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

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.

Pexiganan in Combination with Nisin to Control Polymicrobial Diabetic Foot Infections

“…Due to its broad action spectrum, heat stability, tolerance to low pH and safety profile, nisin has been widely used as a food preservative for over 60 years [25]. Notably, nisin has been shown to be effective against both planktonic cells [26,27] and against biofilms [27][28][29] of multi-drug resistant staphylococci, including strains isolated from DFI [30,31]. Thus, nisin is an AMP with the potential to complement and enhance DFI antibacterial therapies.…”

“…Natural polysaccharides have been considered promising drug delivery systems, mainly because of their non-toxicity, biodegradability, biocompatibility, abundant availability in nature and economical cost [43]. Guar gum, a natural polysaccharide consisting of galactomannan [42], has been considered a safe and versatile system for delivery of bioactive agents, including antibiotics [42] and AMPs [30,31].…”

Methicillin-Resistant Staphylococcus aureus Diabetic Foot Crossed Infection: A Case Report

“…These ulcers are the consequence of a complex interaction of several pathophysiological factors, mainly neuropathic, vasculopathic, and immunopathic. Approximately 15% to 25% of patients with DM develop diabetic foot ulcers (DFUs) over the course of their lifetime [ 3 ]. This leads to a major socioeconomic impact and loss of the patient’s quality of life.…”

“…DFI treatment requires wound care, antimicrobial therapy, and often surgical procedures. As a result, DFIs are the most common diabetic complication requiring hospitalization and the world’s leading cause of nontraumatic lower limb amputation [ 3 ].…”

“…As with other transient flora bacteria, Staphylococcus aureus is both a commensal bacterium and a human pathogen [ 3 , 9 ]. Approximately 15–30% of the human population is colonized with Staphylococcus aureus [ 9 ].…”