Efficacy of the interferon inducer tilorone and its combination with antibacterial drugs in a murine model of secondary bacterial pneumonia caused by S. aureus after influenza infection.

INTRODUCTION: Secondary bacterial pneumonias are complications responsible for most fatalities following influenza infection, and antiviral drugs are used to prevent their development. The aim of the study is to evaluate the efficacy of tilorone and its combination with antibacterial agents in a murine model of secondary bacterial pneumonia caused by Staphylococcus aureus after influenza infection.

MATERIALS AND METHODS: BALB/c mice were infected with influenza virus A/California/04/2009 (pdm H1N1 2009) virus, followed by S. aureus infection four days later. Treatments included the interferon inducer tilorone, comparator oseltamivir, antibacterial agents cefuroxime and amoxicillin, or combinations of antivirals with antibiotics. Efficacy was assessed by increased survival, reduced weight loss, and inhibition of pathogen proliferation in the lungs.

RESULTS: The efficacy of tilorone, as indicated by increased survival, reduced weight loss, and decreased pathogen load in the lungs, in a mouse model of secondary bacterial pneumonia following influenza infection, increased with reducing viral dose, and intraperitoneal administration of the drug was more effective than oral administration. The combination of tilorone with the antibiotic cefuroxime, to which S. aureus was sensitive, was more effective than either agent alone and completely protected animals from death and from viral and bacterial proliferation in the lungs. In contrast, the combination with amoxicillin, to which S. aureus was resistant, had no effect on disease outcome.

CONCLUSION: The efficacy of tilorone in this model depended on viral dose and drug administration route. Combining tilorone with cefuroxime was more effective than monotherapy.