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ORIGINAL ARTICLE |
https://doi.org/10.5005/jp-journals-10018-1389
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Multifactorial Analysis of Biliary Infection in Patients with Hepato-pancreatico-biliary and Associated Intraabdominal Malignancies Admitted to a Teaching Hospital in Northern India
1–5Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India
Corresponding Author: Chinmoy Sahu, Department of Microbiology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, Uttar Pradesh, India, Phone: +91 8004904515, e-mail: sahu.chinmoy@gmail.com
How to cite this article: Kar M, Dubey A, Patel SS, et al. Multifactorial Analysis of Biliary Infection in Patients with Hepato-pancreatico-biliary and Associated Intraabdominal Malignancies Admitted to a Teaching Hospital in Northern India. Euroasian J Hepato-Gastroenterol 2023;13(1):10–17.
Source of support: Nil
Conflict of interest: None
Received on: 18 March 2023; Accepted on: 23 June 2023; Published on: 03 August 2023
ABSTRACT
Background: Blockage of the biliary tract is commonly caused by malignant tumors leading to deranged liver function, responsible for poor prognosis and a high rate of bacteriobilia leading to mortality.
Material and methods: We collected retrospective data from the hospital information system and laboratory registers in our department from 2021 to 2022 to evaluate biliary infections in patients with hepato-pancreatico-biliary and associated intraabdominal malignancies.
Result: A total of 118 (118/234, 50.43%) patients’ bile samples were estimated in this study. Patients’ average age was 53.02 ± 13.49 years, with more patients below the age of 65 years among those with infected bile samples. Eight patients were infected by 102 pathogenic microorganisms. The most common pathogenic microorganism responsible for biliary infection in patients with abdominal malignancies was Escherichia coli (38/102, 37.25%) followed by Klebsiella pneumoniae (21/102, 20.59%) and Enterococcus spp. (18/102, 17.65%). Underlying comorbidities like diabetes mellitus, hypothyroidism, hypoproteinemia, chronic liver disease, immunosuppression, chronic kidney disease, increased hospital stay, admission to the intensive care unit (ICU), and presence of percutaneous transhepatic biliary drain were statistically significant risk factors for isolation of multidrug-resistant pathogenic bacteria.
Conclusion: Our study guided physicians in identifying the associated demographic characteristics, risk factors, and the spectrum of pathogens responsible for bacteriobilia in abdominal cancer patients along with the antibiotic resistance pattern among these isolates and better selection of antibiotics and antibiotic prophylaxis for patients at risk of developing biliary tract infections with multidrug-resistant pathogens.
Keywords: Antibiotic prophylaxis, Bile, Biliary tract, Cholelithiasis, Chronic kidney disease.
HIGHLIGHTS
It determines the annual incidence of patients undergoing surgical procedures for hepato-pancreatico-biliary malignancies and it also identifies the associated demographic characteristics and risk factors.
Identification and resistance of drug of the pathogenic microorganisms isolated from biliary infections in hepatobiliary malignancy patients.
BACKGROUND
Malignant obstruction of the biliary tract is commonly caused by malignant tumors leading to deranged liver function, which can be attributed to poor prognosis.1,2 The two major causes of malignant biliary obstruction are pancreatic adenocarcinoma which accounts for 70% of cases of malignant biliary obstruction and cholangiocarcinoma. A majority (~80%) of pancreatic adenocarcinoma is deemed unresectable and needs palliative drainage.3,4 Biliary tract Infection is attributable to severe complications and morbidity. The increased mortality rate in patients with infected biliary secretions makes timely diagnosis and treatment of biliary tract infection imperative.5,6
Neoplasms contributed to 9.6 million deaths and 121.2 per 100,000 age-standardized death rates (ASDRs) “according to the global burden of diseases (GBD), injuries, and risk factors study 2017”. Overall mortality in gastrointestinal cancers accounted for 36.2 percent of neoplasms-related deaths.7 While the most recent estimates recorded in literature from the According to the global burden of disease research, there were 139,500 fatalities from biliary tract cancer in 2013, up from an estimated 115,400 deaths in 1990, or ASDRs of 2.3 per 100,000 and 3.4 per 100,000, respectively.8 The incidence of biliary tract cancers (mainly gallbladder cancer) in North India is 10–22 per 100,000 population, with a female preponderance, and is similar to other high-incidence nations like South America.9
Rationale for Investigation
Insufficient research has been done on patients with malignant biliary obstruction. Few studies have been done that had reported the emerging incidence of multidrug-resistant bacteria, while the presence of enteric bacteria in biliary secretions reports a negative prognostic impact on liver transplants failing the procedure.10–13
OBJECTIVES
We aimed to determine the annual incidence of patients undergoing surgical procedures for hepato-pancreatico-biliary malignancies at a Tertiary Care Center.
