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Molecules 2017, 22(1), 114; doi:10.3390/molecules22010114

The Impact of Efflux Pump Inhibitors on the Activity of Selected Non-Antibiotic Medicinal Products against Gram-Negative Bacteria

1
Department of Pharmaceutical Microbiology, Medical University of Warsaw, Oczki 3 Str., 02-007 Warsaw, Poland
2
Department of Antibiotics and Microbiology, National Medicines Institute, Chełmska 30/34 Str., 00-725 Warsaw, Poland
*
Author to whom correspondence should be addressed.
Academic Editor: Peter J. Rutledge
Received: 12 December 2016 / Revised: 12 December 2016 / Accepted: 4 January 2017 / Published: 11 January 2017
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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. View Full-Text
Keywords: efflux; efflux pump inhibitor; non-antibiotics; medicinal products; Gram-negative bacteria; MDR; PAβN; drugs; quinolones efflux; efflux pump inhibitor; non-antibiotics; medicinal products; Gram-negative bacteria; MDR; PAβN; drugs; quinolones
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Laudy, A.E.; Kulińska, E.; Tyski, S. The Impact of Efflux Pump Inhibitors on the Activity of Selected Non-Antibiotic Medicinal Products against Gram-Negative Bacteria. Molecules 2017, 22, 114.

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