for Girls, 1 Elshazly St. Faisal, Giza, 11222
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/sjamf.sjamf_61_20

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  Abstract 


Background Acute cholangitis is one of the most serious life-threatening post-endoscopic retrograde cholangiopancreatography (ERCP) complications.. Some have suggested that bacteria may play a role in the induction of post-ERCP cholangitis. Routine prophylactic systemic antibiotic use has an important role in reducing post-ERCP bacteremia. However, the beneficial effects of antibiotic use on preventing post-ERCP cholangitis are unclear.
Aim The aim of the study was to assess post-ERCP cholangitis after intraductal antibiotic therapy in patients with obstructive jaundice.
Patients and methods This cross-sectional prospective study was conducted on 60 Egyptian patients presented with obstructive jaundice who undergo elective ERCP procedure. In all, 20 patients received prophylactic intraductal 1 g ceftriaxone in contrast media; 20 patients received prophylactic intravenous ceftriaxone and 20 patients did not receive antibiotics. Pre-ERCP and post-ERCP laboratory tests and imaging were used to assess post-ERCP cholangitis. The study endpoint was developing cholangitis within 72 h after ERCP.
Results There was highly significant increase in post-ERCP cholangitis in patients who did not receive antibiotics in comparison to other groups.
Conclusion The use of prophylactic antibiotic prior to elective ERCP has a significant role in decreasing the frequency of post-ERCP cholangitis.

Keywords: acute cholangitis, endoscopic retrograde cholangiopancreatography, intraductal antibiotic


How to cite this article:
Ibrahim FM, Abd Elhamed SS, Mahmoud AA, Abdel Rahman EM. Role of intraductal antibiotic in preventing cholangitis in post-endoscopic retrograde cholangiopancreatography patients. Sci J Al-Azhar Med Fac Girls 2020;4:408-14

How to cite this URL:
Ibrahim FM, Abd Elhamed SS, Mahmoud AA, Abdel Rahman EM. Role of intraductal antibiotic in preventing cholangitis in post-endoscopic retrograde cholangiopancreatography patients. Sci J Al-Azhar Med Fac Girls [serial online] 2020 [cited 2020 Oct 26];4:408-14. Available from: http://www.sjamf.eg.net/text.asp?2020/4/3/408/296949




  Introduction Top


Endoscopic retrograde cholangiopancreatography (ERCP) is a safe and effective procedure and has an important role at many pancreaticobiliary disorders, but it may be followed by some complications which differ according to the complexity of intervention such as pancreatitis, bleeding, perforation, and sepsis [1].

One of the most common post-ERCP complications is cholangitis with an incidence rate of 1–5%. Charcot’s triad that has very high specificity strongly suggests the presence of acute cholangitis which relies on clinical signs [2].

The occurrence of cholangitis could be effectively prevented by sterile circumstances of defensive mechanisms of the normal biliary system. While invasive, growing bacteria and bleeding in the biliary system might be occurred due to prolonged ERCP operation resulting in the penetration of bacteria and endotoxins through the bile–blood barrier, which leads to cholangitis [3].

Antibiotics are important in preventing post-ERCP cholangitis [4].

Prophylactic antibiotic was recommended by recent guidelines prior to ERCP in patients with known or suspected biliary obstruction such as hailer stricture and primary sclerosing cholangitis because there is a possibility of incomplete drainage during ERCP procedure [5].

Theoretically, local application of intraductal antibiotics with contrast media will be more beneficial in preventing post-ERCP cholangitis because it will increase the antibacterial concentration within the bile [6].

The aim of this study: is assessment of post-ERCP cholangitis after intraductal antibiotic therapy in obstructive jaundice patients.


  Patients and methods Top


This cross-sectional study was conducted on 60 Egyptian patients. They were presented with obstructive jaundice and undergo elective ERCP procedure. They were divided into three groups. Group A patients who received prophylactic intraductal antibiotic with contrast media; group B patients who received prophylactic intravenous antibiotic; and group C patients who did not receive antibiotics They were selected in the duration from December 2016 to November 2017. This study was conducted at the Faculty of Medicine ‘Girls,’ Al Azhar University and Multidisciplinary Clinic, Gastroenterology Department, Military Medical Academy Hospital. Informed consent was obtained from all patients involved in the study. Also, approval of the ethics committee of Faculty of Medicine, Al Azhar University was obtained.

All patients above 18 years of age presented with obstructive jaundice and undergo elective ERCP procedure were included in this study.

Patients who fulfilled the following criteria were excluded: patients with antibiotic allergy, immunodeficiency patients, patients requiring mandatory antibiotic prophylaxis, pregnant patients, pancreatitis, and pre-ERCP cholangitis.

