Li YT, Yu CB, Huang JR, Qin ZJ, Li LJ. Pathogen profile and drug resistance analysis of spontaneous peritonitis in cirrhotic patients. World J Gastroenterol 2015; 21(36): 10409-10417 [PMID: 26420967 DOI: 10.3748/wjg.v21.i36.10409]
Corresponding Author of This Article
Lan-Juan Li, MD, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79 Qingchun Road, Hangzhou 310003, Zhejiang Province, China. ljli@zju.edu.cn
Research Domain of This Article
Infectious Diseases
Article-Type of This Article
Retrospective Study
Open-Access Policy of This Article
This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Yong-Tao Li, Cheng-Bo Yu, Jian-Rong Huang, Lan-Juan Li, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
Zheng-Ji Qin, Medical Statistics Office of Public Health Department, Nantong University, Nantong 226000, Jiangsu Province, China
ORCID number: $[AuthorORCIDs]
Author contributions: Li LJ designed the research; Li YT performed the research; Yu CB and Huang JR contributed to providing patient data; Li YT and Qin ZJ analyzed the data; Li YT and Li LJ wrote the paper.
Supported by Grants from the National Basic Research Program of China, 973 Program, No. 2013CB531401.
Institutional review board statement: The study was reviewed and approved by the medical ethics committee at The First Affiliated Hospital of Zhejiang University School of Medicine.
Informed consent statement: Patients were not required to give informed consent to the study as the analysis used anonymous clinical data that were obtained after each patient agreed to treatment by written consent. For full disclosure, the details of the study are published on the home page of the First Affiliated Hospital of Zhejiang University School of Medicine.
Conflict-of-interest statement: The authors declare no competing interests.
Data sharing statement: No additional data are available.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Lan-Juan Li, MD, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, College of Medicine, Zhejiang University, No. 79 Qingchun Road, Hangzhou 310003, Zhejiang Province, China. ljli@zju.edu.cn
Telephone: +86-571-87236458 Fax: +86-571-87236459
Received: March 26, 2015 Peer-review started: March 28, 2015 First decision: June 25, 2015 Revised: July 1, 2015 Accepted: September 2, 2015 Article in press: September 2, 2015 Published online: September 28, 2015
Abstract
AIM: To investigate the microbiological characteristics and drug resistance in liver cirrhosis patients with spontaneous peritonitis.
METHODS: We analyzed the data of patients with liver cirrhosis and abdominal infection at the First Affiliated Hospital of Zhejiang University between January 2011 and December 2013. Pathogens present in the ascites were identified, and their sensitivity to various antibiotics was determined.
RESULTS: We isolated 306 pathogenic bacteria from 288 cases: In 178 cases, the infection was caused by gram-negative strains (58.2%); in 85 cases, gram-positive strains (27.8%); in 9 cases, fungi (2.9%); and in 16 cases, more than one pathogen. The main pathogens were Escherichia coli (E. coli) (24.2%), Klebsiella pneumoniae (18.9%), Enterococcus spp. (11.1%), and Staphylococcus aureus (7.5%). Of the 306 isolated pathogens, 99 caused nosocomial infections and 207 caused community-acquired and other infections. The E. coli and K. pneumoniae strains produced more extended-spectrum β-lactamases in cases of nosocomial infections than non-nosocomial infections (62.5% vs 38%, P < 0.013; 36.8% vs 12.8%, P < 0.034, respectively). The sensitivity to individual antibiotics differed between nosocomial and non-nosocomial infections: Piperacillin/tazobactam was significantly more effective against non-nosocomial E. coli infections (4% vs 20.8%, P < 0.021). Nitrofurantoin had stronger antibacterial activity against Enterococcus species causing non-nosocomial infections (36.4% vs 86.3%, P < 0.009).
CONCLUSION: The majority of pathogens that cause abdominal infection in patients with liver cirrhosis are gram-negative, and drug resistance is significantly higher in nosocomial infections than in non-nosocomial infections.
