Walther Tabarelli

Clostridium difficile colitis in solid organ transplantation--a single-center experience.

Clostridium difficile (CD) is one of the most common causes of diarrhea in solid organ transplantation (SOT). Between 1996 and 2005, a total of 2474 solid organ transplants were performed at our institution, of which 43 patients developed CD-associated diarrhea. There were 3 lung, 3 heart, 20 liver, 8 kidney-pancreas, 6 kidney, 1 composite tissue, and 2 multivisceral recipients. Onset of CD infection ranged from 5 to 2453 days posttransplant. All patients presented with abdominal pain and watery diarrhea. Toxins A and B were detected using rapid immunoassay or enzyme immunoassay. Treatment consisted of reduction of immunosuppression, fluid and electrolyte replacement, metronidazole (n=20), oral vancomycin (n=20), and a combination of metronidazole and vancomycin (n=2). Toxic megacolon was seen in five patients. Two of them had colonoscopic decompression, and the remaining three required colonic resection. One of these patients died due to multiorgan failure after cured CD enteritis. The remaining patients were discharged with well-functioning grafts and all are currently alive. CD colitis was a rare complication prior to 2000; 38 of the 43 cases occurred thereafter. We conclude that CD colitis represents a severe complication following SOT. Recently, a dramatic increase in the incidence of this complication has been observed. The development of life-threatening toxic megacolon must be considered in solid organ recipients.

Nocardiosis following solid organ transplantation: a single-centre experience

Nocardiosis is a localized or disseminated bacterial infection caused by aerobic Actinomyces that commonly affects immunocompromised hosts. The aim of this study was to retrospectively review clinical course and outcome of nocardiosis in solid organ recipients at our centre. Five cases of nocardiosis were identified in a series of more than 4000 consecutive solid organ transplants performed at Innsbruck university hospital during a 25‐year period. Of the five patients with nocardiosis, two had undergone multivisceral, one liver, one kidney and one lung transplantation. Three patients with Nocardia asteroides infection were treated successfully and recovered from their infectious disease, however, one lost his renal graft following withdrawal of immunosuppression. The lung recipient recovered from nocardiosis but died later on from Pseudomonas pneumonia. One multivisceral recipient died from Nocardia farcinica‐disseminated infection. Nocardiosis is a rare, difficult‐to‐diagnose‐and‐treat complication following solid organ transplantation. Intestinal recipients might be at increased risk to develop this infection.

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.

Clostridium perfringens Liver Abscess after Pancreatic Resection

BACKGROUND Liver abscess is a rare complication after pancreatectomy. Clostridium perfingens is a rare cause of intrahepatic infections. CASE REPORT A 65-year-old woman with pancreatic cancer underwent explorative laparotomy, during which encasement of the hepatic artery by the tumor was found. Neoadjuvant radiochemotherapy with capecitabine was started, which caused tumor regression, and duodenopancreatectomy was performed. The portal vein was occluded and infiltrated by cancer and therefore was resected and not reconstructed. After a slow recovery, the patient developed hemorrhage at the gastrojejunal anastomosis, which was controlled by fibrin injection. Within a few days, she presented with signs of sepsis, and blood cultures yielded Clostridium perfringens, Streptococcus oralis, Staphylococcus aureus, and Candida albicans. The source of the sepsis proved to be a 9-cm liver abscess, which was drained; cultures grew C. perfringens, Hafnia alvei, and Enterobacter cloacae. Despite antibiotic treatment, the patient died from sepsis and multiorgan failure 27 days after pancreatic surgery. CONCLUSION Such rare infections can follow pancreatic resection with neoadjuvant radiochemotherapy. Clostridium perfringens-associated liver abscess maintains a high mortality rate.

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 (n = 17) 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.