The objectives of this study include:
Identification of the risk factors and underlying comorbidities in hepatobiliary cancer and associated cancer patients who developed infections and
Identification and drug resistance of the pathogenic microorganisms isolated from biliary infections in hepatobiliary malignancy patients.
MATERIAL AND METHODS
Study Design
We retrospectively performed this study in the Microbiology Department at a University Hospital in Northern India from July 2021 to July 2022 for 1 year. Our patient group included all adults admitted to the post-operative ward of the Department of Surgical Gastroenterology who underwent surgical procedures related to the biliary tract and associated organ systems.
Setting
This study was done in the Department of Microbiology in the Trauma Center of a University Hospital in Northern India from December 2018 to September 2022. Our study cohort included patients who underwent intraabdominal surgery and were further diagnosed with hepatic-pancreaticobiliary cancers. The institute ethics committee approved this study (2021-48-EMP-EXP dated 29/11/2021). All procedures were carried out in conformity with the 1975 Helsinki Declaration and the institutional or regional relevant committee on human experimentation’s ethical requirements. Informed consent was waived off as there was no intervention and no privacy data were obtained.
Participants
The study included all patients who underwent intraabdominal surgery and were further diagnosed with hepatic-pancreaticobiliary cancers.
Inclusion Criteria
All bile samples from a patient undergoing intraabdominal surgery were collected and sent to the laboratory within two hours of the procedure.
Exclusion Criteria
All skin contaminants and commensals were excluded from the study while analyzing the infective microorganisms. All samples that were not labeled properly were also excluded.
Variables
All clinical data of hepato-pancreatico-biliary cancer patients extracted from the hospital’s information system were reviewed for underlying comorbidities, risk factors and length of hospital stay. A total of 234 bile samples were contained in our study and processed according to laboratory protocol. Flowchart 1 explains the flow of sample processing performed at our laboratory. Initially, a Grams’ stained smear was prepared for all the samples, and Mac Conkey Agar and Blood agar plates were inoculated and further incubated for 48 hours at 37°C. Microscopic features, characteristics of the colony obtained on culture plates, and biochemical tests were used to identify and characterize the bacterial isolates.10 Antibiotic discs containing Amikacin (30 μg), Ampicillin (10 μg), Ampicillin-Sulbactam (10/10 μg), Aztreonam (30 μg), Ceftazidime (30 μg), Ceftriaxone (30 μg), Cefoperazone-sulbactam (75/10 μg), Ciprofloxacin (5 μg), Cefoxitin (30 μg), Clindamycin (2 μg), Doxycycline (10 μg), Ertapenem (10 μg), Gentamicin (10 μg), Erythromycin (15 μg), Imipenem (10 μg), Levofloxacin (5 μg), Linezolid (30 μg), Meropenem (30 μg), Minocycline (30 μg), Tigecycline (15 μg), Trimethoprim-sulphamethoxazole (1.25/23.75 μg), Teicoplanin (30 μg), Piperacillin-tazobactam (100/10 μg), Vancomycin (30 μg) and Colistin (0.016–256 μg). Test strips of epsilometeric were procured from the company BioMéreux and were used using the instructions of the manufacturer. Sensitivity testing of antibiotics was performed using Kirby Bauer’s disc diffusion method and Epsilometeric strip test, in compliance with the norms of the Laboratory and Clinical and Laboratory Standards Institute (CLSI).11 Clinical and Laboratory Standards Institute guidelines were used to categorize the antibiotics as sensitive, intermediate, and resistant.11 A record of all the diagnostic parameters was extracted from the hospital information system.