Core tip: Monitoring drug resistance in cases of abdominal infection with liver cirrhosis is important for establishing appropriate antibiotic regimes, reducing the generation of drug-resistant bacteria and reducing the associated mortality. Therefore, this study addressed two primary issues regarding spontaneous peritonitis in cirrhotic patients in China: first, the pathogen profile and, second, drug resistance, and determined the differences between nosocomial infections and non-nosocomial infections. Based on these findings, clinicians can select the appropriate antibiotic treatment to control the emergence and development of pathogenic bacteria-resistant strains in intra-abdominal infections.
Citation: Li YT, Yu CB, Huang JR, Qin ZJ, Li LJ. Pathogen profile and drug resistance analysis of spontaneous peritonitis in cirrhotic patients. World J Gastroenterol 2015; 21(36): 10409-10417
Decompensated liver cirrhosis affects 25% to 47% of the population, and ascites is the most common complication; it is characterized by decreased immune function, which consequently leads to abdominal cavity, blood, lung, urinary tract and other infections that worsen with time and have a high fatality rate[1,2]. Studies have shown that decreased immunity combined with weak intestinal motility, increased intestinal permeability, reduced secretion of intestinal antimicrobial peptides and other factors are likely to lead to bacterial translocation in patients with decompensated cirrhosis[3-5]. Spontaneous bacterial peritonitis is a common infection; it causes further deterioration of liver function, multi-organ failure and sepsis, which are associated with poor prognosis and a low survival rate[6-9]. The mortality rate associated with multiple organ failure and septicopyemia caused by spontaneous bacterial peritonitis is still over 75%[10-12]. Therefore, antibiotic therapy for spontaneous peritonitis has become an important means of improving the survival rate in patients with cirrhosis.
Third-generation cephalosporins are mainly used for the treatment of spontaneous bacterial peritonitis; however, it was shown that cefotaxime, one of the most commonly used cephalosporins, had a lower success rate than expected[13]. This is probably attributable to the emergence of antibiotic-resistant pathogen strains. While earlier reports showed that 70% of the cases of spontaneous bacterial peritonitis were caused by gram-negative bacteria such Escherichia coli (E. coli) and Klebsiella pneumoniae[14], this bacterial profile has begun to change and the emergence of resistant bacterial species has been indicated. In recent years, the incidence of gram-positive abdominal infections in patients with decompensated cirrhosis has increased significantly; this phenomenon is attributed to the use of antibiotics that alter the intestinal flora such that it is conducive to the translocation of gram-positive bacteria[15-17]. Another study has attributed the increasing incidence of gram-positive bacterial peritonitis to increased resistance to quinolones, such as norfloxacin, which are also commonly used for the treatment of this infection[18]. Thus, it is important to study in detail the pathogen profiles in spontaneous bacterial peritonitis and resistance of the pathogens to currently used antibiotics. Based on this, clinicians can select the appropriate antibiotic treatment to control the emergence and development of pathogenic bacteria-resistant strains in intra-abdominal infections.
Although some studies have examined the pathogen profiles and drug resistance in spontaneous peritonitis[19,20], there is definitely a need for new and comprehensive data on the same. Therefore, in this study, we retrospectively surveyed and analyzed the types of pathogens and their drug resistance in the ascites culture samples of 288 patients who had cirrhosis with abdominal infection at our hospital between January 2011 and December 2013.
MATERIALS AND METHODS
Clinical data
The medical ethics committee at The First Affiliated Hospital of Zhejiang University School of Medicine approved the protocol for the retrospective study before the clinical data were collected. All cirrhotic patients at our hospital between January 2011 and December 2013 were retrospectively analyzed. Each case history was registered using a unified registration form: the information included gender; age; duration of hospitalization; medical history; clinical manifestations; hospitalization course; disease prognosis; and the results of abdominal ultrasonography, abdominal paracentesis, routine ascites test, ascites culture, liver function test, kidney function test, blood coagulation test, and routine blood examination. If the ascites culture results obtained following abdominocentesis at 48 h after admission was positive, this was considered to indicate a nosocomial infection. If a patient repeatedly tested positive for the same pathogen in the ascites culture examination, only the first result was recorded. The criteria for the diagnosis of spontaneous bacterial peritonitis were positive ascites culture for bacteria and neutrophil count in the ascites sample greater than 250/mm3[21].
