Influence of methicillin-resistant Staphylococcus aureus carrier status in liver transplant recipients

The prevalence of methicillin-resistant Staphylococus aureus (MRSA) has increased worldwide and MRSA has emerged as an important cause of sepsis in cirrhotic patients and liver transplant recipients. In this retrospective study, the prevalence of MRSA colonization and its influence on infections following orthotopic liver transplantation (OLT) was investigated. From August, 2002 until November, 2004, 66 primary cadaver OLT were performed for adult recipients. Antibody induction used Daclizumab (n = 49) or ATG (n = 14). Maintenance immunosuppression consisted of tacrolimus and steroids, with 30 patients receiving mycophenolate mofetil and 4, rapamune. For perioperative anti-infectious prophylaxis cefotaxime, metronidazole, and tobramycin were administered for 48 hours. The preoperatively performed routine swabs revealed MRSA colonization in 12 of 66 (18.2%) patients. The stage of cirrhosis was equivalent for MRSA(-) patients according to Child score. The mean MELD score was significantly higher for MRSA(+) patients (24.3 versus 18.7, P = .036). More MRSA(+) patients were hospitalized at the time of transplantation (14/54 versus 8/12, P = .018). The incidence of posttransplant infections was not significantly different among the two groups. Within the first year 7 of 66 (10.6%) patients died: 3 of 12 (25%) MRSA(+) and 4 of 54 (7.4%) MRSA(-). The 1-year survival was lower in the MRSA(+) group (74.1% versus 94.1%). In conclusion, this study did not show that an MRSA-positive carrier status implies an increased risk for septic complications following OLT. Mortality was increased for MRSA(+), but failed to show a significant difference. A significantly higher MELD score and pretransplant hospitalization for MRSA(+) patients may contribute to the higher mortality and reflect sicker patients.     

Risk factors for Staphylococcus aureus infection in liver transplant recipients.

Staphylococcus aureus is the leading cause of bacterial infection in liver transplant recipients. Preoperative nasal carriage of methicillin-resistant S. aureus (MRSA) is associated with a high risk of infection. We conducted a retrospective cohort study in order to identify independent risk factors for early-onset S. aureus infection after liver transplantation. Patients were screened preoperatively for methicillin-susceptible S. aureus (MSSA) and MRSA nasal carriage. Risk factor analysis was performed by univariate analysis followed by stepwise logistic regression. Of the 323 patients included, 63 (19.5%) patients developed S. aureus infection (36 MRSA, 27 MSSA) within 1 month of surgery. Variables significantly associated with infection in the univariate analysis were MRSA and MSSA nasal carriage, alcoholic cirrhosis, absence of hepatocellular carcinoma, decreased prothrombin ratio, and presence of ascites. In the multivariate analysis, MRSA carriage (odds ratio [OR]: 20.9, P < 0.0001), MSSA carriage (OR: 3.4, P = 0.0004), alcoholic cirrhosis (OR: 2.4, P = 0.01) and decreased prothrombin ratio (OR: 1.2, P = 0.01) were independent predictors of infection. Molecular typing showed that the infecting isolate was identical to the isolate from the nose in most patients. In conclusion, preoperative nasal carriage of MRSA and MSSA is an independent risk factor for S. aureus infection in liver transplant recipients. The infection is most often of endogenous origin. Alcoholic cirrhosis and the severity of liver failure are also associated with a high risk of infection.     

Lack of efficacy of mupirocin in the prevention of infections with Staphylococcus aureus in liver transplant recipients and candidates

BACKGROUND: Infections with Staphylococcus aureus are a significant problem in patients in liver transplant units. An association between prior nasal carriage with and subsequent infections has been documented previously in liver transplant recipients and patients with cirrhosis. However, the role of decolonization with mupirocin applied intranasally for the prevention of S. aureus infections in these patients has not been determined. METHODS: S. aureus nasal carriage was prospectively sought in 70 consecutive liver transplant candidates. Mupirocin two times per day for 5 days was administered to the carriers. Follow-up nasal cultures to document decolonization were performed 5 days after the final application of mupirocin. The primary endpoint was the development of S. aureus infections. RESULTS: Thirty-one of 70 patients (44%) were found to be nasal carriers and 27 of 31 nasal carriers (87%) were successfully decolonized. However, 12 of 27 patients (37%) successfully decolonized became recolonized with S. aureus, and an additional nine patients who were initially noncarriers became newly colonized with S. aureus during the study period. Despite the use of mupirocin, 16 of 70 patients (23%) developed an infection with S. aureus. No isolate was found to be mupirocin resistant. CONCLUSION: Elimination of S. aureus nasal carriage by mupirocin did not prevent S. aureus infections in patients in our liver transplant unit.     