Flowchart 1: Flowchart of the workflow followed in our laboratory
Bias
Most of the information in our study was attained from the electronic records and ward register so a possibility of data bias was strongly suspected due to the lack of necessary information maintained in records.
Study Size
The sample size was arrived at by analyzing the culture results of bile samples from the laboratory registers and electronic records of 4 years.
Quantitative Variables
Most of the quantitative information, including patient ages, was gathered through the hospital’s information system. The length of intensive care unit (ICU) stays and admission were mentioned in the electronic records. The electronic records included information about the ICU admission and stay length. From the day of the patient’s admittance to the day of discharge, the length of our patients’ hospital stays was calculated.
Statistical Methods
The statistical data for our study was performed by observing frequencies. Quantitative variables were expressed as mean and standard deviation (SD). In the analysis of risk factors for multidrug resistance (MDR), the comparison between groups for categorical variables was estimated by using χ2 tests. The results were presented as 95% confidence interval (CIs). Statistical analysis was performed using the software program IBM SPSS Statistics version 20.0 (SPSS Inc.), with p < 0.05 considered statistically significant.
RESULT
Participants
A total of 234 patients underwent a surgical procedure in the Department of Surgical Gastroenterology. Of the 234 patients, 118 (118/234, 50.43%) underwent intraabdominal surgeries for hepatic-pancreaticobiliary malignancies.
Descriptive Data
The mean age of 53.02 ± 13.49 years of patients with a significant number of patients below the age of 65 years underwent surgical procedures for abdominal malignancies at this center (Table 1). Although a female predominance (143/234, 61.11%) was observed in patients with biliary infections, no gender predominance was observed in patients with malignancies.
| Observational parameters | Total bile samples (n = 234) | With underlying hepatobiliary malignancies who underwent surgery (n = 118) | Without underlying hepatobiliary malignancies (n = 116) | p-value | Confidence interval (95% CI) |
|---|---|---|---|---|---|
| Gender | |||||
| Male | 91 (38.89%) | 63 (53.39%) | 28 (24.14%) | <0.001* | 1.21–1.40 |
| Female | 143 (61.11%) | 55 (46.61%) | 88 (75.86%) | <0.001* | 1.53–1.69 |
| Age | |||||
| <65 years | 201 (85.89%) | 89 (75.42%) | 112 (96.55%) | <0.001* | 1.49–1.62 |
| ≥65 years | 33 (14.10%) | 29 (24.58%) | 4 (3.45%) | <0.001* | 1.00–1.24 |
| Causes of obstruction | |||||
| Biliovascular injury | 45 (19.23%) | 3 (2.54%) | 42 (36.20%) | <0.001* | 1.95–2.00 |
| Benign stricture | 56 (23.93%) | 4 (3.39%) | 52 (44.83%) | <0.001* | 1.93–2.00 |
| Indwelling biliary drainage | 174 (74.36%) | 95 (80.51%) | 79 (68.10%) | 0.03* | 1.12–1.27 |
| Cholecystitis | 143 (61.11%) | 46 (38.98%) | 97 (83.62%) | <0.001* | 1.52–1.70 |
| Choledochal cyst | 31 (13.25%) | 5 (4.24%) | 26 (22.41%) | <0.001* | 1.92–1.99 |
| Biliary-enteric anastomosis | 136 (58.12%) | 77 (65.25%) | 59 (50.86%) | 0.031* | 1.26–1.43 |
| Cholelithiasis | 120 (51.28%) | 28 (23.73%) | 92 (79.31%) | <0.001* | 1.68–1.84 |
| Underlying comorbidities | |||||
