Antimicrobial Prophylaxis for Pancreas Transplantation

Robert J. Stratta, MD

Disclosures

November 29, 2005

Question

What is current recommended practice for prophylactic antibacterial and antifungal prophylaxis in kidney-pancreas and pancreas alone transplantation?

John Radomski, MD

Response from Robert J. Stratta, MD

Pancreas and kidney-pancreas transplant recipients have an intermediate risk for bacterial and fungal infections because all are diabetic, are undergoing an intraperitoneal procedure (usually with enteric drainage), have multiple indwelling devices, and typically receive depleting anti-T-cell antibody therapy. If one could adequately prep the bowel prior to transplantation, the risk of bacterial and fungal infections would be decreased. However, in practice, this is logistically difficult because of time constraints and because diabetic patients with enteropathy are not infrequently either intolerant of or unresponsive to vigorous bowel preps.

There are no specific recommendations for anti-infective prophylaxis after pancreas transplantation, but most centers follow some basic guidelines. For surgical site prophylaxis, we recommend using only a first-generation cephalosporin, with the first dose administered within 30 minutes of the skin incision, repeat doses every 3 hours intraoperatively, and then continued dosing for 24 hours postoperatively. However, in the literature, other centers may extend prophylaxis for 48-72 hours and some centers even advocate broad-spectrum coverage (ie, vancomycin and piperacillin-tazobactam) for 7 days postoperatively. For patients allergic to penicillin or cephalosporins, we typically would administer a single preoperative dose of vancomycin and ciprofloxacin and then postoperative dosing of ciprofloxacin for 24 hours. Alternatively, other centers might advocate aztreonam and metronidazole for 2, 3, or 7 days. We believe that broader-spectrum coverage and prolonged courses of antibiotics might predispose to either resistant bacterial or fungal infections, so we try to keep our antibacterial prophylaxis fairly simple and short.

With regard to antifungal prophylaxis, we begin oral fluconazole 200 mg/day on the first postoperative day and continue prophylaxis for 2 months posttransplantation in uncomplicated cases. If the patient undergoes a repeat laparatomy, is treated for acute rejection with either bolus corticosteroids or antilymphocyte therapy, or develops either bacterial sepsis or a cytomegalovirus infection, we continue the fluconazole prophylaxis for an additional 2 months from the last event. A side benefit of fluconazole is increased tacrolimus, cyclosporine, or sirolimus levels, which can be difficult to achieve and maintain in the early postoperative period in the diabetic patient with gastroparesis and enteropathy. It is important to monitor drug levels closely when stopping fluconazole, and we typically double the dose of the calcineurin inhibitor when discontinuing fluconazole.

Most bacterial and fungal infections occur in the first month postoperatively, hence the rationale for stopping prophylaxis at 2 months. If the patient is receiving an anticonvulsant drug or some other strong hepatic microsomal enzyme inducer, then we continue fluconazole indefinitely in order to maintain target calcineurin inhibitor levels, or switch to some other strong hepatic enzyme inhibitor (ie, erythromycin, diltiazem).

I have little experience with (or confidence in) nystatin and clotrimazole as effective agents in pancreas transplant recipients, although we use these agents routinely after kidney transplantation in lieu of fluconazole. The newer antifungal agents (itraconazole, voriconazole, posaconazole, caspofungin, micafungin) and amphotericin preparations are not indicated unless Aspergillus is identified or the patient has a history of Cryptococcus or resistant Candida infection. Probably one of the most important points is to avoid prolonged use of broad-spectrum antibiotics and to remove indwelling devices in a timely fashion. Using the described anti-infective prophylaxis regimen, our incidences of resistant bacterial and any fungal infections after pancreas transplantation have been extremely low.

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