Diagnosis and management of bacterial infections in decompensated cirrhosis

Bacterial infections are one of the most frequent complications in cirrhosis and result in high mortality rates.Patients with cirrhosis have altered and impaired immunity,which favours bacterial translocation.Episodes of infections are more frequent in patients with decompensated cirrhosis than those with compensated liver disease.The most common and life-threatening infection in cirrhosis is spontaneous bacterial peritonitis followed by urinary tract infections,pneumonia,endocarditis and skin and soft-tissue infections.Patients with decompensated cirrhosis have increased risk of developing sepsis,multiple organ failure and death.Risk factors associated with the development of infections are severe liver failure,variceal bleeding,low ascitic protein level and prior episodes of spontaneous bacterial peritonitis (SBP).The prognosis of these patients is closely related to a prompt and accurate diagnosis.An appropriate treatment decreases the mortality rates.Preventive strategies are the mainstay of the management of these patients.Empirical antibiotics should be started immediately following the diagnosis of SBP and the first-line antibiotic treatment is third-generation cephalosporins.However,the efficacy of currently recommended empirical antibiotic therapy is very low in nosocomial infections including SBP,compared to community-acquired episodes.This may be associated with the emergence of infections caused by Enterococcus faecium and extended-spectrum β-lactamaseproducing Enterobacteriaceae,which are resistant to the first line antimicrobial agents used for treatment.The emergence of resistant bacteria,underlines the need to restrict the use of prophylactic antibiotics to patients with the greatest risk of infections.Nosocomial infections should be treated with wide spectrum antibiotics.Further studies of early diagnosis,prevention and treatment are needed to improve the outcomes in patients with decompensated cirrhosis.     

Positive Dialysate Gram Stain Predicts Outcome of Empirical Antibiotic Therapy for Peritoneal Dialysis-associated Peritonitis

Empirical antibiotic treatment with a first-generation cephalosporin plus gentamicin for peritoneal dialysis (PD)-associated peritonitis before culture results are available is still wildly used due to concerns regarding the economic burden and antibiotic-resistant bacterial infections. The aim of this study is to define the factors that predict the outcome of empirical antibiotic therapy for PD peritonitis. This is a retrospective study of patients with PD peritonitis over the last 10 years. Patients who had been treated empirically with intermittent intraperitoneal first-generation cephalosporin and gentamicin were enrolled. Eighty-three patients had 192 episodes of PD peritonitis. In total, 159 peritonitis episodes were treated with intraperitoneal antibiotics combined with first-generation cephalosporin and gentamicin empirically. Twenty-five peritonitis episodes had no pathogens identified by dialysate culture. In total, 122 (122/159, 76.7%) PD peritonitis episodes were caused by bacteria, 9 (9/159, 5.7%) were fungal, and 3 (3/159, 1.9%) were Mycobacterium tuberculosis peritonitis. Sixty-four (64/159, 40.3%) peritonitis episodes were successfully cured by empirical intraperitoneal antibiotic therapy. Empirical antibiotic treatment failed in 95 episodes (95/159, 59.7%). The positive rates of dialysate Gram stain in the empirical treatment success and failure groups were 15.6% and 40.0%, respectively (P = 0.001). The odds ratio of empirical treatment failure with a positive bacteria Gram stain was 3.60 (95% CI: 1.65–7.82). The dialysate Gram staining result was a significant predictor of empirical antibiotics treatment outcome for PD-associated peritonitis. Therefore, using an empirical antibiotic regimen for patients with an initial positive bacterial Gram stain of the dialysate should be introduced cautiously.     

Spontaneous bacterial peritonitis caused by infection with Listeria monocytogenes: a case report and review of the literature

Spontaneous bacterial peritonitis is a frequent and often serious complication of long-standing ascites in the presence of advanced liver disease. Coliform bacteria account for the infection in most cases and are thought to be related to translocation of bacteria from the bowel into the peritoneal cavity. The empiric use of cefotaxime is well established as most of the causative organisms are sensitive to this antibiotic. However, we report on a case of spontaneous bacterial peritonitis in a patient with hepatitis C related cirrhosis who was awaiting liver transplantation caused by infection with Listeria monocytogenes , in which the patient did not improve with empiric antibiotic therapy. This case adds to the 23 others reported in the literature since 1966. Our case raises some concerns about the universal empiric usage of cefotaxime for spontaneous bacterial peritonitis because it does not offer adequate coverage against organisms such as Listeria , enterococci, Pasturella , and anaerobes.     