Hyperlipidemia in liver transplant recipients: Prevalence and risk factors

Hyperlipidemia is common in transplant patients. Although a causal relationship to the use of cyclosporine is accepted, additional risk factors are as yet unidentified. Eighty-five liver transplant recipients treated with standard triple immunosuppression with a survival of at least 6 months were evaluated. Pretransplantation and posttransplantation variables were analyzed as predictive factors of posttransplantation hyperlipidemia. Serum cholesterol and triglyceride levels were considered elevated if they were > 250 mg/dL and > 150 mg/dL, respectively. Before and after transplantation, hyperlipidemia occurred in 8% (95% confidence interval [CI], 3% to 16%) and 66% (95% CI, 55% to 76%), respectively. After transplantation, 47% (95% CI, 36% to 58%) of the patients had isolated high triglyceride levels, 12% (95% CI, 6% to 21%) had both elevated cholesterol and triglyceride levels, and 7% (95% CI, 3% to 15%) had isolated elevated cholesterol levels. Hypertriglyceridemia occurred early after transplantation (67% by first month) and persisted nearly unchanged throughout the first year. In contrast, cholesterol levels increased with time (5%, 13%, and 27% at 1, 3, and 6 months, respectively). In univariate analysis, factors predictive of hypercholesterolemia included female sex, pretransplantation cholestatic liver disease, pretransplantation cholesterol levels > 141 mg/dL, and > 3 methylprednisolone "boluses." In multivariate analysis, only a pretransplantation cholesterol level of > 141 mg/dL (odds ratio [OR], 5.5; 95% CI, 1.4 to 21) was an independent risk factor. Risk factors associated with hypertriglyceridemia included pretransplantation hepatocellular liver disease (OR, 6.8; 95% CI, 1.2 to 40) and posttransplantation renal dysfunction (OR, 5.4; 95% CI, 1.9 to 15.4). Hyperlipidemia is a frequent finding in liver transplant recipients, and hypertriglyceridemia is the most common abnormality. Hypertriglyceridemia can be predicted on the basis of pretransplant hepatocellular disease and posttransplant renal dysfunction. Pretransplant serum cholesterol level is an independent risk factor for posttransplant hypercholesterolemia. (Liver Transpl Surg 1997 Jul;3(4):416-22)     

Staphylococcus aureus bacteremia in patients on chronic hemodialysis

Staphylococcus aureus bacteremia occurred 96 times in 58 of 671 patients on chronic hemodialysis during a nine-year period. Seventy-one instances of bacteremia originated in the vascular access site and resulted in the loss of the access device in 45 episodes. The overall mortality was 8%, and the incidence of infective endocarditis was 4%. Death occurred more often when bacteremia arose from an identifiable site other than the vascular access device (P less than .02). Patients who developed one or more metastatic foci of infection had a higher incidence of primary treatment failure (P less than .001) and a higher mortality (P less than .001) than did those with no metastatic infection. Although meaningful comparisons of differing antibiotic regimens could not be made, patients receiving antibiotic therapy for 28 days or longer relapsed less frequently (P less than .05). These data suggest that chronic hemodialysis patients with S aureus bacteremia have a relatively low mortality and a low risk of infective endocarditis. Antibiotic treatment, however, should be given for at least 28 days in order to minimize the risk of relapse.     

肝移植术后代谢综合征及危险因素分析

目的 研究肝移植术后代谢综合征(metabolic syndrome,MS)及相关症状在肝移植长期生存者中的发生率与危险因素.方法 参照2005年美国心脏协会修订后的美国国家胆固醇教育计划成人治疗方案第3次报告(NCEP-ATPⅢ)标准,评估肝移植术后生存期≥5年的102例受体MS的发生率.选择手术年龄＞50岁、男性、吸烟史、术前指标肥胖、高血压、糖尿病(DM)、高甘油三酯血症(TG)、低高密度脂蛋白血症(HDL)等因素,用Logistic回归分析其中的危险因素.结果 102例肝移植受体中,肥胖、高血压、DM、低HDL、高TG的发生率在术后明显高于术前.术前与术后MS的发生率分别为29.3％及51.9％.术后MS与非MS组相比,术前肥胖、DM、高血压、高TG、高龄、男性、吸烟史更多见于MS组.结论 MS高发于长期生存的肝移植受体人群中.高龄(＞50岁)、术前肥胖及术前DM为发生肝移植术后代谢综合征的独立危险因素.     

