Photodynamic therapy for Acinetobacter baumannii burn infections in mice.
Multidrug-resistant Acinetobacter baumannii infections represent a growing problem, especially in traumatic wounds and burns suffered by military personnel injured in Middle Eastern conflicts. Effective treatment with traditional antibiotics can be extremely difficult, and new antimicrobial approaches are being investigated. One of these alternatives to antimicrobials could be the combination of nontoxic photosensitizers (PSs) and visible light, known as photodynamic therapy (PDT). We report on the establishment of a new mouse model of full-thickness thermal burns infected with a bioluminescent derivative of a clinical Iraqi isolate of A. baumannii and its PDT treatment by topical application of a PS produced by the covalent conjugation of chlorin(e6) to polyethylenimine, followed by illumination of the burn surface with red light. Application of 10(8) A. baumannii cells to the surface of 10-s burns made on the dorsal surface of shaved female BALB/c mice led to chronic infections that lasted, on average, 22 days and that were characterized by a remarkably stable bacterial bioluminescence. PDT carried out on day 0 soon after application of the bacteria gave over 3 log units of loss of bacterial luminescence in a light exposure-dependent manner, while PDT carried out on day 1 and day 2 gave an approximately 1.7-log reduction. The application of PS dissolved in 10% or 20% dimethyl sulfoxide without light gave only a modest reduction in the bacterial luminescence from mouse burns. Some bacterial regrowth in the treated burn was observed but was generally modest. It was also found that PDT did not lead to the inhibition of wound healing. The data suggest that PDT may be an effective new treatment for multidrug-resistant localized A. baumannii infections.
Dai
Tianhong
T
Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, Massachusetts 02114, USA.
Tegos
George P
GP
Lu
Zongshun
Z
Huang
Liyi
L
Zhiyentayev
Timur
T
Franklin
Michael J
MJ
Baer
David G
DG
Hamblin
Michael R
MR
D000151:Acinetobacter Infections / Q000188:drug therapy* / Q000209:etiology*; D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000528:radiation effects*; D000818:Animals; D002056:Burns / Q000150:complications*; D004121:Dimethyl Sulfoxide / Q000737:chemistry / Q000627:therapeutic use; D005260:Female; D051379:Mice; D008807:Mice, Inbred BALB C; D010778:Photochemotherapy; D017319:Photosensitizing Agents / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D011094:Polyethyleneimine / Q000737:chemistry / Q000627:therapeutic use; D011166:Porphyrins / Q000737:chemistry / Q000627:therapeutic use
D017319:Photosensitizing Agents; D011166:Porphyrins; C006969:chlorin; D011094:Polyethyleneimine; D004121:Dimethyl Sulfoxide