Materials
The Bactec blood culture system produced by Becton Dickinson (Mountain View, CA, United States) and antibacterial agents, antimicrobial gradient strips and media produced by Oxoid (Basingstoke, United Kingdom) were used. The antibacterial agents included piperacillin/tazobactam, ampicillin/sulbactam, gentamicin, amikacin, imipenem, meropenem, ciprofloxacin, levofloxacin, moxifloxacin, cefotaxime, ceftriaxone, cefoperazone/sulbactam, cefepime, aztreonam, ceftazidime, penicillin G, oxacillin, erythromycin, vancomycin, clindamycin, tetracycline, rifampicin, and gentamicin, which were used at high concentrations (120 μg). The test strips of vancomycin used were purchased from AB BIODISK (Solna, Sweden).
Susceptibility testing
The Kirby-Bauer (KB) method was used for drug sensitivity testing on Müller-Hinton agar. The results of the drug sensitivity tests were assessed according to the standards of the US Clinical and Laboratory Standards Institute (CLSI) in 2011. Methicillin-resistant Staphylococcus aureus (S. aureus, MRSA) strains and methicillin-resistant coagulase-negative staphylococci (MRCNS) were identified using the standard method for susceptibility testing of antimicrobial drugs recommended by the National Committee for Clinical Laboratory Standards (NCCLS) in 2003, except that oxacillin was replaced by cefoxitin. S. aureus ATCC25923, E. coli ATCC25922 and Pseudomonas aeruginosa ATCC27853 were used as quality-control strains. Paper screening for extended-spectrum β-lactamases (ESBLs) and the enzyme inhibitor enhanced paper confirmatory method recommended by the US CLSI were used to examine ESBL production in E. coli and K. pneumoniae.
Statistical analysis
The variables were counting variables, and the description of the count data is described by a ratio or the rate of the data. The t test was used to analyze measurement data, and the χ2 test was used to analyze count data. P < 0.05 was considered to indicate statistical significance. SPSS 17.0 was used for all the statistical analyses.
RESULTS
Clinical characteristics
The clinical data of 6086 patients with liver cirrhosis were gathered over the three-year study period. Of these patients, 506 had abdominal infections, excluding secondary abdominal infections (ascites fluid neutrophil count was ≥ 250/mm3, a positive ascites fluid culture, and evidence of an intra-abdominal source of infection, demonstrated by surgery, autopsy, or abdominal CT)[22], according to the results of the ascites neutrophil count and bacterial culture. Spontaneous bacterial peritonitis was identified in 288 cases (198 male and 90 female patients; age range, 23-79 years; mean age, 55 ± 12.6 years), and 306 pathogens were isolated. Most patients had advanced liver cirrhosis (68.9%, Child C; 28.6%, Child B; and 2.5%, Child A); the mean Child score was 10.5. A few patients (less than 10%) had received preventive quinolone treatment. Among the 288 patients, 208 had abdominal pain and fever, 22 had septic shock and 42 had multiple organ dysfunction syndrome. Fifty-one of the patients died at the end of the treatment. In 137 cases, the WBC count was ≥ 10.0 × 109 and in 45 cases, the WBC count was ≤ 4.0 × 109.
Isolation and characterization of pathogens
A total of 306 pathogens were isolated from the 288 cases: 178 patients were positive for gram-negative bacteria (58.2%), 85 for gram-positive bacteria (27.8%), 9 for fungi (2.9%), and 16 for more than one pathogen. The main pathogens identified were E. coli (74 strains, 24.2%), K. pneumoniae (58 strains, 18.9%), glucose non-fermenting bacteria (including Acinetobacter baumannii and P. aeruginosa) (6.2%), Enterococcus species (11.1%), coagulase-negative staphylococci (CNS, 5.6%), S. aureus (7.5%), and Streptococcus pneumoniae (3.6%). Among the 306 isolated pathogens, 207 strains caused community-acquired and other hospital-acquired infections in 206 patients (67.6%). Among the 206 patients, 82 had hospital-acquired infections, in whom 99 strains were identified (32.4%). A. baumannii, P. aeruginosa and fungal pathogens caused a significantly higher number of nosocomial than non-nosocomial infections (Table 1). Six MRSA strains were detected [detection rate, 26.1% (6/23)], and five MRCNS strains were detected [29.4% (5/17)]. Fungal infections mainly occurred in patients with nosocomial infections.
