Zinc oxide nanoparticles potentiate the antibacterial and antibiofilm efficacy of imipenem against Klebsiella pneumoniae.

BACKGROUND

Biofilm extracellular polymeric matrix (EPS) biomass plays a central role in bacterial resistance to carbapenems, especially imipenem (IPM), which poses a serious threat to public health.

OBJECTIVES

The present study aims to use ZnO NPs to improve the susceptibility of imipenem-resistant Klebsiella pneumoniae (IRKP) to imipenem (IPM) and to reduce biofilm extracellular polymeric matrix (EPS) biomass.

MATERIAL AND

METHODS

Susceptibility to IPM and biofilm formation were evaluated in 20 uropathogenic K. pneumoniae isolates. ZnO NPs were prepared using an extract of Thymus vulgaris leaves. The effects of sub-minimum inhibitory concentrations (MICs) of IPM and ZnO NPs on biofilm formation were evaluated. The additive effect of sub-MICs of ZnO NPs on IRKP susceptibility to IPM and biofilm formation was assessed.

RESULTS

The diameter of the prepared ZnO NPs was less than 50 nm. Biofilm formation negatively correlated with inhibition zone diameter (r = -0.819, p = 0.001) and positively with IPM MICs (r = 0.79, p = 0.001). Sub-MICs of IPM and ZnO NPs reduced biofilm formation on polystyrene in a concentration-dependent manner. The synergistic role of sub-MICs of ZnO NPs in decreasing the MICs of IPM against K. pneumoniae was observed, from 250 ± 50 μg/mL to 116.6 ± 14.4 μg/mL (at 1/2, 1/4, and 1/8 MICs of ZnO NPs), while 1/16 MIC of ZnO NPs decreased the MICs of IPM to 125 ± 25 μg/mL. The 1/32 and 1/64 MICs of ZnO NPs reduced the MICs of IPM to 141.6 ± 14.4 μg/mL and 158.3 ± 80.36 μg/mL, respectively. The greatest reduction in biofilm extracellular polymeric matrix (EPS) formation was observed at the highest concentrations of the IPM/ZnO NP combination, while the lowest reduction was observed at the lowest concentrations of both materials (p < 0.05).

CONCLUSIONS

The present study demonstrated a synergistic effect of sub-MIC ZnO NPs on the antibacterial and antibiofilm activities of imipenem against K. pneumoniae (IRKP).