H. Bonatti

Cytomegalovirus-related complications in human hand transplantation.

Background. Up to date, 24 hands/thumbs have been transplanted in 18 patients. We herein report on cytomegalovirus (CMV) infection, disease, and the adopted treatment. Methods. Immunosuppression consisted of tacrolimus-based triple-drug therapy with antithymocyte globuline or CD25-receptor antagonist induction. Donor/recipient CMV match was negative/negative (n=8), negative/positive (n=3), positive/positive (n=3), positive/negative (n=3) and unknown in one case. Six patients (three +/−, two +/+, and one −/+) received gancyclovir i.v. followed by oral gancyclovir or valgancyclovir for prophylaxis. Results. Patient and graft survival at a mean follow-up of 42.9 months were 100% and 91%, respectively. Of all patients tested for CMV, 45.5% developed CMV infection or disease. Two patients that were given a CMV-positive graft showed very high viral loads (550 and 1200/200000 leukocytes) after transplantation. Gancyclovir treatment failed to permanently control CMV in 80% of the patients experiencing CMV infection. Those patients requiring more toxic second-line therapies (foscarnet/cidofovir) suffered from side effects such as nephrotoxicity, nausea, vomiting, and diarrhea. Conclusions. CMV infection/disease complicated the postoperative course after composite tissue allograft (CTA) transplantation in five of nine recipients challenged with the virus. The close time correlation suggests an association between virus replication and rejection in some cases. CMV represents the major infectious threat in CTA transplantation. Therefore, CMV-mismatch should be avoided and prophylaxis with valgancyclovir and anti-CMV hyperimmunoglobulin should be mandatory.

Listeria meningitis in transplant recipients.

SummaryINTRODUCTION: Meningitis is a rare complication following organ and stem-cell transplantation and can be caused by a variety of microorganisms. AIM: To retrospectively review the clinical course and outcome of five cases of listeriosis in four organ recipients and one stem-cell recipient during a seven-year period. PATIENTS AND METHODS: Patient records for more than 3500 patients undergoing organ or stem-cell transplantation at the university hospital of Innsbruck during a 27-year period were evaluated. Standard immunosuppression consisted of calcineurin inhibitor-based triple drug therapy with or without ATG or IL2 receptor antagonist induction. RESULTS: The first case affected a 35-year-old woman who received an allogenic bone marrow transplant for advanced breast cancer. Cases two and three related to two male heart recipients. Cases four and five were diagnosed in one male and one female renal recipient. Listeria monocytogenes was isolated from blood in two cases and from cerebrospinal fluid in three. Treatment consisted of ampicillin in all cases with the addition of tobramycin (1), TMPS (1), meropenem (2) or imipenem/cilastatin (1). The deaths of two patients were directly related to L. monocytogenes. CONCLUSIONS: Although listeriosis is a rare complication following transplantation, this infection should be ruled out in individuals presenting with neurological symptoms and fever.ZusammenfassungEINLEITUNG: Meningitis ist eine seltene Komplikation nach Organ- bzw. Stammzelltransplantation und kann durch eine Vielzahl von Mikroorganismen verursacht werden. Ziel dieser Studie war eine retrospektive Analyse über klinischen Verlauf und Outcome bei fünf Transplantationspatienten, die an einer Listerienmeningits erkrankt sind. PATIENTEN UND METHODEN: Die Studienpopulation dieser Arbeit umfasst mehr als 3500 Organ- bzw. Stammzelltransplantationen, die an der Universiätsklinik in Innsbruck während eines Zeitraumes von 26 Jahren durchgeführt wurden. Die Standardimmunosuppression umfasste eine Calcineurininhibitor-basierte Dreifachtherapie, zum Teil unter Verwendung einer Induktionstherapie mit ATG oder eines IL2-Rezeptor-Antagonisten. ERGEBNISSE: Alle Patienten zeigten Zeichen der Meningitis und hatten hohes Fieber sowie eine Erhöhung der Entzündungsparameter. Bei zwei Fällen handelte es sich um eine nosokomiale Erkrankung innerhalb der ersten beiden Wochen nach Transplantation. Beim ersten Fall handelte es sich um eine 35-jährige Frau, die sich aufgrund eines fortgeschrittenen Mamma-Karzinoms einer allogenen Stammzelltransplantation unterziehen musste. Die übrigen vier Betroffenen waren zwei Herz- und zwei Nierenempfänger. Listeria monocytogenes wurde bei zwei Patienten im Blut und bei drei Patienten im Liquor nachgewiesen. Die Behandlung erfolgte in allen Fällen mit Ampicillin. Zusätzlich wurden Tobramycin (n = 1), Meropenem (n = 2) und Imipenem/Cilastatin (n = 1) verabreicht. Zwei Patienten verstarben unmittelbar an den Folgen der Listeriose. SCHLUSSFOLGERUNG: Obwohl die Listerienmeningitis eine seltene Komplikation nach Transplantation darstellt, sollte sie doch bei allen Organempfängern mit hohem Fieber in Erwägung gezogen werden, die eine neurologische Symptomatik entwickeln.

