Effect of N-Acetylcysteine in Combination with Antibiotics on the Biofilms of Three Cystic Fibrosis Pathogens of Emerging Importance

Effect of N-Acetylcysteine in Combination with Antibiotics on the Biofilms of Three Cystic Fibrosis Pathogens of Emerging Importance.

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Item Type: Article
Status: Published
Official URL: https://doi.org/10.3390/antibiotics10101176
Journal or Publication Title: Antibiotics
Volume: 10
Number: 10
Page Range: p. 1176
Date: 27 September 2021
Divisions: Tuberculosis
Depositing User: General Admin
Identification Number: 10.3390/antibiotics10101176
ISSN: 2079-6382
Date Deposited: 07 Dec 2021 21:00

Cystic fibrosis (CF) is a genetic disorder causing dysfunctional ion transport resulting in accumulation of viscous mucus that fosters chronic bacterial biofilm-associated infection in the airways. Achromobacter xylosoxidans and Stenotrophomonas maltophilia are increasingly prevalent CF pathogens and while Burkholderia cencocepacia is slowly decreasing; all are complicated by multidrug resistance that is enhanced by biofilm formation. This study investigates potential synergy between the antibiotics ciprofloxacin (0.5-128 µg/mL), colistin (0.5-128 µg/mL) and tobramycin (0.5-128 µg/mL) when combined with the neutral pH form of N-Acetylcysteine (NACneutral) (0.5-16.3 mg/mL) against 11 cystic fibrosis strains of Burkholderia, Stenotrophomonas and Achromobacter sp. in planktonic and biofilm cultures. We screened for potential synergism using checkerboard assays from which fraction inhibitory concentration indices (FICI) were calculated. Synergistic (FICI ≤ 0.5) and additive (0.5 > FICI ≥ 1) combinations were tested on irreversibly attached bacteria and 48 h mature biofilms via time-course and colony forming units (CFU/mL) assays. This study suggests that planktonic FICI analysis does not necessarily translate to reduction in bacterial loads in a biofilm model. Future directions include refining synergy testing and determining further mechanisms of action of NAC to understand how it may interact with antibiotics to better predict synergy.

Keywords: Achromobacter; Burkholderia; FICI; NAC; Stenotrophomonas; biofilm; cystic fibrosis; synergy.

Aiyer, Aditi
Visser, Simone K.
Bye, Peter
Britton, Warwick J.
Whiteley, Gregory S.
Glasbey, Trevor
Kriel, Frederik H.
Farrell, Jessica
Das, Theerthankar
Manos, Jim
Last Modified: 07 Dec 2021 21:00
URI: https://eprints.centenary.org.au/id/eprint/1159

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