Investigation of polymyxin-induced immunotoxicity in vitro and in vivo

Antibiotic resistance is a critical global health threat. Polymyxin antibiotics were revived as the last resort against Gram-negative multidrug-resistant bacteria. The use of aerosolised polymyxins is encouraging, as it allows polymyxin delivery directly to the infection site with limited systemic toxicity and reduced propensity for resistance development. However, there is a significant knowledge gap in the effect of polymyxins on the lung innate immune system, which is critical for optimising their clinical use. Thus, the overall aim of this study was to investigate the potential polymyxin toxicity in human macrophages and neutrophils and to provide mechanistic findings on their immunotoxicity.