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.     

Hepatic iron content and the risk of Staphylococcus aureus bacteremia in liver transplant recipients

Iron is a critical nutrient source and contributes to staphylococcal pathogenesis. We assessed the role of hepatic explant iron overload as a risk factor for Staphylococcus aureus bacteremia in liver transplant recipients. Seven of 13 cases with S aureus bacteremia (53.8%) had hepatic explant iron concentrations that exceeded normal limits (grade > or = 2). Length of posttransplant intensive care unit stay (P= .013) and hepatocellular carcinoma as underlying liver disease (P = .04), but not hepatic explant iron concentration, correlated with a higher risk of S aureus bacteremia after transplantation. However, noncarriers (patients without S aureus nasal carriage) who developed S aureus bacteremia were more likely to have high hepatic iron content; 4 of 7 (57%) noncarriers with high-grade iron content developed S aureus bacteremia but no noncarriers with low-grade iron content did (P = .07). All noncarriers who became infected had high iron content (grade > or = 2) of the hepatic explant. A readily quantifiable assessment of hepatic iron at the time of transplantation can potentially identify patients without carriage who may be at risk for early S aureus bacteremia.     

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.     

Fungal infections in liver transplant recipients

A retrospective analysis of 462 consecutive orthotopic liver transplantations was undertaken to evaluate incidence, risk factors, clinical course, and outcome of fungal infections. Infections involving Aspergillus (6 cases), Candida (5 cases), Mucor (1 case), and Cryptococcus (1 case) were observed in 2.8% (13/462) of our patients. Twelve of the 13 episodes developed during the first 2 postoperative months. None of the potential risk factors for fungal infections described by other authors (i.e., age, rejection treatment, dialysis, mechanical ventilation, graft failure, long operation time, second transplant, serious nonfungal infection) correlated significantly with the episodes in our patients. However, in patients who exhibited three or more of these potential risk factors the incidence of fungal infections was elevated (P<0.001). Six of seven exogenous infections (Aspergillus, Mucor) began before July 1991 when our department moved from Charlottenburg to Wedding, thus indicating that the incidence of these infections is highly influenced by exposure (P=0.01). Exposure prophylaxis should therefore by meticulously followed, particularly when severely compromised patients are involved, in order to prevent exogenous infections (i.e., Aspergillus/Mucor). Infections involving such patients are combined with a very high mortality (57%). We observed Candida infection as a pathological overgrowth of physiological oropharynx flora into the esophagus and/or trachea in five patients. In each case treatment led to full recovery.

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Pilzinfektionen nach Lebertransplantation

Zusammenfassung Um Inzidenz, Risikofaktoren, klinischen Verlauf und Prognose von Pilzinfektionen nach Lebertransplantation zu klären, wurden die Verläufe von 462 Patienten retrospektiv untersucht, die zwischen Oktober 1988 und Februar 1994 konsekutiv transplantiert wurden. Bei 13 unserer Patienten (2,8%) beobachteten wir Infektionen mit Aspergillus (6mal), Candida (5mal), Mucor (1mal) und Cryptococcus (1mal) Dabei trat die Infektion bei 12 der 13 Patienten bereits während der ersten 2 postoperativen Monate auf. Von den von anderen Autoren beschriebenen potentiellen Risikofaktoren (Alter, Abstoßungsbehandlung, Dialyse, maschinelle Beatmung, Graftversagen, lange Operationszeit, Retransplantation, schwere Allgemeininfektion) korrelierte bei unseren Patienten keine einzige mit den Infektionen. Allerdings war die Inzidenz der Pilzinfektionen bei Patienten, die 3 oder mehr dieser Risikofaktoren zeigten, signifikant erhöht (p<0,001). Ferner traten 6 von 7 exogenen Infektionen (Aspergillus, Mucor) vor dem Umzug unserer Transplantationsstation aus dem 1. Stock eines alten, efeubewachsenen Ziegelbaus in den 7. Stock eines Neubaus im Juli 1991 auf (p=0,01). Dies zeigt, daß die Exposition die Inzidenz von Pilzinfektionen nach Lebertransplantation wesentlich beeinflußt. Daraus folgt, daß insbesondere schwer kompromittierte Patienten einer strengen Expositionsprophylaxe unterzogen wurden müssen, um Infektionen mit Aspelgillus/Mucor zu vermeiden, die bei unseren Patienten eine Letalität von 57% aufwiesen. Bei 5 Patienten beobachteten wir Candidainfektionen als pathologisches Überwuchern der oralen Standortflora in Trachea und/oder Speiseröhre, die unter Therapie ausnahmslos ausheilten.

