Chin Med J 2012;125(10):1772-1776

1772

Original article
Clinical study of distribution and drug resistance of pathogens in
patients with severe acute pancreatitis
SU Mao-sheng, LIN Mao-hu, ZHAO Qing-hua, LIU Zhi-wei, HE Lei and JIA Ning
Keywords: pathogen; drug resistance; severe acute pancreatitis
Background Previous researches about necrotic pancreatic tissue infections are numerous, but the study on systemic
infection related to the severe acute pancreatitis (SAP) treatment period is limited. This study aimed to investigate the
distribution and drug resistance of pathogenic bacteria in patients who had hepatobiliary surgery for SAP during the past
three years.
Methods A retrospective study was conducted on the distribution, category and drug resistance of pathogenic bacteria
in patients who had hepatobiliary surgery for SAP from 2008 to 2011.
Results A total of 594 pathogenic bacteria samples were isolated. Among them 418 isolates (70.4%) were Gram
bacteria negative, 142 isolates (23.9%) were Gram bacteria positive, and 34 isolates (5.7%) were found fungi. The most
common Gram negative bacteria were Escherichia coli (19.8%), and the dominant Gram positive pathogenic bacteria
were Enterococcus faecium. The distribution of SAP-related infectious pathogens was mainly in peritoneal drainage fluid,
sputum, bile, and wound secretions. Almost all the Gram negative pathogenic bacteria were sensitive to carbapenum.
Extended-spectrum -lactamases (ESBLs) producing strains were more resistant to penicillins and cephalosprins than
the ESBLs non-producing strains. Staphylococcus was sensitive to vancomycin and linezolid. The drug resistance of
meticillin-resistant staphylococcus (MRS) to commonly used antibiotics was higher than meticillin-sensitive streptococcus
(MSS). Enterococcus sp. exhibited lower drug-resistance rates to vancomycin and linezolid.
Conclusions Gram negative bacteria were the dominant SAP-related infection after hepatobiliary surgery. A high
number of fungal infections were reported. Drug resistant rates were high. Rational use of antibiotics according to the site
of infection, bacterial species and drug sensitivity, correctly executing the course of treatment and enhancing hand
washing will contribute to therapy and prevention of SAP-related infection and decrease its mortality.
Chin Med J 2012;125(10):1772-1776

evere acute pancreatitis (SAP) is a major critical

disease of hepatobiliary surgery in the intensive care
unit (ICU). Inflammatory cytokines produced by necrotic
pancreatic tissue are released into the bloodstream and
injure organs. Its mortality rate still remains as high as to
30% despite the current SAP therapies1 that have made
great progress. SAP-related infections are a major factor
that contribute to mortality (50%80% mortality).2,3 In
addition to necrotic pancreatic tissue infections, the
categories
of
infections
also
include
other
intra-abdominal infections, lung infections, venous
catheter infections, wound infections, urinary tract
infections, and bloodstream infections. There are
extensive previous researches about the necrotic
pancreatic tissue infections, but the researches of
systemic infection related to the SAP treatment period are
still limited. On the other hand, antimicrobial agents for
the treatment of SAP associated infections have an
irreplaceable position along with surgical drainage.
Therefore we conducted a survey of microbiological
examination of 594 multiple infection specimens in
severe pancreatitis cases admitted to Peoples Liberation
Army General Hospital during August 2008July 2011.
We studied the distribution of SAP related pathogen
infection and analyzed the drug resistance in order to find
the characteristics of bacterial distribution and antibiotic
sensitivity. This information will have important

