Rationale and evidence for the adjunctive use of N-acetylcysteine in multidrug-resistant infections

Bacterial multidrug resistance has been a serious issue for healthcare systems in recent decades, responsible for many infections and deaths. Due to the increasing incidence of antimicrobial resistance and scarce treatment options, research is focused on finding possible therapeutic adjuvants able to increase the effi- cacy of antibiotics. The aim of this article is a re-view of available evidence on the use of N-ace-tylcysteine (NAC).MEDLINE/PubMed was searched for appro-priate keywords. In vitro and in vivo preclinical studies, clinical studies, reviews, and meta -anal-yses were retrieved and selected based on rel-evance. A narrative review article was written, reporting published evidence and the expert opinion of the authors.Among possible adjunctive treatments, NAC has attracted the interest of researchers as a can-didate for re-purposing. It is a widely used drug with a good tolerability profile, mainly used as a mucolytic agent, with antioxidant, anti-inflam- matory properties and antibacterial activity. NAC acts on different mechanisms and stages of infec-tions, resulting in inhibition of biofilm formation, disruption of preformed biofilms, and reduction of bacterial viability. NAC may be administered as an aerosol in many types of infections, includ-ing cystic fibrosis, bronchiectasis and infective flare of chronic obstructive pulmonary disease (COPD), and by the intravenous route in severe systemic infections (including septic shock) such as those caused by carbapenemase (KPC)-pro-ducing Klebsiella pneumoniae (Kp) and Carbape-nem-Resistant Acinetobacter baumannii (CR-Ab).A rationale exists for using NAC as an adjunc-tive treatment in multidrug-resistant (MDR) in-fections, based on in vitro, in vivo and clinical evidence, and future research is needed to iden-tify candidate patients and optimal schedules for specific clinical conditions.