Summary of doctoral dissertation: The clinical, laboratorial features and treatment of spontaneous bacterial peritonitis in cirrhosis

MINISTRY OF EDUCATION
DEPARTMENT OF DEFENSE
AND TRAINING
THE CLINICAL RESEARCH INSTITUTE OF MEDICINE SCIENCE 108

---------- ----------

VU THANH TRUNG

THE CLINICAL, LABORATORIAL FEATURES AND
TREATMENT OF SPONTANEOUS BACTERIAL
PERITONITIS IN CIRRHOSIS

Subject: Gastroenterology
Code: 62.72.01.43

SUMMARY OF THE THESIS

HANOI - 2019


THIS STUDY IS COMPLETED
CLINICAL RESEARCH INSTITUTE OF MEDICINE SCIENCE 108

Science instructors:
1. Prof.Dr. MAI HONG BANG
2. Assoc. PHAN QUOC HOAN
Reviewer 1:
Reviewer 2:
Reviewer 3:

The thesis has been defended before the Institute of Dissertation thesis
at the Institute: 14 hours on September 11, 2018

The thesis can be found at:
1. National library
2. Library of the Clinical Medicine Research Institute 108


1
INTRODUCTION AND AIMS
Cirrhosis is the common end-stage disease of a variety of chronic
hepatitis. Worldwide, cirrhosis is thought to be the leading cause of
death in the 14th. There are many types of infections that occur in
cirrhosis and spontaneous bacterial peritonitis (SBP) is a severe and
frequent complication. The incidence of SBP in cirrhotic patients with
ascites is hospitalized from 10% -30%. The main causes of viral
hepatitis are Gram-negative bacteria, commonly known as E. coli,
Klebsiella sp., Enterobacter sp., And some Gram-positive bacteria:
Streptococci, Enterococci. Ascites analysis plays an important role,
determining the diagnosis and direction for treatment of SBP. The
diagnosis of SBP is based on the number of neutrophil counts (> 250
cells / mm3) or / and positive bacteriuria. However, the pathogenic
strains of bacterial pathogens are frequently altered, with increasing
antibiotic resistance of bacterial strains, which makes treatment of SBP
more difficult in patients with cirrhosis. In Vietnam, there are not many
studies on SBP.
Targets:
+ Description of clinical characteristics, subclinical disease
Peritonitis infections spontaneously.
+ Results of identification of bacteria and antibiotics on the

isolates of bacteria.
+ Evaluation of the results of treatment of peritonitis infection
spontaneously in patients with cirrhosis.
NEW CONTRIBUTION OF THE THESIS
The thesis has scientific and practical implications, which are
related to many disciplines such as intestinal digestion, infectivity and
microbiology. In clinical practice, the topic describes the main features
of spontaneous abdominal infections in patients with cirrhosis of the
ascites, the pathogenic strains, the antibiotic sensitivity assessment
Bacteria isolates and evaluated the efficacy of the regimen starting with
two antibiotics: Cefotaxime 4g / day + Ciprofloxacin 1g / day, effective
treatment with antibiotics and experience.
STRUCTURE OF THE THESIS
The dissertation has 121 pages, including: research introduction
and objectives (2 pages), overview (36 pages), subjects and methods
(25 pages), research results (27 pages) Comment (29 pages), conclusion
(2 pages). The thesis has 32 tables, 12 charts, 15 images, 189 references
including 9 Vietnamese documents and 180 English documents.


2
Chapter I
OVERVIEW DOCUMENT
1.1. History
Spontaneous peritonitis was first described in German medical
journals in 1907 by Krencker E. Subsequently, the findings on SBP
were described in France by: Brule M 1939), Cachin M (1955) and
Calori J (1958). However, in 1964, Harold O. Conn introduced the term:
spontaneous bacterial peritonitis (SBP), and this term has been used so
far. The concept of spontaneous peritonitis (SBP) refers to the bacterial

ascites infection, but does not detect the pathway of bacteria and is
capable of medical treatment.
1.2. Epidemiology
In patients with cirrhosis, the mortality rate is related to bacterial
complications of 30-50%. Frequency of infection is 5-7% for external
patients and accounts for 32-34% for internal patients and even up to 45%
for patients with complications of gastrointestinal bleeding. Common
infections in patients with cirrhosis are: Peritonitis, autoimmune
peritonitis - SBP (25% -31%), urinary tract infections - UTI (20% 25%), pneumonia (15% -21% %) sepsis- SEPSIS (12%), soft tissue
infections (11%) ...
About 75% of cases of cirrhosis in cirrhotic patients are Gramnegative bacteria, such as Escherichia coli, Klebsiellaspp,
Enterobacterspp, P. aeruginosa, Vibrio spp, Aeromonas spp. While
Gram positive accounts for 20.2% and anaerobic species accounts for
3.2%. Recently, the prevalence of gram-positive bacterial infections has
been on the rise, according to a study by Marco Fiore et al.
1.3.The pathogenesis of SBP
Conn H.O's BT (bacterial translocation) approach in the 1960s was
the basis for the pathogenesis of SBP.
Today, the mechanism of pathogenesis of SBP is better understood
with the participation of many factors:
Form Factors:
+ Changes in anatomic structure and portal vein pressure.
+ Immune disorders: site and system.
_ Excessive growth of bacteria.
+ Movement path of bacteria:
+ Lymphatic drainage.
+ Blood sugar.