significance for the treatment of SAP-related infections

and decrease SAP-related infection mortality.
METHODS
Subjects
Ten specimens from SAP patients, including sputum,
DOI: 10.3760/cma.j.issn.0366-6999.2012.10.016
Department of Hepatobiliary Surgery (Su MS, Zhao QH, Liu ZW
and He L), Infection Management and Disease Control Division
(Jia N), Chinese Peoples Liberation Army General Hospital,
Beijing 100853, China
Department of Urology, the First Affiliated Hospital of Chinese
Peoples Liberation Army General Hospital, Beijing 100051, China
(Lin MH)
Correspondence to: Dr. HE Lei, Department of Hepatobiliary
Surgery, Chinese Peoples Liberation Army General Hospital,
Beijing 100853, China (Tel: 86-10-66938233. Fax: 86-1068241383. Email: bud-lotus@sohu.com); Dr. JIA Ning, Infection
Management and Disease Control Division, Chinese Peoples
Liberation Army General Hospital, Beijing 100853, China (Tel:
86-10-66875043. Fax: 86-10-66936145. Email: jianing@263.net)
SU Mao-sheng and LIN Mao-hu contributed equally to this
manuscript.
This work was supported by grants from the National Natural
Science Foundation of China (No. 30972523) and the Foundation
of the Twelfth Five-year Plan for Medical Science Development
of Peoples Liberation Army (No. CWS11J109).
Potential conflict of interests relevant to this article: None.

Chinese Medical Journal 2012;125(10):1772-1776

bronchial aspirates, pus and secretions, urine, blood, etc,

were collected by aseptic techniques from hospitalized
patients who underwent hepatobiliary surgery from
August 2008 to July 2011. Pathogenic species were
cultured and isolated from selected specimens.
Bacterial identification and susceptibility test
Blood agar was used for culture of pathogenic bacteria.
Drug susceptibility of Gram negative bacteria was
detected using the Kirby-Bauer (KB) method with 13
antibiotics including amoxicillin/clavulanic acid,
amikacin, ampicillin/sulbactam, cefuroxime, cefotaxime,
imipenem,
ceftazidime,
cefepime,
meropenem,
ciprofloxacin, cefoperazone/sulbactam, piperacillin/
tazobactam, and cotrimoxazole. Drug susceptibility of
Gram-positive bacteria was detected with 12 antibiotics
including gentamicin, penicillin, cefoxitin, ampicillin/
sulbactam,
cefazolin,
levofloxacin,
vancomycin,
erythromycin, clindamycin, cotrimoxazole, rifampicin,
and linezolid. The standard strain of E. coli ATCC25922
was used for quality control. Results were determined
according to guidelines published by the U.S. National
Committee for Clinical Laboratory (NCCLS). Antibiotic
discs and blood agar plate were purchased from Oxoid
Ltd (Basingstok, UK).
RESULTS
Pathogen distribution
Five hundred and ninety-four bacterial samples were
isolated, that included 418 (70.4%) Gram negative
bacterial isolates, 142 Gram-positive bacterial isolates
(23.9%), and 34 fungi isolates (5.7%). Among the
isolated Gram negative pathogenic bacteria, E. coli was
the most common (19.8%), followed by Pseudomonas
aeruginosa (13.0%), and Acinetobacter baumannii
(11.8%). Among the isolated Gram positive pathogenic
bacteria, Entercoccus faecium was the most common
(10.1%), followed by coagulase-negative staphylococci
(5.4%), and Enterococcus faecalis (2.9%). Candida
tropicalis and Candida albicans were the main fungi
strains (Table 1). The main sources of pathogens were
peritoneal drainage fluid, sputum, bile and wound

1773

secretions (Table 2)
Drug susceptibility results
This study showed that the rates of antimicrobial drug
resistance were significantly higher among the main
Gram negative bacteria (including E. coli and K.
pneumoniae strains) in the extended-spectrum
-lactamases (ESBLs) producing strains than in the
ESBLs non-producing strains that came from the
hepatobiliary surgery wards. But the incidence of drug
resistance to carbapenem and to drugs containing enzyme
inhibitors was low, thus these kinds of antibiotics were
the better choice.
The drug resistant rates of Acinetobacter baumannii to
Table 1. Distribution of 594 pathogen strains
Pathogens
Gram negative bacteria
Escherichia coli
Pseudomonas aeruginosa
Acinetobacter baumannii
Klebsiella pneumoniae
Proteus vulgaris
Gram positive bacteria
Enterococcus faecium
Coagulase-negative staphylococci
Enterococcus faecalis
Staphylococcus aureus
Fungi
Candida tropicalis
Candida albicans
Total