Spontaneous bacterial peritonitis: impact of microbiological changes

BACKGROUND: Spontaneous bacterial peritonitis is a serious complication in cirrhotic patients, and the changes in the microbiological characteristics reported in the last years are impacting the choice of antibiotic used in the treatment. AIM: To evaluate the change in the epidemiology and antibiotic resistance of the bacteria causing spontaneous bacterial peritonitis in a 7 years period. METHODS: All the cases of cirrhotic patients with spontaneous bacterial peritonitis with positive cultural examination were retrospectively studied. Two periods were evaluated: 1997-1998 and 2002-2003. The most frequent infecting organisms and the sensitivity in vitro to antibiotics were registered. RESULTS: In the first period (1997-1998) there were 33 cases, 3 (9%) with polymicrobial infection. The most common were: E.coli in 13 (36,11%), Staphylococcus coagulase-negative in 6 (16,66%), K. pneumoniae in 5 (13,88%), S. aureus in 4 (11,11%) and S. faecalis in 3 (8,33%). In 2003-2004, there were 43 cases, 2 (5%) with polymicrobial infection. The most frequent were: Staphylococus coagulase-negative in 16 (35,55%), S. aureus in 8 (17,77%), E. coli in 7 (15,55%) and K. pneumoniae in 3 (6,66%). No one was using antibiotic prophilaxys. The prevalence of S. aureus methicillin-resitant to quinolone and trimethoprim-sulfamethoxazole changed from 25% to 50%, and vancomicin was the only one with absolute activity during all the period. In the same way, the prevalence of E. coli resistant to third generation cephalosporin and to quinolone changed from 0% to 16%. CONCLUSION: There was a modification of the bacterial population causing spontaneous bacterial peritonitis, with high frequency of gram-positive organisms, as well as an increase in the resistance to the traditionally recommended antibiotics. This study suggests a probable imminent inclusion of a drug against gram-positive organisms in the empiric treatment of spontaneous bacterial peritonitis.     

Spontaneous bacterial peritonitis: pathogenesis, diagnosis, and management

Spontaneous bacterial peritonitis (SBP) is a bacterial infection of ascitic fluid which arises in the absence of any other intraabdominal infection source. SBP may develop in all cirrhotic patients with ascites. Gram-negative aerobic bacteria and non-enterococcal Streptococcus spp. are the most common organisms isolated from ascites. Diagnosis necessarily relies on paracentesis and requires a high index of suspicion. The incidence of mortality of the first episode varies between 10% and 46%. Early antibiotic treatment is warranted. Renal impairment develops in approximately one-third of patients with spontaneous bacterial peritonitis and is postulated to arise as a result of a further reduction in effective arterial blood volume. Cefotaxime has been the most extensively studied antibiotic for this infection. It is considered to be one of the first choice antibiotics because of low toxicity and excellent efficacy. Although parenteral antibiotics are generally used, studies evaluated the efficacy of several oral antibiotics in patients with relatively good clinical conditions. The reported probability of spontaneous bacterial peritonitis recurrence one year after the first attack averaged 40 to 69%. Selective intestinal decontamination with 400 mg norfloxacin per day decreased the overall probability of recurrence from 68% to 20% in 1 year of follow-up.     

