Surfactant nanovesicles for augmented antibacterial activity against carbapenemase resistant enterobacteriaceae and extended spectrum beta-lactamases producing bacteria: in vitro and in vivo evaluation

Abstract

Abstract The ubiquitous emergence of bacterial resistance is a challenging problem in infectious diseases treatment. Recently, new research lines employed nano-drug delivery systems to enhance antibacterial activity of the existing antibiotics. Accordingly, the objective of this study is to optimize surfactant nanovesicles to improve the antimicrobial effect of meropenem, ertapenem and tigecycline against Carbapenemase Resistant Enterobacteriaceae (CRE) and extended spectrum beta-lactamases producing bacteria (ESBL). Klebsiella pneumoniae and Escherichia coli were used as the test organisms. In vivo and in vitro evaluations were conducted to prove the efficacy of niosome-encapsulated drugs formulations. The results revealed that surfactant vesicles were able to reduce the MIC values of the tested drugs by nine-fold change compared to their free forms. Scanning Electron Microscope (SEM) showed possible adhesion/fusion of the vesicles encapsulated drugs on the bacterial cells compared to its solution. In vivo investigations using animal skin model confirmed the superiority of nanovesicles drug encapsulation regarding both wound size and histopathological examination. Wound surface area was reduced from 24.6mm2 in absence of drug to reach 13.9, and 6.2mm2 in presence of ertapenem solution or niosomes, respectively. Nanovesicular formulations can be considered as effective drug delivery systems that can diminish bacterial resistance against β-lactams antibiotics.

Keywords

• ESBLs
• CRE
• Surfactant vesicles
• E. coli
• K. pneumoniae