What is Spontaneous Bacterial Peritonitis?

Most of the pathogenic bacteria of SBP are aerobic bacteria, and> 90% are infected by a single species. The pathogenic bacteria mainly come from the intestinal flora, and a few come from the urinary tract, respiratory tract and soft tissue infections. Gram-negative bacilli account for 45% -55%, with Escherichia coli most common, followed by Klebsiella pneumoniae. Gram-positive cocci account for 10% -34%. Streptococcus pneumoniae and other Streptococcus species are common. Other rare bacteria include Staphylococcus, Enterococcus faecalis, Alcaligenes, Haemophilus influenzae, and Salmonella cholerae. Due to the high concentration of oxygen in the ascites, anaerobic and non-aerobic infections are rare.

Xing Huichun	(Chief physician)	Liver Disease Center of Beijing Ditan Hospital
Ou Ni	(Deputy Chief Physician)	Liver Disease Center of Beijing Ditan Hospital
Duan Ying	(Attending physician)	Liver Disease Center of Beijing Ditan Hospital

Spontaneous bacterial peritonitis (SBP) is a common and serious complication in patients with liver cirrhosis and ascites. It is caused by pathogenic bacteria through the intestinal, blood or lymphatic system. Infection that occurs in the abdominal cavity in the case of a source of infection (such as intestinal perforation, intestinal abscess). It is more common in patients with advanced liver cirrhosis and other patients with severe hepatitis and nephrotic syndrome. It is one of the important causes of death in patients with end-stage liver disease. The incidence of SBP in decompensated liver cirrhosis is 10% to 47%. 48% to 57%. With the improvement of early diagnosis and treatment of SBP, the mortality rate has decreased, but the mortality rate is still 20% -40%. Therefore, it is necessary to actively prevent the occurrence of SBP, early diagnosis and early treatment, thereby reducing its morbidity and mortality.

Western Medicine Name: Spontaneous bacterial peritonitis
Affiliated Department: Internal Medicine-Gastroenterology
Disease site: Abdominal cavity

The main symptoms: Fever, abdominal pain, abdominal muscle tension, abdominal tenderness, rebound pain, weakened bowel sounds, etc.
Main cause: Bacterial infections

Etiology of spontaneous bacterial peritonitis

Pathogenesis of spontaneous bacterial peritonitis

SBP is an opportunistic infection caused by intestinal bacteria implanted into the abdominal cavity. The pathogenesis is not completely clear. At present, it is generally believed that it is related to intestinal wall congestion and edema, weakened mucosal barrier effect, bacterial proliferation disorder and bacterial translocation (BT ), And the weakening of the role of the monocyte-macrophage system leads to a decline in the body's immune defense function against infection.

1. Intestinal mucosal barrier weakens and bacteria migrate to the abdominal cavity;

Under normal circumstances there is only a small amount of aerobic (facultative) Gram-negative bacteria in the small intestine. In the case of cirrhosis or severe hepatitis, the intestinal microecology is imbalanced, the intestinal flora is imbalanced, the number of probiotics such as Bifidobacterium and Lactobacillus is significantly reduced, and bacteria such as Enterobacter and Enterococcus overgrow. Toxins and metabolites produced by bacteria, especially endotoxins produced by Gram-negative bacteria, can cause intestinal epithelial cells to be damaged. Hemodynamic changes such as intestinal congestion, edema, and hypoperfusion caused by portal hypertension can also cause intestinal barrier function damage. Diarrhea, gastrointestinal dysfunction, and upper gastrointestinal bleeding can all damage the intestinal epithelial barrier function. At present, most researchers believe that there are three main ways for bacteria to enter the abdominal cavity: intestinal bacteria directly migrate into the ascites: intestinal bacteria-intestinal mucosa-peritoneum. Hematogenous infection: the intestinal bacteria-intestinal capillaries and portal vein system are integrated. Lymphatic infection: the intestinal bacteria-intestinal lymph circulation cycle. Lymphatic infections play an important role in the occurrence of SBP and are considered to be the main pathway for pathogenic infections.