Strains isolated (n) Constituent ratio (%)

418
70.4
118
19.9
77
12.9
70
11.8
56
9.4
10
1.7
142
23.9
60
10.1
32
5.4
17
2.9
11
1.9
34
5.7
12
2.0
10
1.7
594
100

Table 2. Source distribution of 594 specimens

Specimens
Peritoneal drainage fluid
Sputum
Bile
Wound secretions
Blood
Central venous catheter
Tissue
Pleural effusion
Abscess
Urine
Total

n
176
131
80
59
47
42
17
17
15
10
594

Constituent ratio (%)

29.6
22.1
13.5
9.9
7.9
7.1
2.9
2.9
2.5
1.6
100

Table 3. The resistance rates of main Gram-negative bacilli to antimicrobial drugs (%)
Drugs
Amoxicillin/clavulanic acid
Amikacin
Ampicillin/sulbactam
Cefuroxime
Cefotaxime
Imipenem
Ceftazidime
Cefepime
Meropenem
Ciprofloxacin
Cefoperazone/sulbactam
Piperacillin/tazobactam
Cotrimoxazole

Escherichia coli (n=118)

Pseudomonas aeruginosa (n=77)
Acinetobacter baumannii (n=70)
ESBL- (n=48) ESBL+ (n=70)
22.9
62.0

92.3
5.2
16.1
29.3
86.9
38.0
85.7

86.2
14.3
98.0

97.8
8.6
96.7

99.7
0.3
0.4
36.6
83.1
6.8
85.8
29.4
87.3
7.8
89.6
37.4
89.1
1.1
0.3
29.1
82.4
52.3
84.2
36.2
89.2
5.7
47.2
49.6
82.8
7.8
14.5
35.2
89.8
57.4
82.1
92.9
81.7
ESBL-: ESBL non-producing bacteria; ESBL+: ESBL producing bacteria.

Klebsiella pneumoniae (n=56)

ESBL- (n=32) ESBL+ (n=24)
26.7
61.3
5.6
28.1
30.1
94.5
21.4
96.1
13.8
85.5
1.2
1.3
10.5
75.4
9.8
75.9
0.9
1.9
19.4
67.9
12.9
61.8
15.6
43.1
21.4
72.4

Chin Med J 2012;125(10):1772-1776

1774

Table 4. The resistance rates of main Gram-positive bacilli to antimicrobial drugs (%)
Enterococcus faecium
Coagulase-negative staphylococci (n=32)
Staphylococcus aureus (n=11)
Drugs
Enterococcus faecalis (n=17)
(n=60)
MSSCoN (n=11)
MRSCoN (n=21)
MSSA (n=5) MRSA (n=6)
Gentamicin
77.5
9.2
45.2
49.3
21.6
82.1
Penicillin
92.7
65.2
100.0
12.1
88.4
100.0
Cefoxitin

0
100.0

0
100.0
Ampicillin/sulbactam

0.5
100.0

1.4
100.0
Cefazolin

0
100.0

0
100.0
Levofloxacin

11.7
58.3

9.1
89.6
Vancomycin
6.8
0
0
4.5
0
0
Erythromycin

76.2
91.4

70.2
80.4
Clindamycin

35.6
63.8

64.5
71
Cotrimoxazole

28.4
65.1

8.3
14.3
Rifampicin

3.3
76

4.5
16.9
Linezolid
2.9
0
0
6.4
0
0
MSSCoN: methicillin-sensitive staphylococcus coagulase-negative; MRSCoN: methicillin-resistant staphylococcus coagulase-negative; MSSA: methicillin-sensitive
Staphylococcus aureus; MRSA: methicillin-resistant Staphylococcus aureus.

