Wound Antiseptics and European Guidelines for Antiseptic Application in Wound Treatment

Issues arising in wound healing are very common, and chronic wound infections affect approximately 1.5% of the population. The main substances used in wound washing, cleansing and treatment are antiseptics. Today, there are many compounds with a known antiseptic activity. Older antiseptics (e.g., boric acid, ethacridine lactate, potassium permanganate, hydrogen peroxide, iodoform, iodine and dyes) are not recommended for wound treatment due to a number of disadvantages. According to the newest guidelines of the Polish Society for Wound Treatment and the German Consensus on Wound Antisepsis, only the following antiseptics should be taken into account for wound treatment: octenidine (OCT), polihexanide (PHMB), povidone-iodine (PVP-I), sodium hypochlorite (NaOCl) and nanosilver. This article provides an overview of the five antiseptics mentioned above, their chemical properties, wound applications, side effects and safety.

Transcriptional analysis and target genes discovery of Pseudomonas aeruginosa biofilm developed ex vivo chronic wound model

Bacterial biofilms formation is one of the major reasons for treatment failure in chronic wound infections. Therefore, diagnostic biomarkers remain the best option for prevention and treatment of chronic wound infections by biofilms. Herein, Pseudomonas aeruginosa PAO1 was used to mimic biofilm development in porcine skin explants wells as ex vivo wound model. The microscopic imaging showed that PAO1 in porcine skin explants wells formed micro-colonies at 24 h, developed mushroom-like structure at 48 h, and at 72 h mushroom-like structure disappeared, remaining a thin bacterial lawn. RNA-seq data analysis revealed that the expression levels of genes involved in the type II hxc secretion system were significantly higher in biofilms than in planktonic cells, especially the expression of lapA encoding alkaline phosphatase. However, the expression levels of genes associated with denitrification pathway were markedly decreased in biofilms, especially the transcription of nirS encoding nitrite reductase to produce nitric oxide (NO). Therefore, their expressions and products were further detected using RT-qPCR and biochemical assays, respectively. The results found that the expression of lapA and alkaline phosphatase activity were induced, but the expression of nirS and intracellular NO were reduced at the whole biofilms cycle. The study indicates that LapA and NO would play an important role for P. aeruginosa biofilm formation in chronic wound infections. LapA would serve as potential target to monitor chronic wound infections by P. aeruginosa biofilms. Inducing NO would be used to treat chronic wound infections due to P. aeruginosa biofilms.

Transcriptional Analysis and Target Genes Discovery of Pseudomonas Aeruginosa Biofilm Developed Ex Vivo Chronic Wound Model

Bacterial biofilms formation is one of the major reasons for treatment failure in chronic wound infections. Therefore, diagnostic biomarkers remain the best option for prevention and treatment of chronic wound infections by biofilms. Herein, Pseudomonas aeruginosa PAO1 was used to mimic biofilm development in porcine skin explants wells as ex vivo wound model. The microscopic imaging showed that PAO1 in porcine skin explants wells formed micro-colonies at 24 h, developed mushroom-like structure at 48 h, and at 72 h mushroom-like structure disappeared, remaining a thin bacterial lawn. RNA-seq data analysis revealed that the expression levels of genes involved in the type II hxc secretion system were significantly higher in biofilms than in planktonic cells, especially the expression of lapA encoding alkaline phosphatase. However, the expression levels of genes associated with denitrification pathway were markedly decreased in biofilms, especially the transcription of nirS encoding nitrite reductase to produce nitric oxide (NO). Therefore, their expressions and products were further detected using RT-qPCR and biochemical assays, respectively. The results found that the expression of lapA and alkaline phosphatase activity were induced, but the expression of nirS and intracellular NO were reduced at the whole biofilms cycle. The study indicates that LapA and NO would play an important role for P. aeruginosa biofilm formation in chronic wound infections. LapA would serve as potential target to monitor chronic wound infections by P. aeruginosa biofilms. Inducing NO would be used to treat chronic wound infections due to P. aeruginosa biofilms.

Reversal of Polymicrobial Biofilm Tolerance to Ciprofloxacin by Blue Light plus Carvacrol

Chronic wound infections are often caused by multi-species biofilms and these biofilm-embedded bacteria exhibit remarkable tolerance to existing antibiotics, which presents huge challenges to control such infections in the wounds. In this investigation, we established a polymicrobial biofilm composed of P. aeruginosa, S. aureus, K. pneumoniae, and A. baumannii. We tested a cocktail therapy comprising 405-nm blue light (BL), carvacrol (Ca), and antibiotics on the multispecies biofilm. Despite the fact that all strains used to form the biofilm were susceptible to ciprofloxacin (CIP) in planktonic cultures, the biofilm was found to withstand ciprofloxacin as well as BL-Ca dual treatment, mainly because K. pneumoniae outgrew and became dominant in the biofilm after each treatment. Strikingly, when ciprofloxacin was combined with BL-Ca, the multispecies biofilms succumbed substantially and were eradicated at an efficacy of 99.9%. Mechanistically, BL-Ca treatment increased membrane permeability and potentiated the anti-biofilm activity of ciprofloxacin, probably by facilitating ciprofloxacin’s entrance of the bacteria, which is particularly significant for K. pneumoniae, a species that is refractory to either ciprofloxacin or BL-Ca dual treatment. The results suggest that bacterial membrane damage can be one of the pivotal strategies to subvert biofilm tolerance and combat the recalcitrant multispecies biofilms.

Protein-Based Systems for Topical Antibacterial Therapy

Recently, proteins are gaining attention as potential materials for antibacterial therapy. Proteins possess beneficial properties such as biocompatibility, biodegradability, low immunogenic response, ability to control drug release, and can act as protein-mimics in wound healing. Different plant- and animal-derived proteins can be developed into formulations (films, hydrogels, scaffolds, mats) for topical antibacterial therapy. The application areas for topical antibacterial therapy can be wide including bacterial infections in the skin (e.g., acne, wounds), eyelids, mouth, lips, etc. One of the major challenges of the healthcare system is chronic wound infections. Conventional treatment strategies for topical antibacterial therapy of infected wounds are inadequate, and the development of newer and optimized formulations is warranted. Therefore, this review focuses on recent advances in protein-based systems for topical antibacterial therapy in infected wounds. The opportunities and challenges of such protein-based systems along with their future prospects are discussed.

Correction to: Evaluation of the impact of six different DNA extraction methods for the representation of the microbial community associated with human chronic wound infections using a gel‑based DNA profiling method

An amendment to this paper has been published and can be accessed via the original article.