Chronic wounds are wounds failing to proceed through the normal phases of healing in an orderly and timely manner. The definition of time without complete or partial healing differs across countries, ranging from 4 weeks to 3 months [1]. The Wound Healing Society defines four types of chronic wounds: diabetic foot ulcers (DFU), vascular ulcers (containing venous and arterial ulcers), and pressure ulcers (PU) [2].

Infection is a common complication of chronic wounds. Historically, the research on wound infection control and improvement was focused on reducing the “pathogen burden”. However, quantitative consideration of microbial load is insufficient for assessing wound improvement or wound risk of infection [3,4]. Microorganisms in a chronic wound are co-aggregated together within a protective extracellular matrix, constituting a biofilm. This biofilm conformation induces a dramatically increased tolerance to host immune defences and a greater resistance to antimicrobials [5]. Biofilm delays wound healing by inducing an ineffective host inflammatory response and damaging host tissues [6]. For this reason, a management of the biofilm is more relevant for the treatment of chronic wound [7]. In 2011, Dissemond et al. classified wounds into four categories, depending on wound bed clinical and microbiological situation: (1) contaminated or colonised wounds without risk of infection; (2) colonised wounds at risk (WAR) or critically colonised wounds; (3) wounds with local infection; and (4) systemic infections and infected wounds. The authors suggested the use of antiseptic agents for wounds from the second category alongside other treatments [8].

Chronic wound care commences with wound bed preparation via (i) wound cleansing to create a wet or moist environment, favourable to healing. (ii) Wound debridement via removal of devitalised, contaminated tissue from within or adjacent to a wound, until surrounding healthy tissue is exposed [9,10]. Debridement can be mechanical (sharp debridement, surgical), enzymatical, or bio-surgical (e.g., maggot therapy) [11,12,13,14,15]. Negative pressure wound therapy has also been used for bacterial decontamination and wound bed preparation [16]. (iii) Application of a suitable dressing, according to the type of wound. (iv) Antibiotic treatment, exclusively for infected wounds. Other therapies are beneficial to specific wounds: compression therapy is required for venous leg ulcers (VLU) [17]; arterial revascularisation, offloading foot ulcers, and diabetes control are essential in DFU [18,19]; and skin assessment and care, offloading and pressure redistribution, dressings [19,20], and structured educational program are useful for all types of chronic wounds.

In some countries, tap water or saline remain the only recommended agents for wound cleansing. Antisepsis is a common, yet controversial, wound cleansing method. Some studies consider debridement alone insufficient to reduce the biofilm that delays wound healing and suggest antiseptics to delay biofilm reformation and reduce the risk of infection [7,20]. Antiseptic agents may complement the debridement process and control infection.

The primary mode of action of antiseptics can be pharmacological, metabolic, and/or immunological [21]. For the purpose of this review, antiseptic agents are defined as medication that can prevent the growth or destroy microorganisms in or on a living tissue. Following this definition of medication, antiseptic agents must pass through a drug authorisation procedure with a medicine agency [22]. The main antiseptic agents used in chronic wound care are halogenated compounds, alcohol-based agents, biguanides (e.g., polyhexanide also called polyhexamethylenebiguanide or PHMB, chlorhexidine), and quaternary ammoniums (e.g., octenidine). Halogenated compounds include subfamilies such as the iodine/iodophor agents (e.g., povidone iodine, cadexomer iodine) and chlorous agents (hypochlorite, hypochlorous acid) [21,22]. Alternative therapeutics (e.g., honey, silver), while been antimicrobial agents are not antiseptic agents as they did not go through an authorisation procedure for this purpose [23]. They therefore are not part of the antiseptic agents’ classification. International guidelines recommend against the routine use of topical antiseptics to manage infected chronic wounds [24,25,26,27].

2. Antiseptic Agents for Chronic Wounds