Biofilm Dispersal and Wound Infection Clearance With Preclinical Debridement Agents

Biofilms complicate wound care by causing recurrent infections that are often resistant to debridement and are highly antibiotic-tolerant. We investigated whether the addition of a biofilm dispersal agent could improve the efficacy of debridement. The previous studies have indicated that a glycoside hydrolase cocktail of alpha-amylase and cellulase can act as a potent biofilm dispersal agent. With in vitro and ex vivo Pseudomonas aeruginosa biofilm models, we compared glycoside hydrolases against other, clinically relevant, enzymatic debridement agents (papain, bromelain, and collagenase). Glycoside hydrolase biofilm dispersal was dose-dependent. However, at doses of 1% or above, glycoside hydrolases outperformed, or were comparable, to other enzymatic debridement agents. With our in vivo surgical wound infection model, we evaluated biofilm dispersal using infection dissemination as a proxy. We found that sharp debridement followed by multiple glycoside hydrolase treatments enhanced biofilm dispersal. Furthermore, a single dose of glycoside hydrolase in combination with debridement decreased infection load in acute wounds. Similarly, when we treated established 5-day-old infections, we saw a decrease in infection load and no infection dissemination. Overall, our data suggest that debridement enhances the efficacy of a topical antibiotic ointment, allowing for greater infection clearance.