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Kwon, Han, Kim, Oh, Kwon, Jung, Kwon, Kim, and Kim: Changes in Causative Pathogens of Acute Cholangitis and Their Antimicrobial Susceptibility over a Period of 6 Years
Original Article

Korean J Gastroenterol 2014;63(5):299-307.

Published online: 4 October 2014

DOI: https://doi.org/10.4166/kjg.2014.63.5.299

Changes in Causative Pathogens of Acute Cholangitis and Their Antimicrobial Susceptibility over a Period of 6 Years

Jeong Seok Kwon, Jimin Han, Tae Won Kim, Ji-Hye Oh, Hyun Hee Kwon, Jin Tae Jung, Joong Goo Kwon, Eun Young Kim, Ho Gak Kim

Department of Internal Medicine, Catholic University of Daegu School of Medicine, Daegu, Korea

Correspondence to: Jimin Han, Department of Internal Medicine, Catholic University of Daegu School of Medicine, Duryugongwon-ro 17-gil, Nam-gu, Daegu 705-718, Korea. Tel: +82-53-650-3042, Fax: +82-53-624-3281, E-mail: mhan@cu.ac.kr

Received 30 December 2014       Revised 7 March 2014       Accepted 8 March 2014

Copyright © 2014 Korean Ophthalmological Society

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background/Aims

We evaluated changes of causative pathogen in acute cholangitis and their antimicrobial susceptibility over six years and differences between community-acquired and hospital-acquired acute cholangitis at our institution.

Methods

Medical records of 1,596 patients with acute cholangitis and biliary drainage between August 2006 and August 2012 were reviewed retrospectively. Cases were divided according to time: period 1 (August 2006-December 2008, n=645, 40.4%), period 2 (January 2009-August 2012, n=951, 59.6%). Cases were divided according to community-acquired cholangitis (n=1,397, 87.5%) and hospital-acquired cholangitis (n=199, 12.5%). Causative pathogens and antimicrobial susceptibility were investigated in each group.

Results

Causative pathogen was isolated from bile culture in 1,520 out of 1,596 cases (95.2%). The three most frequently isolated Gram-negative bacteria were extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (n=485, 30.4%), E. coli (n=237, 13.2%), and Citrobacter freundii (n=110, 6.9%). Between periods 1 and 2, prevalence of ESBL-producing E. coli and Klebsiella pneumoniae did not show significant change (36.7% vs. 32.1%, p=0.073; 6.6% vs. 6.2%, p=0.732). C. freundii showed a significant increase from period 1 to period 2 (1.7% vs. 13.2%, p=0.000). In both time periods, imipenem was the antimicrobial agent showing the highest rate of susceptibility (93.3% vs. 93.9%, p=0.783). Higher prevalence of ESBL-pro-ducing E. coli and C. freundii was observed in the hospital-acquired cholangitis group (52.1% vs. 31.2%, p=0.000; 15.9% vs. 7.3%, p=0.001).

Conclusions

The most common causative pathogen of acute cholangitis was ESBL-producing E. coli. Prevalence of C. freundii increased over the time period. Imipenem should be reserved as an alternative for resistant pathogens.

Keywords: Cholangitis, Microbial sensitivity tests, Antimicrobial drug resistance

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Fig. 1.
Study flow. Patients with acute cholangitis and biliary drainage were divided into groups according to time period and setting.
kjg-63-299f1.tif
Table 1.
Baseline Characteristics of the Study Subjects (n=1,596)
Characteristic Data
Age (yr) 68.3±13.8
Male 905 (56.7)
ALT (IU/L) 179.6±205.9
AST (IU/L) 185.9±239.8
ALP (IU/L) 594.3±510.8
GGT (IU/L) 395.1±439.6
Bilirubin (mg/dL) 7.1±32.9
CRP (mg/L) 59.76±76.8
Positive growth in blood 116 (14.1)
Positive growth in bile 1,513 (95.2)
Positive growth in both blood and bile 116 (7.6)
Concordant growth between blood and bile cultures 90 (77.6)
Causes of acute cholangitis  
 CBD+IHD stone 1,053 (66)
 Malignant tumor  
  Cholangiocarcinoma 215 (13.5)
  Pancreatic head cancer 59 (3.7)
  GB cancer 35 (2.2)
  AOV tumor 59 (3.7)
  Metastatic cancer 16 (1.0)
 Benign biliary stricture 29 (1.8)
 Others 130 (8.1)

Values are presented as mean±SD or n (%).

CBD, common bile duct; IHD, intrahepatic bile duct; GB, gallbladder;

AOV, ampulla of Vater.