2. Low host immunity;

Humoral immunity is abnormal. These include decreased complement, decreased opsonin activity, and decreased leukocyte chemokines (C3a, C5a, C567). Cellular immune function is reduced. The phagocytic function of the monocyte-phagocytic cell system is reduced: 80% of the phagocytic function of the monocyte-phagocytic cells in the normal body is performed by liver macrophages. Cirrhotic liver macrophages are markedly reduced and are hardly found. And phagocytosis is reduced. Hepatic macrophage opsonin, fibronectin, has also declined, causing endotoxins and bacteria absorbed from the intestine to enter the vein that have not been sufficiently detoxified and cleared by liver macrophages to enter the human circulation.

3. The antibacterial activity of ascites is weakened;

It has been shown that several defensive components such as albumin, fibronectin content, immunoglobulin complement concentration, and opsonin activity in cirrhotic ascites are lower than those in non-cirrhotic ascites. The bactericidal ability of liver cirrhosis also decreased. Ascitic fluid that has lost its antibacterial ability becomes an ideal medium for bacteria, and bacteria can multiply rapidly in ascites.

Clinical manifestations of spontaneous bacterial peritonitis

The onset of SBP can be acute or slow, with varying clinical manifestations. Typical clinical manifestations are fever, abdominal pain, abdominal muscle tension, abdominal tenderness, rebound pain, and decreased bowel sounds. The clinical manifestations of patients with cirrhosis and ascites are mostly atypical, and those with insidious onset only have abdominal discomfort, mild abdominal pain, weakened bowel movements, or abdominal flatulence, which may be the only positive signs. About 13% of the patients were asymptomatic, showing only liver damage or general exacerbations. The following main manifestations may occur in patients with concurrent SBP:

1 fever: one of the main symptoms of this disease. In addition to extreme weakness, shock and a few asymptomatic people, they have fevers to varying degrees, mostly irregular fevers, followed by relaxation or retentive fever. Severe fever is often associated with sepsis.

2 Abdominal pain: There are abdominal pains of varying severity. Those with hidden onset can only have abdominal discomfort. Those with acute onset can have sudden abdominal pain or bloating, often accompanied by loss of appetite, nausea, vomiting, and diarrhea. It should be noted that those with advanced or severe liver cirrhosis, or frail old age, or shock, or a large number of ascites may have no abdominal pain.

3 peritoneal irritation: manifested as abdominal tenderness and rebound tenderness, which can be total abdominal tenderness or even refusal to press, can also be local tenderness or deep tenderness, the degree of rebound tenderness can also vary in severity.

4 Ascites sign: After the occurrence of peritonitis, the ascites often increases rapidly, and the diuretic is ineffective, and there are increasing symptoms of abdominal distension, less food, decreased urine output, inability to lie flat, and even breathing difficulties.

In addition, severe SBP secondary to liver cirrhosis can also be manifested by various complications, such as early onset of hepatic encephalopathy, septic shock, hepatorenal syndrome, upper gastrointestinal bleeding, and liver-lung syndrome, which often lead to rapid deterioration of liver function. , Respiratory cycle failure, and even death, the prognosis is extremely poor.

Clinical classification of spontaneous bacterial peritonitis

Some scholars have classified SBP into 5 types based on different clinical manifestations: Type I is ordinary type: typical fever, abdominal pain, abdominal tenderness, rebound pain and other acute abdominal symptoms; Type II is refractory ascites type: ascites Sexual increase, diuretic effect is poor, ascites stubbornness is not easy to subside; Type III is shock type: Shock manifestation such as blood pressure drop and pulse rate; Type IV is hepatic encephalopathy type: Hepatic coma is the main symptom; Type V is asymptomatic : Ascites examination supports SBP without clinical signs of peritonitis. ^[1]