Table 1 Distribution of the major pathogens in the ascites samples of 288 patients with spontaneous bacterial peritonitis between 2011 and 2013 n (%).
Pathogen
Total (n= 306)
Non-nosocomial infection (n= 207)
Nosocomial infection(n= 99)
P value(χ2test)
Gram-negative bacteria
178 (58.2)
113 (54.6)
65 (65.7)
0.06
Escherichia coli
74 (24.2)
50 (24.1)
24 (24.2)
0.98
Klebsiella pneumoniae
58 (18.9)
39 (18.8)
19 (19.1)
0.94
Acinetobacter spp.
10 (3.3)
2 (0.9)
8 (8.1)
0.001
Pseudomonas aeruginosa
9 (2.9)
2 (0.9)
7 (7.1)
0.003
Enterobacter cloacae
17 (5.6)
12 (5.8)
5 (5.1)
0.79
Aerogenes spp.
10 (3.3)
8 (3.9)
2 (2.0)
0.39
Gram-positive bacteria
85 (27.8)
58 (28.0)
27 (27.3)
0.89
Enterococcus
34 (11.1)
22 (10.6)
12 (12.1)
0.69
Staphylococcus aureus
23 (7.5)
16 (7.7)
7 (7.1)
0.83
Coagulase-negative staphylococci
17 (5.6)
12 (5.8)
5 (5.1)
0.79
Streptococcus pneumoniae
11 (3.6)
8 (3.9)
3 (3.0)
0.71
Fungi
9 (2.9)
2 (0.9)
7 (7.1)
0.004
Drug tolerance of the isolated pathogens
Gram-negative bacteria: Imipenem, meropenem, piperacillin/tazobactam, and amikacin showed good antibacterial activity against E. coli and K. pneumoniae in cases of abdominal infection (sensitivity rate, ≥ 86.2%). Piperacillin/tazobactam was significantly more effective against non-nosocomial E. coli infections; gentamicin, cefoperazone/sulbactam, ceftriaxone, and ampicillin/sulbactam were more effective against non-nosocomial infections caused by K. pneumoniae. The sensitivity rates of P. aeruginosa and Acinetobacter spp. were generally low; however, Acinetobacter spp. showed greater drug tolerance than P. aeruginosa (Table 2). Thirty-four E. coli strains that produced ESBLs were detected [detection rate, 45.9% (34/74)], and 12 K. pneumoniae strains that produced ESBL were detected [detection rate, 20.7% (12/58)]. ESBL was produced in more cases of nosocomial infections than in non-nosocomial infections, and the sensitivity of individual antibiotics differed between nosocomial and non-nosocomial infections: Ampicillin/sulbactam and ceftriaxone were significantly more effective against non-nosocomial K. pneumoniae infections (23.1% vs 57.9%, P < 0.009; 28.2% vs 63.4%, P < 0.011) ( Tables 3 and 4).
Table 2 Drug resistance rate of major gram-negative bacteria to commonly used antibacterial agents.
Antibacterial agents
Escherichia coli (n = 74)
Klebsiella pneumoniae (n = 58)
Acinetobacter spp (n = 10)
Pseudomonas aeruginosa(n = 9)
Strains
Drug resistance rate (%)
Strains
Drug resistance rate (%)
Strains
Drug resistance rate (%)
Strains
Drug resistance rate (%)
Ampicillin/sulbactam
30
40.5
23
39.7
8
80
7
77.8
Piperacillin/tazobactam
7
9.4
8
13.8
6
60
3
33.3
Ceftriaxone
18
24.3
20
34.5
8
80
9
100
Cefepime
31
41.9
15
25.9
7
70
3
33.3
Cefoperazone/sulbactam
12
16.2
17
29.3
4
40
3
33.3
Ceftazidime
33
44.6
17
29.3
7
70
3
33.3
Amikacin
5
6.8
3
5.1
2
20
1
11.1
Gentamicin
37
50
12
20.7
6
60
2
22.2
Ciprofloxacin
37
50
16
27.6
7
70
3
33.3
Aztreonam
26
35.1
13
22.4
6
60
4
44.4
Imipenem
1
1.3
7
12.1
6
60
3
33.3
Meropenem
2
2.7
4
6.9
7
70
2
22.2
Table 3 Comparison of the drug resistance of Escherichia coli to commonly used antibacterial agents between nosocomial and non-nosocomial spontaneous bacterial peritonitis n (%).
