Effectiveness of Posaconazole (POS) in an Inhalational Neutropenic Murine Model of Invasive Pulmonary Aspergillosis against Voriconazole Resistant (VCZ-R) Aspergillus flavus

This chapter discuss about the virulence of a laboratory-selected VCZ-R isolate of A. flavus isolate (cyp51A mutant-K197N) and the efficacy of POS against this isolate were evaluated using a neutropenic murine model of invasive pulmonary aspergillosis by assessing the pulmonary fungal burden and mortality in various groups of mice. . Invasive aspergillosis (IA) continues to be associated with a high mortality despite timely and appropriate therapy in immunocompromised patients. Clinical and environmental isolates of Aspergillus species showing reduced susceptibility to VCZ have been reported. Mortality, despite therapy, remains high, and drug resistance might partly account for treatment failures. In this study, we noted that azole-resistance in A. flavus is dependent on the location of specific mutations in cyp51A. Isolates of VCZ-R A. flavus that demonstrated the K197N mutation, were resistant to VCZ, but retained susceptibility to POS. Hence POS continues to be a valuable option for certain isolates of VCZ-R A. flavus.

In this experimental model of VCZ-R A. flavus mouse infection, posaconazole demonstrated superior effectiveness to that of VCZ in lowering fungal burden (p 0.05) and death (p 0.05). This study showed that POS can be a good alternative for some VCZ-R A. flavus strains.