Safety of Cidofovir Treatment for Suspected or Confirmed Adenovirus Infection in Immunocompetent Pediatric Population

Abstract

Background: Cidofovir (CDV), a nucleoside phosphonate analogue, exhibits activity against severe cytomegalovirus and adenoviral (ADV) infection. Nevertheless, reports of elevated nephrotoxicity rates limited its use to highly vulnerable cases, mainly immunocompromised children with fulminant infection. Limited data exists regarding CDV safety in immunocompetent children. Objective: To evaluate CDV-related toxicity, mainly nephrotoxicity, in immunocompetent children with severe ADV/cytomegalovirus infection. Methods: We conducted a retrospective review of medical records for all immunocompetent children under 18 years of age treated with intravenous CDV from January 2005 to December 2019. Results: Among the 23 patients identified, 21 were diagnosed with severe ADV infection. Median age was 15 months. Twenty-one (91%) children were admitted to the pediatric intensive care unit. Eighteen patients (78%) received standard CDV protocol (5 mg/kg CDV weekly for 2 weeks), 4 (17%) according to nephroprotective low-dose protocol and 1 patient transitioned. The median duration of CDV treatment was 14 days (range: 1–21 days). All patients received hyperhydration and probenecid with each infusion. Acute kidney injury was recorded in 1 patient (with concurrent septic shock) during CDV treatment. Two children exhibited acute kidney injury before CDV initiation, but renal function normalized during CDV treatment. One patient developed transient neutropenia (600 cells/L), apparently as a result of sepsis. No other major adverse effects were noted. Mortality rate was 3/23 (13%), unrelated to CDV toxicity. Conclusions: Our findings suggest that CDV-related nephrotoxicity rate in immunocompetent children may be lower than previously reported, perhaps lower than in the severely immunocompromised population.