3

+ The way of smuggling.
Factors supporting the movement of bacteria:
Environment, nutrition, metabolism, stress, drug use PPIs ...
1.4. Clinical presentations
The main clinical symptoms of SBP include:
- Symptoms of total or local peritonitis.
- infection syndrome.
- Impaired liver function syndrome.
- Hepatic encephalopathy (HE).
- Kidney
- Hepatic renal syndrome (HRS).
- Shock
- Gastrointestinal bleeding.
In particular, asymptomatic SBP, about 1.5% -3.5%.
1.5. Diagnostic tests for SBP
1.5.1. Microbiologic testings
Today, screening facilities use aseptic culture in blood culture
bottles on bacterial culture systems and automatic bacteriostatic
identification. This method has been shown to have a higher positive
rate of implantation than conventional implantation.
1.5.2. Methods of counting the polymorphonuclearneutrophilic
leukocyte (PMN)
The method of counting PMN cells in ascites is crucial to the
diagnosis of SBP. Multi-core counting methods used include:
The classic method of counting white blood cells by Giemsa
staining and microscopic counts is subjective and time consuming.
The automatic / semi-automatic hematopoieticcounting
method has the advantage of fast and accurate and indicates the
percentage of white blood cells in ascites, which makes it easy to
calculate the white blood cell count accurately. PMN = total white

blood cell x% Neutrophil. The SBP is diagnosed valid when the
number of PMN cells> 250 / μL. Automatic blood counting methods
have been shown to have a sensitivity and specificity of 94% and 100%,
respectively. Negative predictive value is 99.1%, positive predictive
value is 100%.
Urine reagent strip testings (Multistix 8SG urine test). The scientific
basis of this method is to detect indirectly leukocyte esterase-leukocyte
esterase cells secreted by these cells. Enzyme esterase activates the color
indicator on the test and performs colorimetry on the machine. This


4
method is qualitative, semi-quantitative. Although the method of urine
testing yielded rapid results at bedside, there was no consensus in the early
diagnosis of SBP, for reasons of low sensitivity and false negative rates.
high, especially in cases where SBP has white blood cell count in low
ascites.
Measurement of Lactoferrin/ Calprotectin in ascites.Lactoferrin
/ Calprotectinis a protein that binds calcium and zinc, which is secreted
by multiplexed white blood cells and proportional to the number of
these cells. This method gives sensitivity and specificity of 95.4% and
85.2%, respectively. However, this method has some limitations:
Difficult to diagnose in cases of SBP have decreased number of white
blood cells multipliers and cases secondary inflammation.
1.5.3. Diagnosis of SBP is based on bacterial DNA present in
ascites
Today, with molecular techniques, bacterial DNA can be detected
in the blood or in ascites. DNA extraction - Real-time polymerase chain
reaction (DNA sequencing) - DNA sequencing. With this technique,
small amounts of bacterial DNA, if present in ascites, will be detected.

Therefore, it is possible to diagnose VMBNKTP at early stage or in
case of previous SBP using antibiotic prophylaxis, which results in
negative culture. However, this is a new technique and there are many
limitations to overcome such as: The rate of homology between culture
and DNA sequencing is not high (50%), negative bacteria DNA
accounts for about half of cases of VMBNKTP negative culture; There
is a lack of standard methods and primers, so many strains of bacteria
have not been identified; No antibiotic evaluation; Secondary
inflammation status was not evaluated.
1.6. Diagnosis
- Definitive diagnosis: SBP is based on the guidelines of the
International Asiatic Society: The number of PMN in ascites> 250 cells
/ mm3 and / or bacteriostatic ascites results in positive culture.
- Differential diagnosis:
+ Secondary peritonitis.
+ Septicemia.
+ Fungal peritonitis.


5
1.7. Treatment
Treatment principle
- Complete treatment.
- Early treatment.
- Select good antibiotics.
- Co-ordinate with antibiotics
1.7.1. Use antibiotics according to antibiotic maps
This is a method of selecting antibiotics sensitive to pathogenic
bacteria in a scientifically and economically reasonable way. Even
when antibiotics are well-defined, antibiotics should be combined to