Cholangitis post-ERCP was diagnosed as the presence of increase in body temperature more than 38°C within 72 h after ERCP (in case of body temperature <38°C before ERCP) or increase in white blood cell (WBCs) count and/or C-reactive protein (CRP) over upper normal limits with elevations of alkaline phosphatase (ALP), aspartate aminotransferase (AST), and alanine aminotransferase (ALT) (IU) levels of more than one and half upper limit of normal level and bilirubin (>2 mg/dl) within 3 days after ERCP. Bile duct lesions from imaging findings showed biliary dilatation and evidence of the etiology on imaging (stricture, stone, stent, etc.) [7].

All patients were subjected to full medical history, complete clinical examination, laboratory investigations pre-ERCP and post-ERCP (72 h) include complete blood count, CRP, total and direct bilirubin, ALP, ALT, and AST. All laboratory tests were done by cobas 311 clinical chemistry autoanalyzer from Roche Diagnostic Company (Switzerland). Also, abdominal ultrasound and abdominal computed tomography were done.

Procedure

ERCP was performed in all patients by the same endoscope (Fujinon ED450XT and Fujinon ED400XL, Olympus Company, USA).

The patients were prepared by fasting overnight and continued fasting for 6 h after the end of the procedure. During the ERCP procedure, the related technique of ERCP included cholangiography, pancreatography, setting nasobiliary drainage, papillary muscle dilatation, sphincterotomy, extracting bile duct stone, bile duct dilatation, and biliary stent placement.

After the procedure, the endoscopist recorded the details of the procedure in the report including the procedure-related risk factors for post-ERCP cholangitis.

Follow up

The study endpoint was developing cholangitis within 72 h after the procedure.

Successful ERCP was categorized when: biliary drainage was restored and bilirubin, ALP, ALT, AST decreased, or remained at least stable after ERCP in stent removal or replacement.

Statistical analysis

The results were statistically analyzed by the Statistical Package for the Social Sciences (IBM), version 20 using χ2 test and/or Fisher’s exact test. The comparison between two groups was done using Independent t test and Mann–Whitney. The comparison between more than two groups was done by using one-way analysis of variance test and Kruskal–Wallis test.

Paired t test and Wilcoxon Rank test was used in the comparison between two groups before and after. The P value was considered significant as the following: P value more than 0.05, nonsignificant; P value less than 0.05: significant; P value less than 0.001: highly significant.


  Results Top


This study was conducted on 60 patients presented with obstructive jaundice undergoing elective ERCP. They were 27 (45%) men and 33 (55%) women; they were divided into three groups of patients: group A included 20 patients who received prophylactic ceftriaxone (1 g) intraductal antibiotic in the contrast media. Group B included 20 patients who received prophylactic ceftriaxone (2 g) intravenous antibiotic before the ERCP procedure. Group C included 20 patients who did not receive prophylactic antibiotic which is considered as the control group. In this study, there were no significant differences in demographic data, comorbidity as well as baseline laboratory investigation between the three groups ([Table 1]), while there were statistically significant differences in WBCs and CRP among group A versus group C and group B versus group C post-ERCP ([Table 2]).
Table 1 Comparison between the three studied groups as regards demographic data, clinical presentation, etiology of obstructive jaundice, comorbidities, and laboratory investigation

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Table 2 Comparison between three studied groups as regards laboratory investigation post-endoscopic retrograde cholangiopancreatography

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As regards the incidence of post-ERCP cholangitis, there was high significant increase of cholangitis in group C in comparison to group A and group B with P value less than 0.01 ([Table 3]).
Table 3 Comparison between studied groups as regards the incidence of cholangitis post-endoscopic retrograde cholangiopancreatography

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Among patients with post-ERCP cholangitis, our result suggested that malignant stricture and stent insertion were associated with increasing the risk of post-ERCP cholangitis. Also, there was statistically significant increase in loss of weight in post-ERCP cholangitis patients in comparison to noncholangitis patients with P value less than 0.01 ([Figure 1], [Table 4]).
Figure 1 Risk factors of cholangitis.

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Table 4 Comparison between patients with and without cholangitis as regards demographic data, clinical presentation, etiology, comorbidities, and procedure of endoscopic retrograde cholangiopancreatography

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Multivariate analysis of post-ERCP cholangitis showed that the level of bilirubin, malignant stricture, stent insertion, and route of antibiotic were independent risk factors for post-ERCP cholangitis (P<0.01), while extraction of bile stone was a protective factor (P<0.01) ([Table 5]).
Table 5 Multivariate regression analysis post-endoscopic retrograde cholangiopancreatography cholangitis

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  Discussion Top


The role of prophylactic antibiotic therapy preceding ERCP is unclear [6].

