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.

     

Fungal infections in transplant recipients receiving alemtuzumab

Recently, we have used an anti-T-cell agent, alemtuzumab, as induction or conversion therapy to achieve a calcineurin (CNI) and steroid-free immunosuppressive regimen. We identified recipients who developed systemic fungal infections after the initiation of alemtuzumab and looked at their outcomes. The study population consisted of all pancreas transplant recipients who received alemtuzumab. Only invasive fungal infections were included in the analysis (eg, fungemia, meningitis, or pneumonia; fungal urinary tract infections were excluded). The organism was confirmed by culture, histopathology, or latex antigen test. Between February 2003 and February 2004, a total of 121 pancreas transplant recipients received alemtuzumab-56 as part of induction, and 65 as part of conversion. Of these, 8 (6.6%) developed an invasive fungal infection; 2 (3.6%) recipients as part of induction therapy and 6 (9.2%) as part of conversion therapy. Mean recipient age was 42.1 years. The mean length of time from alemtuzumab administration (first dose) to the diagnosis of the fungal infection was 115.9 days (range 5 to 318). The organisms identified initially were: Cryptococcus, Histoplasma, Aspergillus, and Candida. Overall, 3 (38%) of the eight patients died during ongoing treatment of their fungal infection: two from sepsis, one due to myocardial infarction. The other five recipients were treated successfully and have functioning grafts. The initial therapeutic agents used included: amphotericin B/liposomal AMB (n = 6), voriconazole (n = 3), capsofungin (n = 2), and fluconazole (n = 1). The use of alemtuzumab as induction or conversion therapy in pancreas transplant recipients may predispose patients to the development of systemic fungal infections. It would be important to determine what the most appropriate prophylaxis regimen would be for these patients.     

Fungal infections in renal transplant recipients.

Infection continues to be a major source of morbidity and the major source of mortality in renal transplant recipients who are susceptible to opportunistic infections. We recently reviewed all renal transplant recipients who had fungi cultured during a three year period. C. albicans and T. glabrata were cultured most frequently. Deep fungal infections occurred in many patients and were frequently observed late in the course of bacterial and viral infections. Ten patients had fungemia, and primary fungal pneumonia occurred in eight patients. Three patients had fungal infection of the central nervous system. Three of eight patients with fungal pneumonia and eight of ten patients with fungemia died as a result of their fungus infections. These patients frequently had poor renal function and were receiving high steroid doses or had recently been treated for kidney rejection. One patient with fungal pneumonia and six patients with fungemia had the fungus cultured from a superficial site. Several patients developed fungal infections late in the course of viral or bacterial infections. Amphotericin-B and 5-fluorocytosine remain the mainstays of antifungal therapy.     

Fungal complications after Candida preservation fluid contamination in liver transplant recipients

Donor‐derived fungal infections can be associated with severe complications in transplant recipients. Donor‐derived candidiasis has been described in kidney transplant recipients where contamination of the preservation fluid (PF) was a commonly proposed source. In liver transplantation, these fungal infections have been less explored. The aim of this study was therefore to determine the incidence and clinical relevance of Candida contamination of preservation fluid in the context of liver transplantation. A 5‐year (2008–2012) retrospective multicentre study involving six French liver transplantation centers was performed to determine the incidence of Candida PF contamination. Postoperative clinical features, outcomes in recipients, and risk factors for Candida‐related complications of liver transplantation were studied. Candida sp. was isolated from 28 of 2107 preservation fluid samples (1.33%). Candida albicans was the most common yeast (n = 18, 64%). Twenty‐two recipients (78.5%) received antifungal therapy (echinocandins in 68%) for 7–37 days. Eight patients developed yeast‐related complications (28.6%) including hepatic artery aneurysms (n = 6) and Candida peritonitis (n = 2). The 1‐year mortality rate among patients after a yeast‐related complication was 62.5%. The incidence of Candida PF contamination was low, but was associated with dramatic postoperative complications and high mortality. Close radiological follow‐up may enable early recognition of the arterial complications associated with PF contamination by Candida.     

