Establishment and validation of a ferret model for systemic antibiotic treatment during influenza A virus infection

The ferret has been widely used to study both the pathogenicity and the transmissibility of respiratory viral infections, but little is known about how host-associated microbial communities alter disease susceptibility owing to the lack of a validated model. Here, we compared the safety of injectable versus oral broad-spectrum antibiotics and their efficacy in reducing culturable bacteria from the upper respiratory tract of ferrets before an influenza A virus challenge. Both injectable and oral antibiotic treatment led to drastic reductions in cultivable bacteria from nasal wash specimens when assessed after 7 days of ongoing treatment. Even when extended to 14 days, there were few adverse events noted and no clinically significant bloodwork changes. During challenge with either a high-dose or low-dose A(H1N1)pdm09 influenza A virus inoculum, all animals became productively infected and had generally similar viral titers and clinical measurements, regardless of antibiotic pretreatment. Collectively, these results support that both antibiotic regimens evaluated in laboratory ferrets can be utilized to further characterize host-microbial interactions in the context of respiratory viral infections and other pathogens, including a needle-free approach that may be suitable for studies of high-consequence pathogens in containment laboratory facilities.