Species differences in the clearance of Staphylococcus aureus bacteremia.

Studies on vascular graft infections may be influenced by species differences in bacteria clearance. The present study compares the bloodstream elimination of Staphylococcus aureus (S. aureus) in dogs and pigs. Four mongrel dogs and four Yorkshire pigs received a 20-min infusion of 10(6) S. aureus labeled with indium-131. Through a catheter placed in the infrarenal aorta, blood samples were removed at intervals for 5 h after infusion. The liver, spleen, and lungs were biopsied at 5 h. Blood and tissue samples were then counted in a gamma counter. The calculated phagocytotic index, k, for dogs was 8.6 X 10(-4), while for pigs it was 1.5 X 10(-3), indicating significantly faster bacterial clearance in pigs (p = .009). After 2 1/2 h, significantly fewer counts were present in pigs at most time points (p less than .05). Organ counts indicated higher counts in the dog liver and spleen and in the lungs of pigs (p less than .0001). This study indicates that S. aureus bacteremia is cleared faster by pigs, primarily by the lungs, compared to dogs, in which liver-spleen clearance predominated. These differences should be considered when the results of graft infection studies are compared.     

Infection in liver transplant recipients

Despite the advances in liver transplantation, infection continues to be a major problem, with an incidence greater than that observed in other solid organ transplantations. The risk of infection is largely determined by the patient's preoperative condition, operative factors, and the status of immunosuppression. Here we describe the current understanding of bacterial, viral, and fungal infection in patients who underwent liver transplantation.     

Impact of donor bacteremia on outcome in organ transplant recipients

Abstract Unavailable. Please See Print Journal.     

Pre-transplant risk factors predicting post-transplant cytomegalovirus infection in liver transplant recipients

Cytomegalovirus (CMV) infection causes significant morbidity and mortality among transplant recipients. Although it is still not clear if a preemptive strategy is superior to a prophylactic strategy, many transplant programs elect for preemptive treatment for post-transplant CMV infection. In order to improve the preemptive strategy, we analyzed a series of liver recipients by means of quantitative real-time polymerase chain reaction (PCR). Ninety-one liver transplant recipients were monitored by real-time PCR for CMV, and the results were analyzed in terms of preoperative conditions. Multivariate analysis revealed fulminant hepatic failure as an underlying disease (odds ratio, 6.8; 95% CI, 1.2-39.2), while an ABO-incompatible graft (odds ratio, 5.0; 95% CI, 1.3-19.1), and a serological combination of the donor (D) being positive with the recipient (R) being negative for CMV (D+/R-) (odds ratio, 5.8; 95% CI, 1.3-26.0) were independently associated with the development of significant CMV infection. Patients with risk factors had higher peak CMV DNA concentrations than those without, and developed CMV infections faster (P = 0.0002). Screening of recipients according to risk factors and PCR monitoring may result in an optimization of the preemptive strategy.     

个体化免疫抑制方案在肝移植高危受者中的应用

目的　评价高危受者肝移植后采用个体化免疫抑制方案的意义。方法　根据受者术前情况的不同制定不同的免疫抑制方案 ,比较采用个体化免疫抑制方案的高危受者与采用常规免疫抑制方案的高危受者和普通受者肝移植术后肾功能衰竭、急性排斥反应、感染发生率 (包括细菌、真菌、巨细胞病毒感染 )以及院内死亡率。结果　采用个体化免疫抑制方案的高危受者肝移植术后肾功能衰竭、细菌及真菌感染的发生率以及院内死亡率均较采用常规免疫抑制方案的高危受者显著降低 (P<0 .0 5) ,与采用常规免疫抑制方案的普通受者相比 ,两个组上述指标的差异无显著性。结论　采用个体化免疫抑制方案较常规免疫抑制方案有更高的安全性 ,可以提高高危受者的肝移植成功率。     

