Preclinical in vitro and in vivo evaluation of omadacycline against multidrug-resistant Acinetobacter baumannii.

Acinetobacter baumannii is an increasing cause of chronic wound infections, especially in military operational settings, and is resistant to many currently available antimicrobial therapies, making treatment options limited. We evaluated the in vitro activity of omadacycline against A. baumannii clinical isolates as well as the in vivo efficacy of omadacycline in mice against the multi-drug resistant (MDR) A. baumannii strain 5075 using both a neutropenic thigh infection model and a dorsal wound model of chronic infection relative to the standard of care drugs tigecycline and doxycycline, respectively. Omadacycline demonstrated efficacy against these two established preclinical models of MDR A. baumannii infection in mice. In the dorsal wound infection model, the most efficacious dose tested (10 mg/kg twice daily for 6 days) resulted in 100% survival, complete clearance of systemic infection, accelerated wound closure, absence of toxicity, significantly reduced inflammatory cytokine responses, and reduced biofilm formation. These results underscore the potential of omadacycline as a promising therapeutic option for combating MDR A. baumannii infections in chronic wound settings and that additional research is warranted.