Reversing Antimicrobial Resistance in Multidrug-Resistant Klebsiella pneumoniae of Clinical Origin Using 1-(1-Naphthylmethyl)-Piperazine

Abstract

Eleven clinical Klebsiella pneumoniae fluoroquinolone-resistant isolates were tested to access the potential of adjuvant therapies to reduce antimicrobial resistance using fixed concentrations of the chemosensitizers chlorpromazine (CPZ), thioridazine (TZ), phenylalanine-arginine-β-naphthylamide (PAβN), and 1-(1-naphthylmethyl)-piperazine-(NMP) with varying concentrations of antimicrobial agents nalidixic acid (NAL), ciprofloxacin (CIP), moxifloxacin (MXF), tetracycline (TET), and chloramphenicol (CHL). Ethidium bromide dye was used together with the chemosensitizers to investigate permeabilization effects. NMP was assessed for its capacity to reduce the mass of biofilm alone and in combination with CIP and MXF. Of the selected chemosensitizers, NMP exhibited the greatest capacity to reverse resistance and inhibit efflux, based on the concentrations tested. Susceptibility to antimicrobial agents including (fluoro)quinolones, TET, and CHL were found to be increased in the presence of NMP, in a concentration-dependent manner. PAβN also demonstrated similar effects when combined with the chemosensitizers tested. In the case of half of the isolates studied, NMP alone reduced preformed biofilm biomass. Combinations of latter along with CIP or MXF were also found to reduce the mass of preformed biofilm, in the case of only some of the bacterial isolates. The capacity of NMP to reduce antimicrobial resistance could be of relevance as a strategy to limit bacterial colonization on abiotic surfaces.

Keywords: 1-(1-naphthylmethyl)-piperazine; Klebsiella pneumoniae; antimicrobial reversal; chemosensitizers.