Psychological risk factors for graft rejection among liver transplant recipients

The purpose of this prospective study was to find psychological risk factors predicting acute, chronic, and psychological rejection in patients undergoing liver transplantation using Cognitive Behavioural Assessment (CBA-2.0). The primary scale included an assessment of fears, personality, obsessive-compulsive symptoms, state and trait anxiety, psychological reactions, and depression. We prospectively recruited 44 patients undergoing orthotopic liver transplantation (OLT). Exclusion criteria were: education level below secondary school, unstable clinical situation in an out-patient setting, fulminant hepatitis, psychotic disorders, neurocognitive deficits, dementia, serious mental retardation, current alcohol or drug abuse, recent ideation of or attempted suicide, and non-adherence to therapy. CBA-2.0 primary scale series of questionnaires were handed out to patients immediately after the medical examination, which had been performed to ascertain eligibility for OLT. Rejection (acute and/or chronic) was diagnosed according to clinical and histopathological criteria. Psychological rejection was diagnosed when patients declared, after transplantation, a refusal of the new organ which caused psychiatric symptoms requiring medical treatment and/or psychotherapy. Analysis of variance and logistic regression of psychological variables was performed to detect possible risk factors for each type of rejection. A greater fear of repulsive animals was able a predictor for an acute rejection episode (odds ratio = 1.1; P < .05). No other psychological pretransplant predictor was noted for chronic or psychological rejection. In patients undergoing OLT, preoperative emotions of fear could predict an acute graft rejection episode. These findings imply that pre-OLT screening should include psychological factors in addition to traditional medical criteria with intervention in selected cases.     

Independent risk factors and natural history of renal dysfunction in liver transplant recipients

Renal dysfunction is common after liver transplantation. However, there are only limited data on the predictors and natural history of renal dysfunction after liver transplantation. In this study, we determined independent predictors and the natural history of renal dysfunction in 172 consecutive liver transplant recipients. Survival and time to development of permanent renal dysfunction (renal dysfunction defined as a sustained decrease in estimated glomerular filtration rate (GFR) of > 30 mL/min/1.73 m² from baseline for at least 6 months, severe renal failure defined as absolute GFR <30 mL/min/1.73 m² for at least 6 months) were determined using the Kaplan-Meier method. Cox regression analysis was used to test the independent effect of a given set of variables on time to development of such an event. Nine percent of patients required immediate dialysis, 35% developed permanent renal dysfunction, and 7% developed severe renal failure. The rate of decline in renal dysfunction was maximal, 6.5 mL/min/1.73 m² /mo, at 1 month after liver transplantation. Pre-existing diabetes mellitus, major surgical infection, and waiting time on the transplant list were independent risk factors for immediate dialysis. Presence of serum creatinine > 1.2 mg/dL at any time before liver transplantation and a baseline GFR <70 mL/min/1.73 m² were independent predictors of permanent renal dysfunction. Diabetes mellitus, coronary artery disease, and primary graft nonfunction predicted the development of severe renal failure. GFR stabilized around 9 months, and presence of decreased GFR > 30mL/min/1.73 m² from baseline at 9 months predicted development of permanent renal dysfunction. An absolute GFR of <30mL/min/1.73 m² occurring as early as 3 months after liver transplantation predicted severe renal failure. Severe renal failure was associated with a significantly lower survival by Cox regression analysis. We have identified risk factors and the natural history of permanent renal dysfunction and severe liver failure in liver transplant recipients. These observations may be useful in the development of nonnephrotoxic immunosuppressive regimens for high-risk liver transplant recipients. (Liver Transpl 2003;9:741-747.)     

Staphylococcus aureus bacteremia in the surgical patient: a prospective analysis of 73 postoperative patients who developed Staphylococcus aureus bacteremia at a tertiary care facility

