The Beneficial Toxicity Paradox of Antimicrobials in Leg Ulcer Healing Impaired by a Polymicrobial Flora: A Proof-of-Concept Study

Abstract

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. Method: 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. Conclusion: 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.

What Is the Evidence for Tissue Regeneration Impairment when Using a Formulation of PVP-I Antiseptic on Open Wounds?

“…The higher‘quality’ literature reviews that are ‘pro’ PVP-I do so as they argue the ‘inappropriateness’ of non-human in vivostudies and laboratory in vitrostudies. In fact, only 1 study investigated the use of PVP-I on chronic ulcers where Fumal et al [18] (a quality article scoring 21 on the READER scoring tool [5]) studied the effect of PVP-I on chronic leg ulcers in comparison to other known medicaments. Their results determined a statistically significant improvement in healing time with the use of PVP-I (p < 0.01) in comparison to silver sulfadiazine and chlorhexidine digluconate.…”

A Clinical Study on the Tolerability of a Liposomal Povidone-Iodine Nasal Spray: Implications for Further Development

“…Therefore, it may be assumed that PVP-I, like other antiseptics, primarily inhibits wound healing. In clinical practice, this is overcompensated by the anti-infective effect [22] . By treating infections or preventing their development PVP-I is providing secondary wound healing support [22,23] .…”

Negative pressure wound therapy with instillation (NPWTi): Current status, recommendations and perspectives in the context of modern wound therapy.

“…66 Povidone-iodine solution did not negatively influence bed wound healing. 67,68 Additionally, in comparison to other antiinfective agents (e.g. neomycin), the sensitization rate of povidone-iodine is relatively low.…”