Diagnosis and identification of spontaneous bacterial peritonitis

Spontaneous bacterial peritonitis

1 peripheral blood white blood cell count:

In general, when the percentage of peripheral white blood cells and neutrophils increases in a short period of time, especially when the percentage of neutrophils increases, it is of certain value to indicate infection. However, patients with advanced liver cirrhosis are often accompanied by hypersplenism or decreased bone marrow hematopoiesis, which causes peripheral white blood cells to decrease. Therefore, many patients with normal peripheral blood white blood cells are normal when liver cirrhosis is complicated by SBP. When there is no obvious abnormality in peripheral blood leukocytes, the occurrence of SBP cannot be ruled out. At this time, it should be combined with clinical manifestations and comprehensive analysis of various factors for further analysis.

2 Ascites check:

Routine examination of ascites includes examination of ascites appearance, specific gravity, qualitative and quantitative protein, assorted count of leukocytes in ascites. The appearance of SBP ascites is mostly pale yellow, and those with higher cell counts appear cloudy. Li Fan mostly tested positive, and the protein quantification was usually less than 10g / L, and the specific gravity was less than 1.018. The pH is around 7.25, mostly less than 7.35. The number of white blood cells is more than 0.5 × 109 / L, and polymorphonuclear leukocytes (PMN)> 0.25 × 109 / L are important indicators for confirming infection.

Ascites bacterial culture: Positive ascites bacterial culture is of diagnostic significance. However, the positive rate of normal ascites culture is low. When the PMN count of ascites is 250 / mm3 (0.25 × 109 / L), the bacterial culture according to conventional methods has only a positive rate of about 50%. Incubation, the bacterial positive rate can reach 80%. In order to increase the positive rate of ascites culture, it is recommended to perform antibiotics before use. Use blood culture bottles to increase bacteria, and send aerobic and anaerobic cultures. Inoculate at least 10ml of ascites. Ascites volume> 10ml, the culture rate can be increased after centrifugation. Clinical symptoms, ascites manifestations, and peripheral white blood cell counts are often found to be in line with SBP in clinical practice, but the positive rates of ascites smears and traditional ascites culture methods are very low, that is, a significant proportion of patients with undetectable ascites This group of patients is called culture-negative neutrophil elevation ascites (CNNA). CNNA and SBP are almost the same clinical phenomenon and are a variant form of SBP.

3. Blood culture: About 50% of patients with SBP can produce the same bacteria as ascites, especially 30% of patients with negative ascites culture can also be positive. However, most literatures report that the positive rate of blood culture is very low. Ye Rongxia reported that the positive rate of blood culture is only 4.6%. Clinically, SBP patients are recommended to perform blood culture and ascites culture at the same time to increase the positive rate of culture.

4 Total ascites protein concentration: In patients with liver cirrhosis, the total protein concentration of ascites is less than 10 g / L, which can be used as the pathogenesis factor of SBP. The occurrence of SBP in patients with cirrhosis is associated with a decrease in total ascites protein. ^[2-3]

Diagnosis of spontaneous bacterial peritonitis

Early diagnosis is the key to treatment. In 1988, China's ascites conference formulated the diagnostic reference standards for liver cirrhosis and ascites complicated with SBP as follows: 1. Peritoneal irritation signs such as fever, abdominal pain and abdominal tenderness, rebound pain, etc. 2. Where ascites white blood cells> 0.5 × 109 / L, PMN> 0.5, SBP could be diagnosed if the ascites culture had pathogenic bacteria growth or smear positive. 3. Ascites white blood cells> 0.5 × 109 / L, PMN> 0.5, combined with clinical manifestations can be diagnosed as SBP. 4. Where ascites leukocytes> 0.3 × 109 / L, PMN> 0.25, even if there is no clinical manifestation, it should be regarded as bacterial ascites, SBP should be highly suspected, and SBP should be treated. 5. If the ascites test fails to meet the above criteria, those with positive tests can also be diagnosed as SBP: Ascites pH <7.30, or serum ascites pH gradient> 0.10, pH measurement of ascites must be completed quickly after ascites is extracted, and ascites after 30 minutes CO2 increases and pH decreases; ascites lactate> 0.63mmol / L, but malignant ascites lactate can also show a high level, and ascites lactate can also increase during acidosis. Pay attention to identify: ascites The test (determining endotoxin) was positive; ascites adenosine deaine (ADA)> 6kU / L, but ADA in malignant ascites can also increase, and ADA reaches higher levels in tuberculous peritonitis.