increase the likelihood of bactericidal activity and to reduce resistance
to antibiotics (antibiotics should not be used alone). The combination of
antibiotics follows the principle of antibiotic combination among
groups: for example: Cephalosporin group TH3 + fluoroquinolone
group TH2; but select antibiotics sensitive in that group.
1.7.2. Use of empirical antibiotics (EAT)
The use of empiric antibiotic therapy (EAT) is a method used for
treatment prior to antibiotic therapy and / or for implantation. negative
bacteria. This method is indicated as soon as the diagnosis of SBP is
determined (cell count> 250 cells / mm3) without waiting for
bacteriologic results. Experimental antibiotic treatment is based on the
results of research on epidemiology and pathogenesis of SBP; the
susceptibility or antibiotic resistance of bacterial species in previous
studies.
The European Consensus Guide and the guidelines of the
International Ascetic Society recommend that the use of the 3rd
generation Cephalosporin Group be the top choice for the treatment of
SBP (Cefotaxime, Ceftriaxone, Cefoperazole). The recommended
standard dose for cefotaxime is 2g every 8 hours (6g / 24 hours). In
cases where patients are not suitable for Cephalosporin, antibiotics such
as amoxicillin-clavulanate are used instead. Antibiotic therapy should
be used with Cephalosporin TH3 and fluoroquinolone.
1.7.3. Use of antibiotics in combination with albumin therapy
Numerous studies have demonstrated that treatment of cefotaxime
with cefotaxime combined with albumin (1.5 g / kg for the first 6 hours
of diagnosis, followed by 1 g / kg for the next 3 days) versus treatment
by cefotaxime alone, it was shown that the patients treated with
combination therapy had a 10% reduction compared with 33%, p =
0.002 and a lower mortality rate (10% vs 29% , p = 0.01) during

6
hospital stay; and follow-up 3 months after discharge (22% with 41%, p
= 0.03).
In patients with SBP, albumin is indicated for all cases of renal
impairment and those with renal impairment: serum creatinine> 1 mg /
dL = 88.4 mmol / L, bilirubin> 4 mg / dL = 68.4 mmol / L, BUN (blood
urea nitrogen)> 30 mg / dL.
1.7.4. Prophylaxis SBP
Antibiotic prophylaxis is indicated for patients:
Cirrhosis with ascites has gastrointestinal bleeding.
Cases with ascites volume <1g / dl and total bilirubin> 3.2 mg / dL
and / or platelet count <98,000 / mm3.
- Cases of premenopausal period have been affected by SBP.
Antibiotics used in prophylaxis: Norfloxacin, Ciprofloxacin,
Rifamycin, Trimethoprim-sulfamethoxazole.


7
Chapter II
OBJECTIVES AND METHODS
2.1. Research subjects
106 patients with decompensated cirrhosis with complications of
SBP,inpatient treated in gastroenterology department, Bach Mai
Hospital, from March 2010 to October 2016.
2.1.1. Criteria for selecting patients
Diagnosed with clinically definitive cirrhosis, there are two
syndromes: hepatic impairment syndrome and portal hypertension
syndrome.
- There is ascites with SBP complications based on guidelines of

the International Asiatic Society: The number of PMN in ascites> 250
cells / mm3 and / or bacterial ascites culture is positive result.
- There has been no antibiotic treatment within the previous month.
2.1.2 Criteria for exclusion of patients
- The cases of ascites are not due to cirrhosis.
- Cirrhosis of the liver associated with liver cancer or other
metastatic tumors in the abdomen.
- Cases of secondary causes of peritonitis include: rupture of
appendicitis, necrotizing cholecystitis, perforation of large intestine.
- Cases of tuberculosis or HIV.
- The cases of spontaneous peritonitis caused by fungus (results of
culture of fungal infection positive ascites).
Peritoneal tuberculosis, acute pancreatitis with abdominal fluid.
2.2. Research Methods
2.2.1 Research design
Is the method: description, cross sectional analysis, vertical
tracking during the treatment.
2.2.2 Study sample size
Use of convenient sample size (106 patients) during 2010-2016.
2.3. Research facilities. System of bacteriostatic, bacteriostatic and
antimicrobial automatic: PHONIX 100 - BD - USA. Siemens automatic
cell counting system - Federal Republic of Germany. Testing machines,
modern imaging equipment are routinely used at Bach Mai Hospital.
2.4. Research steps and research indicators
- Patient selection:
Patients with cirrhosis of the ascites hospitalized for clinical
examination,
routine
clinical
(hematological,

biochemical,


8
immunological
...),
asymptomatic
asymptomaticasymptomaticasymptomatic and implant count Ascites
fluid by blood culture bottles. Patients with a prenatal number> 250
cells / mm3 and no history of antibiotics during the preceding month,
and no exclusion criteria, were selected for the study.
Patients with cirrhosis of the ascites hospitalized for clinical
examination,
routine
clinical
(hematological,
biochemical,
immunological
...),
asymptomatic
asymptomaticasymptomaticasymptomatic and implant count Ascites
fluid by blood culture bottles. Patients with a prenatal number> 250
cells / mm3 and no history of antibiotics during the preceding month,
and no exclusion criteria, were selected for the study.
- Initiate treatment with 2 antibiotics: Cefotaxime 4g / day +
Ciprofloxacin 1g / day for the study group for 3 days (before the results
of antibiotic culture and antibiotic). Evaluate the clinical symptoms and
re-test the hematological and biochemical parameters after 3 days of
treatment.
Evaluation after antibiotic culture and antibiotic: Evaluate the

