I. Overview.
1.Onset: About 30% of patients with cirrhosis develop bacterial infections on admission or during hospitalization, and most of them are combined with ascites. 60% of patients with bacterial infections are community-acquired and 40% are nosocomial-acquired.
2, the most common bacterial infections: spontaneous bacterial peritonitis (SBP), urinary tract infections; pneumonia, cellulitis, etc.
3, risk factors: high Child-Pugh score, ruptured varicose veins bleeding, hypoproteinemia and previous history of SBP.
4, prognosis: after the occurrence of bacterial infection, sepsis and its resulting organ failure and the risk of death are significantly increased, the post-infection morbidity and mortality rate can reach 38%, and if combined with infectious shock, the morbidity and mortality rate can exceed 70%.
Second, the pathogenesis: mainly in patients with cirrhosis, the defense barrier against bacteria is changed and the ability to clear bacteria is reduced.
Main causes.
1, macrophages have a diminished capacity for Fcγ receptor-mediated clearance of antibody-encapsulated bacteria.
2, Defective complement system.
3, Down-regulation of HLA-DR expression in monocytes.
4, Decreased phagocytosis and intracellular killing function of neutrophils.
5, Genetic immunodeficiency: carries nucleotide-binding oligomerization structural domain 2 variants; lack of mannose-binding lectin leads to increased susceptibility to bacterial infection.
6, intestinal dysfunction, increased intestinal mucosal permeability, intestinal bacterial overgrowth and other conditions leading to bacterial translocation.
Third, the diagnosis of bacterial infections.
Mainly rely on: clinical and laboratory tests.
(a) Diagnosis of cirrhosis combined with bacterial infection events should be examined.
1.Physical examination.
Vital signs: body temperature (fever/hypothermia), respiration and heart rate, mean arterial pressure
Abnormal physical findings.
– abdominal pain, pressure pain, rebound pain, intestinal obstruction (SBP or secondary peritonitis)
– Chest signs (pneumonia/spontaneous abscess chest)
–Skin infection (cellulitis)
2. Determination of infection and site of infection.
Blood routine, blood culture, C-reactive protein, calcitoninogen.
Examination of the site of infection.
–X-ray of chest
–Abdominal fluid/pleural fluid routine, biochemical and bacterial culture
–urine routine, sedimentation and bacterial culture
–sputum smear gram stain examination and bacterial culture
–Poop routine and bacterial culture
–Abdominal ultrasonography
3. Disease assessment (possible organ failure)
Cardiovascular system: electrocardiogram, cardiac function tests (cardiac ultrasound, B-type natriuretic peptide BNP), lactate level detection in case of severe sepsis
Liver function: serum transaminase, serum bilirubin, albumin, prothrombin time, blood ammonia, cholinesterase, etc.
Renal function: blood creatinine, electrolytes, blood gas analysis.
Coagulation system: bleeding, fibrinogen, platelet count, clotting time, etc.
Neurological system: state of consciousness.
Metabolism: blood glucose level.
Inflammatory response: blood count, C-reactive protein, hematocrit, SIRS.
Systemic inflammatiory response sydrome (SIRS)
Diagnostic criteria.
①Body temperature ≥38℃ or ≤36℃.
② Heart rate ≥ 90 beats/min.
③ Respiratory rate ≥20 breaths/min, or PaCO2 ≤32mmHg.
④Blood leukocyte count ≥12×109/L or ≤4×109/L, or immature neutrophils >10%.
The presence of two or more of these manifestations suggests the presence of SIRS.
(B) Limitations of commonly used clinical and laboratory infection indicators
1.SIRS.
SIRS diagnostic criteria are defined based on the general population, and the accuracy of diagnosis in the cirrhotic population is low and relatively difficult to apply due to.
(1) The pre-existing hyperdynamic circulatory state in patients with cirrhosis can also lead to tachycardia.
(2) Heart rate is decreased in patients using beta-blockers.
(3) Hepatic encephalopathy can lead to shortness of breath.
(4) Hypersplenism can lead to leukopenia.
