|Year : 2014 | Volume
| Issue : 2 | Page : 157-160
Clinicomicrobiological analysis of patients with cholangitis
SM Shenoy1, S Shenoy1, S Gopal2, BV Tantry2, S Baliga2, A Jain3
1 Department of Microbiology, Kasturba Medical College, Manipal University, Mangalore, Karnataka, India
2 Department of Gastroenterology, Kasturba Medical College, Manipal University, Mangalore, Karnataka, India
3 Department of Community Medicine, Kasturba Medical College, Manipal University, Mangalore, Karnataka, India
|Date of Submission||26-Mar-2013|
|Date of Acceptance||11-Oct-2013|
|Date of Web Publication||2-Apr-2014|
S M Shenoy
Department of Microbiology, Kasturba Medical College, Manipal University, Mangalore, Karnataka
Source of Support: None, Conflict of Interest: None
Acute cholangitis is inflammation of biliary ductal system from infection with an associated biliary obstruction. This retrospective study was done to determine the factors responsible for cholangitis and the microbiological profile of the bile in patients with cholangitis. In the study involving 348 patients, 36.4% had associated malignancy. A total of 54% of the bile samples were positive for aerobic culture. Nearly 66-73% of the Escherichia coli and Klebsiella isolates were Extended spectrum beta lactamases (ESBL) producers. Two isolates of Candida spps were also obtained. Polymicrobial infection was seen in 31.5% of the culture positive cases. Ideal antibiotics in case of cholangitis would be those which are excreted in the bile such as third-generation cephalosporins, ureidopenicillins, carbapenems and fluoroquinolones to combat resistance and polymicrobial aetiology. Anti-fungal drugs may also be necessary if the patient is not responding to biliary decompression and antibacterial agents to prevent fungaemia.
Keywords: Bile culture, cholangitis, endoscopic biliary drainage, ERCP, ESBL
|How to cite this article:|
Shenoy S M, Shenoy S, Gopal S, Tantry B V, Baliga S, Jain A. Clinicomicrobiological analysis of patients with cholangitis. Indian J Med Microbiol 2014;32:157-60
|How to cite this URL:|
Shenoy S M, Shenoy S, Gopal S, Tantry B V, Baliga S, Jain A. Clinicomicrobiological analysis of patients with cholangitis. Indian J Med Microbiol [serial online] 2014 [cited 2020 Jan 19];32:157-60. Available from: http://www.ijmm.org/text.asp?2014/32/2/157/129802
| ~ Introduction|| |
Acute cholangitis refers to inflammation of the biliary ductal system from bacterial or non-bacterial infection, usually in the setting of biliary obstruction.  The main factors in the pathogenesis of the acute cholangitis are biliary tract obstruction, elevated intra-luminal pressure and infection of bile.  The bile is normally sterile but in the presence of obstruction, the chances of cholangitis increases. , The bacteria may gain entry into the biliary tract by retrograde ascent from the duodenum or from portal venous blood or during some instrumentation for removal of stones or stent placement for stricture. The most common organisms isolated in bile are Escherichia coli, Klebsiella spp., Enterococcus spp., Streptococcus spp., Enterobacter spp., Pseudomonas spp. and Candida spp. ,, Microbiology of cholangitis has not changed significantly but the emergence of drug resistance among these organisms has been a matter of concern. The present study was conducted to determine the factors responsible for cholangitis and the microbiological profile of the bile obtained in these cases in our geographic area.
| ~ Materials and Methods|| |
It is a retrospective record-based study of 24 months involving the Departments of Gastroenterology and Microbiology of Kasturba Medical College Hospitals, Mangalore, India. All cases of cholangitis due to diverse aetiology diagnosed in the Department of Gastroenterology during the study period were included. The clinical presentations including fever, jaundice, abdominal pain, pruritus, history of previous gall stones, medical treatments and endoscopic or surgical interventions were recorded. The laboratory investigations like complete blood count (CBC), electrolyte panel, LFT, CRP, ESR, pancreatic enzymes, bile cultures and blood cultures if any were compiled.
The findings of imaging studies like ultrasonography, computed tomography (CT) scanning, endoscopic biliary drainage (ERCP) or Magnetic resonance cholangiopancreatography (MRCP) if present were reviewed. During ERCP or laparotomy, bile for culture was taken either from common bile duct or from the gall bladder. Cultures were performed within an hour of collection. The bile sample was inoculated onto the Sheep blood agar, MacConkey's agar and Thioglycollate broth incubated at 37°C for 24 hours. Bacteria isolated aerobically were identified and the antibiogram pattern of the isolates carried out using standard Kirby Bauer technique and interpreted according to CLSI criteria. ESBL production was tested by disk diffusion method using ceftazidime (30 μg) vs ceftazidime/clavulunic acid (30/10 μg) and cefotaxime (30 μg) vs cefotaxime/clavulunic acid (30/10 μg). Regardless of zone diameters, a ≥5 mm increase in a zone diameter of an anti-microbial agent tested with clavulunic acid vs its zone size when tested alone, indicated ESBL production as in CLSI phenotypic method. Klebsiella pneumoniae ATCC 700603 strain was used as positive control for ESBL production and Escherichia coli ATCC 25922 as negative control for ESBL production.[TAG:2][/TAG:2]
The study was conducted after taking the approval of the institutional ethics committee. Statistical analysis was done by using proportion of sensitive, resistant and intermediate antibiotic sensitivity of bacteria. Statistical package SPSS Version 11.5 was used to do the analysis.