parameters: rate of bacterial culture, structure of bacteria, evaluation of
susceptibility of some major antibiotics Isolated strains of bacteria.
Evaluate the rate of multidrug resistant bacteria.
- Evaluation of treatment results: Patients with antibiotic therapy
results, continued treatment with antibiotics. Patients with multidrug
resistant antibiotics or patients with negative bacteriologic results
should undergo empiric therapy based on the clinical response of the
patient. The treatment duration is from the beginning of antibiotic
treatment to the end of treatment (the patient is removed, the patient is
discharged or the patient progresses, the family is discharged).
Evaluation of factors related to treatment outcome: bacteria,
hepatic nephropathy, hepatic brain syndrome, septicemia ...
2.4 Data analysis and processing
Statistics are processed by SPSS software 20.0. Results were
statistically significant with p <0.05.

Chapter 3. RESULTS


9
3.1. Clinical and laboratory characteristics
3.1.1. Characteristics of age and sex
Table 3. 1 Mean age, sex ratio in cirrhotic patients with SBP
Characteristics
Parameters
Age

The average age

52,1 ±11,7

Biggest
Smallest
Male

85
28
95

(89,6%)

Sex n = 106

Female
11 (10,4%)
Male / Female ratio
9/1
Comments: Average age: 52.1 ±11.7 (28 -85), male / female

ratio: 9/1
3.1.2. Risk factors
Table 3.2 History and risk factors
Characteristics
n = 106 (%)
Alcohol addiction.
54
(50,9%)
Alcoholism + hepatitis B.
21
(19,8%)

Hepatitis B
12
(11,3%)
Hepatitis B + Hepatitis C
5
(4,7%)
Hepatitis C
3
(2,8%)
Undefined reason
11
(10,5%)
Total
106
(100%)
Comment: The incidence of alcoholic cirrhosis is highest in 50.9%.
The prevalence of hepatitis B virus infection was 31.1%, of which,
alcoholism combined with viral hepatitis was 19.8%.


10
3.1.3. Main clinical features in patients with SBP
100

Sepsis

80

HE

60

HRS

40

GI bleeding

20

edema legs
diarrhea

0

abdomen pain
fever

Figure 3.1 General clinical characteristics of the study group
Comment: Common symptoms in SBP are: Fever 85.8%; abdominal
pain 82.1%; 68.9% diarrhea.
3.1.4. Child-Pugh classification

68.9

70
60
50
40

Child A
Child B
Child C

31.1

30
20
10

0

0
Chid A

Child B

Child C

Figure 3.2.Cirrhosis level according to Child-Pugh classification.
Comment: Child-Pugh C has 68.9%, Child-Pugh B 31.1%.


11
3.1.5. Hematological and biochemical findings in cirrhotic patients
with SBP.
Table 3.3 Mean values of hematology and biochemistry.
Test
Parameter
Test

Parameter
White blood
11,95 ±8,06
Glucose
7,55 ±6,78
cells
(1,38- 40,83)
(mmol/l)
(G / L)
3,08 ±0,59
Hemophilia
Ure
11,58 ±12,33
(T / L)
(1,71-4,39)
(mmol/l)
Platelet
102,26 ±69,91
133,98 ±
Creatinin
(G / L)
(11,0-361)
(μmol/l)
112,88
37,22 ±14,21
171,80 ±
Prothrombin
Total bilirubin
(%)
(13,5-86)

(μmol / l)
180,35
143,52 ±
GOT (U/l)
70,45 ±6,52
Protein (g/l)
179,64
GPT (U/l)
61,73 ±66,38
22,07 ±4,16
Albumin (g/l)
Comment
+ Most white blood cells increase above normal levels.
+ Proportion of Prothrombin is very low: 37.22 ±14.21 (%)
+ High blood bilirubin: 171.80 ±180.35
+ Average serum albumin concentration is very low: 22.07 ±
4.16 (g / l).
3.2. Ascites test in patients with SBP
3.2.1. Cellular and biochemical characteristics of ascites
Table 3.4. Cellular and biochemical characteristics of ascites
Characteristics
Parameters
Min
Max
TB
SD
White blood cell count 0,29
52,10
9,982
10,04

(G/L)
Rate of PMN
(%) 50,0%
97,6%
79,0%
10,4%
PMN
0,21
42,5
8,14
8,34
(G/L)
Protein fluid (g/l)
2,4
19,8
11,34
4,80
Comment: Average index of white blood cell ascites: 9,982
± 10.04 (0.29-52.10) G / L. The rate of increase of the Steering
Committee (79.0%). Elevated ascites protein content: 11.34 ±4.8 g / l.
3.2.2. Results of ascites culture in patients with SBP.
106 cases of cirrhosis with SBP were ascites culture by
BATEC 9500 machine system obtained the following results:


12
Table 3.5 Ascites culture results in patients with SBP.
Results of culture
n= 106 (%)
Positive

55
(51,9%)
Negative
51
(48,1%)
Total
106
(100%)
Comment: Positive bacterial results were 51.9%.
And there is 4.7% of cultures were positive for both strains.
3.2.7. Results of bacteriological identification in cirrhotic patients
with SBP
Identification of bacteria (n = 60), on PHONIX 100-BD-US
system. Table 3.6 presents the results of antimicrobial isolation from
ascites in patients with cirrhosis of SBP.
Table 3.6 Results of bacteriological identification.
Strain of bacteria
They - Industry
n = 60
Gram-positive bacteria52/60 (86,7%)
Aeromonashydrophyla Aeromonadaceae
–
1
Proteobacteria
Burkholderiacepacia Bukholderiaceae
–
1
Proteobacteria
Citrobacterkoseri
Enterobacteriaceae

2
Proteobacteria
Eschesrichia coli
Enterobacteriaceae
35
Proteobacteria
Enterobactercloacea
Enterobacteriaceae
2
Proteobacteria
Klebsiellapneumoniae Enterobacteriaceae
7
Proteobacteria
Klebsiellaterigena
Enterobacteriaceae
1
Proteobacteria
Klebsiellaoxytoca
Enterobacteriaceae
1
Proteobacteria
Pseudomonas putida
Pseudomonadaceae
1
Proteobacteria
Vibrio sp
Vibrio – Proteobacteria
1
Gram-positive bacteria 8/60 (13,3%)
Streptococcus

Stretococcaceae
1
pneumoniae
Streptococci A
Stretococcaceae
1


13
Enterococcaceae – Bacili
1
Enterobacteriaceae
5
Proteobacteria
Comment: The gram-negative group is dominated by 86.7%.
Gram-positive bacteria only account for 13.3%. Escherichia coliis the
most common gram negative bacteria: 35/52 (67.3%).
3.3. Complications
Table 3.7. Complications in patients with SBP
Characteristics
n= 106 (100%)
Gastrointestinal bleeding
16
(15,1%)
Hepatic renal syndrome - HRS
34
(32,1%)
Hepatic encephalopathy - HE
21
(19,8%)

Sepsis
16
(15,1%)
Uncomplicated
19
(17,9%)
Remarks: Complications in patients with SBP include: GI
bleeding: 15.1%; HRS (32.1%), HE (19.8%), sepsis (15.1%).
3.4. ANTIBIOTIC
3.4.1. Antibiotic results with Cephalosporin group.
Cephalosporin antibiotics: Cefuroxime (CXM), Ceftazidin (CAZ),
Ceftriaxon (CRO), Cefotaxime (CTX), Cefepim (FEP).
Ecoli
Enterococcus feacalis
Entercocci

62.9%

65%

60%

60%
55%

54.3%

54.3%

54.3%

CRO

CTX

50%
45%
CXM

CAZ

FEP

Figure 3.3 Sensitivity of E. coli to Cephalosporins.
Bacteria


14
70%
65%

68.6%

67.3%
63.4%

62.7%

58.8%

60%
55%

50%
CXM

CAZ

CRO

CTX

FEP

Figure 3.4 Percentage susceptibility of Cephalosporin to bacterial
species.
Comment:
Sensitivity of each antibiotic to the corresponding bacteria:
CXM (62.7%); CAZ (67.3%); CRO (63.4%); CTX (58.8%) and FEP
(68.6%).
E. coli susceptible to Cephalosporin from 54.2% to 62.9%.
3.4.2. Antibiotic results with Carbapenem group
Outcomes of antibiotics: ETP (Ertapenem), IMP (Imipenem), MEM
(Meropenem).
Ecoli
101%
100%
99%
98%
97%

96%
95%
94%
93%
92%
91%

100%

94.3%

94.3%

ETP

IMP

MEM

Figure 3.5 Sensitivity of E. coli to Carbapenem antibiotics
Bacteri


15
101%
100%

100%
99%
98%

97%

96.3%

96.3%

ETP

IMP

96%
95%
94%
MEM

Figure 3.6 Sensitivity of Carbapenem group to bacteria.
Comment:
The sensitivity of each antibiotic of the Carbapenem group to
the corresponding bacteria: ETP: 96.3%; IMP: 96.3%; MEM: 100%.
E. coli susceptible antibiotics (94.3%), IMP (94.3%), MEM
(100%).
3.4.3. Aminoglycoside group and Fluoroquinolone group
Antibiotics for Aminoglycoside and Fluoroquinolone: Tobramycin
(TM), Amikacin (AN), Ciprofloxacin (CIP), Levofloxacin (LVX).
Ecoli
91.1%

100%
80%

68.6%

60%

54.3%

54.3%

CIP

LVX

40%
20%
0%
TM

AN

Figure 3.7 Sensitivity of E. coli to Amynoglycoside and
Fluoroquinolones


16
Bacteria
120%
96.4%

100%
80%

75.0%

60%

57.8%

55.3%

CIP

LVX

40%
20%
0%
TM

AN

Figure 3.8 Sensitivity of Amynoglycoside and Fluoroquinolones to
bacteria
Comment:
The overall sensitivity of antibiotics to the corresponding
bacteria: TM: 75.0%; AN: 96.4%; CIP: 57.8%; LVX: 55.3%.
E coli have medium susceptibility to fluoroquinolones:
54.3%. Aminoglycoside group had high sensitivity to E. coli (91.1%).
3.4.4. Other antibiotic groups
Antibiotics used: Amo + A.clavulanic (AMC); Piper + Tazobactam
(TZP), Cefoperazole + Sulbactam (SCR), Vancomycin (VA).

