With no new antibiotic therapies on the horizon (Consensus Panel, 2010), the role of topical antiseptic/antimicrobial agents may take on greater significance in the coming years. One such antimicrobial agent is polyhexamethylene biguanide (PHMB). PHMB is a compound which has been used in a variety of industries for many years (Consensus Panel, 2010), but has only recently made any significant impact in wound care. Recent years have seen increased reliability on antibiotics, and it is this over reliance that has resulted in bacterial resistance (White et al, 2001).
Against a background of increasing bacterial resistance to antibiotics and the fact that wound bacteria can significantly delay wound healing (Consensus Panel, 2010), it is necessary to prevent the proliferation of bacteria in wounds, while at the same time constraining the prophylactic use of antibiotics. Antiseptics provide an alternative antibacterial strategy, and because they affect multiple targets are less likely to generate bacterial resistance (Gilbert, 2006) when used prophylactically over a prolonged period.
PHMB is a heterodisperse mixture of polymers and is a synthetic compound structurally similar to naturally occurring antimicrobial peptides (AMPs). The basic molecular chain of PHMB can be repeated from two to 30 times, with increasing polymer chain length correlating to increasing antiseptic/antimicrobial efficacy (Consensus Panel, 2010).
AMPs are important in innate immune response and are produced by the majority of living organisms (Consensus Panel, 2010). They have a broad spectrum of activity against bacteria, viruses and fungi (Moore and Gray, 2007), and have been suggested as therapeutic alternatives to antibiotics (Hancock and Sahl, 2006). AMPs are positively charged molecules that bind to bacterial cell membranes and induce cell lysis by destroying membrane integrity, in a similar way to penicillin and cephalosporin antibiotics (Consensus Panel, 2010). AMPs are produced by many cells within the wound, such as keratinocytes and inflammatory neutrophils, where they are thought to play a role in protection against infection (Sorensen et al, 2003).
The structural similarities between PHMB and AMPs mean the former can insert into bacterial cell membranes and kill bacteria in a similar way to AMPs (Moore and Gray, 2007). While it is unclear what the precise action of PHMB on bacteria is, the primary targets appear to be the outer and cytoplasmic membranes (Consensus Panel, 2010). PHMB is thought to adhere to and disrupt target cell membranes, causing them to leak potassium ions and other cytosolic components (Davies et al, 1968; Davies and Field, 1969; Broxton et al, 1984; Yasuda et al, 2003), which results in cell death.
PHMB has been in general use for approximately 60 years (Consensus Panel, 2010) and currently there has been no evidence of the development of resistance (Moore and Gray, 2007). It exerts little toxicity and has been found to be safe and effective in applications as diverse as treatment of eye infections (Larkin et al, 1992) and sanitizing swimming pools (Motta and Triglia, 2005).
PHMB has been available as an antiseptic for some time; recently it has been successfully introduced into wound management within a range of dressings containing 0.2% of the antibacterial agent, including non-adherent primary dressings, gauze, drains and intravenous sponges (Motta and Triglia, 2005; Moore and Gray, 2007).
One of the PHMB-impregnated dressings available on the veterinary market is Kendall™ AMD foam. In these dressings the PHMB molecule has been chemically bound to the base material, providing it with antiseptic/antimicrobial properties when it comes into contact with wound exudate. The product therefore protects against the development of wound infection by decreasing the bacterial load in the dressing and bacterial penetration through the dressing (Consensus Panel, 2010).
Antiseptic/antimicrobial activity in wound care is a central role for any PHMB product. Infection is a major concern because of increased patient morbidity, hospitalization time, expense and the potential toxicity which may be associated with resistant organisms (Lee et al, 2004). In their study Lee et al used PHMB-impregnated gauze on agar plates and this was shown to be more effective than the control gauze at inhibiting the growth of all gram-positive bacteria that were tested. The study noted that bacterial contamination levels of >105 bacteria/g of tissue may result in wound infection; hence this information was used in order to determine the size of inoculum used for the quantitative evaluation. The study concluded that biguanide-impregnated dressings can be used to prevent the growth of bacterial pathogens, and may be particularly useful in preventing the introduction of bacteria into open, effusive wounds. They also noted that the bacterial colonization or migration along intravenous (IV) catherization sites, external fixator skin-pin interfaces and surgical drain or gastrotomy, jejunostomy, or anterior cystostomy tube exit wounds may be inhibited (Garland et al, 2001) (Figure 1). Lee et al (2004) also acknowledged that in vivo wound environments may differ in their protein content, pH, fluid production, and other factors which could affect the efficacy of the dressing chosen.
Wound infection
Wound infection has been well recognized as a factor involved in prolonged wound healing. Wound infection is seen to prolong the inflammatory phase of wound healing, resulting in pain and discomfort to the patient, and unless correctly treated can lead to serious and potentially fatal systemic sepsis (Consensus Panel, 2010).