| ~ Results|| |
During the study period, 348 patients presented with features of cholangitis. The highest distribution of cholangitis was seen in the fifth decade of life with the median age being 47.6 years. The most common clinical presentations were abdominal pain, weight loss, fever and jaundice (63%). Leucocyte count was raised in 89.6% of the cases. Most of the patients had cholestatic jaundice and Alkaline Phosphatase ( ALP) was significantly high in patients with malignant biliary obstruction [Table 1]. Eighteen patients out of 348 presented with features of sepsis, and, in all these cases blood cultures were positive. Patients underwent ERCP and three cases had surgical drainage. 36.4% of patients with cholangitis had associated malignancy of the hepatobiliary system, pancreas or the duodenum, 34.0% had choledocholithiasis and 15.7% had normal cholangiogram. In 13.9% of the cases, cholangitis was due to the block of the stent, which was placed earlier for associated stricture. Renal function was compromised in 37% of elderly patients who had malignancy or any other illness like cardiovascular disorders.
A total of 177 (54%) bile samples were positive for aerobic culture. Pseudomonas aeruginosa (35.7%) and E. coli (29.4%) were predominant among the isolated aerobes. A total of 66% of the E. coli and 73% of the Klebsiella spp were ESBL producing isolates. Enterococcus spp. (23) was the only Gram positive organism isolated in the culture positive cases. Polymicrobial infection was seen in 31.5% of the culture positive cases. A total of 45.1% of the polymicrobial infection was seen during the primary drainage of the biliary tract. Two Candida isolates (Candida albicans and Candida glabrata) were obtained from the bile of patients with malignancy of head of pancreas and Klatskin tumour who had undergone repeat procedures.
| ~ Discussion|| |
Infected bile in cholangitis is a pivotal risk factor in increasing rate of complications such as bacteraemia, wound infection and intra-abdominal sepsis. In this study the median age of the patients was 47.6 years and the male: female ratio was 0.92. This could be due to the large number of cases of malignancy in our study as malignancy is seen mostly in males. We have seen a positive culture rate of 54% in symptomatic disease. Our results are comparable with results of study by Fan et al., who showed 23-46% culture positive rates in symptomatic gallbladder stones. The Gram negative enteric organisms formed 84.3% of the isolates in which Pseudomonas aeruginosa (35.7%), E. coli (29.4%), Klebsiella spp (21.5%) and Citrobacter spp (5%) were the most common organisms. In previous studies, Gram negative enteric aerobes accounted for 70-78% of positive bile cultures, in which E. coli and Klebsiella spp were the most common.  This study was conducted in a tertiary care setup with an in house microbiology laboratory, which may have led to better isolation of the pathogens without any delay in transport. We also recovered two isolates of Acinetobacter species in critically ill patients. Most of the polymicrobial infections (67%) were seen in cases of obstruction due to choledocholithiasis or previous manipulation of the biliary tract. According to Wu et al.,  the stone may be acting as a source of infection with the bacteria trapped in the centre. In such cases, it becomes imperative to remove the stones prior to antibiotic therapy. Candida cholecystitis is a rare disease  and in our study they were isolated from immunosuppressed patients due to malignancy and had previous invasive procedures of the biliary tract like stent placement. This highlights the importance of fungal infection in case of cholangitis and the need for anti-fungal treatment to prevent fungaemia and death in patients who may not respond to antibiotics and biliary drainage.
In this study sensitivity for ampicillin was only 8% [Table 2] and [Table 3]. Cephalosporins showed a very poor sensitivity of 20-26%. However, piperacillin-tazobactum, cefaperazone-sulbactum, imipenem and meropenem had an efficacy ranging from 94% to 100%. Aminoglycosides (gentamicin and amikacin), and quinolones (ciprofloxacin and ofloxacin) had good coverage ranging from 75% to 90%. The isolates from uncomplicated symptomatic choledocholithiasis or cholangitis were sensitive to all the antibiotics as in the study by Abeysuriya et al.  A total of 66% of E. coli and 73% of Klebsiella isolates were ESBL producers. These isolates were usually from patients previously treated with antibiotics, which may have caused selection of resistant gut flora in these patients.
The combination of ampicillin and aminoglycoside provides good coverage against most organisms. Due to high rate of resistance as seen in our study, ampicillin should not be a choice of empirical antibiotic. Aminoglycosides have their own disadvantage in renal failure patients. The ideal antibiotics in case of cholangitis would be those, which are excreted in the bile such as third-generation cephalosporins, ureidopenicillins (azlocillin, mezlocillin and piperacillin), carbapenems and fluoroquinolones. Polymicrobial infection justifies the selection of these broad spectrum antibiotics. , But as long as there is biliary obstruction, the concentration and excretion of the antibiotic will not be accurate. This necessitates the need of immediate biliary decompression along with antibiotic therapy. 
Selection of empirical antibiotic is critical. In our study, we have found multidrug resistant isolates of E. coli, Klebsiella spp and Pseudomonas aeruginosa. Acinetobacter spp, which is an unusual pathogen was also recovered from the bile. Therefore in cases with history of prior instrumentation, hospitalisation, sepsis and with co-morbid conditions like malignancy, combination drugs like piperacillin-tazobactum may be considered as the empirical antibiotic of choice. Effective management of cholangitis involves three steps: appropriate resuscitation, initiation of broad spectrum antibiotics to address the systemic infection and definitive biliary decompression.  Emphasis should be on developing local antibiotic sensitivity data since significant number of cases of cholangitis show polymicrobial aetiology and high rate of antibiotic resistance. The data helps to select the empirical antibiotics depending on the individual cases.
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[Table 1], [Table 2], [Table 3]