The above factors lead to a decrease in the diagnostic value of SIRS diagnostic criteria for patients with cirrhosis complicated by sepsis. In fact, the incidence of SIRS is 10-30% in patients with decompensated cirrhosis without co-infection and 57-70% in patients with co-infection, suggesting that SIRS is not the best indicator for the diagnosis of infection in patients with cirrhosis. However, because SIRS may increase the risk of complications and death associated with portal hypertension, the presence of SIRS at admission or during hospitalization, regardless of co-infection, can be a useful indicator for prognostic assessment of patients with cirrhosis.
2. C-RP and PCT.
Acute phase protein, especially C-RP production, is reduced in patients with liver failure at the time of infection, but remains accurate for diagnosing infection in patients with cirrhosis.
(iii) Diagnosis of SBP.
1.Definition: SBP refers to ascites infection without a clear source of intra-abdominal infection in patients with previously sterile ascites.
2, Diagnosis based on.
① Typical symptoms and signs: abdominal pain and fever; abdominal pressure pain and rebound pain.
②Other clinical manifestations: nausea, vomiting, intestinal obstruction, diarrhea, hepatic encephalopathy, gastrointestinal bleeding and renal impairment, etc.; ③Laboratory infection index: blood routine, CRP, PCT, etc.
④ ascites examination: ascites polymorphonuclear (PMN) count ≥ 250 cells/mm3. ascites lactoferrin ≥ 242ng/mL (sensitivity 96%, specificity 97%). (For patients with hemorrhagic ascites, subtract one PMN per 250 erythrocytes).
3, differential diagnosis: mainly secondary to peritonitis.
Ascites species glucose, lactate dehydrogenase (LDH) and total protein levels are important indicators to differentiate the two (Runyon criteria). Secondary peritonitis is suggested when 2 or more of the following abnormal indicators are present in ascites: glucose <50 mg/dl, protein >10 g/L, LDH > normal serum levels. Sensitivity 67%, specificity 90%.
IV. Treatment of bacterial infections.
(a), treatment principles.
1, once the diagnosis of serious infection, must immediately receive intravenous antibacterial drug therapy.
2, empirical drug use should try to cover all possible pathogenic bacteria associated with the infection without producing adverse effects.
3, empirical drug use should take into account the type of infection, severity, the site of infection and drug-resistant bacteria and other factors.
4.Aminoglycoside antibacterial drugs also cause the risk of renal failure, therefore, even if they are effective for infection, they should be avoided as much as possible.
5.Third-generation cephalosporins have good antibacterial activity against Enterobacteriaceae and non-enterococcal streptococci, are well tolerated, and have been used for many years as a classical choice for empirical antibacterial therapy in patients with cirrhosis co-infection.
(ii) Empirical antimicrobial therapy for community-acquired and nosocomial infections.
1.Treatment of patients with SBP.
(1) Common infectious agents: Escherichia coli, Klebsiella pneumoniae, Enterobacter spp, Streptococcus pneumoniae, Streptococcus griseus, etc.
(2) Recommended medications: First-line regimen: cefotaxime 2g q12h IV or ceftriaxone 1g q12-24h IV or amoxicillin/clavulanic acid 1g/0.2g q6-8h IV.
Other options: ciprofloxacin, levofloxacin, etc. For patients with nosocomial infections in ESBL-producing enterobacteria endemic areas, carbapenems such as meropenem can be used as antimicrobial agents.
2, treatment of patients with urinary tract infections.
(1) Common infectious agents: Escherichia coli, Klebsiella pneumoniae, Enterococcus faecalis, Enterococcus faecalis.
(2) Recommended medication: First-line regimen: combined sepsis: cefotaxime 2g q12h IV or ceftriaxone 1g q12-24h IV or amoxicillin/clavulanic acid 1g/0.2g q6-8h IV.
Uncomplicated infections: ciprofloxacin, levofloxacin or cotrimoxazole, etc.
Other options: Patients with nosocomial infections in ESBL-producing Enterobacteriaceae endemic areas may use carbapenems such as meropenem as antimicrobial agents.
