Exploring novel antimicrobials for the treatment of biofilm infected chronic wound

Chronic wounds are a significant global problem, causing patient morbidity and a substantial financial burden on health services worldwide. The annual spend on wound care in the U.K. and U.S. is estimated at £2 billion and $25 billion, respectively. Wound infection is a major contributing factor to the development and persistence of chronic wounds, with wound bioburden (a combination of total bacterial load, species diversity and presence of pathogenic species) linked to healing outcome. As many as 85% of lower limb amputations are preceded by an infected chronic wound. These clinical and statistical observations clearly suggest that current therapies for wound infection are inadequate, with wound biofilms often implicated. Biofilms are defined as sessile microbial communities characterised by adhesion to a surface and embedded in an extracellular matrix. Wound biofilms are highly tolerant to antibiotic and antimicrobial treatments and interact with wound tissues in manner that is distant to dispersed bacteria. Dressings containing metallic (Ag0) or singly ionic silver (Ag1+) are the most widely available and frequently used topical antimicrobials for infection control in chronic wounds although their effectiveness against wound biofilms are disputed.

Propriety technology now enables higher oxidative states of silver (Ag2+; Ag3+) produced from silver oxysalts to be incorporated into wound dressings. Preliminary in vitro data indicate that silver oxysalts are more efficacious than Ag1+ against planktonic bacteria and biofilms.

The studentship will involve delineation of the mechanisms of action responsible for the efficacy of Ag oxysalt dressings. This will include assessing direct effects on healing and indirect effects, through inhibition of wound biofilms in vivo.

Despite no specific guidelines on antibiotic prescriptions for infected wounds and a scarcity of evidence supporting the effectiveness of antibiotics in the treatment of infected chronic wounds, they are still widely used. In addition, there are no studies, which have assessed the effects of antibiotics on healing mechanisms once infection is cleared. Wound biofilms exhibit high levels of tolerance to antibiotics and therefore are often ineffective. The student will therefore compare the effectiveness and/or synergistic action of systemic antibiotics and Ag oxysalt dressings against wound biofilms in vivo and determine their effects on healing independent of infection.

This studentship will provide training in a wide range of in vitro, ex vivo and in vivo techniques, while giving the student an opportunity to work with the industrial sponsors and gain invaluable clinical, regulatory and commercial experience.