| Diabetes mellitus | 99 (42.31%) | 53 (44.91%) | 46 (39.66%) | 0.415 | 1.46–1.64 |
| Hypothyroidism | 74 (31.62%) | 34 (28.81%) | 40 (34.48%) | 0.351 | 1.63–1.79 |
| Hypoproteinemia | 97 (41.45%) | 63 (53.39%) | 34 (29.31%) | <0.001* | 1.37–1.56 |
| Chronic liver disease | 76 (32.48%) | 51 (43.22%) | 25 (21.55%) | <0.001* | 1.48–1.66 |
| Immunosuppression | 19 (8.12%) | 14 (11.86%) | 5 (4.31%) | 0.034* | 1.82–1.94 |
| Chronic kidney disease | 44 (18.80%) | 28 (23.73%) | 16 (13.79%) | 0.05* | 1.80–1.93 |
| Length of hospital stay (in days) | 19.33 ± 11.89 | 22.30 ± 14.09 | 16.31 ± 8.16 | <0.001* | 3.02–8.96 |
| ICU stay | |||||
| Yes | 33 (14.10%) | 24 (20.34%) | 9 (7.76%) | 0.006* | 1.09–1.41 |
| No | 201 (85.89%) | 94 (79.66%) | 107 (92.24%) | 0.006* | 1.46–1.60 |
| Outcome | |||||
| Alive | 209 (89.32%) | 100 (84.75%) | 109 (93.97%) | 0.022* | 1.45–1.59 |
| Dead | 25 (10.68%) | 18 (15.25%) | 7 (6.03%) | 0.022* | 1.09–1.47 |
The most common causes of biliary obstruction observed in our subgroup of patients suffering from abdominal malignancies include indwelling biliary catheters (95/118, 80.51%) followed by biliary-enteric anastomosis (77/118, 65.25%) and cholecystitis (46/118, 38.98%) as described in Table 1. While all causes of biliary obstruction which include, biliovascular injury, benign strictures, indwelling biliary catheters, cholecystitis, choledochal cysts, biliary-enteric anastomosis, and cholelithiasis (Table 1) were found statistically significant among patients with hepato-pancreatico-biliary malignancies in comparison to procedures for other intraabdominal ailments.
Main Result
The underlying risk factors in our study cohort of hepato-pancreatico-biliary and associated malignancies patients (Table 1). Among those discussed, Hypoproteinemia (63/118, 53.39%) was recognized as the most common comorbidity followed by diabetes mellitus (53/118, 44.91%) and chronic liver disease (51/118, 43.22%). We recognized hypoproteinemia, chronic liver disease, immunosuppression, and chronic kidney disease as significant risk factors in patients with hepatico-pancreatico-biliary malignancies in comparison to those without any malignancies. We identified immunosuppression in patients suffering from autoimmune diseases, undergoing prolonged steroid therapy, and those who underwent organ transplants. The length of hospital stay was significantly longer in the case of patients who underwent surgery for malignancies in comparison to those who did not undergo surgery for abdominal malignancies (Table 1).
The hepato-pancreatico-biliary and associated malignancies are represented in Figure 1. The common malignancies of the biliary system which lead to obstruction in the biliary tract leading to elevated bile levels are carcinoma gall bladder (53/118, 44.92%), periampullary carcinoma (25/118, 21.19%), cholangiocarcinoma (18, 15.25%), and ampullary adenocarcinoma (5/118, 4.24%). We observed 2 (2/118, 1.69%) cases of hepatocellular carcinoma in our study cohort. Among the malignancies associated with the pancreas, the most common site of involvement was the head of the pancreas (10/118, 8.47%). Other abdominal malignancies associated with metastatic spread of hepato- pancreaticobiliary malignancies include 3 (3/118, 2.54%) cases of carcinoma colon and one (1/118, 0.85%) case of carcinoma urinary bladder.
