Silver Nanoparticles Strongly Enhance and Restore Bactericidal Activity of Inactive Antibiotics Against Multiresistant Enterobacteriaceae

Colloids Surf B Biointerfaces. 2016 Jun 1;142:392-399. doi: 10.1016/j.colsurfb.2016.03.007. Epub 2016 Mar 4.

Abstract

Bacterial resistance to conventional antibiotics is currently one of the most important healthcare issues, and has serious negative impacts on medical practice. This study presents a potential solution to this problem, using the strong synergistic effects of antibiotics combined with silver nanoparticles (NPs). Silver NPs inhibit bacterial growth via a multilevel mode of antibacterial action at concentrations ranging from a few ppm to tens of ppm. Silver NPs strongly enhanced antibacterial activity against multiresistant, β-lactamase and carbapenemase-producing Enterobacteriaceae when combined with the following antibiotics: cefotaxime, ceftazidime, meropenem, ciprofloxacin and gentamicin. All the antibiotics, when combined with silver NPs, showed enhanced antibacterial activity at concentrations far below the minimum inhibitory concentrations (tenths to hundredths of one ppm) of individual antibiotics and silver NPs. The enhanced activity of antibiotics combined with silver NPs, especially meropenem, was weaker against non-resistant bacteria than against resistant bacteria. The double disk synergy test showed that bacteria produced no β-lactamase when treated with antibiotics combined with silver NPs. Low silver concentrations were required for effective enhancement of antibacterial activity against multiresistant bacteria. These low silver concentrations showed no cytotoxic effect towards mammalian cells, an important feature for potential medical applications.

Keywords: Antibiotic; Cytotoxicity; Resistant bacteria; Silver nanoparticle; Synergism.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / pharmacology*
  • Cefotaxime / pharmacology
  • Ceftazidime / pharmacology
  • Ciprofloxacin / pharmacology
  • Drug Resistance, Multiple, Bacterial / drug effects*
  • Drug Resistance, Multiple, Bacterial / genetics
  • Drug Synergism
  • Escherichia coli / drug effects*
  • Escherichia coli / enzymology
  • Escherichia coli / genetics
  • Escherichia coli / growth & development
  • Gene Expression
  • Gentamicins / pharmacology
  • Klebsiella pneumoniae / drug effects*
  • Klebsiella pneumoniae / enzymology
  • Klebsiella pneumoniae / genetics
  • Klebsiella pneumoniae / growth & development
  • Meropenem
  • Metal Nanoparticles / chemistry
  • Metal Nanoparticles / toxicity*
  • Microbial Sensitivity Tests
  • Silver / pharmacology*
  • Thienamycins / pharmacology
  • beta-Lactamases / genetics
  • beta-Lactamases / metabolism

Substances

  • Anti-Bacterial Agents
  • Gentamicins
  • Thienamycins
  • Silver
  • Ciprofloxacin
  • Ceftazidime
  • beta-Lactamases
  • Meropenem
  • Cefotaxime