The beneficial toxicity paradox of antimicrobials in leg ulcer healing impaired by a polymicrobial flora: a proof-of-concept study.
BACKGROUND
Some of the views contrasting the beneficial and toxic effects of antimicrobials upon wound healing remain controversial.


OBJECTIVE
To assess the clinical relevance of histological findings following antimicrobial applications on chronic leg ulcers.


METHODS
The present study was performed in three parallel groups of 17 patients suffering from at least 2 similar chronic leg ulcers. Clinical planimetric assessments were performed before and after 3 and 6 weeks of treatment using hydrocolloid dressings. In addition, 1 ulcer in each patient received applications of povidone-iodine (PVP-I), silver sulfadiazine or chlorhexidine digluconate. Histological examinations were made at inclusion and after the 6-week therapy. Time to healing was also recorded.


RESULTS
At entry in the study, fibroblasts, macrophages, neutrophils and vessels were abundant in the ulcers. In addition, focal necrotizing vasculitis was related to the microbiological load. Compared to the control lesions, both the healing rate and time to healing of the leg ulcers showed a modest improvement at the sites receiving silver sulfadiazine (2-7%) or chlorhexidine digluconate (-1 to 5%). By contrast, PVP-I increased significantly the healing rate (4-18%, p < 0.01), and time to healing was reduced by 2-9 weeks (p < 0.01). The 3 antimicrobials decreased the bacterial density, and the vascular margination and migration of inflammatory cells, thus abating the vasculitic changes. PVP-I applications did not alter the microvessels and did not significantly reduce the density in dendrocytes and fibroblasts. By contrast, both silver sulfadiazine and chorhexidine digluconate appeared to alter the superficial microsvasculature including the dendrocyte population.


CONCLUSIONS
Although topical antimicrobials may apparently achieve almost similar activity on the bacterial load inside chronic leg ulcers, the toxicity upon host cells was different among these agents. PVP-I appeared to be an efficient compound in these respects exhibiting a positive and relevant clinical effect.
Fumal
I
I
Department of Dermatopathology, University Medical Center, Liège, Belgium.
Braham
C
C
Paquet
P
P
Piérard-Franchimont
C
C
Piérard
G E
GE
D000891:Anti-Infective Agents, Local / Q000009:adverse effects / Q000627:therapeutic use*; D002710:Chlorhexidine / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D007871:Leg Ulcer / Q000188:drug therapy* / Q000382:microbiology*; D008875:Middle Aged; D011206:Povidone-Iodine / Q000009:adverse effects / Q000627:therapeutic use*; D012837:Silver Sulfadiazine / Q000009:adverse effects / Q000627:therapeutic use; D014945:Wound Healing / Q000187:drug effects*
D000891:Anti-Infective Agents, Local; D011206:Povidone-Iodine; C010882:chlorhexidine gluconate; D002710:Chlorhexidine; D012837:Silver Sulfadiazine