Phosphomycin (FOS).
Bacteria
100%
80%

87.5%

78.6%

85.7%

89.3%

VA

FOS

60.7%

60%
40%
20%
0%
AMC

TAP

SCF

Figure 3.9 Sensitivity of antibiotics to bacterial strains.

Comment:
Piper + Tazobactam (TZP) and Fosfomycine (FOS)
antibiotics were susceptible to Gram-negative bacteria 87.5% and
89.3%; Sensitivity to E. coli was 88.6% and 100%, respectively.


17
The vancomycin group is sensitive to Gram-positive bacteria
(Entercocci, Strpp, Streptococci A) of 85.7%.
3.5. TREATMENT RESULTS
3.5.1. Overall treatment
70

60.4

60
50
40
30
20

Value

21.7
15.1

10

2.8

0
effectivenoneffective severe
death
Figure 3.10 Rate of treatment outcome
Comment:
The rate of effectiveness (disease-free) reached: 60.4%. The
incidence rate was 21.7%, the rate was 15.1% worse and hospital
morbidity was 2.8%.
3.6. Effects of prognostic factors on treatment outcomes.
A total of 106 patients with cirrhosis of SBP, investigating the
influence of factors; bacteria, HC - liver - kidney, brain - liver, for
treatment results as follows.
3.6.1. Evaluate the results of treatment with the results of culture.
Table 3.8. Relationship between treatment outcome and bacteriocin
outcome

Results of
culture
Positive
Negative
Total

Treatment results
Effective Non
Severe
effective
26
17
10
47,3%

30,9%
18,2%
38
6
6
74,4%
11,8%
11,8%
64
23
16
60,4%
21,7%
15,1%

Death
2
3,6%
1
2,0%
3
2,8%

Total
55
100%
51
100%
106
100%

p

0,034


18
Comment:
Negative culture was more effective than positive cultures, with
p <0.05.
3.6.2. Evaluate the relationship between treatment outcome and
liver and kidney syndrome.
Table 3.9. Relationship between treatment outcome and HRS
Treatment results
HRS
p
Effective Non
Severe Death Total
effective
11
10
11
2
34
HRS
32,4%
29,4%
32,4% 8,8% 100%
<0,05
53

13
5
1
72
without
73,6%
18,1%
6,9%
1,4% 100%
64
23
16
3
106
Total
60,4%
21,7%
15,1% 2,8% 100%
Comment:
Better results in patients with SBP do not have accompanying
hepatic nephropathy (p <0.05).
3.6.3. Evaluation of the association between treatment outcome and
HE
Table 3.10. Relationship between treatment outcome and HE
Treatment results
p
HE
Total
Non
Effective

Severe Death
effective
1
11
8
1
21
HE
4,8%
52,3%
38,1% 4,8% 100% <0,05
63
12
8
2
85
without
74,1%
14,1%
9,4%
2,4% 100%
64
23
16
3
106
Total
60,4%
21,7%
15,1% 2,8% 100%

Comment:
The treatment outcome was better in patients without HE,
significantly at p <0.05.


19
Chapter 4
DISCUSSION
4.1. General characteristics.
- Characteristics of age and sex.
In our study, patients with SBP had an average age of 52.2 ±
11.7 years (28-85 years).
The results are similar to those in the world.About sex: In our
study, male accounted for 89.6%, female accounted for 10.4% and male
/ female ratio was 9/1.
- Characteristics of risk factors
There are many risk factors for cirrhosis that have been
studied extensively in the world. In our study, the number of patients
with alcoholism, alcoholism + hepatitis B virus infection, hepatitis B
virus infection accounted for 50.9%; 19.8% and 11.3% respectively.
Research by Le Thanh Quynh Ngan and colleagues found that
the leading risk factors for cirrhosis were cirrhosis (27,45%), hepatitis
B (24,4%), alcoholic cirrhosis alone accounted for 12 , 6%. Studies by
Ho Xuan Tho and colleagues at Gia Dinh People's Hospital also
showed that the rate of hepatitis B and hepatitis C was the highest,
accounting for 33.0%. Oey RC et al. Show that the incidence of
alcoholic cirrhosis due to B / C and autoimmune diseases is 33%, 24%
and 25%, respectively.
4.2. Clinical features in cirrhotic patients
Our study indicates that the primary clinical features of