All wounds become contaminated with bacteria at, or soon after, the time of injury, meaning they are classed as either contaminated or dirty/infected wounds. In the majority of cases this does not slow wound healing and clinical intervention is not required. However, in some patients there is a linear progression of wounds from contamination through colonization to critical colonization and infection (this is termed the ‘infection continuum’; Kingsley 2001; White et al, 2001). Infection is apparent when the sum of the bacterial load and the virulence factors bacteria produce is greater than the host's defenses, resulting in harm to the host (Consensus Panel, 2010). This is seen as the classic signs of wound infection.
Topical antiseptic/antimicrobial agents should be viewed as the first line treatment in the management of bacterial burden, as veterinary practitioners try to move away from dependence on systemic antibiotics. Some preparations have bactericidal effects even against multiresistant organisms such as meticillin-resistant Staphylococcus aureus (MRSA) (Lawrence, 1998; Sibbald et al, 2001), and they have the additional advantage that they do not interfere with the remainder of the protective bacterial flora in other parts of the body.
Wound bioflms
Bacteria are no longer viewed as autonomous entities but it is now realized that they in fact live in a heterogenous community on both animate and inanimate objects; it is recognized that single species communities of bacteria are rare in nature (Cooper and Okhiria, 2008). These communities of organisms living within a three-dimensional extracellular polysaccharide (EPS) matrix are known as biofilms (Consensus Panel, 2010). In the field of wound care, and particularly veterinary wound care, the understanding of biofilms and their effect on wound healing is currently very limited, despite their being a key component in resistant bacterial colonization (Serralta et al, 2001) and further research is called for in this area.
Research carried out into the behaviour of bacteria has revealed that bacteria are more commonly found associated with other bacterial species rather than as an isolated organism or planktonic cells (Dworkin and Shapiro, 1997). Within veterinary medicine there is an increasing awareness of the relevance of biofilms to both small animal and equine wounds with studies on these species beginning to emerge, and current research is ongoing looking at the composition of biofilms in small animal wounds.
PHMB in wound management
PHMB has been incorporated into a range of wound management products which are designed to be incorporated into standard wound care protocols (Table 1). The AMD™ range of infection control dressings (Tyco Healthcare, Basingstoke) is impregnated with 0.2% PHMB. The product range includes Kendall™ Telfa AMD Non-Adherent Wound Dressings (Figure 2), AMD™ Antimicrobial Foam Dressings, and Kerlix™ AMD Antimicrobial Gauze Dressings (Figure 3). Although these products are aimed at wound management, the author regularly uses the Kendall™ AMD Antimicrobial Foam Dressings on stoma sites to prevent wound infections in the more susceptible critical care patients which have feeding tubes, thoracostomy tubes and central venous catheters in situ, and which are prime candidates for hospital acquired infections. Kendall™ AMD antimicrobial foam discs are available specifically for use around indwelling catheters, drains and other such devices (Figure 4).
| Dressing | Manufacturer | Description | Indication |
|---|---|---|---|
| Kendall AMD Antimicrobial Foam Disc Dressing | Covidien, Kendall | Polyurethane foam disc impregnated with broad spectrum antimicrobial (PHMB, 0.5%). Double sided with centre hole and radial slit | For use at exit sites. |
| Kendall AMD Antimicrobial Foam Dressing | Covidien, Kendall | Highly absorbency hydrophilic foam impregnated with broad spectrum antimicrobial (PHMB, 0.5%) | Used as primary dressing in moderately to heavily exuding wounds |
| Kerlix AMD | Covidien, Kendall | Gauze dressing impregnated with PHMB | Used as primary dressing to protect against infection and as secondary dressing to prevent bacterial penetration through and bacterial growth within the dressing. Used in combination with topical negative pressure wound therapy |
| Suprasorb X + PHMB | Activa Healthcare | Bio-cellulose dressing impregnated with PHMB 0.3% | Used in moderately exuding, superficial and deep, critically colonized and infected wounds during all phases of wound healing |
| Telfa AMD | Covidien, Kendall | Absorbent pad dressing with non-absorbent contact layer and non-woven backing. Impregnated with PHMB 0.2%. | Used as primary dressing to cover surgical incisons; dry to lightly exuding wounds; IV lines; to prevent infection |
PHMB, polyhexamethylene biguanide; IV, intravenous (Cowan, 2011).
Suprasorb X (Activa Healthcare) is another wound dressing impregnated with PHMB (0.3%). This dressing is able to regulate the absorption and donation of moisture at the wound-dressing interface thus creating an optimum wound healing environment and the addition of PHMB give the dressing its antimicrobial action. Suprasorb X dressings consist of biosynthetic HydroBalance fibres, which both enhance the dressing's moisture handling capabilities and its tensile strength (Kingsley, 2009).
Conclusion
Human medicine is beginning to see resistance developing to antibiotics such as vancomycin, which is generally reserved for the most serious of infections, and this situation should make vetereunary practitioners wonder what will happen with antibiotic resistance in veterinary patients in future years.
With an ever increasing number of resistant bacterial species developing animals are also at risk of becoming colonized by these species. The veterinary profession needs to be increasingly aware of the risks involved with frivolous use of antibiotics and consider topical antimicrobials as a first choice when dealing with contaminated wounds.
As an antimicrobial, PHMB has been in use for over 60 years, and so far there has been no evidence of resistance. It may well be the way forward for management of wound infections.