A combined therapy of meropenem-ZnO nanoparticles efficiently eliminates carbapenem-resistant Klebsiella pneumoniae biofilms, with reduced nephrotoxicity (in vitro)

• Published in: Letters in applied microbiology 2024-12, Vol.77 (12)
• Main Authors: Mohamed, Alzhraa Ali, Saed, Safaa, El-Sayed, Sara Ramadan, Yassin, Mohamed Taha, Gad, Mohamed, Tartour, Eman, Fathey, Hoda A, Taha, Asmaa S, Mohamed, Asmaa H, Al-Otibi, Fatimah Olyan, AbdelGawwad, Mohamed Ragab, Ahmed, Mohamed M Sayed, Almalki, Susan Ahmed, Abdel-Haleem, Mohamed
• Format: Article
• Language: English
• Subjects: Animals; Anti-Bacterial Agents - pharmacology; Biofilms - drug effects; Carbapenem-Resistant Enterobacteriaceae - drug effects; Carbapenem-Resistant Enterobacteriaceae - genetics; Carbapenems - pharmacology; Chlorocebus aethiops; Humans; Klebsiella Infections - drug therapy; Klebsiella Infections - microbiology; Klebsiella pneumoniae - drug effects; Klebsiella pneumoniae - genetics; Meropenem - pharmacology; Microbial Sensitivity Tests; Nanoparticles - chemistry; Vero Cells; Zinc Oxide - chemistry; Zinc Oxide - pharmacology
• ISSN: 1472-765X; 1472-765X
• DOI: 10.1093/lambio/ovae136

In response to the World Health Organization's research agenda of antimicrobial resistance in human health, this study appraised the antibacterial and antibiofilm synergistic activity of meropenem and ZnO nanoparticles (ZnO-NPs) combination against carbapenem-resistant Klebsiella pneumoniae (CRKP). The minimum inhibitory concentration (MIC) of meropenem in combination was found to be ~1/12 of its MIC alone. The results of microtiter dilution assay showed that the combination was more efficient in reducing the biofilm biomass than meropenem alone or ZnO-NPs alone. The scanning-electron-microscopy micrographs elucidated that the combination of meropenem with ZnO-NPs has significantly enhanced its competence in eradicating the preformed biofilms of CRKP strains. In addition, the relative gene expression results showed that the combination compared to the meropenem alone and ZnO-NPs alone eloquently down-regulated the expression of biofilm genes (mrkA, fimA, and ecpA). Besides, the MTT-assay demonstrated that the combination has limited cytotoxicity against Vero-cells (in vitro). Overall, this study represents an efficient safe enhancement of meropenem to tackle the growing health threat of CRKP and carbapenem-resistant Enterobacterals prevalence.