Antibacterial agents
Non-nosocomial infections (n = 50)
Nosocomial infections (n = 24)
P value (χ2test)
ESBL test
19 (38.0)
15 (62.5)
0.013
Ampicillin/sulbactam
11 (28.0)
12 (66.7)
0.093
Piperacillin/tazobactam
2 (4.0)
5 (20.8)
0.021
Ceftriaxone
7 (14.0)
11 (45.8)
< 0.001
Cefepime
17 (34.0)
14 (58.3)
0.04
Cefoperazone/sulbactam
4 (8.0)
8 (33.3)
0.006
Ceftazidime
16 (32.0)
17 (70.8)
0.002
Amikacin
2 (4.0)
3 (12.5)
0.173
Gentamicin
17 (34.0)
20 (83.3)
< 0.001
Ciprofloxacin
18 (36.0)
19 (79.1)
0.001
Aztreonam
11 (22.0)
15 (62.5)
0.001
Imipenem
1 (2.0)
0 (0)
0.485
Meropenem
0 (0)
2 (8.3)
0.039
Table 4 Comparison of the drug resistance of Klebsiella pneumoniae to commonly used antibacterial agents between nosocomial and non-nosocomial spontaneous bacterial peritonitis n (%).
Antibacterial agents
Non-nosocomial infections(n = 39)
Nosocomial infections(n = 19)
P value (χ2test)
ESBL test
5 (12.8)
7 (36.8)
0.034
Ampicillin/sulbactam
11 (28.2)
12 (63.1)
0.011
Piperacillin/tazobactam
3 (7.7)
5 (26.3)
0.054
Ceftriaxone
9 (23.1)
11 (57.9)
0.009
Cefepime
8 (20.1)
7 (36.8)
0.183
Cefoperazone/sulbactam
8 (20.1)
9 (47.4)
0.035
Ceftazidime
10 (25.6)
7 (36.8)
0.098
Amikacin
2 (5.1)
1 (5.3)
0.983
Gentamicin
5 (12.8)
7 (36.8)
0.034
Ciprofloxacin
10 (25.6)
6 (31.6)
0.635
Aztreonam
8 (20.1)
5 (26.3)
0.619
Imipenem
4 (10.3)
3 (15.8)
0.544
Meropenem
2 (5.10)
2 (10.5)
0.446
Gram-positive bacteria: The antimicrobial activity of vancomycin, nitrofurantoin and rifampin against Staphylococcus spp. in abdominal infections was strong, with a sensitivity rate of ≥ 87%. The antimicrobial activity of gentamicin, clindamycin and moxifloxacin was also strong, with a sensitivity rate of ≥ 60.9%. Enterococcus spp. had drug resistance to a variety of antibacterial agents, but vancomycin, clindamycin and gentamicin had strong antibacterial activity against Enterococcus spp., with a sensitivity rate of ≥ 70.6%. Furthermore, nitrofurantoin had stronger antibacterial activity against Enterococcus spp. that caused non-nosocomial infections. Vancomycin, rifampin, moxifloxacin and nitrofurantoin had good antibacterial activity against S. pneumoniae, with a sensitivity rate of ≥ 71.9%. The sensitivity of individual antibiotics differed between nosocomial and non-nosocomial infections: ofloxacin, levofloxacin, moxifloxacin and clindamycin were more effective against S. aureus strains that caused non-nosocomial infections. Nitrofurantoin had stronger antibacterial activity against Enterococcus spp. that caused non-nosocomial infections (36.4% vs 86.3%, P < 0.009) (Table 5, Table 6 and Table 7).