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.     

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.     

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.     

Skin infections in renal transplant recipients

BACKGROUND: Skin infection is a frequent complication in renal transplant recipients. The purpose of the study was to acquire long-term, period-specific incidence data on the most commonly occurring skin infections in renal transplant recipients. METHODS: A retrospective analysis was performed using medical records of 134 patients, covering a period between 10 and 29 yr. Cumulative incidences of the skin infections were calculated by counting the infections per patient for different time periods and were expressed as a percentage of the total group of patients. The incidence of the skin infections was determined for different post-transplant time periods. RESULTS: A total of 340 skin infections in 105 out of 134 patients were recorded. Some infections, such as candidal infection, herpes simplex infection, and impetigo were most prominent during the first post-transplant year and did not affect many new patients after the first year. Other infections, such as dermatomycoses, herpes zoster, and folliculitis were also affecting a substantial number of new patients after the first post-transplant year. CONCLUSIONS: This study confirms that skin infections among renal transplant recipients are very common and that the spectrum of skin infections differs according to the post-transplant time period.     

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.     

Outcome of infections caused by multiple drug-resistant bacteria in liver transplant recipients

OBJECTIVE: To evaluate the impact of infections caused by multiple-drug-resistant (MDR) bacteria on the clinical outcome of liver transplant recipients. METHODS: Retrospective study including all episodes of bacterial infection diagnosed in patients undergoing liver transplantation from January 19, 1999, to June 30, 2002. The diagnosis of bacterial infection required microbiological documentation. Mortality associated with episodes of infection by MDR bacteria was compared to that observed after antibiotic-susceptible bacterial infections. RESULTS: Among 99 patients undergoing liver transplantation during the study period, there were 57 episodes of bacterial infections. Gram-negative bacilli were the predominant etiologic agents (76%) and Pseudomonas aeruginosa was the most frequent bacterial species found in these cases (23 isolates, 28%). Thirty-six episodes of infection (63%) were caused by MDR bacteria. Mean time after transplantation to the diagnosis of infection was 17 days. Mortality associated with episodes of MDR bacterial infections (nine deaths, 25%) was not significantly different from that observed during episodes of antibiotic-susceptible bacteria (five deaths, 24%; P =.92). CONCLUSION: These data suggest that resistance to multiple antimicrobial agents does not have an impact on the mortality associated to bacterial infections in liver transplant recipients.     

Intra-abdominal infections in pancreas transplant recipients.

During a 7-year period, 116 pancreas transplants were performed in 98 diabetic patients (49 with and 49 without previous kidney transplants) at the University of Minnesota. The posttransplant clinical course of 26 recipients (22%) was complicated by an intra-abdominal infection (8 with and 18 without previous kidney transplants). Infections occurred in 19/57 cases (33%) in which exocrine secretions were managed by enteric drainage, in 5/15 cases (33%) managed by free drainage into the peritoneal cavity, in 1/39 cases (3%) in which the duct was injected with a synthetic polymer, and in 1/2 cases (50%) in which a pancreaticocystostomy was performed. The organisms Escherichia coli, enterococci, bacteroides, and several anaerobes were cultured from the patients with enteric drainage, while staphylococci were associated with the open duct drainage. Fungal infections with Candida were found with all techniques. Surgical and percutaneous drainage was performed in all patients. In 14 patients, functioning and, in four patients, nonfunctioning grafts were removed. In five patients, the infection resolved while the grafts were functioning, and these patients are currently alive and well. Seven of the 26 patients with infections died (27% mortality rate), five after graft removal and two with the graft still in place (1 with and 1 without function), five in the open-duct, and one each in the enteric and urinary drainage categories. In the 90 cases without intra-abdominal infection, only six patients died (4 cardiovascular, 1 anaphylaxis, 1 cytomegalovirus infection), for a mortality rate of 7%.