Recent Advances in Non-Conventional Antimicrobial Approaches for Chronic Wound Biofilms: Have We Found the ‘Chink in the Armor’?

Abstract

Chronic wounds are a major healthcare burden, with huge public health and economic impact. Microbial infections are the single most important cause of chronic, non-healing wounds. Chronic wound infections typically form biofilms, which are notoriously recalcitrant to conventional antibiotics. This prompts the need for alternative or adjunct ‘anti-biofilm’ approaches, notably those that account for the unique chronic wound biofilm microenvironment. In this review, we discuss the recent advances in non-conventional antimicrobial approaches for chronic wound biofilms, looking beyond standard antibiotic therapies. These non-conventional strategies are discussed under three groups. The first group focuses on treatment approaches that directly kill or inhibit microbes in chronic wound biofilms, using mechanisms or delivery strategies distinct from antibiotics. The second group discusses antimicrobial approaches that modify the biological, chemical or biophysical parameters in the chronic wound microenvironment, which in turn enables the disruption and removal of biofilms. Finally, therapeutic approaches that affect both, biofilm bacteria and microenvironment factors, are discussed. Understanding the advantages and limitations of these recent approaches, their stage of development and role in biofilm management, could lead to new treatment paradigms for chronic wound infections. Towards this end, we discuss the possibility that non-conventional antimicrobial therapeutics and targets could expose the ‘chink in the armor’ of chronic wound biofilms, thereby providing much-needed alternative or adjunct strategies for wound infection management.

Efficacy of Using Probiotics with Antagonistic Activity against Pathogens of Wound Infections: An Integrative Review of Literature

“…e Organisation for Economic Cooperation and Development (OECD) emphasizes that it is necessary to strengthen the scientific evidence of alternative therapies [36]. While some alternatives include inhibitors of antimicrobial resistance (e.g., alginate and polyamines), other chemical and biological agents with different mechanisms are currently being investigated: amino-benzimidazole, polyanionic substances, enzymes, potassium permanganate, antimicrobial peptides, metal ions (e.g., silver, bismuth, and copper), halogen ions (e.g., chlorine and iodine), chitosan, phototherapy, various antibodies, as well as bacteriophages and beneficial microorganisms, such as probiotics [37][38][39][40][41]. Interestingly enough, the OECD also states that probiotics are a promising alternative therapy to the topical use of antibiotics due to the increasing occurrence and transmission of antibiotic-resistant microorganisms.…”

Bioengineered Platforms for Chronic Wound Infection Studies: How Can We Make Them More Human-Relevant?

“…Together, this data indicates a shift in the prioritization of chronic wounds from a co-morbid condition to a silent global epidemic with huge public health and economic impact. While conventional antibiotics have been the mainstay of chronic wound infection management, a range of non-conventional antimicrobial approaches, alone and in combination, have been explored (Kadam et al, 2019). To probe the potential of these therapies and develop novel treatment approaches, it is important to better understand the chronic wound infection microenvironment, including its pathophysiological features, host-microbe interactions and effects of various treatments.…”

“…(4) Deficient and defective extracellular matrix production (ECM). (5) Failure of re-epithelialization due to lack of sufficient ECM and scaffold components (Demling, 2006;Kadam et al, 2019).…”

Antibiotic Delivery Strategies to Treat Skin Infections When Innate Antimicrobial Defense Fails

“…As wound biofilms are typically polymicrobial, it is likely that combination treatments containing antimicrobial agents with varied killing mechanisms are needed for treatment and to manage the drug resistant microbes [2,80,88]. Beyond the standard antibiotic therapies, non-conventional strategies may provide better treatment options for wound biofilms [89].…”