Fig. 1: The common malignances among the patients needing intra-abdominal surgeries in our study (N = 118)
We compared the diagnostic parameters among patients with underlying hepatico-pancreatico-biliary malignancies who underwent surgery and those with no hepatico-pancreatico-biliary malignancies, as represented in Table 2. No significant diagnostic importance of procalcitonin assay was observed whereas CA 19.9, a marker of malignancies of pancreatic origin, was found to be significantly raised among patients with malignancies. The aspartate aminotransferase (AST), conjugated, and total bilirubin was also significantly raised in patients with abdominal malignancies in comparison to those with no malignancies.
| Diagnostic parameters | Total bile samples (n = 234) | With underlying hepatobiliary malignancies who underwent surgery (n = 118) | Without underlying hepatobiliary malignancies (n = 116) | p-value | Confidence interval (95% CI) |
|---|---|---|---|---|---|
| Procalcitonin (ng/mL) (mean ± SD) |
2.30 ± 7.97 | 3.01 ± 9.43 | 1.57 ± 6.08 | 0.17 | 0.72–6.98 |
| CA 19.9 (μg/mL) (Mean ± SD) |
377.06 ± 1879.68 | 728.1 ± 2597.69 | 16.87 ± 79.79 | 0.0035* | 13.04–330.31 |
| ALT (SGPT) (mean ± SD) |
65.85 ± 56.44 | 65.44 ± 53.41 | 66.27 ± 59.61 | 0.91 | 0.79–1.24 |
| AST (SGOT) (mean ± SD) |
71.37 ± 50.85 | 79.87 ± 47.73 | 62.64 ± 52.67 | 0.0093* | 1.06–1.55 |
| Conjugated bilirubin (mg/dL) (mean ± SD) |
2.63 ± 3.93 | 3.64 ± 4.11 | 1.70 ± 3.48 | <0.001* | 1.44–3.54 |
| Total bilirubin (mg/dL) (mean ± SD) |
4.24 ± 5.68 | 5.77 ± 6.04 | 2.67 ± 4.83 | <0.001* | 4.395–8.87 |
| Total leukocyte count (cells/cubic mm) (mean ± SD) |
14496.13 ± 7986.32 | 14937.88 ± 6270.01 | 14042.86 ± 9436.29 | 0.39 | 0.92–1.24 |
Eighty (80/118, 67.79%) episodes of biliary infections were reported among the 118 patients who underwent surgical procedures for the removal of the tumor. Among the 80 episodes of biliary infections observed in our study, 58 (72.5%) episodes were monomicrobial and 22 (27.5%) episodes were polymicrobial (Fig. 2). One hundred and two pathogenic bacteria were found responsible for these episodes of biliary infections. The most common pathogen responsible for biliary infection in patients with abdominal malignancies was Escherichia coli (38/102, 37.25%) followed by Klebsiella pneumoniae (21/102, 20.59%) and Enterococcus spp. (18/102, 17.65%) (Fig. 3). The most common gram-negative bacteria (GNB) responsible for biliary infection in patients with abdominal malignancies was Escherichia coli (38/102, 37.25%) followed by Klebsiella pneumoniae (21/102, 20.59%) and Pseudomonas aeruginosa (13/102, 12.75%).
Fig. 2: Distribution of cases of infected bile cultures from patients with hepatico-pancreatico-biliary malignancies based on number of microbes isolated (N = 80)
Fig. 3: Microorganisms isolated from the infected bile samples from hepatico-pancreatico-biliary malignancy patients included in this study (N = 102) MSSA, methicillin sensitive Staphylococcus aureus
Extended-spectrum beta-lactamase (ESBLs) resistance was predominantly recognized among the Gram-negative isolates. Seventy-eight (78/102, 76.47%) isolates were found resistant to ESBL antibiotics. Escherichia coli (27/78, 34.62%) were identified as the most ESBL-resistant isolate, followed by Klebsiella pneumonia (20/78, 25.64%) and Pseudomonas aeruginosa (10/78, 12.82%). Among the above-mentioned isolates, Klebsiella pneumoniae was found 95.24% (20/21, 95.24%) resistant, Pseudomonas aeruginosa was found 76.92% (10/13, 76.92%) resistant, and Escherichia coli was found 71.05% (27/38, 71.05%) resistant to ESBL antibiotics.
