title: The Impact of Efflux Pump Inhibitors on the Activity of Selected Non-Antibiotic Medicinal Products against Gram-Negative Bacteria.
abstract: The potential role of non-antibiotic medicinal products in the treatment of multidrug-resistant Gram-negative bacteria has recently been investigated. It is highly likely that the presence of efflux pumps may be one of the reasons for the weak activity of non-antibiotics, as in the case of some non-steroidal anti-inflammatory drugs (NSAIDs), against Gram-negative rods. The activity of eight drugs of potential non-antibiotic activity, active substance standards, and relevant medicinal products were analysed with and without of efflux pump inhibitors against 180 strains of five Gram-negative rod species by minimum inhibitory concentration (MIC) value determination in the presence of 1 mM MgSO₄. Furthermore, the influence of non-antibiotics on the susceptibility of clinical strains to quinolones with or without PAβN (Phe-Arg-β-naphthylamide) was investigated. The impacts of PAβN on the susceptibility of bacteria to non-antibiotics suggests that amitriptyline, alendronate, nicergoline, and ticlopidine are substrates of efflux pumps in Gram-negative rods. Amitriptyline/Amitriptylinum showed the highest direct antibacterial activity, with MICs ranging 100-800 mg/L against all studied species. Significant decreases in the MIC values of other active substances (acyclovir, atorvastatin, and famotidine) tested with pump inhibitors were not observed. The investigated non-antibiotic medicinal products did not alter the MICs of quinolones in the absence and in the presence of PAβN to the studied clinical strains of five groups of species.
authors.affiliation: Department of Pharmaceutical Microbiology, Medical University of Warsaw, Oczki 3 Str., 02-007 Warsaw, Poland. alaudy@wp.pl.
authors.forename: Agnieszka E
authors.initials: AE
authors.lastname: Laudy
authors.affiliation: Department of Pharmaceutical Microbiology, Medical University of Warsaw, Oczki 3 Str., 02-007 Warsaw, Poland. ewa_kulinska@vp.pl.
authors.forename: Ewa
authors.initials: E
authors.lastname: Kulińska
authors.affiliation: Department of Pharmaceutical Microbiology, Medical University of Warsaw, Oczki 3 Str., 02-007 Warsaw, Poland. s.tyski@nil.gov.pl.|Department of Antibiotics and Microbiology, National Medicines Institute, Chełmska 30/34 Str., 00-725 Warsaw, Poland. s.tyski@nil.gov.pl.
authors.forename: Stefan
authors.initials: S
authors.lastname: Tyski
mesh_terms: D000212:Acyclovir / Q000494:pharmacology; D019386:Alendronate / Q000494:pharmacology; D000639:Amitriptyline / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000069059:Atorvastatin / Q000494:pharmacology; D004151:Dipeptides / Q000494:pharmacology*; D004338:Drug Combinations; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects / Q000235:genetics; D004926:Escherichia coli / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D015738:Famotidine / Q000494:pharmacology; D019450:Genes, MDR / Q000187:drug effects*; D007711:Klebsiella pneumoniae / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D008278:Magnesium Sulfate / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D009530:Nicergoline / Q000494:pharmacology; D011550:Pseudomonas aeruginosa / Q000187:drug effects* / Q000254:growth & development / Q000378:metabolism; D015363:Quinolones / Q000494:pharmacology; D012475:Salmonella / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D013988:Ticlopidine / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D004151:Dipeptides; D004338:Drug Combinations; D015363:Quinolones; C474925:phenylalanylarginine-naphthylamide; D000639:Amitriptyline; D015738:Famotidine; D008278:Magnesium Sulfate; D000069059:Atorvastatin; D009530:Nicergoline; D013988:Ticlopidine; D019386:Alendronate; D000212:Acyclovir
keywords: Gram-negative bacteria; MDR; PAβN; drugs; efflux; efflux pump inhibitor; medicinal products; non-antibiotics; quinolones