Long term complications following 54 consecutive lung transplants

BACKGROUND Due to the complex therapy and the required high level of immunosuppression, lung recipients are at high risk to develop many different long term complications. METHODS From 1993-2000, a total of 54 lung transplantation (LuTx) were performed at our center. Complications, graft and patient survival of this cohort was retrospectively analyzed. RESULTS One/five and ten-year patient survival was 71.4%, 41.2% and 25.4%; at last follow up (4/2010), twelve patients were alive. Of the 39 deceased patients, 26 died from infectious complications. Other causes of death were myocardial infarction (n=1), progressive graft failure (n=1), intracerebral bleeding (n=2), basilary vein thrombosis (n=1), pulmonary emboli (n=1), others (n=7). Surgical complication rate was 27.7% during the first year and 25% for the 12 long term survivors. Perioperative rejection rate was 35%, and 91.6% for the 12 patients currently alive. Infection incidence during first hospitalization was 79.6% (1.3 episodes per transplant) and 100% for long term survivors. Commonly isolated pathogens were cytomegalovirus (56.8%), Aspergillus (29.4%), RSV (13.7%). Other common complications were renal failure (56.8%), osteoporosis (54.9%), hypertension (45%), diabetes mellitus (19.6%). CONCLUSIONS Infection and rejection remain the most common complications following LuTx with many other events to be considered.

Experience with the use of piperacillin–tazobactam in pediatric non-renal solid organ transplantation

Abstract:  Bacterial infection remains a major problem after solid organ transplantation (SOT), especially in children. Piperacillin–tazobactam (Pip–Tazo) is a beta‐lactam‐antibiotic combination with a broad spectrum of activity including gram‐positive cocci as well as gram‐negative rods, non‐fermentative and anaerobic bacteria. The aim of this retrospective study was to critically review our experience with Pip–Tazo as perioperative prophylactic agent in pediatric non‐renal SOT. Between 1993 and 2003 Pip–Tazo was used as initial perioperative prophylaxis in 45 pediatric patients who underwent a total of 49 transplants (36 liver‐, seven cardiac‐, two lung‐, and four small bowel‐) at our department. Median age of the children was 7.9 (range 0.5–18.1) years. A total of 34 rejection episodes following 27 transplants were diagnosed. During first hospitalization 44 infectious episodes were observed. Bacteria were responsible for 22 episodes including sepsis (n = 10), pneumonia (n = 5), wound infection (n = 4), urinary tract infection (n = 1), and clostridial colitis (n = 2). The isolated organisms were gram‐positive cocci (n = 12), gram‐negative rods (n = 3), non‐fermentative bacilli (n = 4), and anaerobes (n = 3). Ten episodes were caused by Pip–Tazo resistant bacteria. Twenty‐one of these infections were observed following antirejection therapy with pulse steroids. At later time points nine infectious episodes were successfully treated with a second course of Pip–Tazo. During follow up, eight patients died. Six deceased perioperatively: five from infection including aspergillosis (n = 4) and Pneumocystis jiroveci pneumonia (n = 1) and cerebrovascular bleeding (n = 1) and two children later on. At present 37 children (82%) are alive with well functioning graft after a median follow up of 39.2 (range 0.6–123.5) months. No severe side effects caused by Pip–Tazo were observed in any of the children. Pip–Tazo may be a suitable single agent for perioperative prophylaxis in pediatric non‐renal solid organs recipients, however, a prospective comparative study is needed to make final conclusions.

Course of transplant recipients treated with Ertapenem in the prophylaxis and treatment of infections: a first experience