Theoretically, the benefit of direct antimicrobial injection into the bile tract is increased because in the case of biliary obstruction there was limitation in the penetration of antibiotics into the bile. The effect of intraductal antibiotic injection in contrast media has been investigated by several studies with conflicting results in the prevention of ERCP cholangitis [5].

In this study, there were no statistically significant difference between the studied groups as regards demographic data, clinical presentation, etiology of obstructive jaundice, comorbidities, and laboratory investigation pre-ERCP. Also, our study found that the stone in the common bile duct is the most common indication for ERCP in all groups of patients (60%), followed by malignant stricture with 26.7% and stent exchange with 13.3%.

In agreement with Voiosu et al. [8] it has been reported that the benign disease (53.5%) is the most common cause of biliary obstruction followed by a malignant obstruction (13%), while Wobser et al. [5] found that secondary sclerosing cholangitis is the most common cause of biliary obstruction in 44 cases, then primary sclerosing cholangitis in 20 patients, and then malignant stricture in eight patients (cholangiocarcinoma, pancreatic carcinoma, and metastasis); thus, most of the study population were high-risk group for post-ERCP infections.

Bacteremia might occur due to contamination of bile with bacteria or due to an increase in intraductal pressure during ERCP contrast medium injection, leading to bilovenous reflux, especially if adequate drainage and decompression are not associated [1].

Ceftriaxone was chosen in our study because of its efficacy against most Gram-negative  Escherichia More Details coli which is the pathogen most frequently found in biliary tract infection and its penetration into the biliary tree [9].

Wobser et al. [5] added gentamicin, vancomycin, and fluconazole to contrast media in 42 patients matched to 42 controls without antibiotic administration. In addition, 43/84 (51.3%) of patients received a systemic antibiotic. Acute cholangitis was the main indication for antibiotic use.

But Norouzi et al. [10] added gentamicin (10 mg) or distilled water to each 10 ml contrast medium during ERCP. Also, all patients received intravenous 2 g ceftriaxone 30 min before ERCP and daily for 3 days.

Voiosu et al. [8] used one of the five main antibiotics (ciprofloxacin, amoxicillin, ceftriaxone, gentamicin, and imipenem) in prophylaxis of cholangitis and another group did not receive any antibiotic before ERCP.

Cholangitis had occurred in our study in four (20%) patients in group C with statistically significant increase of WBC and CRP in comparison to patients in groups A and B. However, there was no statistically significant difference in both groups (A, B) as regards the incidence of post-ERCP infection. This supports that prophylactic ceftriaxone has an important role in reducing post-ERCP cholangitis.

In agreement with our result Wobser et al. [5] reported a significant decrease of post-ERCP cholangitis when adding antibiotics to contrast medium during ERCP in the studied group in comparison to the control group, P value of 0.045.

In contrast to Norouzi et al. [10], Voiosu et al. [8], and Ishigaki et al. [11] found no significant difference in the incidence of post-ERC cholangitis or pancreatitis in each group with and without antibiotic added to contrast media. So they did not recommend routine prophylactic antibiotics use pre-ERCP except for patients without adequate drainage [12].

As regards the risk factors of developing cholangitis post-ERCP, malignant stricture (cholangiocarcinoma and pancreatic carcinoma) and patients who underwent stent insertion had an increased risk for developing cholangitis more than those without stent insertion with P value less than 0.05. Also, our study suggested that increased bilirubin pre-ERCP and absence of prophylactic antibiotic were risk factors for post-ERCP infection but bile stone extraction decreases the frequency of infection.

This is because of repeated biliary infection that could be occurred by tumor obstructing the intrahepatic bile duct, as invasion of biliary duct with bacteria was easier. So, inserting a stent or endoscopic nasal biliary drainage provided adequate drainage and lower biliary infection [13].

In agreement with our result Chen et al. [3] confirmed the protective role of stone extraction as they found highly significant decrease of post-ERCP cholangitis (24/2101, 1.14%) in comparison to patients without stone extraction (78/2113, 3.66%). Also, hilar obstruction and history of previous ERCP were very important risk factors for cholangitis.

Also, in the study conducted by Erturul et al. [14] on 503 patients showed that large biliary stent insertion was a protective factor against post-ERCP cholangitis, while hilar cholangiocarcinoma and large common bile duct dilatation increased the incidence of cholangitis.

In contrast to Norouzi et al. [10] who reported that there was no relation between type, number, and location of stent insertion with increased risk of post-ERCP cholangitis, stent insertion increased the incidence for cholangitis with no explanation for this result.

As regards the stability of antibiotic with contrast media, some in vitro studies proved that aminoglycosides maintained its bactericidal properties when added to contrast media during ERCP procedures [5], while the stability and the effectiveness of adding ceftriaxone to contrast media had not been discussed before.

