Effect of N-acetylcysteine on the activity of antibiotics against relevant respiratory pathogens

INTRODUCTION: Discordant data have been reported on the effect of N-acetylcysteine (NAC) on the activity of important antibiotic classes. In particular a recent study suggested that the antagonism previously observed with fluoroquinolones macrolides and aminoglycosides was likely due to an experimental confounding factor (ie low pH of NAC solutions in distilled water) and not to NAC itself AIMS: To investigate the NAC effect at neutral pH on the activity of several antibiotics against a large collection of relevant respiratory pathogens METHODS: Antibiotic susceptibility of 39 reference strains or clinical isolates from respiratory infections of several bacterial species ( Staphylococcus aureus , Streptococcus pneumoniae , Streptococcus pyogenes , Corynebacterium striatum , Pseudomonas aeruginosa , Acinetobacter baumannii , Stenotrophomonas maltophilia , Haemophilus influenzae , Moraxella catarrhalis , Klebsiella spp, Escherichia coli , Enterobacter cloacae ) were tested in NAC absence and presence (1.6mg/ml and 8mg/ml), according to Clinical and Laboratory Standards Institute guidelines. Antibiotics tested included aminoglycosides, beta-lactams, colistin, fluoroquinolones, linezolid, macrolides, minocycline, trimethoprim-sulphamethoxazole, vancomycin. A modulatory effect was considered a ≥4-fold modification of the minimum inhibitory concentration (MIC) RESULTS: NAC didn9t interfere with the activity of the antibiotics tested, with the exception of carbapenems (imipenem, meropenem and ertapenem) for which a dose-dependent antagonistic effect was observed with all tested species CONCLUSIONS: NAC is not antagonistic with most antibiotics used for the treatment of respiratory infections, except carbapenems.