common antibiotics were 81.7%99.7%. The incidence of

drug resistance to amikacin, meropenem, and ceftazidime
was low in Pseudomonas aeruginosa (Table 3). Among
Gram positive bacteria, the drug resistance of
methicillin-resistant S. aureus (MRSA) to commonly
used antibiotics was higher than in methicillin-sensitive S.
aureus (MSSA). Vancomycin and linezolid resistant
Staphylococcus spp. were not detected. Resistance rates
to linezolid and vancomycin in enterococcus were low
(Table 4).
DISCUSSION
SAP is a serious type of acute pancreatitis, in which the
mortality rate may be up to 30%.1 Features of SAP
include local complications (pancreatic necrosis and
pseudocyst) and systemic complications (organ
dysfunction, shock, and acute respiratory distress
syndrome (ARDS)), inflammatory mediators, and
cytokine production by necrotic pancreatic tissue that is
released into the bloodstream and affects various organs.
Infection related complications are the main critical
circumstances of SAP. The infection of necrotic pancreas
tissue often occurs in the second phase of SAP. This
phase is usually recorded in the second week (24%
patients) and the fourth week of the disease (71%
patients).2 Septic complications of pancreatitis develop in
40%70% of patients with 50%80% mortality.2,3 The
mortality correlates with the extent of pancreatic necrosis.
According to current studies, infection in SAP is
considered to cause a fatal outcome unless treated with
surgical necrosectomy and lavage,4-6 or with percutaneous
catheter drainage (PCD).7,8 It has become the most
important risk factor of death from necrotizing
pancreatitis.9
SAP-related infections not only include infections of
necrotic
pancreatic
tissue,
but
also
include
intra-abdominal infections, lung infections, catheter
related infections, wound infections, urinary tract
infections, and bloodstream infections. Infection
associated with the necrotic pancreas is described in
many reports.10-12 However, in the treatment of SAP, the
associated multi-system infections also play an important

role in the prognosis. In our literature review we found

few studies about such conditions. Antimicrobial agents
have an irreplaceable position in the treatment of SAP
associated infections, along with surgical drainage. Even
leading surgical centers have reported that mortality rates
associated with early surgery are 20%50% or even
higher.13,14 Our results report the microbiological species
isolated from SAP-accompanied infections. In this
research, we found the main infection sites were
abdominal drainage fluid, sputum, bile juice, and wound
secretions. This result was related to the character of
hepatobiliary disease such as complicated disease range,
longer time operation and NPO (Nihil per os), lower
immune system, more invasive catheter and
broad-spectrum antibiotics, etc. The pancreas and the area
around it were the main infection sites. Infection can
occur via haematogenous spread, transmural migration
through the bowel wall, via ascites to the pancreas, via
the lymphatics to the circulation, or via the duodenum to
the main pancreatic duct.15,16
Five hundred and ninety-five bacterial isolates were
found, of which 418 were Gram negative, 142 were Gram
positive, and there were 34 fungi. Among the Gram
negative isolates, E. coli was the most frequently
identified. P. aeruginosa and A. baumannii were the
second most frequently identified strains. In the Gram
positive bacteria group, the dominant pathogens were E.
faecium, coagulase negative staphylococci and E.
faecalis. The main fungi were C. tropicalis and C.
albicans.
In this study, the results of drug sensitivity testing showed
that the antimicrobial activities of carbapenems, the third
generation cephalosporins plus enzyme inhibitors, and
penicillin antibiotics were better against E. coli and K.
pneumoniae. The drug resistance rates of Gram positive
bacteria to erythromycin and penicillin were higher than
other drugs. No vancomycin resistant bacterial strain was
found. The drug resistance rate of P. aeruginosa and A.
baumannii, which were opportunistic pathogens, showed
a gradually increasing trend compared with previous
studies. Because of the existence of various drug
resistance mechanisms, antibiotic selection has become

