Re-evaluation of polihexanide use in wound antisepsis in order to clarify ambiguities of two animal studies

Abstract

Objective: Due to classification of the agent polihexanide (PHMB) in category 2 ‘may cause cancer’ by the Committee for Risk Assessment of the European Chemicals Agency in 2011, the users of wound antiseptics may be highly confused. In 2017, this statement was updated, defining PHMB up to 0.1% as a preservative safe in all cosmetic products. In the interest of patient safety, a scientific clarification of the potential carcinogenicity of PHMB is necessary. Methods: A multidisciplinary team (MDT) of microbiologists, surgeons, dermatologists and biochemists conducted a benefit-risk assessment to clarify the hazard of antiseptic use of PHMB. Results: In two animal studies, from which the assessment of a carcinogenic risk was derived, PHMB was administered orally over two years in extremely high concentrations far above the NO(A)EL (no-observed-(adverse-) effect level) in rats and mice. Feeding in the NO(A)EL range resulted in no abnormal effects. In one male in the highest dose group of 4000ppm PHMB, an adenocarcinoma was found, which the author attributed to chronic inflammation of the colon with systemic atypical exposure. The increasing incidence of hemangiosarcomas highly probably resulted from increased endothelial proliferation, triggered by the exceedingly high dosage fed, because PHMB is not genotoxic and there is no evidence for epigenetic effects. Discussion: It is well known that PHMB is not absorbed when applied topically. Considering the absence of genotoxicity and epigenetic effects together with the interpretation of the animal studies, it is the consensus of the multidisciplinary experts that a carcinogenic risk from PHMB-use for wound antisepsis can be ruled out. Conclusion: On this basis and considering their effectiveness, tolerability and clinical evidence, the indications for PHMB based wound antiseptics are justified.

Antimicrobial and Antioxidative Activity of Newly Synthesized Peptides Absorbed into Bacterial Cellulose Carrier against Acne vulgaris

“…Nevertheless, the concentration of antimicrobial substances in modern antiseptics used for local treatment of wound and/or skin lesions frequently exceeds a value of 250 mg/L. The most prominent examples are octenidine- and polihexanide-containing antiseptics, of the aforementioned concentrations of antimicrobial substances equal of 1000 mg/L [ 46 , 47 ]. Regardless of the numerous positive features of commercial applied antiseptics for wounds, they nonetheless display specific limitations that peptides do not.…”

Staphylococcus aureus Keratitis: Incidence, Pathophysiology, Risk Factors and Novel Strategies for Treatment

“…One such example is the metal organic framework AGMNA, which includes silver (a known antimicrobial agent) and an anti-metabolite, 2-thio-nicotinic acid (H2MNA) [31]. This compound has been investigated as a substitute for the more widely used component polyhexanide, for which there are concerns due to its suspected carcinogenic effects [71]. AGMNA demonstrated higher effectiveness than polyhexanide against S. aureus, despite showing no signs of in vivo or in vitro toxicity [72].…”

Efficacy of universal preoperative decolonization with Polyhexanide in primary joint arthroplasty on surgical site infections. A multicenter before-and after-study

“…Therefore, alternative substances and decolonization strategies have been evaluated or are currently being used [18,19]. Polyhexanide is a safe antiseptic substance, which is widely used for wound disinfection [20][21][22]. A randomized controlled trial showed no superiority for the decolonization of MRSA carriers when compared to placebo [21].…”