ZusammenfassungGRUNDLAGEN: Infektionen sind die häufigsten Komplikationen nach Organtransplantationen. Bakterien gehören zu den häufigsten Erregern, wobei Entwicklung von Resistenzen gegen Antibiotika Anlass zu besonderer Sorge gibt. Ertapenem, ein neues Antibiotikum der Carbapenemgruppe mit langer Halbwertszeit, wurde kürzlich in die klinische Praxis eingeführt. METHODIK: Zwischen Jänner 2004 und Dezember 2004 wurden an der Innsbrucker Universitätsklinik insgesamt 50 Leber- und 32 Pankreastransplantationen durchgeführt. Vier Leber- und zwei Pankreasempfänger erhielten eine Prophylaxe oder Therapie mit Ertapenem. ERGEBNISSE: Fünf Männer und eine Frau mit einem mittleren Alter von 45 Jahren wurden mit Ertapenem behandelt. Die Immunsuppression bestand in einer Induktionstherapie mit ATG im Falle der zwei Pankreasempfänger und mit IL-2 Rezeptorantagonisten bei den drei Leberempfängern, gefolgt von Takrolimus, Mycophenolat Mofetil und Steroiden bei fünf Patienten. Ein Leberempfänger erhielt Cyclosporin A, Mycophenolat Mofetil und Steroide ohne Induktionstherapie. Beide Pankreasempfänger wurden wegen Transplantatpankreatitis und intraabdomineller Infektion mit Ertapenem behandelt. Der erste Leberempfänger erhielt Ertapenem prophylaktisch während einer Relaparotomie wegen intraabdomineller Blutung am zehnten postoperativen Tag. Der zweite und dritte Patient erhielten Ertapenem wegen Fieber unbekannter Ursache und der letzte Patient wegen einer Pneumonie mit extended-spectrum-betalactamase (ESBL) produzierenden Klebsiellen. Fünf Infektionsepisoden wurden erfolgreich behandelt; der letzte Patient verstarb an einer Sepsis durch Endokarditis, hervorgerufen durch die vorher isolierte ESBL-produzierende Klebsiella terrigena. Ein anderer Patient verstarb acht Monate später an einer Aspergillose. SCHLUSSFOLGERUNGEN: Diese erste Serie von Leber- und Pankreasempfängern, welche Ertapenem erhielten, zeigt, dass dieses neue Carbapenem bei Transplantatempfängern einsetzbar ist, insbesondere bei Verdacht auf ESBL-produzierende Stämme oder wenn aerob-anaerobe Mischinfektionen vorliegen. Bei Infektionen mit ESBL produzierenden Keimen scheint eine verlängerte Antibiotikatherapie notwendig.SummaryBACKGROUND: Infection remains the most common complication of solid organ transplantation (SOT) and bacteria are the most common causing organisms. Development of resistance gives reasons for concern. Ertapenem, a new carbapenem with long half life has recently been introduced in clinical practice. METHODS: Between January 2004 and December 2004 a total of 50 liver- and 32 pancreas transplants were performed at the Innsbruck Medical University Hospital. Four liver and two pancreas recipients received Ertapenem for prophylaxis or treatment of bacterial infections. RESULTS: There were five men and one woman with a mean age of 45 (range 32–60) years. Immunosuppression consisted of induction therapy with ATG in the two pancreas recipients and of IL-2 receptor antagonists in three liver recipients followed by tacrolimus, mycophenolate-mofetil and a steroid taper. One liver recipient received cyclosporine A, MMF and steroids without induction. Both pancreas recipients were treated with Ertapenem for graft pancreatitis and intraabdominal infection. The first liver recipient received Ertapenem prophylactically during relaparotomy for intraabdominal hemorrhage on day 10 post transplant; the second and the third patient for fever of unknown origin and the last for pneumonia caused by extended spectrum betalactamase producing Klebsiella. In five of the six cases infectious episodes were treated successfully; however, the last patient died from sepsis associated with endocarditis caused by ESBL producing Klebsiella and another liver recipient died eight months post transplant from aspergillosis. CONCLUSIONS: This first series of liver and pancreas recipients receiving Ertapenem shows that the new compound may be a suitable agent for treatment of infections in this selected population, in particular if ESBL producing strains may be involved and if a mixed spectrum of pathogens must be expected. Infections caused by ESBL producing pathogens may require prolonged therapy.

Successful Management of a Proximal Pancreatic Duct Fistula Following Pancreatic Transplantation

Peripancreatitis and pancreatic fistulas remain common complications of pancreas transplantation [1]. Frequently this is associated with reperfusion injury or injuries originating during retrieval or back table preparation. In many cases intraabdominal infection causes peripancreatitis, however, also peripancreatitis can be followed by superinfection of necrotic tissue [2, 3]. Also, fistulas to the small bowel or colon of the recipient can develop, and in some cases the duodenal segment of the graft or a leakage at the duodenojejunostomy can be the cause of such complications [4]. Treatment consists of control of the intraabdominal infection by empiric antibiotic therapy and, once pathogens are isolated by directed antibiotic therapy, drainage of fluid collection and antisecretory compounds such as somatostatin or