The diagnostic criteria for the SBP of the International Ascites Society (IAC) in 2000 are also available for clinical diagnosis.

SBP diagnostic criteria and treatment: 1. Admission can be diagnosed with any of the following: (1) local peritoneal manifestations (abdominal pain, vomiting, diarrhea, intestinal obstruction); (2) systemic infection manifestations (fever, increased WBC, septic shock); (3) none Hepatic encephalopathy with a clear cause; (4) Radical renal impairment without a clear cause; (5) Gastrointestinal bleeding without antibiotic prophylaxis. 2. 2. Ascites PMN> 2.5 × 109 / L, or the ratio of PMN to RBC in bloody ascites is 1: 250. 3. A blood culture bottle is used for ascites inoculation and culture at the bedside, and the amount is not less than 10ml; blood culture is performed at the same time.

Differential diagnosis of spontaneous bacterial peritonitis

It is mainly distinguished from secondary peritonitis and tuberculous peritonitis.

1. Secondary peritonitis secondary to surgical abdomen or abdominal surgery, the main points of identification are: sudden onset, often accompanied by obvious symptoms of sepsis, acute peritoneal irritation, the "triad of peritonitis" prominent; abdominal cavity The puncture was purulent, the residue of digestive tract contents, decreased ascites biochemical glucose (L), increased albumin (> 10g / L), and increased LDH (> serum LDH level). Bacterial smears and cultures are not single bacteria, and are mostly mixed. Bacterial infection; X-ray film shows free gas under the diaphragm when the organs in the cavity are perforated. If necessary, endoscopic, laparoscopic, or laparotomy.

2. The main basis for the identification of tuberculous peritonitis : patients with a history of tuberculosis or tuberculosis lesions in other parts; may be accompanied by symptoms of tuberculosis such as afternoon hot flashes, night sweats; abdominal percussion showed a characteristic kneading feeling; ascites lymphocytes increased, resistance Acid staining was positive; erythrocyte sedimentation increased and serum tuberculosis antibodies were positive; experimental anti-sputum treatment was effective. ^[4-5]

Treatment of spontaneous bacterial peritonitis

The treatment of liver cirrhosis and ascites complicated with SBP is a complex comprehensive treatment. The important treatment is to effectively control the infection, followed by the active prevention and treatment of complications such as hepatic encephalopathy, hepatorenal syndrome, shock, etc., to correct water and electrolyte disorders and strengthen support. Treatment, etc.

