title: Photodynamic topical antimicrobial therapy for infected foot ulcers in patients with diabetes: a randomized, double-blind, placebo-controlled study--the D.A.N.T.E (Diabetic ulcer Antimicrobial New Topical treatment Evaluation) study.
abstract: This study was designed to assess the antimicrobial effect and tolerability of a single dose of a photo-activated gel containing RLP068 in the treatment for infected foot ulcers in subjects with diabetes. A randomized, double-blind, parallel series, placebo-controlled phase IIa trial was performed with three concentrations of RLP068 (0.10, 0.30, and 0.50 %), measuring total and pathogen microbial load on Day 1 (before and 1 h after topical gel application and photoactivation with 689 nm red light), on Days 3, 8, and 15, as add-on to systemic treatment with amoxicillin and clavulanic acid. Blood samples were also drawn 1, 2, and 48 h after administration for the assessment of systemic drug absorption. The trial was performed on 62 patients aged ≥18 years, with type 1 or type 2 diabetes and infected foot ulcer, with an area of 2-15 cm(2) and a maximum diameter ≤4.6 cm. A dose-dependent reduction in total microbial load was observed (-1.92 ± 1.21, -2.94 ± 1.60, and -3.00 ± 1.82 LogCFU/ml for 0.10, 0.30, and 0.50 % RPL068 vs. -1.00 ± 1.02 LogCFU/ml with placebo) immediately after illumination, with a progressive fading of the effect during follow-up. No safety issues emerged from the analysis of adverse events. Systemic absorption of RLP068 was negligible. Photodynamic antimicrobial treatment with RLP068 of infected diabetic foot ulcers is well tolerated and produces a significant reduction in germ load. Further clinical trials are needed to verify the efficacy of this approach as add-on to systemic antibiotic treatment.
authors.affiliation: Azienda Ospedaliera Universitaria Careggi, Florence, Italy, edoardo.mannucci@unifi.it.
authors.forename: Edoardo
authors.initials: E
authors.lastname: Mannucci
authors.forename: Stefano
authors.initials: S
authors.lastname: Genovese
authors.forename: Matteo
authors.initials: M
authors.lastname: Monami
authors.forename: Giovanni
authors.initials: G
authors.lastname: Navalesi
authors.forename: Francesco
authors.initials: F
authors.lastname: Dotta
authors.forename: Roberto
authors.initials: R
authors.lastname: Anichini
authors.forename: Fabio
authors.initials: F
authors.lastname: Romagnoli
authors.forename: Gianfranco
authors.initials: G
authors.lastname: Gensini
mesh_terms: D000328:Adult; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000627:therapeutic use*; D001419:Bacteria / Q000187:drug effects; D003922:Diabetes Mellitus, Type 1 / Q000150:complications*; D003924:Diabetes Mellitus, Type 2 / Q000150:complications*; D017719:Diabetic Foot / Q000188:drug therapy* / Q000209:etiology / Q000382:microbiology; D004341:Drug Evaluation; D005260:Female; D006801:Humans; D007211:Indoles / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009942:Organometallic Compounds / Q000627:therapeutic use; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry / Q000627:therapeutic use*; D014456:Ulcer / Q000188:drug therapy* / Q000209:etiology / Q000382:microbiology; D055815:Young Adult
chemical_list: D000900:Anti-Bacterial Agents; D007211:Indoles; D009942:Organometallic Compounds; D017319:Photosensitizing Agents; C477806:RLP068