Table 5 Drug resistance rate of the major gram-positive bacteria against commonly used antibacterial agents.
Antibacterial agents
Enterococcus (n = 34)
Staphylococcus aureus(n = 23)
Coagulase-negative staphylococci(n = 17)
Streptococcus pneumoniae(n = 11)
Strains
Drug resistance rate (%)
Strains
Drug resistance rate (%)
Strains
Drug resistance rate (%)
Strains
Drug resistance rate (%)
Penicillin
26
76.5
21
91.3
15
88.2
10
90.9
Oxacillin
23
67.6
12
52.2
13
76.5
7
63.3
Erythromycin
19
55.9
14
60.9
12
70.6
8
72.7
Cefazolin
25
73.5
13
56.5
10
58.8
7
63.3
Nitrofurantoin
18
52.9
2
8.7
1
5.9
2
18.1
Rifampicin
5
14.7
3
13.0
2
11.8
1
9.1
Clindamycin
8
23.5
6
26.1
6
35.3
4
36.4
Levofloxacin
28
82.4
10
43.4
7
41.2
4
36.4
Ciprofloxacin
26
76.5
11
47.8
8
47.1
6
54.5
Gentamicin
10
29.4
3
13.0
4
23.5
2
18.1
Moxifloxacin
14
41.1
9
39.1
5
29.4
2
18.1
Vancomycin
2
5.9
0
0
0
0
0
0
Table 6 Comparison of the drug resistance of Enterococcus species to commonly used antibacterial agents between nosocomial and non-nosocomial spontaneous bacterial peritonitis n (%).
Antibacterial agents
Non-nosocomial infections (n = 22)
Nosocomial infections (n = 12)
P value (χ2test)
Penicillin
16 (72.7)
10 (83.3)
0.486
Oxacillin
14 (63.6)
9 (75.0)
0.498
Erythromycin
10 (45.5)
9 (75.0)
0.097
Cefazolin
14 (63.6)
11 (91.7)
0.077
Nitrofurantoin
8 (36.4)
10 (83.3)
0.009
Rifampicin
3 (13.6)
2 (16.7)
0.812
Clindamycin
5 (22.7)
3 (25.0)
0.881
Levofloxacin
18 (81.8)
10 (83.3)
0.912
Ciprofloxacin
18 (81.8)
8 (66.7)
0.320
Gentamicin
4 (18.2)
6 (50.0)
0.052
Moxifloxacin
7 (31.8)
7 (58.3)
0.133
Vancomycin
1 (4.5)
1 (8.3)
0.645
Table 7 Comparison of the drug resistance of Staphylococcus aureus to commonly used antibacterial agents between nosocomial and non-nosocomial spontaneous bacterial peritonitis n (%).
Antibacterial agents
Non-nosocomial infections (n = 16)
Nosocomial infections (n = 7)
P value (χ2test)
Penicillin
15 (93.8)
6 (85.7)
0.529
Oxacillin
6 (37.5)
6 (85.7)
0.033
Erythromycin
9 (56.3)
5 (71.4)
0.493
Cefazolin
8 (50.0)
5 (71.4)
0.340
Nitrofurantoin
2 (12.5)
0 (0)
0.328
Rifampicin
2 (12.5)
1 (4.3)
0.907
Clindamycin
2 (12.5)
4 (57.1)
0.025
Levofloxacin
4 (25.0)
6 (85.7)
0.007
Ciprofloxacin
5 (31.3)
6 (85.7)
0.016
Gentamicin
2 (12.5)
1 (4.3)
0.907
Moxifloxacin
3 (18.6)
6 (85.7)
0.002
Vancomycin
0 (0)
0 (0)
NS
DISCUSSION
In this study, we isolated 306 pathogens from ascites culture samples of 288 hospitalized patients with liver cirrhosis and abdominal infection over a period of 3 years: gram-negative bacteria formed the majority of the pathogens (58.2%), and mainly included E. coli, K. pneumoniae, A. baumannii, A. hydrophila, P. aeruginosa, Burkholderia cepacia and other glucose non-fermenting bacteria. Other studies have also shown that gram-negative bacteria formed the majority of pathogens in patients with liver cirrhosis complicated with spontaneous bacterial peritonitis[10,23]. However, the findings from these studies, including the present study, are in contrast to the more recent trends, which have shown an increase in the number of infections caused by gram-positive bacteria. For example, Alexopoulou et al[24] showed that 55% of the spontaneous bacterial peritonitis cases in cirrhotic patients were caused by gram-positive cocci. Furthermore, Piroth et al[25] showed that gram-positive cocci formed the majority of pathogenic bacteria in cases of spontaneous bacterial peritonitis and ascites; the authors supposed that this was related to the use of prophylactic antibiotics in patients with liver cirrhosis (which altered the intestinal flora), the use of invasive procedures and other factors. Our data showed that the use of prophylactic antibiotics was not too high in our group of patients with liver cirrhosis, which probably explains why more gram-negative than gram-positive bacteria were isolated.