Carbapenem resistance has been identified as an emerging problem among bacterial pathogens from various sites of infection. Fifty-eight (58/102, 56.86%) bacterial pathogens isolated in this study were found to be resistant to Carbapenem antibiotics. Escherichia coli (22/58, 37.93%) was identified as the most ESBL-resistant isolate, followed by Klebsiella pneumoniae (19/58, 32.76%) and Pseudomonas aeruginosa (10/58, 17.24%). Among the above-mentioned isolates, Klebsiella pneumoniae was found 90.48% (19/21, 90.48%) resistant, Pseudomonas aeruginosa was found 76.92% (10/13, 76.92%) resistant, and Escherichia coli was found 57.89% (22/38, 57.89%) resistant to ESBL antibiotics.
Fluoroquinolone resistance was observed among 85 (85/102, 83.33%) pathogenic bacteria. Escherichia coli (33/85, 38.82%) was found most resistant to fluoroquinolones followed by Klebsiella pneumoniae (20/85, 23.53%) and Pseudomonas aeruginosa (11/85, 12.94%). Among the above-mentioned isolates, Klebsiella pneumoniae was found 95.24% (20/21, 95.24%) resistant, Escherichia coli was found 86.84% (33/38, 86.84%) resistant and Pseudomonas aeruginosa was found 84.62% (11/13, 84.62%) resistant to fluoroquinolone antibiotics.
p and Morganella morganii were deemed as emerging pathogens responsible for multidrug-resistant infections from various sites. Although we isolated only two (2/102, 1.96%) isolates of A. baumannii and three (3/102, 2.94%) isolates of Morganella morganii from the infected bile samples, all of them were resistant to all the first-line antibiotics used against them. Among the second-line drugs, Acinetobacter baumannii was established as susceptible to Colistin in 50% (1/2, 50%) of isolates and was recognized as susceptible to minocycline in 50% (1/2, 50%) isolates. Only one (1/2, 50%) isolate of Acinetobacter baumannii was resistant to all second-line drugs along with Ceftazidime – avibactam and aztreonam synergy which was absent.
Among Gram-positive cocci, Enterococcus spp. (18/102, 17.65%) was identified as the most common Gram-positive pathogen recognized among those isolated from infected bile samples. Out of the 18 Enterococcus spp. isolates, 14 (14/18, 77.78%) isolates were ampicillin resistant. One (1/102, 0.98%) Staphylococcus spp. isolate was identified but was not resistant to Cefoxitin which acts as a marker of methicillin resistance, and was identified as Methicillin-sensitive Staphylococcus aureus. Vancomycin and Teicoplanin were found effective in the treatment of 27 (27/35, 77.14%) isolates of Enterococcus spp. and all Staphylococcus spp. (4/4, 100%) were sensitive to it.
The demographic and risk factors responsible for the isolation of multidrug-resistant bacteria from hepato-pancreatico-biliary malignancy patients were described in Table 3. We isolated 61 (61/102, 59.80%) multidrug bacterial isolates from patients suffering from abdominal malignancies. The mean age of the patients suffering from multidrug-resistant biliary infections was 54.80 ± 11.64 years and a female (29/61, 47.54%) preponderance was observed among these patients. All underlying comorbidities like diabetes mellitus, hypothyroidism, hypoproteinemia, chronic liver disease, immunosuppression, and chronic kidney disease were significantly associated with the isolation of multidrug-resistant isolates from bile samples of patients suffering from abdominal malignancies. The increased length of hospital stays, admission to the ICU, and presence of percutaneous transhepatic biliary drain were statistically significant risk factors for the isolation of multidrug-resistant pathogenic bacteria from patients in our study cohort.
