Silke Wiesmayr

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.

Malignancies of the colorectum and anus in solid organ recipients.

Patients undergoing solid organ transplantation (SOT) are at increased risk for developing malignancies due to the long term immunosuppression. Data on malignancies of the large intestine after various types of SOT are rare. A total of 3595 SOTs were performed between 1986 and 2005 at our center and retrospectively analyzed with regard to the incidence and course of malignancies of the colon, rectum, and anus. Standard immunosuppression consisted of calcineurin inhibitors in combination with azathioprine or mycophenolate mofetil and steroids with or without antithymocyte globulin or IL‐2 receptor antagonist induction. A total of 206 patients (5.7%) developed malignancies. Colorectal adenocarcinoma was diagnosed in nine patients (0.25%; mean age at diagnosis 65 years) at a mean of 5.3 years after transplantation. Five patients (55%) died 7.2 years post‐transplant due to cardiovascular disease (n = 4) and tumor progression (n = 1). Four patients developed anal neoplasia (0.11%) 7 years post‐transplant with 100% 1‐year survival. Five patients showed post‐transplant lymphoproliferative disorders (PTLD) with intestinal involvement. The incidence of anal but not of colorectal cancers in our transplant recipients differed from that of immunocompetent individuals of corresponding age (0.11% vs. 0.002% and 0.25% vs. 0.3%). PTLD may involve the colon.

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.

Long-term glomerular filtration rate following pediatric liver transplantion

Abstract:  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.

Severe Intra-abdominal Infection due to Streptococcus Milleri Following Adjustable Gastric Banding

Background: Laparoscopic adjustable gastric banding represents a safe and effective bariatric surgical method. Nevertheless, complications such as intraabdominal infections are associated with high morbidity and mortality. Case Report: A 50-year old morbidly obese female patient underwent adjustable gastric banding with the Swedish band (SAGB). After an uneventful postoperative follow-up of 2 years, she developed band infection due to colon microperforation during endoscopic polypectomy. As the causative microorgansim, Streptococcus Milleri was revealed. Band removal was required, and recovery was quite prolonged. Conclusion: Intra-abdominal infection with Streptococcus Milleri can cause severe and life-threatening disease. Therefore, early diagnosis and surgical intervention combined with body weight adapted antibiotic therapy for a sufficiently long period of time seems necessary. In patients with intra-abdominal implanted devices such as the SAGB who undergo endoscopic polypectomy, antibiotic prophylaxis should therefore be considered.

Mycobacterium chelonae Skin Infection in Kidney-Pancreas Recipient

To the Editor: Mycobacterium chelonae is rapid growing and is ubiquitous in the environment, including soil, water, domestic and wild animals, and milk and fruit products. It can be associated with infections of the soft tissue, lung, bone, joint, central nervous system, and eye. M. chelonae infections in an immunocompromised host are disseminated in >50% of those infected; chronic use of steroids, even in low doses, seems to be the most important predictive factor for disseminated disease (1,2). In immunocompetent hosts, nontuberculous mycobacteria can colonize body surfaces and be secreted for prolonged periods without causing disease. In hematopoietic stem cell and solid organ transplant recipients, infections with nontuberculous mycobacteria are common and may be a source of illness and death (3). We describe a case of localized cutaneous M. chelonae infection after a dog bite in a kidney-pancreas transplant recipient.

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.

Rothia dentocariosa sepsis in a pediatric renal transplant recipient having post‐transplant lymphoproliferative disorders

Abstract: Background: Rothia dentocariosa (RD) is a Gram‐positive rod that colonizes the human oral cavity and can cause infective endocarditis.

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.

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.