Long-term prophylaxis of spontaneous bacterial peritonitis in patients with cirrhosis

OBJECTIVE: To review the literature regarding long-term prophylaxis of spontaneous bacterial peritonitis (SBP) in patients with cirrhosis. DATA SOURCES: A MEDLINE (1967-September 2004) and bibliographic search of the English-language literature was conducted using the search terms spontaneous bacterial peritonitis, cirrhosis, antimicrobial, and prophylaxis. DATA SYNTHESIS: Long-term antimicrobial prophylaxis has been shown to decrease recurrent SBP in cirrhotics with a prior episode. Prophylaxis in patients with low ascitic fluid protein has also been shown to reduce the incidence of SBP; however, studies are too in-homogeneous to identify subgroups that benefit the most. CONCLUSIONS: Long-term antimicrobial therapy should be considered for secondary prophylaxis of SBP. Studies should be done to confirm this benefit and identify subsets of patients with low ascitic fluid protein who clearly benefit.     

Outpatient management of cirrhosis: a narrative review

Cirrhosis is the 12th leading cause of death in the United States. Individuals with cirrhosis are at risk for many potential complications. Complications can be managed or detected early with proper outpatient management. The most lethal of these complications is bleeding esophageal varices. All patients with cirrhosis should be screened for the presence of varices and treated when indicated. The most common complication seen in these patients is ascites. Ascites can be treated with dietary modifications and a diuretic regimen. Other potential complications include spontaneous bacterial peritonitis, hepatocellular carcinoma, hepatic encephalopathy, hepatorenal syndrome, and hepatopulmonary syndrome. The outpatient management of these complications will be discussed in this paper, along with the use of vaccinations, educating patients about the avoidance of hepatotoxic drugs, and when to refer a patient for liver transplant.     

Le sepsis dans la cirrhose

Patients with cirrhosis are at risk of developing sepsis and sepsis-induced organ failure as well as dying. Spontaneous bacterial peritonitis (SBP) is the most common site of severe infections. Bacterial infections are equally distributed among one of the following three categories: community-acquired, healthcare-associated and nosocomial. The incidence of sepsis caused by multiresistant bacteria is increasing. In patients with cirrhosis and severe sepsis, high production of pro-inflammatory cytokines seems to play a role in the development of organ failure (including worsening of liver function). The underlying molecular mechanisms that explain cytokine overproduction in cirrhosis are poorly understood. In patients with cirrhosis and sepsis, the identification of failing organs is assessed using the Sequential Organ Failure Assessment (SOFA) scale. Emergent empiric, broad-spectrum and non-nephrotoxic antibiotic therapy should be started. The choice of antibiotics depends on whether or not patients are at risk of developing infection due to extended-spectrum β-lactamase-producing Enterobacteriaceae. In patients with SBP without shock treated with antibiotics, intravenous albumin administration decreases the occurrence of hepatorenal syndrome and improves survival. Two randomized control studies on extracorporeal liver support systems have shown an improvement of hepatic encephalopathy but no benefit for survival. Bacterial sepsis is preventable by using norfloxacin in patients with variceal hemorrhage or in the setting of primary or secondary prophylaxis of SBP.     