Table 2.
Comparison of Baseline Characteristics between Period 1 and 2
Characteristic Period 1(n=645) Period 2(n=951) p-value
Age (yr) 69.3±13.8 68.62±13.8 0.914
Male 386 (59.8) 522 (54.9) 0.051
ALT (IU/L) 184.7±213.6 175.8±200.0 0.082
AST (IU/L) 178.1±214.9 191.0±254.7 0.144
ALP (IU/L) 593.1±505.5 598.2±521.2 0.803
GGT (IU/L) 394.2±381.0 396.7±475.2 0.458
Bilirubin (mg/dL) 8.64±45.52 6.04±19.8 0.016
CRP (mg/L) 59.3±68.6 60.2±80.9 0.175
Positive growth in blood 66 (19) 50 (10.4) 0.001
Positive growth in bile 621 (96.3) 899 (94.5) 0.120
Causes of acute cholangitis      
 CBD+IHD stone 417 (64.7) 636 (66.9) 0.361
 Malignant tumor      
  Cholangiocarcinoma 87 (13.5) 128 (13.5) 1.000
  Pancreatic head cancer 20 (3.1) 39 (4.1) 0.345
  GB cancer 14 (2.2) 21 (2.2) 1.000
  AOV tumor 22 (3.4) 37 (3.9) 0.686
  Metastatic cancer 10 (1.6) 6 (0.6) 0.078
 Benign biliary stricture 13 (2.0) 16 (1.7) 0.703
 Others 62 (9.6) 68 (7.2) 0.111

Values are presented as mean±SD or n (%).

CBD, common bile duct; IHD, intrahepatic bile duct; GB, gallbladder

AOV, ampulla of Vater.

Table 3.
Changes in Causative Pathogens and Their Antimicrobial Susceptibility over the Time Period of Six Years
Variable Culture(+) in period 1(n=621) Culture(+) in period 2(n=899) p-value Culture(+) in both (n=1,520)
Causative pathogen, n (%)        
 Gram-negative        
  E. coli 112 (19.4) 125 (14.6) 0.020 211 (13.2)
  ESBL-producing E. coli 210 (36.7) 362 (32.1) 0.073 485 (30.4)
  K. pneumoniae 37 (6.4) 65 (7.6) 0.405 99 (6.2)
  ESBL-producing K. pneumoniae 38 (6.6) 53 (6.2) 0.732 91 (5.7)
  Pseudomonas aeruginosa 41 (7.1) 37 (4.3) 0.024 72 (4.5)
  Citrobacter freundii 10 (1.7) 100 (13.2) 0.000 110 (6.9)
  Enterobacter cloacae 36 (6.3) 50 (6.2) 0.725 86 (5.4)
  Acinetobacter baumanii 21 (3.7) 16 (1.9) 0.036 37 (2.3)
Susceptible antimicrobial agent, n (%)        
 Aminoglycoside        
  Amikacin 293 (80.9) 515 (90) 0.000  
 Quinolone        
  Ciprofloxacin 185 (52.4) 204 (49.4) 0.426  
 Beta-lactams        
  Ampicillin 56 (18.1) 59 (12) 0.022  
  Piperacillin-tazobactam 219 (65.6) 348 (68.1) 0.455  
  Cefotetan 79 (55.6) 172 (74.8) 0.000  
  Ceftazidime 130 (53.9) 277 (49.7) 0.281  
  Cefepime 232 (64.3) 358 (62.3) 0.578  
  Imipenem 336 (93.3) 540 (93.9) 0.783  

ESBL, extended-spectrum beta-lactamase; E. coli, Escherichia coli; K. pneumoniae, Klebsiella pneumoniae.

Table 4.
Comparison of Baseline Characteristics between Community-acquired Cholangitis and Hospital-acquired Cholangitis
  Community-acquired cholangitis (n=1,397) Hospital-acquired cholangitis (n=199) p-value
Age (yr) 68.6±13.9 70.9±12.6 0.230
Male 799 (57.2) 109 (54.8) 0.541
ALT (IU/L) 181.6±206.0 125.1±188.6 0.133
AST (IU/L) 187.3±241.4 145.8±176.2 0.198
ALP (IU/L) 579.2±514.9 568.2±515.6 0.432
GGT (IU/L) 399.5±445.7 300.6±221.2 0.023
Bilirubin (mg/dL) 7.1±33.4 4.6±7.1 0.564
CRP (mg/L) 60.2±77.1 50.4±66.9 0.119
Positive growth in blood 112 (14.1) 47 (11.8) 1.000
Positive growth in bile 1,321 (94.6) 199 (100) 0.000
Causes of acute cholangitis      
 CBD+IHD stone 924 (66.3) 129 (64.2) 0.577
 Malignant tumor      
  Cholangiocarcinoma 182 (12.9) 33 (16.4) 0.183
  Pancreatic head cancer 52 (3.7) 7 (3.5) 1.000
  GB cancer 29 (2.1) 6 (3.0) 0.436
  AOV tumor 54 (3.9) 5 (2.5) 0.425
  Metastatic cancer 13 (0.9) 3 (1.5) 0.430
 Benign biliary stricture 26 (1.9) 3 (1.5) 0.703
 Others 117 (8.2) 13 (7.5) 0.784

Values are presented as mean±SD or n (%).

