Differential susceptibility of adenovirus clinical isolates to cidofovir and ribavirin is not related to species alone
Abstract
Background: We have previously reported that human adenovirus (HAdV) reference strains clearly show species-dependent resistance to ribavirin, whereas different species of HAdV are equally sensitive to cidofovir. All the serotypes tested were susceptible to cidofovir, whereas only serotypes from species C were sensitive to ribavirin.
Here, we aimed to extend these investigations to clinical isolates. Methods: In vitro, we tested 126 isolates obtained from 65 patients included in a European survey of HAdV infection.
Results: Among the 126 isolates tested, all presented cidofovir 50% inhibitory concentration (IC(50)) in the same range as the HAdV 5 reference strain. Regarding ribavirin, all isolates from species C (79 tested) showed an IC(50) comparable with previously reported results for reference strains; however, 24/32, 2/6 and 3/3 tested isolates from species A, B and D, respectively, were shown to have a ribavirin IC(50) comparable with the HAdV 5 reference strain (species Q, contrary to previous observations for reference strains of the same species.
Among patients who were treated with cidofovir for disseminated HAdV infection, >= 4 sequential isolates could be obtained from 9 patients; no variation in cidofovir susceptibility could be detected. Conclusions: Cidofovir is active in vitro in all HAdV clinical isolates.
Ribavirin was revealed to be active on most HAdV isolates from species A, B and D, and in all isolates from species C. Finally, no resistance to cidofovir became apparent in sequential isolates obtained from treated patients.