Spontaneous bacterial peritonitis: variant syndromes

Spontaneous bacterial peritonitis (SBP), a fascinating disease that had been reported perhaps 50 times in varying guises over the preceding century, suddenly burst forth in the 1960s and was recognized in clusters of cases almost simultaneously in Paris, London, and West Haven, Connecticut. The spectrum of the disease has broadened. Initially, it was associated almost exclusively with alcoholic cirrhosis, but it has now been found in association with posthepatitic cirrhosis, cryptogenic cirrhosis, chronic active liver disease, and, occasionally, in biliary cirrhosis and cardiac cirrhosis. Recently, it has been reported in alcoholic hepatitis and acute viral hepatitis. It occurs occasionally in malignant ascites and in pancreatitis in the absence of cirrhosis. It is surprisingly common in disseminated lupus, in which it occurs relatively more commonly than in alcoholic cirrhosis. A similar syndrome, primary peritonitis, occurs frequently in children with nephrotic ascites. The clinical pattern of SBP has broadened. Initially it consisted of abdominal pain, fever, rebound tenderness, hypoactive bowel sounds, hypotension, encephalopathy, and cloudy ascites with large numbers of polymorphonuclear leukocytes in ascitic fluid. Each and every symptom, sign, and laboratory abnormality may be absent; indeed, the syndrome can be completely silent. Initially, the causative bacteria appeared to be almost exclusively enteric, but now the list of bacteria isolated in cases of SBP looks like a bacteriology textbook. Anaerobes are rare. Multiple organisms usually suggest nonspontaneous origin such as perforation or vasopressin induction. The differentiation between spontaneous and nonspontaneous bacterial peritonitis is crucial in the differential diagnosis. The great majority of cases of SBP develop in the hospital, 80% more than one week after admission. It is therefore a nosocomial disease that may be precipitated by procedure-induced bacteremia, gastrointestinal bleeding, or diarrhea, and it tends to occur in patients with low ascitic fluid protein (complement) concentrations and severe portal-systemic shunting.     

Cirrhosis: diagnosis, management, and prevention

Cirrhosis is the 12th leading cause of death in the United States. It accounted for 29,165 deaths in 2007, with a mortality rate of 9.7 per 100,000 persons. Alcohol abuse and viral hepatitis are the most common causes of cirrhosis, although nonalcoholic fatty liver disease is emerging as an increasingly important cause. Primary care physicians share responsibility with specialists in managing the most common complications of the disease, screening for hepatocellular carcinoma, and preparing patients for referral to a transplant center. Patients with cirrhosis should be screened for hepatocellular carcinoma with imaging studies every six to 12 months. Causes of hepatic encephalopathy include constipation, infection, gastrointestinal bleeding, certain medications, electrolyte imbalances, and noncompliance with medical therapy. These should be sought and managed before instituting the use of lactulose or rifaximin, which is aimed at reducing serum ammonia levels. Ascites should be treated initially with salt restriction and diuresis. Patients with acute episodes of gastrointestinal bleeding should be monitored in an intensive care unit, and should have endoscopy performed within 24 hours. Physicians should also be vigilant for spontaneous bacterial peritonitis. Treating alcohol abuse, screening for viral hepatitis, and controlling risk factors for nonalcoholic fatty liver disease are mechanisms by which the primary care physician can reduce the incidence of cirrhosis.     

Spontaneous bacterial peritonitis is associated with high levels of interleukin-6 and its secondary mediators in ascitic fluid

Abstract. We investigated 37 patients with ascites and liver cirrhosis in order to examine whether on the basis of correlation of cytokines and acute phase proteins of the ascitic fluid, prognosis of spontaneous bacterial peritonitis can be made. Significantly enhanced levels of interleukin-6, as well as acute phase reactants a-l-antitrypsin and C-reactive protein were found in the ascitic fluid of patients with spontaneous bacterial peritonitis. The levels of tumour necrosis factor alpha (TNF-α), neopterin, interleukin 2–receptor and granu-locyte-macrophage colony stimulating factor were higher in patients with spontaneous bacterial peritonitis, but without statistical significance, whereas no differences were found between the interferon gamma, interleukin-2 and interleukin-1 levels. In addition, interleukin-6, TNF-α and neopterin levels were found to correlate significantly with the outcome of the disease. These findings show that acute phase reaction occurs in the ascitic compartment in correlation with the development of spontaneous bacterial peritonitis.     