patients with cirrhosis of the SBP include:
- Fever is the most common symptom of 85.8%, clinical
manifestations of infection syndrome. According to Nguyen Thi Chi,
the rate of fever is 86.3%. According to Navasa M, the fever rate was
63% -76%. However, in the study of Nguyen Thi Van Anh only
recorded 37.8% of fever cases.
Abdominal pain is 82.1%. This percentage is 76% in
Navasa M, 68.6% in Nguyen Thi Chi. Abdominal pain is continuous,
spreading throughout the abdomen, sometimes accompanied by
vague or abdominal distention or abdominal distention. In particular,
3.8% of the cases of surgical abdominal incidence with peritoneal /
peritoneal positive. This situation accounted for 1.96% in the study
of Nguyen Thi Chi.


20
Loose sewage accounted for 68.9%. According to Nguyen Thi
Chi, liquid stools accounted for 64.7%. Colposcopy and abdominal pain
are thought to be an indication of excessive bowel proliferation - SIBO.
4.3. Characteristics of blood-chemistry biochemical tests in patients
with SBP
The results generally show that the parameters are different
from the physiological constants. In fact, these parameters are
grouped by means of group mean values, so it is difficult to see
differences in the values of the parameters when comparing two
groups with non- SBP cirrhosis. Evans LT et al. Found no association
between serum albumin, bilirubin and INR levels between cirrhotic
patients with SBP and no SBP. In contrast, some authors such as Le
Thanh Quynh Ngan, Rubén Terg said that there are differences in
biochemical parameters (total bilirubin, blood creatinine, blood

albumin, ascites) have SBP and not SBP. The combination of
independent biochemical factors to assess the severity of the disease:
Child-Pugh (Albumin, Bilirubin,% prothrobin); MELD score
(Bilirubin, creatinine, INR), many authors agree: there is significant
difference between the two groups SBP and not SBP.
A recent study by Jun BG et al confirmed that serum creatinine
levels> 2 mg / dL (176.4 μmol / L) were associated with a high risk of
death in patients with acute myocardial infarction. 30 days, with a
sensitivity of 77.4%, specificity of 74.3%.
In our study, the incidence of SBP with bilirubin> 4 mg / dL (>
100 μmol / L) was 46.2% and blood creatinine> 1 mg / dl (88.4 μmol /
L). ) was 32%, corresponding to the prevalence of hepatorenal
syndrome (32.1%).
4.4. Examine the number of PMN
The number of PMN in ascites is the silver standard for
diagnosing SBP. The defined diagnostic value is at> 250 cells /μl. Other
authors argue that the cutoff of the PMN is 500 cells / μl for sensitivity and
specificity in the SBP diagnosis is highest. In fact, the average value of the
PMN is very high and has a large amplitude. In our study, the total WBC
was 9,982 ± 10,040 cells / μl. The prevalence of PMN was 79.0 ±10.4 (%).
The mean number of PMN is 8,140 ± 8,340 cells / l. According to Nguyen
Thi Chi, this indicator is 6,492 ±13,870 cells / l; of Jun BG and cs: 5,722.6 ±
12,755.1 cells / l. Reginato TJB et al. Found that the mean PMN values
were 10,082.5 ±35,181.3 cells / l, with a percentage of 79.8 ±20.1% ).
4.5. Characteristics of ascites culture results


21
In this study, we used the BD- BACTEC 9050 blood culture
system and automatic ascites and the results showed that the rate of

positive bacterial culture was 51.9% (55/106).Including 50 out of 106
patients (47.2%) had one bacterium and 5/106 (4.7%) had two different
types of bacteria. The results of our study are consistent with the results
of Nguyen Thi Chi and Pham Thi Thu Ho with 56% positive cultures,
of which 2% have two co-growing bacteria. Recent research by Oey
RC et al shows that the prevalence of SBP is caused by a wide variety
of bacterial species, accounting for 7.9% (6/76 cases), and the trend of
SBP is caused by many strains of bacteria appearing around The last 5
years.
4.6. Identification of bacteria
From positive cultures (n = 60), we isolated the pathogenic
strains. The results showed that Gram-negative bacteria accounted for
the majority of 86.7% (52/60). Gram-positive bacteria were found to
account for only 13.3% (8/60). Escherichia coli was highest in gram
negative bacteria: 35/52 (67.3%), followed by Klebsiellapneumoniae:
7/52 (13.5%). The results of our study are consistent with the literature
as well as most studies on SBP said that the main cause of the disease is
Gram negative bacteria group, led by E.coli. Some domestic studies
such as Le ThanhQuynhNgan et al showed that Gram-positive / Grampositive bacteria were 75% / 25%, in which gram-positive S. aureus had
16.6% (4/24); Research by Nguyen Thi Chi et al. Showed that E. coli
was 42.8% (12/28), K.pneumonie (14.3%) and S. aureus (3.6%).
4.7. Antibiotic maps
- Antibiotic results with Cephalosporin group.
In our study, the susceptibility of Escherichia coli to
Cephalosporins: Cefuroxime (CXM), Ceftazidine (CAZ), Ceftriaxone
(CRO), Cefotaxime (CTX) and cefepime (FEP) The respondents were:
54.3%; 60%, 54.2%; 54.2% and 62.9%. As such, Escherichia coliis
most sensitive to Cefepim (62.9%), with the remaining 54.2% -60.0%.
Overall antibiotic susceptibility for all strains was as follows:
CXM (62.7%), CAZ (67.3%), CRO (63.4%), CTX (58.8%), FEP

