Successfully treating biofilms of extensively drug resistant Klebsiella pneumoniae isolates from hospital patients with N-Acetyl Cysteine

Abstract

Klebsiella pneumoniae is one of the leading causes of community and nosocomial infections. Reduced treatment options against extensively drug resistant (XDR) - K. pneumoniae, is a serious concern in hospital settings, and hence, WHO has categorized it as a critical priority pathogen. Biofilm forming ability is a common virulence mechanism amongst K. pneumoniae that is associated with antibiotic tolerance up to 1000X MIC and hence, are difficult to treat. N-acetyl cysteine (NAC) is an FDA approved mucolytic drug used to treat acetaminophen-associated toxicity and obstructive pulmonary diseases. In this study, we assessed antibacterial and antibiofilm activity of NAC against clinical isolates of XDR K. pneumoniae, obtained from Madras Medical Mission Hospital, India. To assess the biofilm eradication ability of NAC, we grew biofilms in 96 well plates and treated the mature biofilms with different concentrations of NAC. We observed that the biofilms of only 3 isolates of XDR K. pneumoniae could be eradicated at a concentration as low as 20mg/ml. Although increasing the concentration of NAC to 80mg/mL could significantly reduce the biofilms of all the isolates up to 4-5 Log, NAC at a concentration of 100 mg/mL successfully eradicated the mature biofilms of all the isolates of XDR K. pneumoniae. This in vitro study demonstrates the potential of NAC as an efficient agent against the biofilms of clinical isolates of XDR-K. pneumoniae and thus provides a promising alternative to antibiotics.