Winning the Race: Bacterial Growth versus Dynamic Dosage of Antimicrobial Compounds

Abstract

Great pain and suffering to patients as well as high financial burden to health care systems are caused by chronic wounds. The interrupted wound healing mechanism is often due to increased bacterial load, whereof conventional treatment via antibiotics is affected by a recent increase in developing multiple antibiotic resistances. This suggests alternative treatments like wound dressings that release antimicrobial substances. A model for dynamic dosage of the antiseptic compound polyhexamethylene biguanide (PHMB) was introduced to investigate the time-kill behaviour of Gram-negative Pseudomonas aeruginosa and Gram-positive Staphylococcus aureus. This was hypothesised to allow findings about dependences on pharmacodynamic and pharmacokinetic parameters. Such knowledge might grant conclusions about necessary release kinetics of PHMB in wound dressings. Four different concentration profiles of PHMB were used, starting at 0 μM and then reaching the respective minimum inhibitory concentration (MIC) against bacteria after 3, 6, 9, and 24 h by linear increase. Bacteria were cultured in these concentration profiles for 48 h and regular viable count was performed. Reaching the MIC of PHMB after 3 h resulted in killing Pseudomonas aeruginosa, reaching it after 6 h showed inhibited growth and reaching it after 9 h or later showed no effect. Staphylococcus aureus still were killed by reaching the MIC of PHMB after 6 h, whereas reaching it after 9 h showed inhibited growth only. Reaching it later did not affect bacterial growth. After 48 h of culturing, all populations recovered to stationary growth phase. PHMB seemed to be more potent against Gram-positive Staphylococcus aureus. Conclusions about pharmacodynamic and pharacokinetic parameters of the effect of PHMB on bacteria were impeded as only a series of increasing, but no decreasing concentration gradients was tested. However, a greater effect during higher initial concentrations suggests dependence on the maximum concentration and on the time until the MIC is reached. Despite the necessity of further research that includes for instance a later decrease in concentration of PHMB, these early results suggest PHMB in wound dressings to be released as fast as possible and in a determined bactericidal dosage after application to the wound in order to act with highest efficacy of bacteria toxicity.