肝硬化并自发性细菌性腹膜炎患者腹水培养的病原菌分布及耐药性分析

目的探讨自发性细菌性腹膜炎患者腹水病原菌特点及耐药,为临床合理用药提供依据。方法回顾性分析医院诊断为肝硬化并自发性细菌性腹膜炎（534例）患者的腹水细菌培养阳性结果,依据不同感染菌将患者进行分组,比较各组内细菌所占百分比,同时针对优势菌株（大肠埃希菌、屎肠球菌）进行耐药率分析。结果细菌培养阳性病例为 61 例, 占总病例数的11.42%,共分离出病原菌 78株, 45 例患者为单菌感染(73.8%),16例患者为复合菌感染(26.2%),其中15例为两种菌感染,占复合细菌感染的93.8%;78株细菌中革兰阴性菌40株(51.3%), 其中以大肠埃希菌为主,占革兰阴性菌的37.5%;革兰阳性菌32株(41.0%),其中以屎肠球菌为主,占革兰阳性菌的59.38%,且屎肠球菌总菌株数（19株）高于大肠埃希菌（15株）;真菌6株,占总菌株数的7.7%;大肠埃希菌对氨苄西林、左氧氟沙星、复方新诺明及头孢呋辛耐药率较高,分别是93.3%、80.0%、73.3%;对亚胺培南、阿米卡星耐药率较低,均为6.7%;未见对厄他培南、美洛西林的耐药菌株。屎肠球菌对氨苄西林、青霉素、左氧氟沙星、诺氟沙星耐药率较高,分别是68.4%、63.2%、57.9%、42.1%;发现对万古霉素耐药的1例菌株,为屎肠球菌;未发现对利奈唑胺耐药的菌株。结论肝硬化并发自发性细菌性腹膜炎患者腹水细菌感染以屎肠球菌和大肠埃希菌为主,耐药严重,临床应依据感染病原菌的类型和药敏合理选择抗生素。     

Spontaneous bacterial peritonitis

Spontaneous bacterial peritonitis is an infection of the ascitic fluid of patients who, in general, have severe chronic liver disease. Several variants of this disease exist including bacterascites, culture-negative neutrocytic ascites, and secondary bacterial peritonitis. Spontaneous bacterial peritonitis is frequently manifested by signs and symptoms of peritonitis although the findings may be subtle; however, occasionally it may be completely without clinical manifestation. The clinician must have a high index of suspicion in order to make this diagnosis at a relatively earlier stage of infection. An abdominal paracentesis is required to make the diagnosis of spontaneous bacterial peritonitis. This paracentesis should be performed on all patients who are admitted to the hospital for ascites and should be repeated if there is any manifestation of bacterial infection during the hospitalization. Patients with severe intrahepatic shunting--as manifested by marked redistribution of activity from the liver to the spleen and to the bone marrow on liver-spleen scan as well as patients with an ascitic fluid total protein concentration of less than 1 g/dl--appear to be particularly susceptible to bacterial infection of their ascites. In order to optimize the yield of ascitic fluid culture, it is probably appropriate to inject blood culture bottles with ascites at the bedside immediately after the abdominal paracentesis. The mortality of spontaneous bacterial peritonitis continues to be very high. Perhaps routine admission paracentesis and prompt empiric antibiotic therapy with a third-generation cephalosporin will decrease the mortality of this infection if the Gram stain of the ascitic fluid demonstrates bacteria or the ascitic fluid neutrophil count is greater than 250 cells/cu mm. Repeating the paracentesis after 48 hours of treatment to reculture the fluid and reassess the ascitic fluid neutrophil count appears to be the best way to assess efficacy of treatment. After 48 hours of treatment the ascitic fluid neutrophil count should be less than 50% of the original value if the antimicrobial therapy is appropriate. The optimal duration of antibiotic treatment is unknown; however, until controlled trials provide data regarding duration of treatment it is appropriate to treat with parenteral antibiotics for 10 to 14 days. Research is also needed to determine if there are measures which can be taken to prevent the development of spontaneous peritonitis.     