Spontaneous bacterial peritonitis and extraperitoneal infections in patients with cirrhosis

Infections are a frequent complication and a major cause of death among patients with cirrhosis. The important impact of infections in general and especially spontaneous bacterial peritonitis on the course of disease and prognosis of patients with cirrhosis has been recognized for many years. Nevertheless, such importance has recently increased due to the comprehension of infection as one of the most prominent risk factors for patients to develop acute-on-chronic liver failure. Furthermore, the issue of infections in cirrhosis is a focus of increasing attention because of the spreading of multidrug resistant bacteria, which is an emerging concern among physicians assisting patients with cirrhosis. In the present paper, we will review the current epidemiology of infections in patients with cirrhosis and particularly that of infections caused by resistant bacteria, demonstrating the relevance of the subject. Besides, we will discuss the current recommendations on diagnosis and treatment of different kinds of infections, including spontaneous bacterial peritonitis, and we will highlight the importance of knowing local microbiological profiles and choosing empirical antibiotic therapy wisely. Finally, we will debate the existing evidences regarding the role of volume expansion with albumin in patients with cirrhosis and extraperitoneal infections, and that of antibiotic prophylaxis of spontaneous bacterial peritonitis.     

Pathophysiology, complications, and treatment of ascites

In the past few years, there have been important advances in the field of pathogenesis and management of ascites and spontaneous bacterial peritonitis in cirrhosis. A new pathogenic theory of ascites and renal dysfunction in cirrhosis has been presented, and previously ill-defined conditions, such as refractory ascites and hepatorenal syndrome, have been defined precisely. The reintroduction of therapeutic paracentesis has modified markedly the way in which patients hospitalized for ascites are treated. The use of potent and safe antibiotics has improved the resolution rate and survival of patients with spontaneous bacterial peritonitis, and the use of oral antibiotics will simplify the management of this condition in the near future. Finally, prophylactic antibiotic regimens represent a major step forward in the prevention of spontaneous bacterial peritonitis in subsets of cirrhotic patients with a great risk of developing this complication.     

Bacterial peritonitis secondary to a perinephric abscess. Case report and differentiation from spontaneous bacterial peritonitis

A cirrhotic patient is described who presented with Escherichia coli septic arthritis as the first manifestation of a perinephric abscess. Results of baseline abdominal paracentesis were unremarkable. After 10 days of antibiotics, abdominal paracentesis was repeated because of recurrence of fever; E. coli peritonitis was confirmed. Subsequent autopsy revealed a perinephric abscess. Development of bacterial peritonitis during antibiotic treatment is distinctly unusual in the "spontaneous" form of peritonitis and should raise suspicion of secondary bacterial peritonitis.     

The impact of bacterial infections on survival of patients with decompensated cirrhosis

Introduction. Bacterial infection in cirrhotic patients is a severe complication that requires early recognition and specific therapeutic care.Material and methods. In this review the various aspects of diagnosis and management of infections that may impact survival in cirrhosis are analyzed.Results. Active search for infections allows early detection and its treatment with suitable antibiotics has reduced mortality rates in spontaneous bacterial peritonitis, the main infection in patients with decompensated cirrhosis. Other common infections, such as bacteremia and septicemia or urinary tract, lung, skin and soft tissue infections must be thoroughly investigated so that antibiotic treatment can be started early. As intestinal bacterial translocation is one of the most important mechanisms for development of bacterial infections, selective intestinal decontamination is able to prevent these infections in populations at risk. After the first episode of spontaneous bacterial peritonitis, poorly absorbed oral antibiotics, such as quinolones, must be started and continued. Moreover, when there is upper gastrointestinal bleeding, infection prevention should be based on oral administration of quinolones or intravenous administration of cephalosporins, both for seven days, to avoid morbidity and early lethality. With the advent of resistance to commonly used antibiotics and recent reports of multiresistant bacteria, there is a need for stricter control when administering antibiotics to cirrhotic patients.Conclusion. Existing knowledge of therapy and prophylaxis for bacterial infections in cirrhotic patients, which undoubtedly improve survival, should be disseminated and applied in clinical practice for the benefit of the population at large.     

