Antibacterial and antibiofilm activities of diclofenac against levofloxacin-resistant Stenotrophomonas maltophilia isolates; emphasizing repurposing of diclofenac

Abstract

Background and Objectives: Stenotrophomonas maltophilia is an opportunistic pathogen causing nosocomial infections. Diclofenac is an anti-inflammatory drug that is considered a non-antibiotic drug. This study assessed the antibacterial and antibiofilm effects of diclofenac and levofloxacin/diclofenac combination against levofloxacin resistant isolates.
 Materials and Methods: Minimum inhibitory concentration was determined using broth microdilution method for levo- floxacin, diclofenac, and levofloxacin/diclofenac combination. Biofilm forming capacity and biofilm inhibition assay were determined. Relative gene expression was measured for efflux pump genes; smeB, and smeF genes and biofilm related genes rmlA, spgM, and rpfF without and with diclofenac and the combination.
 Results: Diclofenac demonstrated MIC of 1 mg/ml. The combination-with ½ MIC diclofenac- showed synergism where levofloxacin MIC undergone 16-32 fold decrease. All the isolates that overexpressed smeB and smeF showed a significant decrease in gene expression in presence of diclofenac or the combination. The mean percentage inhibition of biofilm for- mation with diclofenac and the combination was 40.59% and 46.49%, respectively. This agreed with biofilm related genes expression investigations.
 Conclusion: Diclofenac showed an antibacterial effect against Stenotrophomonas maltophilia. The combination showed in-vitro synergism, significant reduction in biofilm formation and in the relative level of gene expression. Furthermore, it can potentiate the levofloxacin activity or revert its resistance.