Discussion
For burns,14 trauma wounds and diabetic feet,15 the application of topical antimicrobials is vital when there is suspected risk or frank evidence of wound infection. When selecting an appropriate disinfectant, both its antibacterial efficacy and toxicity to wound cells must be considered.
Here, we selected and compared povidone-iodine, chlorhexidine acetate and PHMB, which are all commonly used in clinical therapy and have broad-spectrum bactericidal efficacies.10 In this study, we set disinfectant concentrations that are frequently used in clinical practice. Dilution ratios were used to identify cytotoxicity and bactericidal efficacy. In this manner, horizontal comparisons can be made and misinterpretations often associated with comparing absolute concentrations can be avoided.16 The bacteria tested are species typically found in wounds and the two cell types, HF and HaCat, used in the experiments, are known to play important roles in wound healing.
Studies have shown that the direct application of standard disinfectants to wounds significantly reduces cellular activity, even when the contact time is only 5 s. This could impair or delay wound healing. However, the wound is complete, and there is some compensation. Moreover, the presence of dead cells on the wound surface may impede access of the disinfectant to wound cells.17 This suggests that it is more beneficial to apply normal saline than disinfectants to aid wound healing in cases where there is no evidence of obvious wound infection.
Disinfectants are not immediately eliminated on contact with the wound. Certain slow-release disinfectant formulations maintain prolonged contact with the wound tissue. The residual concentration of slow-release disinfectants was relatively low. Nevertheless, our study suggested that, even at very low disinfectant concentrations, prolonged exposure may cause substantial cytotoxicity. Povidone-iodine was the most cytotoxic of the three disinfectants tested in this study, with a significant impact on cellular activity. Even when diluted to 1/512 of the standard concentration, povidone-iodine induced pronounced morphological changes in cells. At higher concentrations, povidone-iodine solidified the cells. In contrast, chlorhexidine acetate and PHMB had relatively lower cytotoxicity than povidone-iodine. In general, cytotoxicity decreased with contact time and concentration. At a 1/512 dilution, neither chlorhexidine acetate nor PHMB had a dramatic effect on cell survival. However, chlorhexidine acetate was less toxic to HF, whereas PHMB was comparatively less toxic to HaCat. Thus, PHMB is suitable for the treatment of shallow wounds primarily repaired by keratinocyte growth and migration.
All three disinfectants showed similar effects on apoptosis. Therefore, disinfectants may have negative impacts on the overall long-term wound healing prognosis as they increase apoptosis and are directly cytotoxic.
S. aureus, A. baumannii and K. pneumoniae are the common causative bacteria in wound infections. Povidone-iodine, chlorhexidine acetate and PHMB have good antibacterial efficacy against these species. The MICs and MBCs of all three disinfectants were significantly lower than the standard concentrations. Nevertheless, the MIC and MBC dilution ratios for povidone-iodine were lower than those for the other two disinfectants. Thus, povidone-iodine has a relatively weak antibacterial efficacy in vitro.
Despite the useful data reported, this study had certain limitations. Cytotoxicity tests were conducted in vitro. This environment is physically different from that of wounds. Our research raises some questions regarding traditional wound treatment. If there is no risk of infection in the wound, it is not necessary to use a disinfectant. However, determining whether there is a risk of infection in the wound is a new and difficult task.