     

Characteristics and management of splenic artery aneurysm in liver transplant candidates and recipients

The incidence of splenic artery aneurysm (SAA) in patients with cirrhosis ranges from 7 per cent to 17 per cent. SAA rupture after liver transplantation (LT) is reported to result in significant morbidity and mortality. We report our experience with SAA in LT candidates. From September 1995 through August 2002, 14 LT candidates were diagnosed with SAA. Twenty SAA occurred in 14 patients with an average diameter of 20 mm. Eleven patients qualified for LT; to date, seven have been transplanted. No intervention for SAA occurred prior to LT. Of the seven patients transplanted, four had SAA identified prior to LT. Three were treated at LT and are alive; the fourth had postoperative splenic artery embolization followed by splenectomy and expired on day 109 from duodenal ulcer complications. Three of seven patients had undiagnosed SAA at LT. One required emergency splenectomy for SAA rupture and is alive at 44 months. The remaining two received no treatment; one suffered a late septic death and one is alive at 15 months. No ruptures occurred in our pre-LT population, suggesting that definitive management can await LT. We recommend that all patients undergo four-phase computed tomography or magnetic resonance angiography (MRA) as part of the LT evaluation and that identified SAA be resected at transplantation.     

Mortality associated with carbapenem-resistant Klebsiella pneumoniae infections in liver transplant recipients

Resistant bacterial infections are important causes of morbidity and mortality after liver transplantation (LT). This was a retrospective cohort study evaluating the outcomes associated with carbapenem-resistant Klebsiella pneumoniae (CRKP) infections after LT. In a 2005-2006 cohort of 175 consecutive LT recipients, 91 infection episodes were observed in 61 patients (35%). The mortality rate 1 year after LT was 18% (32/175). Enterococcus (43%) and Klebsiella species (37%) were the most frequently isolated bacteria. CRKP infections occurred in 14 patients, and 10 of these patients (71%) died. Seven of these deaths occurred within 30 days of the CRKP infection. The median time to the onset of CRKP infections was 12 days (range = 1-126 days) after LT. The survival rate was significantly lower for patients with a CRKP infection versus patients without a CRKP infection (29% versus 86%, log-rank P < 0.001). In a multivariate analysis, the only pre-LT and post-LT clinical variables significantly associated with death were a Model for End-Stage Liver Disease score ≥ 30 (hazard ratio = 3.4, P = 0.04) and a post-LT CRKP infection (hazard ratio = 4.9, P = 0.007). In conclusion, the outcomes associated with CRKP infections in LT recipients are poor. Because the optimal treatment strategies for CRKP infections remain undefined, improved preventive strategies are needed to curtail the devastating impact of CRKP in LT recipients.     

The influence of calcium mupirocin nasal ointment on the incidence of Staphylococcus aureus infections in haemodialysis patients

Mupirocin was used in haemodialysis patients in an attempt to eradicate nasal carriage of Staphylococcus aureus and to prevent infection caused by this microorganism. The effectiveness of calcium mupirocin as a 2% nasal ointment OB2 (16 patients for 104 patient-months) was compared to that of placebo (18 patients for 147 patient-months) in a double-blind study. Mupirocin or placebo were applied in both anterior nares thrice daily for 2 weeks and subsequently three times weekly for a total of 9 months. During therapy, S. aureus was recovered from only 6% of the nasal cultures in the mupirocin group compared to 58% in the placebo group (P less than or equal to 0.01). Only one S. aureus infection was documented in the mupirocin group compared to six in the placebo group (P less than or equal to 0.05). The S. aureus strain causing the single infection in the mupirocin group was of a different phage type to that of the original nasal strain. In contrast, at least four of the six strains causing infection in the placebo group were of similar phage type to the original nasal strain. All S. aureus isolates remained mupirocin sensitive (MIC less than or equal to 1 mg/l). In conclusion, mupirocin nasal ointment was effective in eradicating nasal carriage of S. aureus and in preventing S. aureus infections in patients on haemodialysis.     

