Phase IIa randomized, placebo-controlled study of antimicrobial photodynamic therapy in bacterially colonized, chronic leg ulcers and diabetic foot ulcers: a new approach to antimicrobial therapy

Abstract

Background: With increasing problems of antibiotic resistance, photodynamic therapy (PDT) is being developed as a novel antimicrobial treatment. Following light activation, cationic photosensitizer PPA904 [3,7-bis(N,N-dibutylamino) phenothiazin-5-ium bromide] kills a broad spectrum of bacteria in vitro and this has a variety of potential clinical applications.

Objectives: To determine if PDT in bacterially colonized chronic leg ulcers and chronic diabetic foot ulcers can reduce bacterial load, and potentially lead to accelerated wound healing.

Methods: Sixteen patients with chronic leg ulcers and 16 patients with diabetic foot ulcers (each eight active treatment/eight placebo) were recruited into a blinded, randomized, placebo-controlled, single-treatment, Phase IIa trial. All patients had ulcer duration > 3 months, bacterially colonized with > 10 colony-forming units cm . After quantitatively assessing pretreatment bacterial load via swabbing, PPA904 or placebo was applied topically to wounds for 15 min, followed immediately by 50 J cm of red light and the wound again sampled for quantitative microbiology. The wound area was measured for up to 3 months following treatment.

Results: Treatment was well tolerated with no reports of pain or other safety issues. In contrast to placebo, patients on active treatment showed a reduction in bacterial load immediately post-treatment (P < 0·001). After 3 months, 50% (four of eight) of patients with actively treated chronic leg ulcer showed complete healing, compared with 12% (one of eight) of patients on placebo.

Conclusions: This first controlled study of PDT in chronic wounds demonstrated significant reduction in bacterial load. An apparent trend towards wound healing was observed; further study of this aspect with larger patient numbers is indicated.