There were not enough studies that answered this question, and none have reported a significant clinical advantage. This is because, they were small and subjected to type II error [15].

Some centers to decrease post-ERCP complications recommended the addition of antibiotics to contrast media [16].

To decrease the incidence of post-ERCP septic complications, we need perfect operating techniques, effective drainage to all multiple biliary ducts, adequate decompression, reduce operating time, good choice of appropriate patients, improving the strength of the accessories and cleaning and disinfection of endoscopes. Meanwhile, we need to adopt some precautions or choose other safe and less invasive treatments. Our suggestion is that if a large sample size is used, this outcome may be strongly enforced.


  Conclusion Top


Intraductal antibiotic injection prior to elective ERCP has an effective role in the prevention of post-ERCP cholangitis.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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Szary NM, Al-Kawas FH. Complications of endoscopic retrograde cholangiopancreatography: how to avoid and manage them. Gastroenterol Hepatol 2013; 9:496–504.  Back to cited text no. 1
    
2.
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Chen M, Wang L, Wang Y, Wei W, Yao Y-L, Ling T-S et al. Risk factor analysis of post-ERCP cholangitis: a single-center experience. Hepatobiliary Pancreat Dis Int 2018; 00:1–5.  Back to cited text no. 3
    
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Wobser H, Gunesch A, Klebl F. Prophylaxis of post-ERC infectious complications in patients with biliary obstruction by adding antimicrobial agents into ERC contrast media- a single center retrospective study. BMC Gastroenterol 2017; 17:10.  Back to cited text no. 5
    
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Kim NH, Kim HJ, Bang KB. Prospective comparison of prophylactic antibiotic use between intravenous moxifloxacin and ceftriaxone for high-risk patients with post-ERCP cholangitis. Hepatobiliary Pancreat Dis Int 2017; 16:512–518.  Back to cited text no. 6
    
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Kiriyama S, Takada T, Strasberg SM, Solomkin JS, Mayumi T, Pitt HA et al. New diagnostic criteria and severity assessment of acute cholangitis in revised Tokyo Guidelines. J Hepatobiliary Pancreat Sci 2012; 19:548–556.  Back to cited text no. 7
    
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Voiosu TA, Bengus A, Haidar A, Rimbas M, Zlate A, Balanescu P et al. Antibiotic prophylaxis prior to elective ERCP does not alter cholangitis rates or shorten hospital stay: results of an observational prospective study of 138 consecutive ERCP. Maedica (Buchar) 2014; 9:328–332.  Back to cited text no. 8
    
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Kaya M, Beştaş R, Bacalan F, Bacaksız F, Arslan EG, Kaplan MA. Microbial profile and antibiotic sensitivity pattern in bile cultures from endoscopic retrograde cholangiography patients. World J Gastroenterol 2012; 27:3585–3589.  Back to cited text no. 9
    
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Norouzi A, Khatibian M, Afroogh R, Chaharmahali M, Sotoudehmanesh R. The effect of adding gentamicin to contrast media for prevention of cholangitis after biliary stenting for non-calculous biliary obstruction, a randomized controlled trial. Indian J Gastroenterol 2013; 32:18–21.  Back to cited text no. 10
    
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Ishigaki T, Sasaki T, Serikawa M, Kobayashi K, Kamigaki M, Minami T et al. Evaluation of antibiotic use to prevent post-endoscopic retrograde cholangiopancreatography pancreatitis and cholangitis. Hepatogastroenterology 2015; 62:417–424.  Back to cited text no. 11
    
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Bai Y, Gao F, Gao J, Zou D-W, Li Z-S. Prophylactic antibiotics cannot prevent endoscopic retrograde cholangiopancreatography-induced cholangitis: a meta-analysis. Pancreas 2009; 38:126–130.  Back to cited text no. 12
    
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Ertuğrul I, Yüksel I, Parlak E, Ciçek B, Ataseven H, Başar O et al. Risk factors for endoscopic retrograde cholangiopancreatography-related cholangitis: a prospective study. Turk J Gastroenterol 2009; 20:116–121.  Back to cited text no. 14
    
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Usmani A, van Gorkom KN, Lorke DE, Petroianu G, Azimullah S, Nurulain SM. In vitro assessment of the antibiotic efficacy of contrast media and antibiotics and their combinations at various dilutions. Br J Radiol 2010; 83:394–400.  Back to cited text no. 15
    
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Mishkin D, Carpenter S, Croffie J, Chuttani R, DiSario J, Hussain N. ASGE technology status evaluation report: radiographic contrast media used in ERCP. Gastrointest Endosc 2005; 62:483.  Back to cited text no. 16
    


    Figures

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    Tables

  [Table 1], [Table 2], [Table 3], [Table 4], [Table 5]



 

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