Of the 306 isolated pathogens, 99 were responsible for hospital-acquired infections (32.4%); this finding was similar to that of Ariza et al[26], who found that 40.9% of cases of spontaneous bacterial peritonitis were nosocomial infections. Our patient population comprised a high number of cases with advanced cirrhosis (70.9% with Child C type). They had severe fever, abdominal pain and other symptoms of peritonitis.
In our study, the most predominant pathogen was E. coli (24.2%), followed by K. pneumoniae (18.9%) and then enterococci (11.1%). Moreover, the percentages of MRSA and MRCNS were 26.1% and 29.4% respectively. These findings are similar to some recent and older studies on the pathogen profile of spontaneous bacterial peritonitis[19,20,24,25]. Furthermore, fungal pathogens caused 2.9% of the infections, which was similar to a previous report[27]. It is therefore important to start anti-fungal treatment as soon as fungal species are discovered in the ascites culture of cirrhotic patients with peritonitis.
Our data showed that resistance of the major gram-negative as well as gram-positive bacteria to third-generation cephalosporins was higher in nosocomial infections than in non-nosocomial infections, which is in agreement with Song et al[28]’s findings and a recent study by Sheikhbahaei et al[20]. Imipenem, meropenem, piperacillin/tazobactam, and amikacin had good antibacterial activity against E. coli and K. pneumoniae in abdominal infections (sensitivity rate, ≥ 86.2%). However, E. coli and K. pneumoniae showed high resistance against gentamicin, ampicillin and cephalosporins; this is in keeping with the recent trend observed by Park et al[19]. Therefore, the findings indicate that preference should be given to the first group of antibiotics when treating cirrhotic patients with peritonitis caused by E. coli and K. pneumoniae strains. Furthermore, piperacillin/tazobactam showed significantly stronger activity against non-nosocomial infections caused by E. coli, and gentamicin, cefoperazone/sulbactam, ceftriaxone, and ampicillin/sulbactam showed stronger activity against non-nosocomial infections caused by K. pneumoniae.
The sensitivity of P. aeruginosa and Acinetobacter spp. to the antibiotic agents was low, but Acinetobacter spp. had stronger drug tolerance than P. aeruginosa. The drug resistance of gram-negative bacteria against quinolone antibiotics was higher than that of gram-positive bacteria, particularly in cases of nosocomial infections, which is consistent with the results of previous studies[29].