3. Patients with pneumonia infection.
(1) Common infectious agents: Streptococcus pneumoniae, Mycoplasma pneumoniae, Legionella, Haemophilus influenzae, Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus.
(2) Recommended medications: Community-acquired: Ceftriaxone 1g q12-24h IV or amoxicillin/clavulanic acid 1g/0.2g q6-8h IV combined with macrolides (azithromycin, erythromycin, etc.) class or quinolones (levofloxacin, ciprofloxacin, moxifloxacin).
For nosocomial infections: meropenem or ceftazidime + quinolones. If there is a risk of MRSA infection, intravenous vancomycin or linezolid, etc.
4. Soft tissue infections.
(1) Common infectious agents: Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa.
(2) Recommended medications: community-acquired: amoxicillin/clavulanic acid 1g/0.2g q6-8h IV or ceftriaxone 1g q12-24h IV + cloxacillin (2g q6h).
Nosocomial infection: Meropenem or ceftazidime + glycopeptides.
(iii) Albumin therapy.
Bacterial infections in patients with cirrhotic ascites can cause deterioration of hemodynamic status and may lead to renal failure (hepatorenal syndrome), which can be triggered by biliary, gastrointestinal and complicated urinary tract infections, but the most common trigger is SBP. 70% to 90%). In particular, patients with bilirubin >4 mg/dl or creatinine >1.0 mg/dl have a higher risk of hepatorenal syndrome (33%-57%), and significant results can be obtained with albumin expansion. For patients with bilirubin <4 mg/dl or creatinine <1.0 mg/dl the risk of hepatorenal syndrome is low (8%) and albumin may not be used.
The usual dose of albumin: 1.5g/kg given after diagnosis and 1.0g/kg on day 3.
V. Prevention of bacterial infection.
1.Actively treat the primary disease and improve liver function.
2.Enhance the body’s resistance and avoid various triggers of infection.
3.Preventive antimicrobial drug application (limited to high-risk groups of cirrhosis who may have bacterial infection).
Indications for prophylactic antimicrobial drug treatment in patients with cirrhosis
Indications
Antibacterial drug type and dose
Duration of treatment
Gastrointestinal bleeding
Norfloxacin 400mg q12h PO
Ceftriaxone 1g qd IV for patients with advanced cirrhosis (at least 2 of the following are present: ascites, severe malnutrition, hepatic encephalopathy, or jaundice for 7 days)
Primary prophylaxis in patients with low protein ascites (<15g/L).
Secondary prophylaxis.
Norfloxacin 400mg q12h PO for patients with advanced cirrhosis in the presence of: Child-Pugh ≥9 points and bilirubin ≥3mg/dL and/or renal impairment (blood creatinine >1.2mg/dl, urea nitrogen >25mg/dl or blood sodium ≤130mmol/L)
Norfloxacin 400mg qd PO long-term
VI. Summary.
1. Bacterial infection is the most common complication and the primary cause of death in patients with cirrhosis. The main pathogenesis is immunodeficiency (mainly acquired factors, genetic factors are also involved) and bacterial translocation.
2, Early diagnosis of infection is critical. The accuracy of C-reactive protein, calcitoninogen and SIRS diagnostic criteria is low in the cirrhotic population; therefore, new diagnostic tools are needed.
3, The diagnosis of SBP relies on laparotomy ascites examination, Runyon criteria and timely abdominal CT examination help to identify secondary peritonitis.
4, Timely and correct antimicrobial therapy is the basis of treatment for patients with cirrhosis co-infection. Third-generation cephalosporins remain the gold standard for the treatment of community-acquired infections, and empirical treatment of nosocomial or health care facility-associated infections requires reference to the local bacterial resistance situation.
5. Intravenous albumin supplementation can reduce the incidence of renal damage and improve in-hospital survival in patients with SBP with poor liver and kidney function.
6, Prophylactic antimicrobial drugs limited to use in high-risk cirrhotic patients will help reduce the prevalence of multibacterial resistance.