Spontaneous bacterial peritonitis: The clinical challenge of a leaky gut and a cirrhotic liver

Spontaneous bacterial peritonitis(SBP) is a frequent, life-threatening bacterial infection in patients with liver cirrhosis and ascites. Portal hypertension leads to increased bacterial translocation from the intestine. Failure to eliminate invading pathogens due to immune defects associated with advanced liver disease on the background of genetic predisposition may result in SBP. The efficacy of antibiotic treatment and prophylaxis has declined due to the spread of multi-resistant bacteria. Patients with nosocomial SBP and with prior antibiotictreatment are at a particularly high risk for infection with resistant bacteria. Therefore, it is important to adapt empirical treatment to these risk factors and to the local resistance profile. Rifaximin, an oral, nonabsorbable antibiotic, has been proposed to prevent SBP, but may be useful only in a subset of patients. Since novel antibiotic classes are lacking, we have to develop prophylactic strategies which do not induce bacterial resistance. Farnesoid X receptor agonists may be a candidate, but so far, clinical studies are not available. New diagnostic tests which can be carried out quickly at the patient’s site and provide additional prognostic information would be helpful. Furthermore, we need tools to predict antibiotic resistance in order to tailor first-line antibiotic treatment of spontaneous bacterial peritonitis to the individual patient and to reduce mortality.     

Oral, nonabsorbable antibiotics prevent infection in cirrhotics with gastrointestinal hemorrhage

To investigate if oral, nonabsorbable antibiotics prevent bacterial infections in cirrhotics with gastrointestinal hemorrhage, 140 consecutive patients were randomly allocated into two groups: 68 patients (Group I) were given oral, non absorbable antibiotics (gentamicin + vancomycin + nystatin or neomycin + colistin + nystatin) from the inclusion into the trial up to 48 hr after cessation of the hemorrhage, or until emergency surgery or death in those cases who continued bleeding; and 72 patients (Group II) did not receive oral, nonabsorbable antibiotics. Both groups were similar in relation to clinical and laboratory data and characteristics of the hemorrhage. The incidence of infection was significantly lower in Group I than in Group II (11 patients in Group I and 25 in Group II developed proved infections; p less than 0.025). This difference was due to the fact that spontaneous bacteremia and peritonitis and urinary tract infection caused by enteric bacteria occurred almost exclusively in Group II. Two patients of Group I and 10 of Group II developed spontaneous bacteremia and/or peritonitis caused by enteric bacteria (p less than 0.025). These results indicate that prophylactic administration of oral, nonabsorbable antibiotics markedly reduces the incidence of infections caused by enteric bacteria in cirrhotic patients with gastrointestinal hemorrhage.     

Can septicemia and ascitic fluid infections in cirrhotic patients be treated by the oral route alone?

The aim of this study was to determine the efficacy of oral antibiotics in the treatment of severe infections in cirrhosis. Twenty-two patients (17 males, 5 females) with spontaneous bacteremia (n = 7) or bacterial peritonitis (n = 15) were treated with oral pefloxacin 400 mg per 24 hr alone (n = 1) or in combination with another oral antibiotic, trimethoprimsulfamethoxazole (n = 13), amoxicillin (n = 6), cefadroxil (n = 2), or metronidazole (n = 1). In patients with spontaneous bacteremia, all organisms were found to be sensitive to oral antibiotics, and a favorable response was elicited in 6 out of 7 (86 p. cent) within 3 days (mean) of treatment. In patients with spontaneous peritonitis, ascitic fluid cultures were positive in 11 cases, and organisms were sensitive to pefloxacin in 9 out of 11 cases. A favorable response was elicited in 13 out of 15 within 2 to 8 days of treatment. Fourteen patients died (64 p. cent), 3 of infection (bacteremia n = 1, peritonitis n = 2), and 11 patients of causes unrelated to infection, mainly variceal hemorrhage, hepatorenal syndrome or hepatocellular carcinoma, although the clinical symptoms of infection were controlled. One-year survival was 57 p. cent in patients with bacteremia and 33 p. cent in those with bacterial peritonitis. Oral treatment was well tolerated in all patients. We suggest that most bacteremia and spontaneous bacterial peritonitis in cirrhotic patients can be treated with oral antibiotics. In some patients, this may be accomplished on an out patient basis.     