Chinese Medical Journal 2012;125(10):1772-1776

more difficult. It also accounts for the occurrence of

uncontrollable multi-site infections in patients after an
operation and increases mortality. In the study by Tsui et
al,17 cultured organisms were usually multidrug-resistant,
including Gram negative bacteria, Gram positive bacteria,
and fungi. These organisms were mainly included, for
example, P. aeruginosa, Xanthomonas maltophilia,
enterococcus, methicillin-resistant S. aureus, C. albicans
and C. krusei. A high isolation rate of A. baumannii was
found in another study18 which was considered to
correlate with the high rate of intensive care unit
(ICU)-acquired infection in patients with severe sepsis.
Fungi, which are considered to be caused by extensive
use of extended-spectrum antibiotics, are frequently
isolated in cases of severe sepsis. The incidence of
invasive fungal infection is reported to be 28.3% in the
severe sepsis patients.18-20 But Tsui et al17 reported a
relatively low incidence of fungal infections. They
considered it to still be unclear whether the use of
long-term antibiotic treatment promoted fungal
infections.
All of the Gram negative pathogenic bacterial strains
were sensitive to carbapenem in this investigation. So for
experimental treatment of infection, carbapenems, the
third generation cephalosporins plus enzyme inhibitors,
and penicillin should be chosen first. Peng et al 21
reported that almost all of the Gram negative pathogenic
bacteria were sensitive to carbapenum. Aminoglycosides
should be used cautiously because of their ototoxicity and
nephrotoxicity in spite of their good antibacterial activity.
ESBLs producing strains were more resistant to
penicillins and cephalosprins than ESBLs non producing
strains. Staphylococcus was sensitive to vancomycin and
linezolid. The drug resistance of meticillin-resistant
staphylococcus (MRS) was higher to commonly used
antibiotics than meticillin-sensitive streptococcus (MSS).
Vancomycin and linezolid showed lower drug-resistance
rates against Enterococcus sp. In order to avoid or slow
the development of the drug resistant bacterial strains,
combinations of two kinds of antibiotics were necessary
for complicated and critical patients. The study also
indicated that surgeons should increase the sample test
rate of surgical infection patients so as to improve the
specificity of the prescription. Before the pathogen
cultured results are available, antibiotics against both
Gram negative and Gram positive bacteria could be
selected for treatment. After getting results, we should
quickly adjust antibiotics according to bacteria culture
results and the disease progression. This could reduce the
occurrence and dissemination of drug resistant bacterial
strains.

1775

quality of care provided. Thus more attention should be

paid to sanitary precautions for decreasing the occurrence
of drug resistant bacterial strains, such as hand washing in
the ICU.18
In conclusion, for pathogen distribution of SAP-related
infection in hepatobiliary surgery, Gram negative bacteria
were dominant, and an increased number of fungal
infections were reported. Drug resistant rates were high.
Rational use of antibiotics according to the site of
infection, bacterial species and drug sensitivity, correctly
monitoring the course of treatment and enhancing hand
washing will contribute to therapy and prevention of
SAP-related infections and decrease their mortality.
REFERENCES
1.

2.

3.
4.
5.

6.

7.

8.

9.

10.

11.
12.

On the other hand, the occurrence of SAP associated

infections is the result of complex interactions probably
involving
patients underlying
conditions,
the
characteristics of the patient population, the extensive use
of extended-spectrum antibiotics, low attention to
sanitary precautions, the invasive interventions, and the

13.

