title: Pomegranate pericarp extract enhances the antibacterial activity of ciprofloxacin against extended-spectrum β-lactamase (ESBL) and metallo-β-lactamase (MBL) producing Gram-negative bacilli.
abstract: A methanolic extract of Punica granatum (pomegranate) fruit pericarp (PGME) was tested in combination with ciprofloxacin against extended-spectrum β-lactamase (ESBL) producing Escherichia coli, Klebsiella pneumoniae, and metallo-β-lactamase (MBL) producing Pseudomonas aeruginosa, which were screened for their resistance profile against fluoroquinolone antibiotics. The minimum inhibitory concentrations (MIC) of ciprofloxacin and PGME, alone, were determined, and synergy of ciprofloxacin-PGME combinations evaluated by checkerboard assay and fractional inhibitory concentration (FIC). Nineteen out of forty-nine strains exhibited synergy with ciprofloxacin (FIC of 0.125-0.5 for ciprofloxacin) further verified by agar-well assay. This could be due to the bacterial efflux pump inhibitor (EPI) activity of the polyphenolic constituents of PGME. However, the isolates exhibiting a high level of ciprofloxacin resistance did not respond to ciprofloxacin-PGME combinations, which could be due to target site modification not influenced further by EPI activity of PGME. Again, some strains were sensitive or weakly resistant to ciprofloxacin, which exhibited 'indifference' to the combination, probably due to a lack of over-expressed efflux mechanism. Thus, a synergy of a ciprofloxacin-PGME combination was demonstrated for the first time against ESBL- and MBL-producing Gram-negative bacilli, and the efficacy of an existing drug improved with the help of an inexpensive alternative therapy.
authors.affiliation: Department of Pharmaceutical Technology, Jadavpur University, Kolkata 700032, India.
authors.forename: Diganta
authors.initials: D
authors.lastname: Dey
authors.forename: Sukalyani
authors.initials: S
authors.lastname: Debnath
authors.forename: Sudipta
authors.initials: S
authors.lastname: Hazra
authors.forename: Subhalakshmi
authors.initials: S
authors.lastname: Ghosh
authors.forename: Ratnamala
authors.initials: R
authors.lastname: Ray
authors.forename: Banasri
authors.initials: B
authors.lastname: Hazra
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000494:pharmacology*; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D004357:Drug Synergism; D004926:Escherichia coli / Q000187:drug effects; D005419:Flavonoids / Q000032:analysis; D024841:Fluoroquinolones / Q000494:pharmacology; D007711:Klebsiella pneumoniae / Q000187:drug effects; D029561:Lythraceae / Q000737:chemistry*; D008826:Microbial Sensitivity Tests; D010936:Plant Extracts / Q000032:analysis / Q000494:pharmacology*; D059808:Polyphenols / Q000032:analysis; D011550:Pseudomonas aeruginosa / Q000187:drug effects; D001618:beta-Lactamases / Q000378:metabolism
chemical_list: D000900:Anti-Bacterial Agents; D005419:Flavonoids; D024841:Fluoroquinolones; D010936:Plant Extracts; D059808:Polyphenols; D002939:Ciprofloxacin; D001618:beta-Lactamases