失代偿期肝硬化腹水并发白发性细菌性腹膜炎52例临床分析

目的探讨失代偿肝硬化腹水并发自发性细菌性腹膜炎（SBP）的临床特点及治疗方法。方法回顾性分析52例肝硬化腹水并发SBP患者的临床资料。结果52例肝硬化腹水并发SBP患者中,腹水细菌培养阳性率为3．85％,致病菌以革兰阴性杆菌为主,多数患者缺乏典型腹膜炎的症状及体征。结论及时准确的早期诊断和有效抗菌素治疗可明显提高SBP患者的治愈率。     

Prevention and treatment of infections in patients with cirrhosis

Patients with cirrhosis have altered immune defenses and are considered immunocompromised individuals. Changes in gut motility, mucosal defense and microflora allow for translocation of enteric bacteria into mesenteric lymph nodes and the blood stream. Additionally, the cirrhotic liver is ineffective at clearing bacteria and associated endotoxins from the blood thus allowing for seeding of the sterile peritoneal fluid. Thus, hospitalised cirrhotic patients, particularly those with gastrointestinal hemorrhage, are at high risk of developing bacterial infections, the most common being spontaneous bacterial peritonitis. Given the significant morbidity and mortality associated with spontaneous bacterial peritonitis and the fact that half of the cases are community acquired, all hospitalised cirrhotic patients should have a diagnostic paracentesis to exclude infection. Those admitted with gastrointestinal bleed and a negative paracentesis require short-term prophylaxis with norfloxacin. A third generation cephalosporin is the treatment of choice for spontaneous bacterial peritonitis and, once the acute infection is resolved, secondary prophylaxis with oral norfloxacin is warranted. Patients who develop renal dysfunction at the time of active infection have the highest mortality and require adjunctive albumin therapy. This article reviews the pathogenesis of SBP, the evidence behind the antibiotics used, the rationale for adjunctive albumin therapy in the setting of acute renal failure, and the role of prophylactic antibiotics in specific high-risk populations.     

A Recent Evaluation of Empirical Cephalosporin Treatment and Antibiotic Resistance of Changing Bacterial Profiles in Spontaneous Bacterial Peritonitis

The aim of this research is to evaluate the recent changes in microorganisms causing spontaneous bacterial peritonitis in cirrhotic patients, antibiotic resistance, and response to empirical cephalosporin therapy. A total of 218 patients with ascites secondary to cirrhosis were enrolled. Parenteral cefotaxime or cefepime was given to patients who had a neutrophil count of 250/mm³ or more or a positive bacterial culture of ascitic fluid. Antibiotic failure was defined by an absence of clinical improvement and an insufficient decrease in neutrophil count of ascites (<25% of initial value) by the third day of therapy. Of all the patients, 44.6% had culture-negative neutrocytic ascites, 24.8% had spontaneous bacterial peritonitis, and 10.1% had monomicrobial nonneutrocytic bacterascites. Growth in culture was observed in 76 patients (34.9%). The two most common isolated bacteria were Escherichia coli (33.8%) and coagulase-negative Staphylococcus (CoNS; 19.7%). The two cephalosporins were effective against E. coli (82%) and but not against CoNS (44%), while levofloxacin showed reasonable activity against both E. coli (71%) and CoNS (90%) in vitro. We confirmed a recent increased incidence of spontaneous bacterial peritonitis caused by Gram-positive bacteria. Levofloxacin seems to be a good alternative treatment for patients with uncomplicated spontaneous ascites infections.     

Enterococcus casseliflavus and Enterococcus gallinarum as causative agents of spontaneous bacterial peritonitis

Infection by multidrug resistant bacteria is arousing as a relevant issue among hospitalized subjects and is of particular interest in patients with cirrhosis given the frequent use of broad spectrum antibiotics and their altered immune response. We report the first case report of spontaneous bacterial peritonitis (SBP) caused by Enterococcus casseliflavus and the sixth case of SBP caused by Enterococcus gallinarum.     