| Observational parameters | Multidrug resistant isolates (n = 61/102, 59.80%) | Drug susceptible isolates (n = 41/102, 40.20%) | p-value | Confidence interval (95% CI) |
|---|---|---|---|---|
| Age (Mean ± SD ) | 54.80 ± 11.64 | 51.23 ± 13.45 | 0.031* | 1.01–1.14 |
| Gender | ||||
| Male | 20 (32.79%) | 18 (29.51%) | 0.002* | 1.31–1.64 |
| Female | 29 (47.54%) | 12 (19.67%) | 0.002* | 1.15–1.44 |
| Causes of obstruction | ||||
| Biliovascular injury | 2 (3.28%) | 0 (0.0%) | 0.014* | 1.90–2.02 |
| Benign stricture | 1 (1.64%) | 0 (0.0%) | 0.004* | 1.94–2.02 |
| Indwelling biliary drainage | 40 (65.57%) | 27 (44.26%) | 0.004* | 1.07–1.30 |
| Cholecystitis | 24 (39.34%) | 7 (11.47%) | 0.003* | 1.37–1.66 |
| Choledochal cyst | 2 (3.28%) | 2 (3.28%) | 0.016* | 1.90–2.02 |
| Biliary-enteric anastomosis | 28 (45.90%) | 18 (29.50%) | 0.005* | 1.28–1.57 |
| Cholelithiasis | 13 (21.31%) | 6 (9.84%) | 0.019* | 1.61–1.88 |
| Underlying comorbidities | ||||
| Diabetes mellitus | 25 (40.98%) | 13 (21.31%) | 0.012* | 1.34–1.63 |
| Hypothyroidism | 19 (31.15%) | 9 (14.75%) | <0.001* | 1.47–1.75 |
| Hypoproteinemia | 25 (40.98%) | 14 (22.95%) | 0.010* | 1.34–1.63 |
| Chronic liver disease | 22 (36.06%) | 12 (19.67%) | 0.021* | 1.41–1.70 |
| Immunosuppression | 5 (8.20%) | 5 (8.19%) | 0.012* | 1.81–1.99 |
| Chronic kidney disease | 16 (26.23%) | 5 (8.19%) | 0.003* | 1.54–1.81 |
| Length of hospital stay (in days) | 25.00 ± 15.84 | 18.73 ± 9.89 | <0.001* | 1.15–1.55 |
| Admission to ICU present | 12 (19.67%) | 8 (13.11%) | 0.004* | 1.63–1.88 |
| Management on PTBD# after surgery | 38 (62.29%) | 23 (37.70%) | 0.021* | 1.10–1.35 |
| Outcome | ||||
| Alive | 40 (65.57%) | 24 (39.34%) | 0.003* | 1.25–1.50 |
| Dead | 10 (16.39%) | 6 (9.84%) | 0.003* | 1.12–1.68 |
DISCUSSION
To our best knowledge, this is one of the few studies in the literature that determines the incidence of bacterial infections and antibiotic sensitivity patterns associated with abdominal cancer patients. We identified 234 patients with suspected bacteriobilia in our study cohort, out of which, 118 (118/234, 50.43%) patients were suffering from hepato-pancreatico-biliary and associated malignancies. The mean age of patients was 53.02 ± 13.49 years with male predominance which agrees with a study conducted by Herzog et al.14 As known in the literature, a healthy individual has a sterile biliary system but bacterial colonization of the biliary system can be associated with biliary pathology.15 Biliary obstruction is a well-known cause of bacteriobilia.16 A study by Negm et al.17 supports our notion that malignant biliary strictures increase the risk of colonization.