Antibacterial treatment for spontaneous bacterial peritonitis

1.1 Empirical treatment: Patients with advanced liver cirrhosis and chronic severe hepatitis should receive empirical anti-infective treatment as soon as infection symptoms, signs, and / or ascites neutrophils are greater than 0.25 × 109 / L. The empirical antibacterial treatment of SBP should follow the principles of broad spectrum, sufficient amount and low renal toxicity. The third-generation cephalosporins are preferred: the third-generation cephalosporins have a broad antibacterial spectrum, low renal toxicity, a large distance between the therapeutic dose and the toxic dose, and can quickly penetrate the abdominal cavity to reach a bactericidal concentration, so it has now become an empirical treatment for SBP Drug of choice. Commonly used drugs are ceftriazine, cefotaxime, ceftazidime, and cefoperazone. Amoxicillin / clavulanic acid: It has a broad antibacterial spectrum, is stable to -lactamase, and is not prone to drug resistance. It is equivalent to cefotaxime in the treatment of SBP, and has a low price and small adverse reactions. It can be used as An alternative to cefotaxime. Fluoroquinolones: It is a broad-spectrum, highly bioavailable, easy-to-use, and inexpensive drug, but with the widespread use of such drugs in recent years, E. coli has significantly increased its drug-resistant strains. Therefore, it is not recommended for patients with severe abdominal infections with severe liver disease. At the same time, due to toxicity to cartilage of young animals, infants and young children should use such drugs with caution. Aminoglycosides such as amikacin: have good antibacterial activity against staphylococcus and gram-negative bacilli, but have nephrotoxicity and ototoxicity, so in patients with cirrhosis and severe hepatitis who often have hepatorenal syndrome Avoid using it, but it has a synergistic effect with -lactams, and some drug-resistant bacteria are often sensitive to this kind of drugs. Monitor kidney function regularly during use. Aztreonam, a monocyclic -lactam antibiotic, is a narrow-spectrum antibiotic, which has less interference with the normal intestinal flora, so it is not easy to cause imbalance in the flora in the body. The disadvantage is that it is expensive and therefore not considered as experience. Sexual anti-infective treatment.

With the extensive use of broad-spectrum -lactamase antibiotics, Gram-negative extra-spectrum -lactamase (ESBLs) resistant strains have been increasing. For SBP with nosocomial infections, SBP that has been recently treated with antibiotics for severe abdominal infections (within 3 months) and more severe SBP should avoid the use of antibacterials such as cephalosporin and aztreonam. -lactam + Enzyme inhibitor antibiotics such as cefoperazone + sulbactam, oxypiperazine penicillin + tazobactam, and aminoglycoside antibiotics such as etimicin with less renal toxicity. Severe infections can be treated with carbapenem antibiotics such as subampenem and meropenem. Bacterial drug resistance in different regions and hospitals is different, and the current and local epidemic trends and trends of drug-resistant bacteria should be adjusted to adjust the use of antibiotics.

1.2 Targeted anti-infection treatment: Prior to obtaining pathogenic bacteria, empirical use of antibiotics is the main method. Once pathogenic bacteria are cultured, narrow-spectrum antibiotics should be selected according to drug sensitivity experiments. For those with negative bacterial culture for the first time, review the ascites PMN 48 hours after the empirical treatment. If the value decreases by more than 50%, it indicates that the treatment is effective and continue to use the original antibiotic. Otherwise, it should be replaced with another antibiotic immediately. The course of antibiotics should be individualized. The general course of treatment is 10-14 days. The symptoms and signs disappear. Ascites PMN <2.5 × 109 / L. Ascites bacteria culture is negative.

Local management of spontaneous bacterial peritonitis in the abdominal cavity

Intraperitoneal injection of antibiotics: Topical antibiotics can easily induce multi-drug resistance and are no longer used. Abdominal puncture fluid and peritoneal lavage: In the case of cirrhotic ascites combined with SBP, if diuretic resistance occurs, or the ascites is significantly cloudy, flocculent, or bloody ascites, it is feasible to perform intraperitoneal puncture drainage and peritoneal puncture irrigation wash. The simple discharge of ascites is prone to complications such as hypovolemia, hyponatremia, renal impairment, and hepatic encephalopathy. It is necessary to input a sufficient amount of albumin to expand blood volume while a large amount of fluid is released, which can prevent systemic hemodynamics and Impaired renal function and significantly reduced complications. The ascites was drained at one time, and the saline-free albumin was infused intravenously at a rate of 10 g of albumin supplemented with 1 L of ascites after drainage. If 3 to 5 L is discharged each time, the amount of albumin can be appropriately reduced, and 6 to 8 g of albumin can be added to 1 L of ascites.