CBD, common bile duct; IHD, intrahepatic bile duct; GB, gallbladder; AOV, ampulla of Vater.

Table 5.
Comparison of Causative Pathogens and Their Antimicrobial Susceptibility between Community-acquired Cholangitis and Hospital-acquired Cholangitis
  Culture(+) in community-acquired cholangitis (n=1,321) Culture(+) in hospital-acquired cholangitis (n=199) p-value Culture(+) in both (n=1,520)
Causative pathogen, n (%)        
 Gram-negative        
  E. coli 226 (18.2) 11 (5.8) 0.000 211 (13.2)
  ESBL-producing E. coli 386 (31.2) 99 (52.1) 0.000 485 (30.4)
  K. pneumoniae 100 (8.0) 2 (1.1) 0.000 99 (6.2)
  ESBL-producing K. pneumoniae 77 (6.6) 14 (7.9) 0.546 91 (5.7)
  Pseudomonas aeruginosa 68 (5.5) 10 (5.3) 1.000 72 (4.5)
  Citrobacter freundii 84 (7.3) 26 (15.9) 0.001 110 (6.9)
  Enterobacter cloacae 77 (6.6) 9 (5.0) 0.424 86 (5.4)
  Acinetobacter baumanii 30 (2.4) 7 (3.8) 0.308 37 (2.3)
Susceptible antimicrobial agent, n (%)        
 Aminoglycoside        
  Amikacin 735 (86.9) 73 (83) 0.708  
 Quinolone        
  Ciprofloxacin 368 (52.7) 21 (30.9) 0.001  
 Beta-lactams        
  Ampicillin 112 (15.5) 3 (3.8) 0.003  
  Piperacillin-tazobactam 529 (69.2) 38 (47.5) 0.000  
  Cefotetan 232 (68.6) 19 (55.9) 0.178  
  Ceftazidime 394 (55.3) 13 (15.1) 0.000  
  Cefepime 556 (65.7) 34 (37.8) 0.000  
  Imipenem 79 (94.1) 82 (90.1) 0.168  

ESBL, extended-spectrum beta-lactamase; E. coli, Escherichia coli; K. pneumoniae, Klebsiella pneumoniae.

Table 6.
Comparison of Antimicrobial Susceptibility of Extended-spectrum Beta-lactamase-producing Escherichia coli between Period 1 and 2
Antimicrobial agent, n (%) ESBL(+) E. coli in period 1(n=210) ESBL(+) E. coli in period 2(n=362) p-value
Aminoglycoside      
 Amikacin 183 (86.3) 218 (80.1) 0.089
Quinolone      
 Ciprofloxacin 17 (8.1) 11 (5.0) 0.241
Beta-lactams      
 Ampicillin 3 (1.4) 3 (1.1) 1.000
 Piperacillin-tazobactam 181 (85.8) 169 (67.6) 0.000
 Cefotetan 88 (90.7) 164 (92.7) 0.644
 Ceftriaxone 2 (1.0) 4 (2.4) 0.421
 Cefepime 4 (1.9) 8 (2.9) 0.563
 Imipenem 208 (99.5) 272 (99.6) 1.000

ESBL, extended-spectrum beta-lactamase; E. coli, Escherichia coli.

Table 7.
Comparison of Antimicrobial Susceptibility of Extended-spectrum Beta-lactamase-producing E. coli between Community-acquired Cholangitis and Hospital-acquired Cholangitis
Antimicrobial agent, n (%) ESBL(+) E. coli in community-acquired cholangitis (n=386) ESBL(+) E. coli in hospital-acquired cholangitis (n=99) p-value
Aminoglycoside      
 Amikacin 318 (82.6) 83 (83.8) 0.881
Quinolone      
 Ciprofloxacin 25 (7.3) 3 (3.4) 0.231
Beta-lactams      
 Ampicillin 6 (1.6) 0 (0.0) 0.353
 Piperacillin-tazobactam 284 (77.2) 66 (71.0) 0.223
 Cefotetan 187 (91.7) 65 (92.9) 1.000
 Ceftriaxone 5 (1.8) 1 (1.2) 1.000
 Cefepime 11 (2.9) 1 (1.0) 0.474
 Imipenem 382 (99.7) 98 (99.0) 0.369

ESBL, extended-spectrum beta-lactamase; E. coli, Escherichia coli.

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