We report positivity in bile cultures of 50.43% (118/234, 50.43%) in this study which agrees with a study conducted by Haag et al.10 which reported a 62% incidence of bacteriobilia in cancer patients and low in comparison to a study conducted by Herzog et al.14 which reported an incidence of almost 90% incidence of bacteriobilia in cancer patients. We isolated 102 pathogenic microorganisms from 80 episodes of bacteriobilia with a predominance of bacteriobilia attributable to GNB (82/102, 80.39%) with the most common microorganism isolated being Escherichia coli (38/102, 37.25%) followed by Klebsiella pneumoniae (21/102, 20.59%). The above interpretation was in agreement with a study by Herzog et al.14 that predominantly demonstrated the isolation of GNB where the most common pathogenic microorganism isolated was Escherichia coli followed by Klebsiella pneumoniae. Whereas a study by Haag et al.10 showed predominant gram-positive cocci bacteriobilia in patients that underwent endoscopic retrograde cholangiopancreatography (ERCP) in obstructive malignancies of the biliary tract. Increased isolation of Enterococcus spp. from bile cultures was also observed in our study which was similarly observed in studies from other institutes where the empirical therapy for bacteriobilia commonly covered GNB, leading to the slight increase of Gram-positive Enterococci spp.10,18
We recorded a high level of antibiotic resistance among the commonly isolated microorganisms. Escherichia coli was most susceptible to Amikacin and imipenem among the first-line drugs, while multidrug-resistant Escherichia coli tested for susceptibility to Colistin were found 100% (38/38, 100%) susceptible. Higher susceptibility of Escherichia coli to Amikacin was recorded in a study by Zhao et al.18 A resistance of 89.47% to third-generation cephalosporins among Escherichia coli isolates from infected bile samples was recorded in our study which is very high in comparison to a study by Yun et al.19 which record a resistance of 20–60%.
The ever-increasing use of penicillins and cephalosporins has led to reduced effectiveness in treating severe infections. Extended-spectrum β-lactamases (ESBL) character of a microorganism was found to resist the effect of penicillins and cephalosporins.20 Highest ESBL producing character among microorganisms isolated from the infected bile samples was Morganella morganii (3/3, 100%), followed by Klebsiella pneumoniae (20/21, 95.24%) and Escherichia coli (27/38, 71.05%) which corroborates with a study by Zhao et al.18 Carbapenems were found to be resistant in more than 50% (58/102, 56.86%) of isolates which is much higher in contrast to a study by Zhao et al.18 which could be attributed to the rampant use of carbapenems leading to the slow but steady emergence of carbapenem-resistant microorganisms.21
As we already know there is a trend of increasing incidence of Enterococcus spp. in various studies which also mirrors the finding of our study.22,23 In agreement with previously published articles, the Enterococcus spp. isolates were reported to be more than 90% susceptible to linezolid, vancomycin, and teicoplanin.18 Vancomycin was regarded as the drug of choice for the empirical treatment of Enterococcus spp. which was also recommended by the Tokyo Guidelines 2018.24
The use of newer technologies like ERCP and other ultrasonographic techniques has helped in testing the bile samples directly from the suspected site of infection. This also helps in the recognition of the antibiotic-resistant pattern of the microbes isolated from the infected bile samples.22 Thus, the antibiotic sensitivity pattern will direct the identification of the antibiotic coverage that needs to be provided for prophylactic treatment of risk factors associated with biliary tract malignancies which need surgical procedures leading to bacteriobilia.25,26
Our research was limited by various factors; firstly, this is a retrospective observational study at a single tertiary care center. Secondly, the findings of our study only represent the spectrum of bacteriobilia and antibiotic resistance at a single center and are not representative of the rate of infection in other hospitals of the region.
CONCLUSION
This study provides insight into the annual incidence of patients undergoing surgery for hepato-pancreatico-biliary malignancies and identifies associated demographic characteristics, risk factors, and the spectrum of pathogens responsible for bacteriobilia along with the antibiotic resistance pattern among these isolates.
ORCID
Mitra Kar https://orcid.org/0000-0001-9744-9653
Akanksha Dubey https://orcid.org/0000-0002-5546-6110
Sangram Singh Patel https://orcid.org/0000-0001-5344-0729
Chinmoy Sahu https://orcid.org/0000-0002-5440-7717
Anjali Yadav https://orcid.org/0000-0002-7281-675X
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