Spontaneous bacterial peritonitis: a therapeutic update

Spontaneous bacterial peritonitis (SBP) is one of the main infectious complications of cirrhosis and occurs in 8-30% of hospitalized patients with ascites. SBP is characterized by infection of the ascitic fluid (AF) in the absence of any primary focus of intra-abdominal infection. The main route by which the AF becomes infected is the hematogenous route. The pathogenic mechanism by which infection develops is bacterial translocation from the intestinal flora to the mesenteric lymph nodes and from there to the bloodstream. Contributing factors are an increased growth of Gram-negative aerobic bacilli in the jejunum, changes in the intestinal barrier and in addition factors which could reduce the local flow of blood. For clinical diagnosis, patients with SBP may present signs of peritoneal irritation and pain, together with changes in gastrointestinal motility, sometimes with nausea, vomiting, diarrhea or ileus. Many patients, however, may not present any symptoms or signs as a result of the presence of SBP. Diagnostic paracentesis of the AF must be performed for every patient with cirrhosis, hospitalized with ascites. Laboratory diagnosis of SBP is carried out by polymorphonuclear count in the AF, together with a positive culture from the AF, which is characteristically monomicrobial. Escherichia coli has been the main bacterium isolated from AF as well as other Gram-negative bacteria from the Enterobacteriaceae family and Streptococcus genus. A more rapid diagnosis of SBP can be obtained via the use of leukocyte esterase, which is present in biological fluids and reacts with a component of the dipstick, changing its color. During the acute phase of SBP, antibiotics should be initiated promptly once the clinical and laboratory diagnosis of SBP has been made, before the result of AF culture. Cefotaxime or other third-generation cephalosporins have been considered the first-choice empirical antibiotics in the treatment of cirrhotic patients with SBP, and is efficacious in approximately 90% of cases. Broad-spectrum quinolones, which are almost completely absorbed after oral administration and diffuse rapidly through the AF, are currently used for oral treatment of uncomplicated SBP. Patients who have already had a previous episode of SBP, with a 69% probability of recurrence within a year, will benefit from prophylactic treatment. Cirrhotic patients with a high risk of SBP and other infections, such as those with gastrointestinal bleeding, also benefit from primary prophylaxis and norfloxacin has been used with success.     

Finding the cause of ascites. The importance of accurate fluid analysis

Diagnostic paracentesis with ascitic fluid analysis is critical to the accurate diagnosis and management of ascites. Recent advances have improved the evaluation of ascitic fluid, among them the serum-ascites albumin difference for discriminating between ascites caused by liver disease and ascites due to malignancy. The ascitic fluid polymorphonuclear leukocyte concentration is the best index for the rapid presumptive diagnosis of spontaneous bacterial peritonitis. Familiarity on the part of the clinician with ascitic fluid interpretation and with ascitic fluid characteristics in various diseases will increase the chances of controlling ascites early.     

Complement and immunoglobulin levels in serum and ascitic fluid of patients with spontaneous bacterial peritonitis,malignant ascites,and tuberculous peritonitis

BACKGROUND: We determined complement and immunoglobulin levels in ascitic fluid and serum of 47 patients with spontaneous bacterial peritonitis, malignant ascites, or tuberculous ascites. METHODS: Paracentesis was done to confirm the underlying cause of ascites. Biochemical, hematologic, and microbiologic investigations were also done. RESULTS: The highest serum and ascitic fluid C3 and C4 levels and ascitic fluid IgM, IgA, and IgG levels were found in patients with tuberculosis. Ascitic fluid C3 level was found to be higher in the tuberculous group than in the patients with spontaneous bacterial peritonitis or malignant ascites. Ascitic fluid C4 levels were higher in patients with tuberculosis than in those with spontaneous bacterial peritonitis. CONCLUSION: We believe that further studies of the in vivo kinetics of immunoglobulins and complement in ascitic fluid of various causes are necessary for a better understanding of the host defense mechanisms of these fluids.     

Spontaneous meningococcal peritonitis: a report of two cases.

Two patients with spontaneous bacterial peritonitis caused by Neisseria meningitidis are described. In both cases immediate diagnosis was possible by examination of the ascitic fluid. Meningococcal peritonitis supports the hypothesis that the hematogenous spread of bacteria into the ascitic fluid may be one of the mechanisms of spontaneous bacterial peritonitis.     

