A wound offers an ideal environment for the growth and proliferation of a variety of microorganisms which, in some cases, may lead to localised or even systemic infections that can be catastrophic for the patient; the development of biofilms exacerbates these infections. Over the past few decades, there has been a progressive development of antimicrobial resistance (AMR) in microorganisms across the board in healthcare sectors. Such resistant microorganisms have arisen primarily due to the misuse and overuse of antimicrobial treatments, and the subsequent ability of microorganisms to rapidly change and mutate as a defence mechanism against treatment (e.g., antibiotics). These resistant microorganisms are now at such a level that they are of grave concern to the World Health Organization (WHO), and are one of the leading causes of illness and mortality in the 21st century. Treatment of such infections becomes imperative but presents a significant challenge for the clinician in that treatment must be effective but not add to the development of new microbes with AMR. The strategy of antimicrobial stewardship (AMS) has stemmed from the need to counteract these resistant microorganisms and requires that current antimicrobial treatments be used wisely to prevent amplification of AMR. It also requires new, improved or alternative methods of treatment that will not worsen the situation. Thus, any antimicrobial treatment should be effective while not causing further development of resistance. Some antiseptics fall into this category and, in particular, polyhexamethylene hydrochloride biguanide (PHMB) has certain characteristics that make it an ideal solution to this problem of AMR, specifically within wound care applications. PHMB is a broad-spectrum antimicrobial that kills bacteria, fungi, parasites and certain viruses with a high therapeutic index, and is widely used in clinics, homes and industry. It has been used for many years and has not been shown to cause development of resistance; it is safe (non-cytotoxic), not causing damage to newly growing wound tissue. Importantly there is substantial evidence for its effective use in wound care applications, providing a sound basis for evidence-based practice. This review presents the evidence for the use of PHMB treatments in wound care and its alignment with AMS for the prevention and treatment of wound infection.

The prevalence of chronic, non-healing skin wounds in the general population, most notably diabetic foot ulcers, venous leg ulcers and pressure ulcers, is approximately 2% and is expected to increase, driven mostly by the aging population and the steady rise in obesity and diabetes. Non-healing wounds often become infected, increasing the risk of life-threatening complications, which poses a significant socioeconomic burden. Aiming at the improved management of infected wounds, a variety of wound dressings that incorporate antimicrobials (AMDs), namely polyhexanide (poly(hexamethylene biguanide); PHMB), have been introduced in the wound-care market. However, many wound-care professionals agree that none of these wound dressings show comprehensive or optimal antimicrobial activity. This manuscript summarizes and discusses studies on PHMB-releasing membranes (PRMs) for wound dressings, detailing their preparation, physical properties that are relevant to the context of AMDs, drug loading and release, antibacterial activity, biocompatibility, wound-healing capacity, and clinical trials conducted. Some of these PRMs were able to improve wound healing in in vivo models, with no associated cytotoxicity, but significant differences in study design make it difficult to compare overall efficacies. It is hoped that this review, which includes, whenever available, international standards for testing AMDs, will provide a framework for future studies.

This review deals with three categories of active substances for disinfectant products, their modes of action (MOA), and how MOA can help predict propensity for resistance in microorganisms. Within the European Union applications for approval of disinfectants of all kinds must be submitted in a few years, and documentation on MOA and resistance must be part of those applications. Peracetic acid is an unspecific, pervasive oxidizer of C-C double bonds and reduced atoms. This MOA would imply poor chance for development of resistance in microorganisms, as borne out by the absence of such reports in the literature. The quaternary ammonium compounds (QAC\'s) are much more specific in their antimicrobial mechanism. Even very low concentrations cause damage to the cytoplasmic membrane due to perturbation of the bilayers by the molecules\' alkyl chains. Development of microbial resistance to QAC\'s, as well as cross-resistance to antibiotics, are particularly well documented. The polymer PHMB is antimicrobial because it disturbs the cell membrane\'s bilayer by interacting with it along the surface of the membrane. Resistance to the polymer appears not to develop despite many years of use in many fields. However, PHMB\'s toxicity to humans upon inhalation dictates great caution when deploying the substance.