预防肝移植患者肺部感染的集束化护理管理

目的 探讨肝移植围术期预防肺部感染的集束化护理管理效果。 方法 将222例肝移植患者按住院时间分为对照组102例、观察组120例;对照组实施围术期常规护理,观察组实施预防肺部感染集束化护理管理。 结果 住院期间观察组肺部感染发生率显著低于对照组,肺部感染发生时间较对照组显著延迟（P＜0.05,P＜0.01）。观察组护理满意率高于对照组,但差异无统计学意义（P＞0.05）。 结论 实施预防肺部感染集束化护理管理可有效降低肝移植患者肺部感染发生率。     

Parasitic infections in transplant recipients

Parasitic infections are important complications of organ transplantation that are often overlooked in the differential diagnosis of post-transplantation pyrexial illness. Although their frequency is unknown, they seem to be much less prevalent than bacterial and viral infections. Only 5% of human pathogenic parasites have been reported to cause significant illness in transplant recipients. Infection can occur via transmission with the graft or blood transfusion, or be acquired de novo from the environment. Recrudescence of dormant infection can lead to active disease. Post-transplantation parasitic disorders tend to cluster into two clinical profiles. First, an acute systemic illness with anemia, constitutional manifestations and variable stigmata of organ involvement; acute graft dysfunction can lead to confusion and acute rejection. Protozoa including malarial Plasmodium, Leishmania, Trypanosoma and Toxoplasma are associated with this profile. The second typical manifestation encompasses a few localized syndromes, usually associated with the lower gastrointestinal tract, caused by either protozoa (Cryptosporidium and microsporidia) or nematodes (Strongyloides and Ascaris). Dissemination of localized infections can lead to life-threatening systemic manifestations. A high index of suspicion is essential, as diagnosis requires special sampling techniques and laboratory procedures. Definitive diagnosis is usually achieved by detecting the parasite in the patient's tissues or body fluids by histological examination or culture, or by polymerase chain reaction amplification of the parasite-specific antigen sequence. Antibody detection using serological techniques is also possible in a few parasitic infections. Certain lesions have characteristic radiological appearances, hence the value of imaging, particularly in the cerebral syndromes. Treatment is usually straightforward (broad spectrum or specific drugs), yet some species are drug resistant.     

Cytotoxic T-cell-mediated defense against infections in human liver transplant recipients.

Previous studies have shown that postoperative infection is highest in transplant recipients with preexisting high levels of cytotoxic T lymphocytes (CTLs). To study this phenomenon, 106 adult liver transplant recipients were divided into 3 groups, based on hierarchical clustering of the CD3(+)CD8(+)CD45 isoform fractions prior to living donor liver transplantation (LDLT). Group I had the highest naive T-cell levels (subset CD45RO(-)CCR7(+)), Group II had the highest effector/memory (EM) T-cell levels (subset CD45RO(+)CCR7(-)), and Group III had the highest effector T-cell levels (subset CD45RO(-)CCR7(-)). In Group I, CTLs upregulated in response to invading pathogens much earlier and more rapidly than the other groups; this response was associated with CD4(+) T-cell help, downregulation of CD27(+)CD28(+) subsets, and upregulation of interferon-gamma and perforin expression. In contrast, in Groups II and III, CTLs upregulated slowly following persistent viral infection and did not respond efficiently to acute infection. In addition, Group II's cytolytic responses were due mainly to upregulation of the CD8(+) EM T-cell fraction, whereas Group III's cytolytic responses were attributable to upregulation of effector T cells. The prevalence of EM or effector T cells was dependent on differentiation of the CD8(+) phenotype before LDLT. In conclusion, in most infected transplant recipients who died, generation of CD8(+) CTLs had been suppressed without associated CD4(+) T-cell help.     

