In Pursuit of a Better Biocide Composition: Synergistic and Additive Effects of QAC-Based Formulations Against Planktonic and Biofilm Cultures.

Managing bacterial infections and the spread of microbial resistance is one of the most critical and complex tasks of modern healthcare infrastructures. Antiseptics and disinfectants such as biocides play a significant role in controlling microbial resistance by reducing the microbial load on surfaces, skin, and environments, thereby limiting the opportunity for pathogens to proliferate and develop resistance. Herein, we tested the different interactions of quaternary ammonium compound (QAC)-based biocide compositions in pursuit of a better antimicrobial performance. An extensive microbiological analysis was conducted for 12 selected compositions of various combinations of mono-QACs, bis-QACs, and alcohols on 17 strains of bacteria of the ESKAPEE group and fungi, including 11 clinical highly resistant varieties, highlighting synergistic or additive dynamics. The evaluation showed noticeable improvements in activity, with up to 16-fold MBC and 32-fold MBEC reductions for alcohol-based compositions of lead QAC. Moreover, synergistic interactions were detected and confirmed via an optimized checkerboard assay for pyridinium QAC combinations against planktonic Gram-positive S. aureus with a fractional inhibitory concentration index (FICI) and fractional bactericidal concentration index (FBCI) of 0.39-0.5 and Gram-negative A. baumannii biofilms. The studied biocides demonstrated the long-term preservation of antimicrobial efficiency without resistance development during a 40-day period and do not induce QAC-associated cross-resistance for four commercially available antibiotics with similar mechanisms of action.