title: Experimental and statistical methods to evaluate antibacterial activity of a quaternary pyridinium salt on planktonic, biofilm-forming, and biofilm states.
abstract: Robust evaluation and comparison of antimicrobial technologies are critical to improving biofilm prevention and treatment. Herein, a multi-pronged experimental framework and statistical models were applied to determine the effects of quaternary pyridinium salt, 4-acetyl-1-hexadecylpyridin-1-ium iodide (QPS-1), on Streptococcus mutans in the planktonic, biofilm-forming and biofilm cell states. Minimum inhibitory and bactericidal concentrations (MIC and MBC, respectively) were determined via common methods with novel application of statistical approaches combining random effects models and interval censored data to estimate uncertainties. The MICs and MBCs for planktonic and biofilm-forming states ranged from 3.12 to 12.5 μg ml-1, with biofilm values only ≈ 8 times higher. Potent anti-biofilm activity and reactive structural features make QPS-1 a promising antibacterial additive for dental and potentially other biomedical devices. Together, the experimental framework and statistical models provide estimates and uncertainties for effective antimicrobial concentrations in multiple cell states, enabling statistical comparisons and improved characterization of antibacterial agents.
authors.affiliation: a Biosystems and Biomaterials Division , National Institute of Standards and Technology , Gaithersburg , MD , USA.|d Center for Drug Evaluation and Research , Food and Drug Administration , Silver Spring , MD , USA.
authors.forename: Daneli
authors.initials: D
authors.lastname: López Pérez
authors.affiliation: a Biosystems and Biomaterials Division , National Institute of Standards and Technology , Gaithersburg , MD , USA.
authors.forename: Paula J
authors.initials: PJ
authors.lastname: Baker
authors.affiliation: b Statistical Engineering Division , National Institute of Standards and Technology , Gaithersburg , MD , USA.
authors.forename: Adam L
authors.initials: AL
authors.lastname: Pintar
authors.affiliation: c Dr Anthony Volpe Research Center , American Dental Association Foundation , Gaithersburg , MD , USA.
authors.forename: Jirun
authors.initials: J
authors.lastname: Sun
authors.affiliation: a Biosystems and Biomaterials Division , National Institute of Standards and Technology , Gaithersburg , MD , USA.
authors.forename: Nancy J
authors.initials: NJ
authors.lastname: Lin
authors.affiliation: a Biosystems and Biomaterials Division , National Institute of Standards and Technology , Gaithersburg , MD , USA.
authors.forename: Sheng
authors.initials: S
authors.lastname: Lin-Gibson
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D018441:Biofilms / Q000187:drug effects* / Q000254:growth & development; D003627:Data Interpretation, Statistical; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008826:Microbial Sensitivity Tests; D015233:Models, Statistical; D010933:Plankton / Q000187:drug effects / Q000502:physiology*; D011726:Pyridinium Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013295:Streptococcus mutans / Q000187:drug effects / Q000502:physiology*
chemical_list: C000622003:4-acetyl-1-hexadecylpyridin-1-ium; D000900:Anti-Bacterial Agents; D011726:Pyridinium Compounds
keywords: Antimicrobial; biofilm; interval censored data; minimum bactericidal concentration; minimum inhibitory concentration; quaternary pyridinium salt