Treatment of Adenoviral Acute Respiratory Distress Syndrome Using Cidofovir With Extracorporeal Membrane Oxygenation

Abstract

Adenovirus infections are associated with respiratory (especially upper respiratory) infection and gastrointestinal disease and occur primarily in infants and children. Although rare in adults, severe lower respiratory adenovirus infections including pneumonia are reported in specific populations, such as military recruits and immunocompromised patients. Antiviral treatment is challenging due to limited clinical experience and lack of well-controlled randomized trials. Several previously reported cases of adenoviral pneumonia showed promising efficacy of cidofovir. However, few reports discussed the efficacy of cidofovir in acute respiratory distress syndrome (ARDS). We experienced 3 cases of adenoviral pneumonia associated with ARDS and treated with cidofovir and respiratory support, including extracorporeal membrane oxygenation (ECMO). All 3 patients showed a positive clinical response to cidofovir and survival at 28 days. Cidofovir with early ECMO therapy may be a therapeutic option in adenoviral ARDS. A literature review identified 15 cases of adenovirus pneumonia associated with ARDS.

Influenza and Viral Pneumonia

“…For instance, case reports and series have reported the use of cidofovir for the treatment of severe pneumonia caused by adenovirus in nonimmunocompromised patients. 96,97 Even though patients had clinical improvement in these series, those studies were uncontrolled and thus do not allow a firm conclusion as to the efficacy of cidofovir. Antiviral treatment for pneumonia caused by viruses of the Herpesviridae family in immunocompetent hosts has been reported in severe cases.…”

A case series of children with adenovirus pneumonia: three-year experiences in a tertiary PICU

“…There are limited antiviral drugs available for adenovirus. Cidofovir is an antiviral drug which use has been associated with signi cant reductions of adenovirus load and, in some series improved survival in reports [10,28] . Until recently, Cidofovir is not available in China till 2019, and has been neither widely used in children, nor has it been used in our cases.…”

“…Whether high levels of IL-6 and IL-10 in patients with adenovirus infection contribute the worse outcome warrants further investigation. ECMO support for severe adenoviral infection has been reported in several studies [10,33,34] . Retrospective data from the extracorporeal life support organization (ELSO) registry showed that pediatric patients with AV infection supported with ECMO, had a survival to hospital discharge of 38% which was even lower in neonates [8] .B More recently, Ramanathan et al observed over the last 25 years ELSO registry across all age groups who needed ECMO for severe adenoviral pneumonia in neonatal, pediatric, and adult patients, the hospital mortality was 58% with no signi cant improvement from 1992 to 2016 [12] .…”

“…However, the outcome is still far from satisfactory [9][10][11][12] . Furthermore, there is little information available for identifying risk factors for morbidity and mortality with severe adenovirus pneumonia in PICU [13] .…”

Other Respiratory Viruses as a Cause of Community-Acquired Pneumonia

“…150 Small studies suggest that cidofovir, the nucleoside analogue of cytidine monophosphate, may be considered in the treatment of both immunocompetent and immunocompromised patients with severe disease. 151,152 As an example, in a recent report of 89 patients in Korean military hospitals with severe HAdV pneumonia who were treated with cidofivir, drug administration within 7 days was associated with a reduced risk of respiratory failure. 153 However, the use of cidofivir is limited by significant side effects including nephrotoxicity and neutropenia.…”