(68.6%). Thus, cefotaxime (CTX) has the lowest sensitivity compared
to other antibiotics in the same Cephalosporin group.
- Antibiotic results with Carbapennem group.
We also performed antibiotic therapy with the Carbapennem
group, including the specific antibiotics: Ertapenem, Imipenem,
Meropenem. Results of the antibiotic showed Escherichia coli sensitive


22
to Ertapenem, Imipenem, Meropenem respectively: 94.3%, 94.3%,
100%. The overall sensitivity of the Carbapenem group to all isolates
was: Sensitivity of ETP (96.3%), IMP (96.3%) and MEM (100%).
- Antibiotic with Aminoglycoside and Fluoroquinolone
Antibiotic results showed that Escherichia coli susceptible to
Tobramycin (68.6%), Amikacin (91.1%). In the Fluoroquinolone group,
Escherichia coli susceptible to Ciprofloxacin (54.3%) and Levofloxacin
(54.3%). The overall susceptibility of these antibiotics to all isolates
was as follows: TM (75%), AN (96.4%), CIP (57.8%), LVX 55.3%).
- Results of other antibiotics
Antibiotics that are used as a treatment include: Amo +
A.clavulanic (AMC); Piper + Tazobactam (TZP), Cefoperazole +
Sulbactam (SCF), Vancomycin (VA). Phosphomycin (FOS). The
results showed that the sensitivity of E.coli to antibiotics was as follows:
AMC (61.8%), TZP (88.6%), SCF (80%), FOS (100% %). For Gram (+)
bacteria, Vancomycin (VA) antibiotics are highly susceptible to
enterococci (80%) and susceptible to 85.7% of all Gram (+) isolates.
4.8. Outcome of SBPtreatment
In assessing clinical efficacy and clinical parameters, we based
the evaluation of Fernandez J and colleagues in two categories:
effective and ineffective. Results of the study showed that: The

treatment was effective: 64/106 (60.4%), not effective: 42/106 patients
(39.6%).
Efficacy of SBP depends on many factors and is associated
with other complications associated with cirrhosis. In our study, the
effectiveness of SBP was associated with positive bacterial culture,
HRS, HE. Projections of ineffective treatment were significantly higher
in those cases with positive bacteriuria and /or with the abovementioned complications, with p <0.05.


23
CONCLUSION
Based on the results of our study in 106 patients with ascites
undergoing cirrhosis with SBP, we draw some conclusions as follows.
1. Clinical, subclinical characteristics in SBP patients
- Mean age: 52.1 ± 11.7 (28 -85), Age group: 51-60 years old
accounts for the highest proportion (38.7%). Male more males than
females, male / female ratio: 9/1.
- Cirrhosis levels: Child-Pugh B and C were 31.1% and 68.9%,
respectively.
- The main clinical signs in cirrhotic patients with SBP include:
Fever 85.8%; abdominal pain 82.1%; 68.9% diarrhea..
- Hematological and biochemical tests: Prothrombin ratio is
very low: 37.22 ± 14.21 (%); Very high blood bilirubin: 171.8 ±
180.3μmol / L. Average blood albumin level was very low: 22.07 ±
4.16 (g / l).
Complications associated with SBP include: Gastrointestinal
bleeding due to esophageal varices (15.1%), HRS (32.1%), and HE
(19.8% ), septicemia: (15.1%).
Numbers of PMN (> 250 cells / mm3) accounted for 104 out of
106 patients (98.1%).

2. Characteristics of bacteria and antibiotics
Results of culture positive ascites (51.9%). Gram-negative
bacteria are dominant (86.7%). Escherichia coliwas highest with 67.3%,
followed by Klebsiella pneumonia 13.4%. Gram-positive bacteria only
account for 13.3%.
Antibiotic results showed that: Cephalosporin group 3rd and
Fluoroquinolone group had moderate sensitivity (50% -70%) for
bacterial isolates, especially E. coli. Carbamenem and Fosfomycin
groups are highly susceptible to bacterial isolates> 90%. There are
18/60 (30%) cases of multi-resistant bacteria.
3. Results of treatment of cirrhosis patients with SBP
- Treatment results: The rate of effective treatment: 64/106
patients (60.4%), ineffective: 42/106 patients (39.6%).
- Cefotaxime combination with Ciproflxacin has a good
response, suitable for the treatment of initial experience and treatment
before antibiotic map.
- Experimental results did not differ from the results of
antibiotic treatment.