Synergistic interactions of quercetin with antibiotics against biofilm associated clinical isolates of Pseudomonas aeruginosa in vitro

Abstract

Development of extreme resistance to multiple antibiotics is the major concern in infections due to biofilm forming Pseudomonas aeruginosa. The existing antibiotics have become ineffective against biofilm associated infections and hence, in this study, the combinatorial efficacy of antibiotics with a quorum sensing inhibitor (quercetin) was tested against biofilm forming P. aeruginosa isolates. The effect of drug combinations was studied by the checkerboard method. The fractional inhibitory concentration index (FICI) was calculated for determining the synergistic effect. Additionally, biofilm cell viability, time-kill and live-dead assays were performed to study the combinatorial effect. MIC of quercetin against all the P. aeruginosa strains was 500 g/mL. However, quercetin at 125 g/mL showed synergistic effect with [1/2] x MIC or [1/4] x MIC of all the antibiotics against all the strains. Quercetin (125 g/mL) with [1/2] MIC of levofloxacin and tobramycin combinations were highly effective with [≥]80% killing of biofilm associated cells. Increasing the concentration to 250 g/mL with [1/2] x MIC antibiotics could completely inhibit the biofilm cell viability in quercetin combination with amikacin and tobramycin. The findings show that quercetin combinations can enhance the treatment outcome against P. aeruginosa infection and this approach may reduce antibiotic overuse and selection pressure.\n\n\n\nO_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=118 SRC=\"FIGDIR/small/601336_ufig1.gif\" ALT=\"Figure 1\">\nView larger version (27K):\norg.highwire.dtl.DTLVardef@1cca26dorg.highwire.dtl.DTLVardef@1bbcc0forg.highwire.dtl.DTLVardef@5216b5org.highwire.dtl.DTLVardef@150c53d_HPS_FORMAT_FIGEXP M_FIG Graphical abstract C_FIG