Reinhold Kafka

Infectious complications following 72 consecutive enteric‐drained pancreas transplants

New immunosuppressive protocols and advanced surgical technique resulted in an improved outcome of pancreatic transplantation (PTx) with infection remaining the most common complication. Seventy‐two enteric‐drained whole PTxs performed at the Innsbruck University Hospital between September 2002 and October 2004 were retrospectively analyzed. Prophylactic immunosuppression consisted of either the standard protocol consisting of single bolus antithymocyteglobuline (ATG) (Thymoglobulin, Sangstat or ATG Fresenius) induction (9 mg/kg), tacrolimus (TAC), mycophenylate mofetil (MMF) and steroids (38 patients) or a 4‐day course of ATG (4 mg/kg) tacrolimus and steroids with MMF (n = 19), or Sirolimus (n = 15). Perioperative antimicrobial prophylaxis consisted of Piperacillin/Tazobactam (4.5 g q 8 h) in combination with ciprofloxacin (200 mg q 12 h) and fluconazole (400 mg daily). Ganciclovir was used for cytomegalovirus (CMV) prophylaxis if donor was positive and recipient‐negative. Patient, pancreas, and kidney graft survival at 1 year were 97.2%, 88.8%, and 93%, respectively, with no difference between the groups. All retransplants (n = 8) and single transplants (n = 8) as well as all type II diabetics and nine of 11 patients older 55 years received standard immunosuppression (IS). The rejection rate was 14% and infection rate 46% with no difference in terms of incidence or type according to the three groups. Severe infectious complications included intra‐abdominal infection (n = 12), wound infection (n = 7), sepsis (n = 13), respiratory tract infection (n = 4), urinary tract infection (n = 12), herpes simplex/human herpes virus 6 infection (n = 5), CMV infection/disease (n = 7), post‐transplant lymphoproliferative disorder (PTLD, n = 3), invasive filamentous fungal infection (n = 4), Clostridial/Rotavirus colitis (n = 1), and endocarditis (n = 1). All four patients in this series died of infectious complications (invasive aspergillosis n = 2) (one with Candida glabrata superinfection), invasive zygomycosis (n = 1), PTLD (n = 1). Five grafts were lost (vascular thrombosis n = 3, pancreatitis n = 1, noncompliance n = 1). Infection represented the most frequent complication in this series and all four deaths were of infectious origin. Better prophylaxis and management of infections now should be the primary target to be addressed in the field of pancreas transplantation.

Bloodstream infection following 217 consecutive systemic-enteric drained pancreas transplants

BackgroundCombined kidney pancreas transplantation (PTx) evolved as excellent treatment for diabetic nephropathy. Infections remain common and serious complications.Methods217 consecutive enteric drained PTxs performed from 1997 to 2004 were retrospectively analyzed with regard to bloodstream infection. Immunosuppression consisted of antithymocyteglobuline induction, tacrolimus, mycophenolic acid and steroids for the majority of cases. Standard perioperative antimicrobial prophylaxis consisted of pipercillin/tazobactam in combination with ciprofloxacin and fluconazole.ResultsOne year patient, pancreas and kidney graft survival were 96.4%, 88.5% and 94.8%, surgical complication rate was 35%, rejection rate 30% and rate of infection 59%. In total 46 sepsis episodes were diagnosed in 35 patients (16%) with a median onset on day 12 (range 1–45) post transplant. Sepsis source was intraabdominal infection (IAI) (n = 21), a contaminated central venous line (n = 10), wound infection (n = 5), urinary tract infection (n = 2) and graft transmitted (n = 2). Nine patients (4%) experienced multiple episodes of sepsis. Overall 65 pathogens (IAI sepsis 39, line sepsis 15, others 11) were isolated from blood. Gram positive cocci accounted for 50 isolates (77%): Coagulase negative staphylococci (n = 28, i.e. 43%) (nine multi-resistant), Staphylococcus aureus (n = 11, i.e. 17%) (four multi-resistant), enterococci (n = 9, i.e. 14%) (one E. faecium). Gram negative rods were cultured in twelve cases (18%). Patients with blood borne infection had a two year pancreas graft survival of 76.5% versus 89.4% for those without sepsis (p = 0.036), patient survival was not affected.ConclusionSepsis remains a serious complication after PTx with significantly reduced pancreas graft, but not patient survival. The most common source is IAI.