The detection rate of ESBL-producing E. coli was higher than that of ESBL-producing K. pneumoniae (45.9% vs 20.7%). Moreover, ESBL production was higher in cases of nosocomial infections than in cases of non-nosocomial infections. Previous studies have also shown that ESBL production was higher in cirrhotic patients with nosocomial infection than in those with non-nosocomial infection; ESBL production improves bacterial resistance and consequently results in increased mortality[10,30]. Our results showed a significant difference in the meropenem resistance of E. coli between nosocomial and non-nosocomial infections; this was probably related to the widespread use of carbapenems. The aminoglycoside and β-lactamase inhibitor complex had higher activity against ESBL-producing E. coli and K. pneumoniae strains. Although glucose non-fermenting bacteria have higher sensitivity to commonly used antibiotics, the detection rate of non-fermenting bacteria in clinical specimens has been increasing every year. This trend is probably related to the use of mechanical ventilator-assisted ventilation, atomization devices, cardiopulmonary bypass, various types of catheters, and the long-term use of high doses of cephalosporins, carbapenems and other antibacterial drugs; thus, non-fermenting bacteria are important pathogens in nosocomial infection[31,32]. Therefore, patients with cirrhosis who are likely to have abdominal infection should be treated with the enzyme complex comprising aminoglycoside and β-lactamase inhibitors and diene hydrocarbon enzyme antibacterials that have strong activity against gram-negative bacteria. Aminoglycoside antibiotics have high renal toxicity and weak activity against a number of drug-resistant strains, so they are not usually preferred for the treatment of cirrhosis.
The antimicrobial activity of vancomycin, nitrofurantoin and rifampin against Staphylococcus spp. in abdominal infections was strong (sensitivity rate, ≥ 87%). Furthermore, the susceptibility of Staphylococcus spp. to gentamicin, clindamycin and moxifloxacin was also strong (sensitivity rate, ≥ 60.9%). Enterococcus was resistant to a variety of antibacterial agents, but showed high sensitivity to vancomycin, rifampin, clindamycin and gentamicin (sensitivity rate, ≥ 70.6%). Furthermore, nitrofurantoin showed stronger activity against Enterococcus spp. in non-nosocomial infections than in nosocomial infections. Vancomycin, rifampin, moxifloxacin and nitrofurantoin had strong antibacterial activity against S. pneumoniae (sensitivity rate, ≥ 71.9%); ofloxacin, levofloxacin, moxifloxacin and clindamycin had greater activity against S. aureus strains in non-nosocomial infections. Thus, when there is evidence of Staphylococcus spp. in abdominal infections, glycopeptide antibiotics should be the preferred medication.
Cirrhosis with secondary bacterial infection in patients is an important cause of liver function deterioration and other complications, thus early diagnosis and prompt treatment are important[2,33]. This study is a retrospective analysis, so there are some selection biases and limitations due to the limited sample size. Nonetheless, the findings are important and they lay the foundation for future improvements in the culture, sensitivity tests and the antibiotic regime for spontaneous bacterial peritonitis in cirrhotic patients.
COMMENTS
Background
Spontaneous bacterial peritonitis (SBP) is a common and severe complication in cirrhotic patients with ascites. Monitoring drug resistance in cases of abdominal infection with liver cirrhosis is important for establishing the appropriate antibiotic regimes, reducing the generation of drug-resistant bacteria and reducing the associated mortality.
Research frontiers
Changes in the epidemiology of the causative bacteria in SBP and bacterascites and in their susceptibility to antibiotics have been associated with low treatment efficacy of traditional therapy in nosocomial infections.
Innovations and breakthroughs
This study addressed two primary issues regarding spontaneous peritonitis in cirrhotic patients in China: first, the pathogen profile and, second, drug resistance. The majority of pathogenic bacteria that cause abdominal infection in liver cirrhosis are gram-negative, and drug resistance is significantly higher in nosocomial infections than in non-nosocomial infections.
Applications
Based on this study, clinicians can select the appropriate antibiotic treatment to control the emergence and development of pathogenic bacteria-resistant strains in intra-abdominal infections.
Terminology
Extended Spectrum β-Lactamases, are usually produced by Escherichia coli, Klebsiella pneumoniae, and Acinetobacter baumannii, and can hydrolyze penicillin antibiotics, cephalosporins, and single ring β-internal-amide antibiotics. MRSA: Methicillin-resistant Staphylococcus aureus.
Peer-review
This is a very interesting study, and is important mainly because it describes and analyses the etiological agents and drug resistance which are responsible for SBP.
Footnotes
P- Reviewer: de F Higuera-de la Tijera M S- Editor: Yu J L- Editor: Webster JR E- Editor: Zhang DN
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