The importance of active efflux systems in the quinolone resistance of clinical isolates of Salmonella spp.

The aim of this study was to determine the importance of the active elimination of antibiotics by active efflux systems, in the decrease in fluoroquinolone sensitivity of clinical isolates of Salmonella spp. as well as the intrinsic antibiotic activity of certain active efflux system inhibitors. The effect of the active efflux system on the decrease in sensitivity to nalidixic acid, ciprofloxacin, ofloxacin and sparfloxacin was studied by investigating the variation in the in vitro activity of these compounds when assayed in association with reserpine and MC 207.110. The active efflux systems inhibited by reserpine displayed low activity in the elimination of these compounds, whereas those inhibited by MC 207.110 showed high activity in the elimination of nalidixic acid and sparfloxacin, but were less effective in the elimination of ofloxacin and ciprofloxacin. These two compounds did not exhibit intrinsic inhibitory activity against Salmonella spp. at the concentrations assayed. These mechanisms of resistance to antibiotics are complex and vary depending on the chemical composition of the antibiotics used, and perhaps the inhibitors of these systems, although they do not exhibit any intrinsic antibiotic activity, may be used as adjuvants to increase the activity of certain antibiotics. These mechanisms complement the mutations in the gyrA gene and this supports the thesis that it is necessary to lower the breakpoint established by the NCCLS for ciprofloxacin, since the strains studied have resistance mechanisms that reduce the activity of this drug and may favour the emergence of resistant mutants during treatment. (C) 2004 Elsevier B.V. and the International Society of Chemotherapy. All rights reserved.