Acetylcysteine increases sensitivity of ceftazidime-avibactam–resistant enterobacterales with different enzymatic resistance to ceftazidime-avibactam in vitro and in vivo

Abstract

Abstract Background Ceftazidime-avibactam (CZA) improves treatment outcomes for infections caused by carbapenem-resistant organisms, but has led to serious bacterial resistance. Acetylcysteine (NAC) is an approved medication that protects the respiratory tract through antioxidant and anti-inflammatory effects. Results This study found that NAC combined with CZA effectively inhibits the growth of CZA-resistant clinical Enterobacterales strains. The CZA/NAC combination inhibits biofilm formation in vitro and decreases bacterial burden in a mouse thigh infection model. The combination is biocompatible and primarily increases cell membrane permeability to cause bacterial death. Conclusions These findings prove that the CZA/NAC combination has potential as a treatment for CZA-resistant Enterobacterales infections.

Keywords

• Enterobacterales
• Ceftazidime-avibactam
• Antimicrobial resistance
• Acetylcysteine