Ganciclovir Dosing Strategies and Development of Cytomegalovirus Resistance in a Kidney Transplant Recipient: A Case Report.

In renal transplant recipients, delayed graft function and accompanying renal impairment may lead to therapeutic underexposure of valganciclovir. We describe a case of a cytomegalovirus (CMV)-seronegative kidney transplant recipient from a CMV-seropositive donor, whose course was complicated during valganciclovir prophylaxis by CMV disease, ultimately progressing to ganciclovir, foscarnet, and cidofovir resistance. Assessments and adjustments for renal dysfunction, according to both Cockgroft-Gault and Modification of Diet in Renal Disease study equations, are described. Therapy was complicated by outpatient parenteral therapy with pump-administered antiviral therapy, which may have led to drug underexposure and the fostering of antiviral resistance. Suppression was ultimately achieved in conjunction with reduction in immunosuppressive therapy, CMV immunoglobulin, and initiation of leflunomide. At-risk recipients may benefit from 24 hour creatinine clearance assessments, direct creatinine clearance measurement, or therapeutic drug monitoring. Optimal dosing strategies in recipients with impaired kidney function remain undefined, with limited pharmacokinetic data to date.

Resolution of acyclovir-associated neurotoxicity with the aid of improved clearance estimates using a Bayesian approach: A case report and review of the literature.

WHAT IS KNOWN AND OBJECTIVE: Neurotoxicity is a side effect of acyclovir. We report the first case, to our knowledge, whereby Bayesian-informed clearance estimates supported a therapeutic intervention for acyclovir-associated neurotoxicity. CASE SUMMARY: A 62-year-old male with the diagnosis of disseminated zoster was being treated with intravenous (IV) acyclovir when he developed symptoms of acute neurotoxicity. Acyclovir had been dose-adjusted for renal dysfunction according to traditional creatinine clearance estimates; however, as the patient was also on vancomycin, Bayesian estimates of vancomycin clearances were performed, which revealed a 2-fold lower creatinine clearance. In response to the Bayesian estimates, acyclovir was discontinued, and improvements in mentation were noted within 24 hours. WHAT IS NEW AND CONCLUSION: Alternate approaches to estimate renal function beyond Cockcroft-Gault, such as a Bayesian approach used in our patient, should be considered when population estimates are likely to be inaccurate and potentially dangerous to the patient.

Prolonged norovirus infection after pancreas transplantation: a case report and review of chronic norovirus.

Norovirus is a major cause of self-limited gastroenteritis worldwide. Prevention and treatment are thwarted by rapid viral evolution, and thus supportive care remains the mainstay of therapy. Chronic infection in immunocompromised hosts is increasingly described. We report a case of norovirus infection lasting 2543 days in a pancreas transplant recipient. Serial fecal specimens were obtained, from which a map of genetic relatedness was derived. The clinical course was complicated by renal failure that progressed to end-stage renal disease. Minimization of immunosuppression was associated with resolution of the infection. Subsequently, the patient experienced a suspected allograft rejection that did not compromise pancreas function. The patient later underwent living-related renal transplantation without recurrence of enteritis.

Impact of repeat testing of living kidney donors within 14 days of the transplant procedure: a multicenter retrospective survey.

BACKGROUND: A transmission of human immunodeficiency virus (HIV) from a live kidney donor prompted recommendations by the New York State Department of Health and the US Centers for Disease Control and Prevention that all live donors undergo additional screening for HIV, hepatitis B virus (HBV), and hepatitis C virus (HCV) within 7-14 days of the donation procedure. There are concerns that re-screening will result in delays and cancelled transplants. METHODS: We surveyed live-donor transplant centers in New York State to assess their screening protocols and outcomes. Nine live-donor programs (kidney and liver centers) responded. RESULTS: All but 1 program has a formal repeat screening policy. Overall, no cancellations occurred, but 2 centers experienced transplantation delays, generally as the result of technician and laboratory procedural mistakes necessitating repeat phlebotomy. Testing is typically coordinated with pre-surgical visits, additional laboratory tests, and physical examinations. In the initial evaluation, serology was most frequently used (all 9 centers), with few centers utilizing nucleic acid testing (NAT) (HIV NAT, 1; HBV NAT, 2; HCV NAT, 2). Repeat testing modalities varied: HIV antibody (5, 55%), HIV NAT (8, 88%), hepatitis B surface antigen (5, 55%), hepatitis B surface antibody (2, 22%), hepatitis B core antibody (3, 33%), HBV NAT (3, 33%), HCV antibody (3, 33%), and HCV NAT (5, 55%). CONCLUSION: Most respondents have policies to re-test living donors within 14 days of the transplant procedures. Rarely, centers encountered repeat testing-associated delays, but no cancellations occurred.

Considerations for screening live kidney donors for endemic infections: a viewpoint on the UNOS policy.

In February 2013, the Organ Procurement and Transplantation Network mandated that transplant centers perform screening of living kidney donors prior to transplantation for Strongyloides, Trypanosoma cruzi and West Nile virus (WNV) infection if the donor is from an endemic area. However, specific guidelines for screening were not provided, such as the optimal testing modalities, timing of screening prior to donation and the appropriate selection of donors. In this regard, the American Society of Transplantation Infectious Diseases Community of Practice, together with disease-specific experts, has developed this viewpoint document to provide guidance for the testing of live donors for Strongyloides, T. cruzi and WNV infection, specifically identifying at-risk populations and testing algorithms, including advantages, limitations and interpretation of results.

Hermansky Pudlak syndrome: an unusual form of procto-colitis

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder consisting of oculocutaneous albinism, platelet dysfunction and systemic complications associated with lipofuscin deposition in the reticuloendothelial system. HPS has been associated with a granulomatous enterocolitis with pathologic features suggestive of Crohn's disease. It remains uncertain if HPS represents a truly distinct form of granulomatous enterocolitis. We report a series of two patients with HPS treated in Puerto Rico, and the results from medical and surgical intervention for gastrointestinal disease. Our experience with HPS patients has shown the difficult management of perineal disease similar in the management of Crohn's. However, complications from the bleeding diathesis necessitate caution during surgery and potential anesthesia complications. Furthermore, avoidance of a perineal wound is preferred, and when possible, ileostomies have fewer complications than colostomies as they do not involve the small bowel.

Puerto Rico experience with plugs in the treatment of anal fistulas

BACKGROUND: Anorectal fistula is a common problem that affects quality of life. Main objective of therapy has been to eradicate the fistula tract while preserving fecal continence. Latest good results for anal fistula treatment have been an anal fistula plug. This study was undertaken to determine if these results could be reproduced in Puerto Rico. METHOD: From January 2003 to January 2008, two experienced colorectal surgeons performed this new operation in 23 consecutive patients. A multivariable analysis was undertaken including age, sex, location of the fistula, previous surgeries, Seton placement before the insertion of the plug, continence pre and post operation, as well as close follow up. No patient with inflammatory bowel disease was included. RESULTS: We had a good result or healing of the fistula in 14 of 23 patients for a success rate of 60%. We had a subgroup of patients who did slightly better and had a healing rate of 66% compared to the 60% of the whole group. It appears to be a trend in favor of the Seton group but is not statically significant. We had 9 failures of 23 patients or 39%. Suppuration was noticed in three patients and all three had failures of the plug with recurrences. CONCLUSIONS: This new operation is another alternative to add to our armamentarium but we need to search for an operation that decreases the incidence of recurrences we had in our study while maintaining function of the sphincters.