Unresolved issues in the prophylaxis of bacterial infections in patients with cirrhosis

Bacterial infections are highly prevalent and a frequent cause of hospitalization and short-term mortality in patients with cirrhosis. Due to their negative impact on survival, antibiotic prophylaxis for bacterial infections in high-risk subgroups of patients with cirrhosis has been the standard of care for decades. Patients with prophylaxis indications include those at risk for a first episode of spontaneous bacterial peritonitis(SBP) due to a low ascitic fluid protein count and impaired liver and kidney function, patients with a prior episode of SBP and those with an episode of gastrointestinal bleeding. Only prophylaxis due to gastrointestinal bleeding has a known and short-time duration. All other indications imply longlasting exposure to antibiotics-once the threshold requirement for initiating prophylaxis is met-without standardized criteria for re-assessing antibiotic interruption. Despite the fact that the benefit of antibiotic prophylaxis in reducing bacterial infections episodes and mortality has been thoroughly reported, the extended use of antibiotics in patients with cirrhosis has also had negative consequences, including the emergence of multi-drug resistant bacteria.Currently, it is not clear whether restricting the use of broad and fixed antibiotic regimens, tailoring the choice of antibiotics to local bacterial epidemiology or selecting non-antibiotic strategies will be the preferred antibiotic prophylaxis strategy for patients with cirrhosis in the future.     

Spontaneous meningococcal peritonitis

Two patients with spontaneous bacterial peritonitis caused byNeisseria 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.     

Spontan bakterielle Peritonitis bei Leberzirrhose

Spontaneous bacterial peritonitis is the most common bacterial infection in patients with liver cirrhosis and ascites. The diagnosis is based on a cell count of more than 250 polymorphonuclear granulocytes per mm³ ascites. Spontaneous bacterial peritonitis results from bacterial translocation from the gut lumen and an altered immune response in cirrhotic patients. Clinically, spontaneous bacterial peritonitis often presents as deterioration of liver function and development of hepatic encephalopathy. In certain cases, the disease can also lead to sepsis with organ failure. Spontaneous bacterial peritonitis has a limited prognosis and antibiotic therapy is mandatory. Antibiotic treatment is usually initiated with third generation cephalosporins or chinolons. The success of antibiotic therapy should be validated by a decrease in ascitic neutrophil count after 48 hours. A secondary prophylaxis is an established treatment after survival of the first episode of spontaneous bacterial peritonitis. A primary prophylaxis of the disease is effective in patients with low ascites protein levels and reduced liver and/or kidney function. Cirrhotic patients with gastrointestinal hemorrhage also benefit from prophylactic antibiotic treatment.     

Bacterial infections in cirrhosis: epidemiological changes with invasive procedures and norfloxacin prophylaxis.

The extensive use of invasive procedures and of long-term norfloxacin prophylaxis in the management of cirrhotic patients may have influenced the epidemiology of bacterial infections in cirrhosis. We conducted a prospective evaluation of all bacterial infections diagnosed in patients with cirrhosis in a Liver Unit between April 1998 and April 2000. A total of 405 patients presented 572 bacterial infections in 507 admissions. Spontaneous bacterial peritonitis was the most frequent infection (138 cases). Gram-positive cocci were responsible for 53% of total bacterial infections in the study, being the main bacteria isolated in nosocomial infections (59%). Patients requiring treatment in an intensive care unit and those submitted to invasive procedures presented a higher rate of infections caused by gram-positive cocci (77% vs. 48%, P <.001 and 58% vs. 40%, P <.02, respectively). Fifty percent of culture-positive spontaneous bacterial peritonitis in patients on long-term norfloxacin administration (n = 93) and 16% in patients not receiving this therapy (n = 414) were caused by quinolone-resistant gram-negative bacilli, P =.01. The rate of culture-positive spontaneous bacterial peritonitis caused by trimethoprim-sulfamethoxazole-resistant gram-negative bacilli was also very high in patients on long-term norfloxacin administration (44% vs. 18%, P =.09). In conclusion, infections caused by gram-positive cocci have markedly increased in cirrhosis. This phenomenon may be related to the current high degree of instrumentation of cirrhotic patients. Quinolone-resistant spontaneous bacterial peritonitis constitutes an emergent problem in patients on long-term norfloxacin prophylaxis, with trimethoprim-sulfamethoxazole not being a valid alternative.