Severe endocarditis in transplant recipients – an epidemiologic study*

Infective endocarditis (IE) is reported with an incidence of 6/100u2003000 inhabitants in the general population. Even though immunosuppression predisposes to systemic infection, reports regarding IE after solid organ transplantation (SOT) are sparse. From 1989 to 2004, 2556 patients underwent SOT at the University Hospital Innsbruck. During this period, 27 transplant recipients were diagnosed IE. Nine patients (33.3%) were diagnosed at autopsy, eight patients (29.6%) were cured by antibiotic treatment and 10 patients (37.1%) underwent surgery. Overall mortality was 44.4% (12 patients). Staphylococcus was the predominant microorganism in 16 cases (59.3%), fungal infection was present in four patients (14.8%). Incidence of IE was 1% (95% CI: 0.67–1.49), indicating a 171‐fold risk compared with the overall population. IE after SOT constitutes a significant problem and is associated with an excessive high mortality. Alertness to this condition is indicated, as we might diagnose more cases of IE in the future.

Long-term glomerular filtration rate following pediatric liver transplantion

Abstract:u2002 In adult patients a significant proportion of chronic renal failure after liver transplantation (LTX) has been described. This was attributed mainly to nephrotoxicity caused by Calcineurin inhibitors (CNI). If these results are transferable to pediatric patients was the aim of this study.

Hemolytic uremic syndrome following Campath-1H induction

Hemolytic uremic syndrome (HUS) is a rare complication following solid organ transplantation. We report on a patient who underwent renal transplantation using Campath‐1H induction and tacrolimus maintenance therapy who developed HUS, which was managed by plasma exchange and switch to Rapamycin. However, graft function could not be restored.

Group milleri streptococci: significant pathogens in solid organ recipients.

Group milleri streptococci (GMS) comprise a heterogeneous group of streptococci including the species intermedius, constellatus and anginosus. They may cause chronic intra‐abdominal and intrathoracic abscesses, which are difficult to treat. This is a retrospective analysis including 45 transplant recipients in whom GMS were isolated. The epidemiology, clinical significance and the impact on the outcome in all transplant patients with infections caused by GMS during a 4‐year period (2001–2004) was evaluated. The 45 solid organ recipients (88 isolates) included 34 liver‐, four kidney/pancreas‐, one kidney‐, two small bowel‐, three combined liver/kidney‐ and one combined kidney/small bowel transplant recipient. In 42 cases GMS caused intra‐abdominal infection, in two cases pleural empyema and in one case soft tissue infection. Only a single isolate of GMS was cultured from blood. In 54 of the 88 specimens (61%), which grew GMS, other pathogens were also isolated. GMS frequently caused recurrent cholangitis (nu2003=u200317) associated with anastomotic and nonanastomotic biliary strictures. These cases were managed by repeated stenting or surgical intervention and prolonged antibiotic therapy. No patient died directly related to GMS infection and all except one case responded to combined surgical/antibiotic treatment. One pancreas graft was lost because of erosion haemorrhage associated with an abscess. GMS were susceptible to penicillin G, carbapenems and clindamycin, whereas cephalosporins and quinolones showed intermediate activity or resistance in some cases, and GMS in general were found resistant to aminoglycosides. GMS may cause serious infections in transplant recipients which are difficult to treat. Their prevalence in transplant surgical site infections thus far may have been underestimated.

Regarding diarrhea in liver transplant recipients: etiology and management.