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.

Colonic perforation associated with leukocytoclastic vasculitis caused by Sirolimus toxicity following renal transplantation.

Target of Rapamycin (TOR) inhibitors have been introduced in clinical transplantation during the past decade. Common side effects of TOR inhibitors include diarrhea and abdominal discomfort, acne, pancytopenia and wound healing disturbances because of the antiproliferative effects [1,2]. Furthermore, ulcers within the oral cavity have been described. A 35-year-old male patient with phosphoribosyl transferase inhibitor deficiency underwent his fourth kidney transplantation after three failures because of recurrent disease. At this time the patient had developed 66% preformed antibodies, however, the crossmatch was negative. Initial immunosuppression consisted of Tacrolimus, Sirolimus (SIR) and steroids. One week later, the patient developed acute vascular rejection (C4d positive signal on renal biopsy), which was treated with bolused steroids (500 mg of methylprednisolone on three consecutive days) and extensive plasma exchange. This was followed by multiple sessions of immunoapheresis over 6 weeks. Ganciclovir prophylaxis was given for 3 months. Tacrolimus dose was reduced and mycophenolic acid was added and the patient was kept on quadruple drug therapy. The remaining course was uncomplicated; the graft recovered and functioned well. Sixteen-months post-transplant, the patient developed respiratory tract infection and was prescribed Clarithromycin by his general practitioner. Few days later, he presented with severe abdominal pain, fever and watery diarrhea accompaigned by deterioration of the renal graft function. Colonoscopy showed multiple ulcers at various parts of the colon. Histology revealed unspecific ulcerations – no cause for the lesions could be identified, enteric pathogens such as Salmonella, Clostridium difficile and Rotavirus were excluded [3,4]. Repeated testing for cytomegalie virus (CMV) or Ebstein-Barr-virus (EBV) replication were also negative. Conservative treatment with metronidazol and ciprofloxacin was initiated; C-reactive protein and leukocyte count decreased and the patient’s condition and the renal graft function improved. The following day SIR level was measured, which was as high as 25 ng/dl. The agent was immediately withdrawn. After initial improvement, the patient’s condition deteriorated again and he finally developed acute abdomen with graft failure. Abdominal X-ray demonstrated massive intraperitoneal air and CT scan identified a thickened colonic wall and sigmoid perforation (Fig. 1). The sigmoid colon was resected and antibiotic therapy was changed to piperacillin/tazobactam (4.5 g q 8 h). After initial improvement, the patient developed sepsis and died because of multiorgan failure. Autopsy showed a steatosed liver, active colitis with multiple ulcers and ulceration at the cardioesophageal junction. Histology of colonic and gastric ulcers revealed atypical inflammatory changes within the wall with signs of vasculitis (Fig. 2). The blood vessels within the mesenterium were infiltrated by fibrin deposits. The histological features were consistent with leukocytoclastic vasculitis (LCV). The ulcerations were suspected to be of ischemic origin because of the vasculitis. Leukocytoclastic vasculitis is a necrotizing vasculitis with segmental areas of transmural infiltration and disruption of the vessel architecture by neutrophils with fibrinoid necrosis [5]. It is known to be caused by autoimmune diseases, infections and drugs. SIR is absorbed from the upper gastrointestinal tract and 50% of the drug is metabolized in the gut mucosa [6]. As LCV mainly involved mesenteric blood vessels, causing ischemic ulcers within the dependent colonic segments, colonoscopic biopsies could not identify the process. LCV has been described primarily in the skin but many patients present with systemic manifestations involving joints, kidneys and the gastrointestinal tract. SIR associated cutaneous LCV has been reported after kidney–pancreas and lung transplantation and in children [7,8,9]. It is tempting to suspect, that the required intensified immunosuppression in this patient also contributed to the development of LCV. SIR has been shown to be a useful agent in transplantation, however, SIR toxicity must be considered as a possible differential diagnosis in patients presenting with severe abdominal pain and/or gastrointestinal ulcers. Physicians must be educated on the potential drug interaction of SIR and some antimicrobial agents such as macrolides.