Spontaneous bacterial peritonitis albumin treatment

A study published by Sort et al. In 1999 showed that patients with liver cirrhosis complicated by SBP and intravenous injection of albumin on the basis of the antibiotic cefotaxime can reduce the incidence and mortality of renal insufficiency. Methods: The first day of hospitalization was injected with albumin (1.5g / kg) once, and the third day (1g / kg). The mechanism of renal damage in patients with liver cirrhosis and SBP may be related to the decrease of effective arterial blood volume. Dilation with albumin can prevent renal damage and reduce mortality.

Supportive treatment for spontaneous bacterial peritonitis

Give active intravenous nutritional support, supplement excellent protein rich in branched chain amino acids, and strictly control blood sugar (<8mmol / L), which is important for improving the body's immunity and promoting infection recovery.

Prognosis of spontaneous bacterial peritonitis disease

The prognosis of SBP is extremely poor, which can easily lead to fatal complications such as septic shock, hepatorenal syndrome, upper gastrointestinal bleeding and liver failure, and the recurrence rate is about 70% per year, so prevention is very important. The main preventive measure is selective intestinal decontamination (SID), which uses antibiotics to remove aerobic flora. In 2004, the recommendations of the American College of Hepatology Society for the treatment of liver cirrhosis and ascites suggest that patients with ascites, lower total ascites protein, patients with liver cirrhosis with gastrointestinal bleeding, and those who have experienced SBP but have recovered are at high risk for SBP. Prophylactic oral antibiotics (norfloxacin or compound neonomin or neomycin) are used for primary prevention. However, the prophylactic administration of antibiotics does not comply with the principle of antibiotics and is prone to drug resistance. If bacterial resistance occurs, the prognosis is poor.

Prevention of spontaneous bacterial peritonitis

The use of gastric motility drugs and oral probiotics can also prevent SBP. 1. Regulation of intestinal micro-ecology: Supplement probiotics: Bifidobacterium, Lactobacillus and Bacillus licheniformis are anti-inflammatory microorganisms of the intestine. By inhibiting the growth of harmful bacteria, restore the intestinal micro-ecological balance and repair the intestinal epithelial barrier. Supplementation of probiotics: Lactulose, lactitol and other oral or high-level enemas can promote the beneficial growth of beneficial bacteria in the intestine to break down sugars and inhibit harmful bacteria in the intestines to break down proteins; their acidic metabolites can promote intestinal origin Excretion of toxins. 2. Maintain intestinal barrier function: glutamine (GLN) is an important energy source for rapidly dividing cells (such as intestinal epithelial cells, lymphocytes and other immune cells), and is an essential amino acid for the condition of critically ill patients. When the intestinal barrier is damaged and bacterial endotoxin is translocated, GLN supplementation can reduce the intestinal membrane atrophy, repair the intestinal barrier, reduce the permeability of the intestinal wall, and promote the proliferation of lymphocytes, monocytes and macrophages, and enhance immune function This can reduce intestinal bacterial endotoxin translocation and reduce the risk of infection and multiple organ damage. The dosage of GLN is 1.5 to 2.0 mg / kg per day added to the amino acid solution at least 5 times by intravenous drip. The speed should not exceed 0.1 g amino acid / h, and it should be used continuously for at least 6 days.

Expert opinion on spontaneous bacterial peritonitis

About half of SBP may not have any symptoms or atypical symptoms, so those with moderate ascites should undergo laparotomy after hospitalization. Ascites culture and blood culture should be performed at the same time to improve the positive rate of ascites culture. Patients with severe liver disease have no obvious cause of general deterioration or rapid deterioration of liver and kidney function. SBP diagnosis should be considered. Jaundice deepens in the short term. Hepatic encephalopathy may be related to SBP. SBP must be detected early and treated in a timely manner. Once the diagnosis of spontaneous bacterial peritonitis is clear, antibiotic therapy should be given, and albumin therapy can improve the efficacy. Patients who have experienced SBP, patients with gastrointestinal bleeding, and liver cirrhosis with ascites protein below 10g / L may consider long-term oral antibiotics to prevent SBP recurrence. The prognosis after SBP is poor, and suitable patients should consider liver transplantation.