Antibiotic Prophylaxis in Renal and Liver Transplantation?

Milan Kinkhabwala, MD


September 21, 2000


What is the ideal antibiotic regimen for patients who will receive renal and liver transplants; when should the antibiotic therapy begin and what is the duration? Is vancomycin indicated in such a regimen?

Pedro Martinez, MD

Response from Milan Kinkhabwala, MD

Anti-infective prophylaxis and treatment in transplantation has become more important with the growth of extra-renal organ transplantation and with the increasing use of more potent immunosuppression. This confirms the general paradigm in transplantation that more immunosuppression always comes at the price of more infectious risk. For example, it is unlikely that the introduction of modern immunosuppressive agents would have been so successful without better prophylaxis for CMV infection. With the emergence of antibiotic resistance in potentially pathogenic organisms such as enterococcus, however, it is important to adopt a strategy that minimizes indiscriminate antibiotic use.

The strategy for anti-infective prophylaxis at our center closely follows standard surgical guidelines that are widely published in the literature. All solid organ transplant operations are, by definition, clean-contaminated operations, for which only a single dose of preoperative antibiotic targeting the expected organisms is indicated.

For uncomplicated renal transplantation we irrigate the bladder prior to beginning the operation with a topical antibiotic solution such as neomycin, kanamycin, or bacitracin. Cefazolin is administered intravenously (IV) "on call" to the operating room. The antibiotic should be administered prior to skin incision. Penicillin-allergic patients are given either vancomycin or clindamycin. The wound is irrigated with topical antibiotic solution prior to closure. While the data do not substantiate a benefit of topical wound irrigation in routine general surgery, in immunosuppressed patients topical antibiotic irrigation may reduce bacterial counts in the wound and thereby reduce the incidence of wound infection. Broad-spectrum antibiotics are generally unnecessary in renal transplantation.

In both liver and pancreas transplantation, antibiotic prophylaxis should cover both gram-positive and gram-negative organisms. We use 3-dose Unasyn prophylaxis, although there are many other single-agent alternatives including piperacillin/tazobactam and Timentin. These agents cover a wide range of organisms including gram-positive, anaerobic, and gram-negative species. We tend to extend antibiotic prophylaxis for several days in complicated liver transplant recipients who have a history of recent bacterial peritonitis, prolonged preoperative intensive care unit (ICU) stays, cholangitis, or prolonged operations with a greater likelihood of contamination. Penicillin-allergic patients are prophylaxed with vancomycin or clindamycin, as well as IV ciprofloxacin. Routine abdominal irrigation with antibiotic solution is also employed.

The issue of systemic fungal prophylaxis is not yet resolved. While prophylaxis with fluconazole does reduce the overall incidence of fungal infections, graft and patient survival are not affected. Fluconazole also does not cover the fungal species that are most likely to cause major morbidity in transplant recipients (eg, Aspergillus and Torulopsis) and causes drug interactions with calcineurin inhibitors. There are no data supporting the use of amphotericin B in prophylaxis. We routinely use only topical oral antifungal prophylaxis with Nystatin (or similar agent) in all of our solid organ transplant recipients. Fluconazole prophylaxis is used in selected patients with a prolonged pretransplant ICU course, prolonged use of broad-spectrum antibiotics, or evidence of yeast colonization in at least 2 sites. Fluconazole is also employed for treatment of established non-life-threatening fungal infection such as oral or esophageal candidiasis. Serious systemic fungal infections are always treated with amphotericin B.

Finally, viral prophylaxis remains a controversial issue. While most centers have adopted routine prophylaxis for Herpes species (herpes simplex and varicella zoster) using acyclovir, the optimal regimen for cytomegalovirus (CMV) is not established. The availability of more sensitive surveillance assays for CMV like the pp65 antigen assay has allowed some centers to adopt a pre-emptive approach, where treatment with ganciclovir is only initiated with evidence of CMV viremia. Other centers use routine CMV prophylaxis depending on donor-recipient CMV status, which is closely correlated with risk for CMV disease. The various agents available for treatment and/or prophylaxis of CMV contribute to the general lack of consensus on the optimal regimen. This is a topic for a formal monograph.