Piacik M, Rydzewska G, Milewski J, Olszewski S,

Furmanek M, Walecki J, et al. The results of severe acute
pancreatitis treatment with continuous regional arterial
infusion of protease inhibitor and antibiotic. Pancreas 2010;
39: 863-867.
Mifkovic A, Pindak D, Daniel I, Pechan J. Septic
complications of acute pancreatitis. Bratisl Lek Listy 2006;
107: 296-313.
Beger HG, Rau B, Mayer J, Pralle U. Natural course of acute
pancreatitis. World J Surg 1997; 21: 130-135.
Beger HG. Surgical management of necrotizing pancreatitis.
Surg Clin North Am 1989; 69: 529-549.
Charnley RM, Lochan R, Gray H, OSullivan CB, Scott J,
Oppong KE. Endoscopic necrosectomy as primary therapy in
the management of infected pancreatic necrosis. Endoscopy
2006; 38: 925-928.
Uhl W, Warshaw A, Imrie C, Bassi C, McKay CJ, Lankisch
PG, et al. IAP guidelines for the surgical management of
acute pancreatitis. Pancreatology 2002; 2: 565-573.
Baril NB, Ralls PW, Wren SM, Selby RR, Radin R, Parekh
D, et al. Does an infected peripancreatic fluid collection or
abscess mandate operation? Ann Surg 2000; 231: 361-367.
Szentkereszty Z, Kerekes L, Hallay J, Czako D, Spy P.
CT-guided percutaneous peripancreatic drainage: a possible
therapy in acute necrotizing pancreatitis. Hepatogastroenterology 2002; 49: 1696-1698.
Sun B, Dong CG, Wang G, Jiang HC, Meng QH, Li J, et al.
Analysis of fatal risk factors for severe acute pancreatitis: a
report of 141 cases. Chin J Surg (Chin) 2007; 45: 1619-1622.
Bchler MW, Gloor B, Mller CA, Friess H, Seiler CA, Uhl
W. Acute necrotizing pancreatitis: treatment strategy
according to the status of infection. Ann Surg 2002; 232:
619-626.
Beger HG, Rau B, Isenmann R. Natural history of necrotizing
pancreatitis. Pancreatology 2003; 3: 93-101.
Beger HG, Bittner R, Block S, Bchler M. Bacterial
contamination of pancreatic necrosis. A prospective clinical
study. Gastroenterology 1986; 91: 433.
Rodriguez JR, Razo AO, Targarona J, Thayer SP, Rattner
DW, Warshaw AL, et al. Debridement and closed packing for
sterile or infected necrotizing pancreatitis: insights into
indications and outcomes in 167 patients. Ann Surg 2008;

Chin Med J 2012;125(10):1772-1776

1776

14.

15.

16.
17.

18.

247: 294-299.
Fernndez-del Castillo C, Rattner DW, Makary MA,
Mostafavi A, McGrath D, Warshaw AL. Debridement and
closed packing for the treatment of necrotizing pancreatitis.
Ann Surg 1998; 228: 676-684.
Noor MT, Radhakrishna Y, Kochhar R, Ray P, Wig JD, Sinha
SK, et al. Bacteriology of infection in severe acute
pancreatitis. JOP 2011; 12: 19-25.
Lee TW, Soh CR. Reducing pancreatic infection in acute
pancreatitis. Sgh Proceedings 2007; 16: 112-117.
Tsui NC, Zhao E, Li Z, Miao B, Cui Y, Shen Y, et al.
Microbiological findings in secondary infection of severe
acute pancreatitis: a retrospective clinical study. Pancreas
2009; 38: 499-502.
Cheng B, Xie G, Yao S, Wu X, Guo Q, Gu M, et al.
Epidemiology of severe sepsis in critically ill surgical

19.

20.

21.

patients in ten university hospitals in China. Crit Care Med

2007; 35: 2538-2546.
Trikudanathan G, Navaneethan U, Vege SS. Intra-abdominal
fungal infections complicating acute pancreatitis: a review.
Am J Gastroenterol 2011; 106: 1188-1192.
Vege SS, Gardner TB, Chari ST, Baron TH, Clain JE, Pearson
RK, et al. Outcomes of intra-abdominal fungal vs. bacterial
infections in severe acute pancreatitis. Am J Gastroenterol
2009; 104: 2065-2070.
Peng YB, Huang J, Qin S, Wu J, Mao EQ, Tang YQ, et al.
Investigation of distribution of bacteria and fungi in severe
acute pancreatitis. Chin J Surg (Chin) 2010; 48: 496-501.

(Received March 12, 2012)

Edited by WANG Mou-yue