Diabetic foot infections: Application of a nisin-biogel to complement the activity of conventional antibiotics and antiseptics against Staphylococcus aureus biofilms

PLoS One. 2019 Jul 24;14(7):e0220000. doi: 10.1371/journal.pone.0220000. eCollection 2019.

Abstract

Background: Diabetic foot infections (DFIs) are a frequent complication of Diabetes mellitus and a major cause of nontraumatic limb amputations. The Gram-positive bacterium Staphylococcus aureus, known for its resilient biofilms and antibiotic resistant profile, is the most frequent DFI pathogen. It is urgent to develop innovative treatments for these infections, being the antimicrobial peptide (AMP) nisin a potential candidate. We have previously proposed the use of a guar gum biogel as a delivery system for nisin. Here, we evaluated the potential of the nisin-biogel to enhance the efficacy of conventional antibiotics and antiseptics against DFIs S. aureus clinical isolates.

Methods: A collection of 23 S. aureus strains isolated from DFI patients, including multidrug- and methicillin-resistant strains, was used. The antimicrobial activity of the nisin-biogel was tested alone and in different combinations with the antiseptic chlorhexidine and the antibiotics clindamycin, gentamicin and vancomycin. Isolates' in vitro susceptibility to the different protocols was assessed using broth microdilution methods in order to determine their ability to inhibit and/or eradicate established S. aureus biofilms. Antimicrobials were added to the 96-well plates every 8 h to simulate a typical DFI treatment protocol. Statistical analysis was conducted using RCBD ANOVA in SPSS.

Results: The nisin-biogel showed a high antibacterial activity against biofilms formed by DFI S. aureus. The combined protocol using nisin-biogel and chlorhexidine presented the highest efficacy in biofilm formation inhibition, significantly higher (p<0.05) than the ones presented by the antibiotics-based protocols tested. Regarding biofilm eradication, there were no significant differences (p>0.05) between the activity of the combination nisin-biogel plus chlorhexidine and the conventional antibiotic-based protocols.

Conclusions: Results provide a valuable contribution for the development of complementary strategies to conventional antibiotics protocols. A combined protocol including chlorhexidine and nisin-biogel could be potentially applied in medical centres, contributing for the reduction of antibiotic administration, selection pressure on DFI pathogens and resistance strains dissemination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Bacterial Agents / administration & dosage
  • Anti-Bacterial Agents / pharmacology
  • Anti-Infective Agents, Local / administration & dosage
  • Anti-Infective Agents, Local / pharmacology
  • Biofilms*
  • Chlorhexidine / administration & dosage
  • Chlorhexidine / pharmacology
  • Diabetic Foot / complications
  • Diabetic Foot / microbiology*
  • Drug Combinations
  • Galactans / chemistry
  • Humans
  • Hydrogels / chemistry*
  • Mannans / chemistry
  • Nisin / administration & dosage*
  • Nisin / pharmacology
  • Plant Gums / chemistry
  • Staphylococcal Infections / complications
  • Staphylococcal Infections / drug therapy*
  • Staphylococcal Infections / microbiology
  • Staphylococcus aureus / drug effects*
  • Staphylococcus aureus / pathogenicity
  • Staphylococcus aureus / physiology

Substances

  • Anti-Bacterial Agents
  • Anti-Infective Agents, Local
  • Drug Combinations
  • Galactans
  • Hydrogels
  • Mannans
  • Plant Gums
  • Nisin
  • guar gum
  • Chlorhexidine

Grants and funding

This work was supported by FCT – Fundação para a Ciência e a Tecnologia (Project PTDC/SAU-INF/28466/2017) and by CIISA - Centro de Investigação Interdisciplinar em Sanidade Animal, Faculdade de Medicina Veterinária, Universidade de Lisboa (Project UID/CVT/276/2019). RS and EC acknowledge FCT for their PhD fellowships (SFRH/BD/100571/2014 and SFRH/BD/131384/2017, respectively).