Transjugular intrahepatic portosystemic shunt (TIPS)

Transjugular intrahepatic portosystemic stent shunt (TIPS) implantation is an intervention to reduce elevated portal pressure by implantation of a stent shunt between hepatic and portal vein by transjugular approach. Elevated portal pressure is mostly caused by cirrhosis of the liver but Budd-Chiari-syndrome, venoocclusive disease, and portal vein thrombosis can also be responsible. The main indications for TIPS implantation are intractable variceal hemorrhage, prophylaxis for recurrent variceal bleeding after failure of endoscopic prophylaxis, and prophylaxis for recurrent variceal bleeding from gastric varices in the fundus. New data show that treatment of refractory ascites using TIPS implantation also leads to improved patient survival. Primary bleeding prophylaxis is not an indication for TIPS implantation. Absolute contraindications are progressive liver failure, decompensation of the right ventricle, pulmonary hypertension, and higher degree hepatic encephalopathy. The main problems after TIPS implantation are a high rate of restenosis, which frequently requires reintervention with TIPS dilatation or reimplantation, and undesirable side effects in patients after TIPS implantation for indications without proven benefit. Due to a number of prospective randomized controlled trials, the indications and contraindications for TIPS are now well defined, thus leading to a reduction of side effects and a more precise use of this important therapeutic modality for portal hypertension.     

Cirrhosis and chronic liver failure: part I. Diagnosis and evaluation

Cirrhosis and chronic liver failure are leading causes of morbidity and mortality in the United States, with the majority of preventable cases attributed to excessive alcohol consumption, viral hepatitis, or nonalcoholic fatty liver disease. Cirrhosis often is an indolent disease; most patients remain asymptomatic until the occurrence of decompensation, characterized by ascites, spontaneous bacterial peritonitis, hepatic encephalopathy, or variceal bleeding from portal hypertension. Physical examination of patients with cirrhosis may reveal a variety of findings that necessitate a hepatic- or gastrointestinal-based work-up to determine the etiology. Some patients already may have had laboratory or radiographic tests that incidentally uncovered signs of cirrhosis and its comorbidities. No serologic or radiographic test can accurately diagnose cirrhosis. A significant correlation has been demonstrated between persistently elevated liver function tests and biopsy-proven underlying hepatic disease; thus, a more targeted serologic work-up is indicated in patients whose liver function test results are persistently abnormal. Unnecessary medications and surgical procedures should be avoided in patients with cirrhosis. Referral for liver biopsy should be considered only after a thorough, non-invasive serologic and radiographic evaluation has failed to confirm a diagnosis of cirrhosis; the benefit of biopsy outweighs the risk; and it is postulated that biopsy will have a favorable impact on the treatment of chronic liver disease.     

肝硬化食管胃静脉曲张的内镜治疗

肝硬化食管胃静脉曲张出血是危及生命的门脉高压并发症。食管静脉曲张一级预防策略为非选择性β受体阻滞剂（non selective beta blockers,NSBBs）或内镜下静脉曲张套扎术（endoscopic variceal ligation,EVL）,急性出血时首选EVL,其二级预防推荐NSBBs联合EVL。胃静脉曲张出血中,食管胃静脉曲张1型（gastroesophageal varices type 1,GOV1）应用EVL,食管胃静脉曲张2型（gastroesophageal varices type 2,GOV2）和孤立胃静脉曲张（isolated gastric varices,IGV）推荐内镜下组织胶注射术。预防胃静脉曲张再出血方面,内镜下组织胶注射术和经颈静脉肝内门体分流术（transjugular intrahepatic portosystemic shunt,TIPS）可应用于GOV2型和IGV,EVL、NSBBs或内镜下组织胶注射术可应用于GOV1型。胃静脉曲张一级预防可选用NSBBs或内镜下组织胶注射术。     