Successful management of osteosynthesis infection caused by Enterococcus faecium after severe leg trauma

ZusammenfassungGRUNDLAGEN: Infektionen von alloplastischem Material werden meist durch Staphylokokken verursacht. Enterokokken sind selten Auslöser von Infektionen nach osteosynthetischen Verfahren. Enterococcus faecium ist gegen viele Antibiotika resistent; Glycopeptide sind Mittel der Wahl. METHODIK: Wir berichten über einen 41-jährigen Mann, welcher im Rahmen eines Arbeitsunfalls eine drittgradig offene Quetschverletzung mit Kettenfrakturen des rechten Femurschaftes, medialen Femurkondylen, der distalen Tibia, des Mittelfußes und der Zehen erlitt. ERGEBNISSE: Die Erstversorgung umfasste das Stabilisieren der Brüche mittels Fixateur externe, Fasziotomie und Debridement der Wunden und Applikation eines VAC-Systems. Am dritten posttraumatischen Tag wurde der Oberschenkelbruch osteosynthetisch durch eine LISS-Platte versorgt. Erneut wurden Gewebsnekrosen debridiert und das VAC-System gewechselt. Nach vier Wochen wurde die Haut mit einem Meshgraft-Autotransplantat gedeckt. Während der siebenten Woche kam es zu einem Ausriss der LISS-Platte, und ein neues System musste implantiert werden. Aus nekrotischem Gewebe im Bereich der Ausrissstelle wurde Enterococcus faecium isoliert. Eine Behandlung mit intravenösem Vancomycin wurde begonnen. Der Patient musste sich zwei weiteren chirurgischen Eingriffen mit Debridement von Nekrosen und Implantation von autologer Spongiosa und BMP 7 unterziehen. Die antibiotische Therapie wurde mit Linezolid p.o. für weitere sechs Wochen fortgeführt. Der Fixateur externe konnte entfernt werden und der Patient tolerierte moderate mechanische Belastung gut. Nach neun Wochen zeigten Röntgen und CT einen weitgehend regenerierten Oberschenkelknochen und ein gutes Ergebnis im Bereich des Sprunggelenkes. Sechs Monate im Anschluss an das komplizierte Trauma war der Patient wieder im Stande, ohne Hilfe zu gehen, und es gab keinen Hinweis für eine Neuinfektion. SCHLUSSFOLGERUNGEN: Die multimodale Vorgehensweise mit schrittweiser Rekonstruktion der schweren Weichteilschädigung als auch der knöchernen Verletzungen erlaubte eine Wiederherstellung mit einem guten funktionellen und kosmetischem Ergebnis. Linezolid erwies sich als effektives Antibiotikum in der oralen Therapie dieser schweren Enterokokkeninfektion.SummaryBACKGROUND: Infection of alloplastic material is usually caused by staphylococci. Enterococci rarely have been implicated in infections after osteosynthesis. Enterococcus faecium is resistant to most antibiotics with glycopeptides being considered the treatment of choice. METHODS: We describe the case of a 41-year-old male, who sustained a trauma during a working accident with multiple open fractures of the right femur, tibia, food and toes. RESULTS: Initial treatment included stabilizing the fractures using external fixation and debridement of wounds with the application of a vacuum assisted device. On the third day post trauma, the fracture was stabilized by osteosynthesis with LISS lateral and of the median condyle. Repeatedly, soft tissue necroses were debrided and the VAC-system changed and after four weeks the skin was covered with a MESH graft. During the seventh week the patient got a fracture of the LISS and a new system had to be implanted. Enterococcus faecium was isolated and treatment was started with Vancomycin. The patient underwent another two surgical interventions with debridement of necroses and implantation of autologous spongiosa and BMP 7. External fixation was removed and moderate mechanical stress was tolerated. Antibiotic therapy was switched to oral linezolid for another six weeks. Nine weeks later, CT scan showed a regenerated femur and ankle joint. Six months following the complicated trauma, the patient was able to walk again. CONCLUSIONS: Multimodal approach with stepwise reconstruction of the severely traumatized tissue allowed recovery from this injury with a good functional result. Linezolid proved useful in the oral therapy of this severe enterococcal infection.