This Made Easy section describes the mode of action, supporting evidence and practical application of the Prontosan® (B. Braun) range of wound cleansing agents. Regular cleansing and debridement are basic principles of wound bed preparation (WBP) and modern wound management[1-3]. These actions can address the barriers to healing by removing devitalised tissue, re-balancing the bioburden and reducing exudate to help prepare the wound bed for closure. The removal of biofilms and preventing their regrowth is commensurate with effective wound bed preparation[4,5].

Authors: Bradbury S, Fletcher J.

What is Prontosan® Wound Irrigation Solution and Gel?
Prontosan® Wound Irrigation Solution, Prontosan®  Wound Gel and Prontosan®  Wound Gel X are wound cleansers made from purified water and two key ingredients:

• Polyhexamethylene biguanide (PHMB), an antimicrobial agent (0.1%)
• Betaine, a surfactant (0.1%) (Box 1).

These products can be used for cleansing, rehydrating and decontaminating acute and chronic wounds that are at risk of infection by aiding the removal of bacteria and debris, and disrupting biofilm. The irrigation solution can be used to rinse the wound prior to application of the gel, which is available in two preparations. Prontosan Wound Gel can be used on small wounds, cavities and other difficult to reach areas. Prontosan Wound Gel X is highly viscous and can be used when larger quantities are required.

The role of wound cleansing in WBP
WBP has gained international recognition as a measured approach to accelerate wound healing, or to facilitate the effectiveness of other therapeutic measures[1-3].

Bacterial contamination of both acute and chronic wounds will inevitably occur to some extent due to the loss of skin barrier function[6], especially if this is prolonged and associated with underlying pathology or decreased host resistance[7]. This may also put the patient at risk of potentially life-threatening sepsis8.
Maintaining the wound bioburden at a level the host can control is therefore vital in preventing the onset of infection and associated increased patient morbidity[9].

The presence of biofilms in chronic wounds as a cause of delayed healing has recently gained acceptance [4,10,11]. Biofilms are complex microbial communities living within a three-dimensional extracellular polysaccaride (EPS) matrix embedded in a thick slimy blanket of sugars and proteins. The matrix acts as a barrier, protecting the micro-organisms from cellular and chemical attack[12].

Biofilms are not visible to the naked eye and cannot be detected by routine swabbing4. However, in a study using electron microscopy of wound biopsies, James et al[13] demonstrated the existence of biofilms in 30 of 50 chronic wounds, and in only one of 16 acute wounds.

The concept of biofilms may help to explain many clinical challenges and why wound care can be difficult and unpredictable[14]. Wolcott et al[15] has proposed the concept of wound biofilm management as a method to manage infection, involving regular debridement to aid in the removal and suppression of biofilms[4].


How does Prontosan support WBP?
Wounds may require cleansing if there is excess or problematic exudate, when there is slough and necrotic tissue or foreign material such as dirt and debris in the wound, or the wound is obviously infected.

Although water may be used as a wound cleanser, and has not been seen to increase the risk of infection or delay healing16, the use of specifically designed wound cleansing agents may have the potential to improve clinical outcomes through their additional wound cleansing modalities9. Evidence is emerging that the combination of PHMB with a surfactant (betaine) has an increased ability to penetrate difficult-to-remove coatings, lifting debris, bacteria and biofilm from the wound[17].


How does Prontosan work?
Role of polyhexamethylene biguanide
PHMB is a synthetic compound that has been in use for more than 60 years in various forms, including contact lens cleaners, mouth-washes, and more recently in wound management products, to reduce surface bioburden. It has demonstrated good clinical safely with no evidence of resistance and minimal toxicity[18,19].

It has been suggested that PHMB is structurally similar to naturally occurring antimicrobial peptides (AMPs)[20]. AMPs are produced by most living organisms and have a broad spectrum of activity against bacteria, viruses and fungi18. They are positively charged molecules that bind to bacterial cell membranes and induce cell lysis by destroying membrane integrity. PHMB is thought to work by breaking down the lipopolysaccharide layer (LPS) of the bacteria cell wall to kill bacteria[21]. This action is quick and so bacteria are unlikely to develop resistance to PHMB[22].

Role of betaine
Betaine is an amphoteric alkaloid surfactant that has a very mild action making it suitable for dermatological use. On a molecular level, betaine has a water-loving 'head' that is attracted to water molecules, and a hydrophobic water-hating 'tail' that repels water and attracts dirt and debris. The hydrophilic head remains in the solution, pulling the dirt and debris away from the wound and causing it to become suspended in the irrigating fluid enabling it to be flushed away.

As a result of its betaine (surfactant) component, Prontosan has a lower surface tension than that of water, making it a more efficient cleanser. Many wounds are coated with denatured proteins, lipoproteins and lipids from cell membranes and carbohydrates. As these compounds denature (break down) they lose their solubility and coat the wound surface. The resulting low surface tension induced by the surfactant supports the physical removal of debris and bacteria17 (Figure 1).

Betaine also interferes with the production of homoserine lactone, a signalling molecule used in the cell-to-cell communication of biofilms (known as quorum sensing), which play a role in biofilm pathogenicity[23]. The ability of betaine to disrupt biofilms is particularly beneficial as biofilms are now known to be resistant to cleansing with normal saline, which simply glides over the biofilm without removing it.


What is the evidence for the use of Prontosan?
Several in vitro and in vivo studies compare the use of Prontosan with other sterile wound cleansing solutions. An in vitro study[24] found that Prontosan was more effective at removing wound coatings when compared to four sterile wound cleansing solutions. Prontosan was the only solution where the test coatings disintegrated and the denatured proteins solubilised[24]. This is supported by clinical evaluations that have reported increased healing rates and reduced incidence of wound infection (Table 1).


How safe is Prontosan?
In an in vitro study to compare five commonly used skin antiseptics, all agents displayed effective antibacterial properties with Prontosan and Lavasept showing the best test results. Prontosan inhibited bacterial proliferation at the lowest concentration and demonstrated little cell toxicity at high concentrations[25]. It exhibited no adverse effect on fibroblast proliferation (cells vital to the wound healing process) at any concentration.

PHMB has been found to have no known toxic risks[18] and a low risk of sensitivity on contact[26,27]. Thus, Prontosan has a low allergic potential and can be used on sensitive or irritated skin. Studies have also shown that Prontosan is easy to use, has resulted in greater patient comfort at dressing changes and can be used long term[9, 17, 28].

Both the irrigation solution and the gels are sterile, colourless, odourless, ready-to-use products. They can be used in combination with all standard and advanced dressings (except larval therapy), and can be directly applied from the bottle or pod, or on a wet compress.

Unlike systemic antibiotics, Prontosan does not interfere with protective bacterial flora in other parts of the body, such as the gut, and can be used as an alternative to antibiotic prophylaxis in surgical wounds for the prevention of surgical site infections[18].