BACKGROUND: Staphylococcus aureus is a frequent cause of infection and bacteremia in the postoperative patient. Unfortunately, there have been no prospective studies evaluating these patients, so the incidence of complications, subsequent treatment algorithms, and prognosis remain undefined. The objectives of this prospective study of postoperative Staphylococcus aureus bacteremia (SAB) were to define the primary sources of bacteremia and to identify the common complications of SAB in the postoperative setting. METHODS: A registry was developed into which 309 consecutive adult patients with SAB were prospectively enrolled between September 1994 and December 1996. Seventy-three of these patients (23.6%) developed SAB in the postoperative setting. RESULTS: Analysis of the clinical features of these 73 postoperative patients revealed three important results. First, infective endocarditis is surprisingly common in postoperative patients with SAB and the classical stigmata of endocarditis are often absent. Transesophageal echocardiography was performed in 31 of 73 patients; 10 of these patients (32.3%) met Duke Criteria for definite endocarditis, but only 3 of these patients had vegetations detected by transthoracic echocardiography, and only 2 patients had peripheral stigmata of infective endocarditis. Second, the development of SAB after cardiothoracic surgery was strongly associated with underlying S. aureus mediastinitis. Twenty-one of the 23 patients who developed SAB after median sternotomy had mediastinitis (positive predictive value 91.3%). In many cases, the diagnosis of mediastinitis was not apparent when SAB was detected. Third, complications, relapses, and mortality were high in postoperative patients with SAB. Fourteen of 73 patients (19.2%) developed multiple noncardiac metastatic complications, including metastatic abscesses (5), septic emboli (3), pneumonia or empyema (2), septic arthritis (1), epidural abscess (1), and other metastatic foci (7). Twelve of 73 patients (16.4%) had recurrent staphylococcal infection after treatment of their first episode of SAB, including 8 patients (11.0%) with recurrent bacteremia. Of patients who survived, those with recurrent staphylococcal infection were more likely to have an infected surgical wound than were patients who were cured of infection (p = 0.05). Finally, mortality attributable to SAB (11.0%), and all-cause mortality (21.9%), was high. CONCLUSIONS: SAB in the postoperative setting is often a severe disease with high morbidity and mortality. A thorough diagnostic evaluation is indicated in surgical patients with S. aureus bacteremia to ensure the early detection of metastatic infections such as infective endocarditis and to define foci such as mediastinitis re quiring surgical intervention.     

Fungal infections in liver transplant recipients

Sixty-two adults who underwent orthotopic liver transplantations between February 1981 and June 1983 were followed for a mean of 170 days after the operation. Twenty-six patients developed 30 episodes of significant fungal infection. Candida species and Torulopsis glabrata were responsible for 22 episodes and Aspergillus species for 6. Most fungal infections occurred in the first month after transplantation. In the first 8 weeks after transplantation, death occurred in 69% (18/26) of patients with fungal infection but in only 8% (3/36) of patients without fungal infection (P less than 0.0005). The cause of death, however, was usually multifactorial, and not solely due to the fungal infection. Fungal infections were associated with the following clinical factors: administration of preoperative steroids (P less than 0.05) and antibiotics (P less than 0.05), longer transplant operative time (P less than 0.02), longer posttransplant operative time (P less than 0.01), duration of antibiotic use after transplant surgery (P less than 0.001), and the number of steroid boluses administered to control rejection in the first 2 posttransplant months (P less than 0.01). Patients with primary biliary cirrhosis had fewer fungal infections than patients with other underlying liver diseases (P less than 0.05). A total of 41% (9/22) of Candida infections resolved, but all Aspergillus infections ended in death.     

Skin cancer in liver transplant recipients

Skin cancer is the most common malignancy arising inthe posttransplantation setting. Multiple factors contribute to the high risk for cutaneous carcinoma in immunosuppressed organ-transplant recipients. We review the phenomenon of skin cancer in solid-organ transplant recipients and further delineate the problem in the context of liver transplantation. Skin cancer is a significant medical and surgical problem for organ-transplant recipients. With prolonged allograft function and patient survival, the majority of solid-organ transplant recipients will eventually develop skin cancer. Although squamous cell carcinoma is the most common cutaneous malignancy in this population, basal cell carcinoma, melanoma, and Kaposi's sarcoma, as well as uncommon skin malignancies, may occur. Highly susceptible patients may develop hundreds of squamous cell carcinomas, which may be life threatening. Management strategies focus on regular full-skin and nodal examination, aggressive treatment of established malignancies, and prophylactic measures to reduce the risk for additional photodamage and malignant transformation. Skin cancer is a substantial cause of morbidity and even mortality among solid-organ transplant recipients. As a byproduct of immunosuppression, liver transplant recipients experience a high incidence of skin cancer and should be educated and managed accordingly.