内镜下套扎术联合药物治疗食管静脉曲张出血的疗效观察

目的观察内镜下食管静脉曲张套扎术联合药物治疗肝硬化食管静脉曲张出血的临床疗效。方法回顾性分析2007年2月-2010年8月56例确诊为肝硬化食管静脉曲张出血患者,随机分为联合治疗组和对照组,各28例。对照组行胃镜下套扎术联合生长抑素、泮托拉唑;联合治疗组行内镜下套扎术联合生长抑素、泮托拉唑、普萘洛尔等药物治疗。观察所有食管静脉曲张出血患者1、3、6、12、18个月后随访,两组近期再出血率、食管曲张静脉消失率及复发率、不良反应及并发症的情况。结果联合治疗组曲张静脉消失率、不良反应及并发症与对照组比较,差异无统计学意义(P>0.05);联合治疗组近期再出血及食管静脉曲张复发等发生率明显低于对照组,差异有统计学意义(P<0.05)。结论食管静脉曲张套扎术联合药物是治疗食管静脉曲张出血一种安全有效的方法,疗效确切,提高了患者生存率。     

肝硬化合并自发性腹膜炎患者血清和腹水降钙素原检测的意义

目的：通过研究肝硬化合并自发性细菌性腹膜炎（SBP）患者血清和腹水降钙素原（PCT ）的变化探讨其在肝硬化合并SBP早期诊断中的价值。方法对92例肝硬化腹水患者应用免疫荧光法测定血清、腹水中PCT 并与腹水常规和细菌培养结果进行比较。结果 SBP组及非SBP组患者血清PCT水平明显高于对照组,差异有统计学意义（P＜0．05）,SBP组血清和腹水PCT水平明显高于非SBP组;血清PCT对腹膜炎诊断的敏感度为89．3％,腹水中PCT对腹膜炎诊断的敏感度为71．4％。结论血清及腹水PCT 水平对肝硬化腹膜炎的早期诊断有重要价值且血清PCT 具有更高的早期诊断价值。     

肝硬化食管胃静脉曲张破裂出血与再出血危险性预测的研究进展

肝硬化食管静脉曲张破裂出血与再出血危险性预测有门静脉高压、食管胃静脉曲张出血史、瞬时弹性成像术、多层螺旋CT成像、肝硬化脾肝体积比、内镜下食管静脉曲张套扎术后、内镜治疗后随访的顺应性、血清腹水白蛋白梯度、血小板计数进行性下降、出血的控制时间、细菌感染和病毒复制。本文就这些方面作一综述。     

Bacterial peritonitis in a patient with malignant ascites caused by pancreatic carcinoma: Case report and review of literature

Bacterial peritonitis, an infection of the ascitic fluid, can be classified etiologically as spontaneous or secondary bacterial peritonitis. The former is mainly caused by portal hypertension and its subsequent effects, whereas the latter is caused by the direct dissemination of bacteria into the peritoneal cavity. Previous reports have described some distinguishing features of these two entities. Here, we report the first known case of bacterial peritonitis with Aeromonas hydrophilia and Escherichia coli in a patient with malignant ascites associated with pancreatic carcinoma who exhibited features of both spontaneous and secondary peritonitis. Our report suggests that clinicians should also consider bacterial peritonitis in patients with malignant ascites who present with ostensibly cancer-related symptoms.     

The Care of the Decompensated Cirrhotic Patient

Liver cirrhosis is among the leading causes of death in the United States, and decompensated cirrhosis is a complicated disease state that can present with various complications such as thrombocytopenia, coagulopathy, ascites, bleeding varices, hepatic encephalopathy, hepatorenal syndrome, anasarca, and jaundice. Each episode of decompensation is associated with an increase in mortality rate. Therefore, it is necessary for providers to equip themselves with a proper understanding of cirrhosis and its complex comorbidities to improve outcomes. Current literature regarding the management of cirrhosis and its complications was reviewed and summarized in this article.