Prevention of Staphylococcus aureus burn wound colonization by nasal mupirocin

BACKGROUND: There are two important routes for the transmission of Staphylococcus aureus to the burn wound. In the endogenous route, patients naturally carrying S. aureus colonize their own wounds, whereas in the exogenous route burn wounds are cross-infected from other sources. In this study we evaluated the effect of blocking the endogenous route on S. aureus burn wound colonization by mupirocin application in the nose of patients at the time of admission. METHODS: From September 2000 to January 2002 all patients with burns admitted to a single dedicated Burn Centre received nasal mupirocin upon admission. This period was compared to two control periods (C1: July 1999 to July 2000 and C2: January 2002 to January 2003) for S. aureus burn wound colonization. The colonization risk was analysed, adjusting for confounding, with Cox proportional hazard regression. RESULTS: A total of 98 patients did not have S. aureus burn wound colonization at the time of admission and were, thus, considered at risk for S. aureus acquisition during their stay. As compared to C1, the relative risk of acquiring S. aureus in their wound was 0.48 (95% CI: 0.24-0.97) in the mupirocin period and 0.55 (95% CI: 0.28-1.1) during the C2 period. S. aureus nasal/pharyngeal colonization was a significant independent risk factor for wound colonization (RR: 2.3; 95% CI: 1.2-4.2). CONCLUSION: Nasal mupirocin may contribute to risk reduction of S. aureus wound colonization in patients with burns.     

Tobacco and alcohol use in lung transplant candidates and recipients

Tobacco and alcohol use among lung transplant candidates and recipients is unknown. Our first goal was to describe tobacco and alcohol use before and after lung transplant in patients with cystic fibrosis (CF) and other pulmonary diseases (non-CF). Our second goal was to determine whether demographic variables, depression, anxiety and social support predicted tobacco and alcohol use. Self-report data from transplant candidates and recipients, and transplant nurse coordinator ratings of post-transplant smoking and drinking were utilized. Data from two samples were analyzed. Sample 1 comprised 219 patients being evaluated for lung transplant, and sample 2 comprised 45 transplant recipients who were 1-7 yrs post-transplant. The results from analyzing sample 1 indicated that 72% of non-CF patients and 16% of CF patients had a history of smoking cigarettes, and the majority of patients in both groups had consumed alcohol in the past. For CF patients, past smoking was related to higher depression scores, and past drinking was related to higher education and lower social support. For non-CF patients, a history of smoking was associated with being Caucasian and older. For CF patients, a history of drinking was associated with being older and less depressed, and for non-CF patients a history of drinking was associated with higher education and lower social support. Post-transplant 100% of recipients reported abstinence from tobacco, and over 60% reported abstinence from alcohol. Transplant coordinator ratings corroborated that no transplant recipients were using tobacco products or consuming alcohol in an excessive or problematic manner. For both groups, consuming alcohol after transplant was related to lower levels of social support. In conclusion, lung recipients remain abstinent from tobacco, and although over 30% of patients consume alcohol after transplant, it is not at problematic levels. Smoking and drinking behaviors were related to demographic variables, depression, and low social support.     

Chemoprophylaxis with isoniazid in liver transplant recipients

A patient receiving a liver graft needs to be treated with immunosuppressive drugs to avoid rejection. These kinds of drugs predispose the patient to the reactivation of latent infections such as tuberculosis (TB). Therefore, it is necessary to establish treatment regimens to prevent this. We retrospectively analyzed all consecutive patients undergoing liver transplantation (LT) at our center between January 1, 2000 and December 31, 2010. Latent tuberculosis infections (LTBIs) were diagnosed with positive tuberculin skin test results. After LT, infected patients were treated with isoniazid for 6 months; the treatment began soon after transplantation, and the patients were followed until the end of the study. During this period, 53 patients had LTBI data. All these patients were treated with isoniazid after LT. The median observation period after LT was 52 months (range = 12-129 months). No cases of TB reactivation were reported during follow-up. Only 4 patients presented alterations in liver enzymes related to this treatment, and they showed clear improvement after the treatment was stopped. None of these patients showed severe graft dysfunction. In conclusion, preventive isoniazid appears to be a safe drug for use in LTBI patients after LT. The treatment may be established just after LT without important graft dysfunction or severe consequences for the patient. Liver Transpl, 2012. ? 2012 AASLD.