In the August 2005 edition of your journal, the etiology and management of diarrhea after liver transplantation (LT) was discussed in an extensive review by Ginsburg and Thuluvath. Diarrhea occurred in about 10% of adult patients following LT. The authors reported post-transplant episodes of acute diarrhea to be frequently related to immunosuppressive medications such as mycophenolate mofetil, tacrolimus and sirolimus, and infectious agents with Clostridium difficile (CD) being the most relevant one. Overall, CD was causative in about one third of all cases. Second in line for infectious reasons were Cytomegalovirus associated infections (15%-40%). A variety of other viruses also rarely were responsible for episodes of diarrhea after LT. Rotavirus (RV), a member of the family Reoviridae, was also mentioned. Rotavirus is the most common cause of viral enteritis in infants and young children, with an estimated 9 million annual cases of severe diarrhea globally, causing approximately 87,0000 deaths worldwide in 1985. Rotavirus infections are commonly transmitted fecal-orally and often require hospital admission because of excessive fluid losses in children up to 5 years. In immunocompromised or elderly patients an even more severe course of the disease has been reported. Only symptomatic treatment is currently recommended for RV infection, as treatment with various antiviral agents or immunoglobulins has shown disappointing results. We would like to report our institutional findings on RV-related enteritis following LT during a tenyears period between 1994 and 2004. We investigated infectious causes of enteritis in 305 adult and 39 pediatric liver transplant recipients. Testing for Rotavirus, using an immunochromatograficor enzymelinked immunosorbent-assay, was routinely performed in all pediatric organ recipients and from 2003 also in all adult liver recipients who presented with diarrhea. We found a much higher incidence of Rotavirus-associated enteritis compared to the numbers reported in the literature (1.3-2.6%). Out of 344 liver recipients, RV-associated diarrhea was diagnosed in 16 patients (4.7%), all of them presenting with prolonged diarrhea and significant fluid loss. The median onset of RV enteritis was 117 (11-2159) days post transplant. While RV caused enteritis in three adult LT recipients, pediatric liver recipients were found to be at a much higher risk. Thirteen out of the 39 children, i.e. 33.3%, had RV-infection. Two children presented with several episodes of RV associated diarrhea. Within the same 344 patients, 22 (6.4%), including two multivisceral transplant recipients, had CD infection. Six liver recipients (1 adult and 5 pediatrics) had both RV and CD infections with simultaneous isolation of both pathogens. All developed secondary infection including infected ascites (n 1), pneumonia (n 1) and multiorgan failure with death (n 1 pediatric). Clostridium difficile colitis was diagnosed in ten children (28.2%). Therefore, Rotavirus was the most common pathogen causing post-transplant diarrhea in our pediatric liver population, while in the adult population, Clostridium difficile was the most common enteric infection. None of our patients with RV or CD enterocolitis required surgical intervention, however, all patients were severely ill with significant fluid and electrolyte losses, requiring intensive care and prolonged fluid resuscitation. As previously reported, during RV enteritis a rise in tacrolimus trough levels was also observed in our patients, and reduction of immunosuppression was carried out in all our patients. We feel it is important to consider Rotavirus as a possible cause of diarrhea also in adults. Even co-infection might be observed. In conclusion, liver recipients with diarrhea should undergo stool testing for RV and CD. In order to avoid nosocomial outbreaks, pediatric and adult liver recipients should be kept separated. In our series infection was the most common cause of diarrhea with CD and RV being by far the most common pathogens. Once available, pre-transplant vaccination against RV might be considered for adult solid organ recipients.

CYTOMEGALOVIRUS MISMATCH AS MAJOR RISK FACTOR FOR DELAYED GRAFT FUNCTION FOLLOWING PANCREAS TRANSPLANTATION: 2976

M. Maglione1, M. Biebl2, H. Bonatti3, G. Goebel4, T. Ratschiller5, S. Schneeberger6, G. Brandacher7, P. Hengster4, C. Margreiter6, N. Berger8, W. Mark9, J. Pratschke6, R. Margreiter9 1Center Of Operative Medicine, Department Of Visceral, Transplant And Thoracic Surgery, Innsbruck Medical University , Innsbruck/ AUSTRIA, 2, Medical University Innsbruck, Innsbruck/AUSTRIA, 3Surgery, University of Virginia, Charlottesville/VA/UNITED STATES OF AMERICA, 4Department For Medical Statistics, Informatics And Health Economics, Innsbruck Medical University, Innsbruck/AUSTRIA, 5Department Of Visceral, Transplant And Thoracic Surgery, Medical University Innsbruck, Innsbruck/ACT/AUSTRIA, 6Transplant Surgery, University Hospital, Innsbruck/AUSTRIA, 7Department Of Visceral, Transplant And Thoracic Surgery, Innsbruck Medical University, Innsbruck/AUSTRIA, 8Department Of Visceral, Transplant, And Thoracic Surgery, Innsbruck Medical University, Innsbruck/AUSTRIA, 9Visceral, Transplant And Thoracic Surgery, Medical University Innsbruck, Innsbruck/AUSTRIA