Intravenous Cidofovir therapy for disseminated adenovirus in a pediatric liver transplant recipient

Background. No definitive antiviral therapy exists for adenovirus (ADV) in immunosuppressed hosts. Cidofovir (CDV), a broad spectrum anti-DNA viral agent, has previously been shown to be of therapeutic benefit in life-threatening adenoviral disease in bone marrow stem-cell recipients. Methods. A 71/2-month-old girl with a history of biliary atresia developed fevers, hematochezia, tachypnea, and laboratory evidence of hepatitis and pancreatitis 12 days after liver transplantation. A stool culture, oropharyngeal culture, blood viral culture, and blood polymerase chain reaction (PCR) confirmed ADV. Cidofovir 1 mg/kg intravenously three times per week was initiated. The patient received intravenous hydration and probenecid with the infusions to reduce the nephrotoxicity of CDV. Immunosuppression was reduced to achieve tacrolimus trough levels of approximately 8 ng/mL and prednisone at 0.1 mg/kg per day. Complete blood cell count, urinalysis, and viral studies were obtained weekly. Results. Detection of ADV DNA by PCR made a transition from positive to negative during CDV therapy. Blood viral cultures became negative after two CDV doses. Alanine aminotransferase normalized by 5 weeks of therapy. CDV was discontinued after 7 weeks secondary to transient acidosis and proteinuria. The patient never developed azotemia, neutropenia, or ocular abnormalities. Conclusions. CDV was associated with improved clinical status, viral clearance, and minimal transient side effects in a pediatric liver transplant recipient with disseminated adenoviral disease. The current report documents clearance of disseminated ADV infection in a liver transplant recipient receiving CDV infusions.

[1]  V. Emery,et al.  Cytomegalovirus (CMV) Resistance to Antivirals , 2001, American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons.

[2]  N. Kapoor,et al.  Adenoviral infections and a prospective trial of cidofovir in pediatric hematopoietic stem cell transplantation. , 2001, Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation.

[3]  A. L. Le Faou,et al.  Treatment of adenovirus infections in patients undergoing allogeneic hematopoietic stem cell transplantation. , 2001, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[4]  E. Gluckman,et al.  Successful treatment of adenovirus disease with intravenous cidofovir in an unrelated stem-cell transplant recipient. , 1999, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[5]  P. Piedra,et al.  Disseminated adenovirus disease in immunocompromised and immunocompetent children. , 1998, Clinical infectious diseases : an official publication of the Infectious Diseases Society of America.

[6]  C. Kemper,et al.  Randomized, controlled study of the safety and efficacy of intravenous cidofovir for the treatment of relapsing cytomegalovirus retinitis in patients with AIDS. , 1998, Journal of acquired immune deficiency syndromes and human retrovirology : official publication of the International Retrovirology Association.

[7]  J. Cherrington,et al.  Clinical uses of cidofovir , 1997, Reviews in medical virology.

[8]  D. Carrigan Adenovirus infections in immunocompromised patients. , 1997, The American journal of medicine.

[9]  P. McDonnell,et al.  Evaluation of Cidofovir (HPMPC, GS-504) against adenovirus type 5 infection in vitro and in a New Zealand rabbit ocular model. , 1996, Antiviral research.

[10]  T. Starzl,et al.  Adenoviral infections in pediatric liver transplant recipients. , 1987, JAMA.

[11]  R. Feigin,et al.  Textbook of Pediatric Infectious Diseases , 1986 .

[12]  G. Holland,et al.  Vitrectomy and silicone oil tamponade for cidofovir-associated hypotony with ciliary body detachment. , 1999, Retina.

[13]  T. Starzl,et al.  Adenovirus infection in pediatric liver transplant recipients. , 1992, The Journal of infectious diseases.