PubMed · 14220220
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S L VINCI. 1965. LABOR BY INDUCTION.. https://pubmed.ncbi.nlm.nih.gov/14220220/
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OBJECTIVES: Infections caused by Staphylococcus aureus might be treated with agents whose primary indications are for other infections. Clofazimine, an established anti-mycobacterial drug, could be such a candidate. However, the anti-staphylococcal properties of clofazimine have not been fully described and its mode of action, possibly involving inhibition of both RNA polymerase and a membrane-located target, has not been explored in detail. We have now conducted experiments to address these issues. METHODS: Using established procedures, we examined the activity of clofazimine against a range of clinical isolates of S. aureus and determined whether it was bactericidal, exhibited a post-antibiotic effect (PAE), or interacted synergically with other agents. The potential for emergence of clofazimine-resistant mutants was also examined. Mode of action studies involved macromolecular synthesis assays, cross-screening against rifampicin-resistant mutants, susceptibility of RNA polymerase to clofazimine in vitro and several methods to detect drug-induced membrane damage. RESULTS: Clofazimine demonstrated good anti-staphylococcal activity encompassing MSSA, MRSA and GISA. It was bactericidal and resistant mutants could not be isolated. Clofazimine did not exhibit a PAE and failed to act synergically with other drugs. No evidence for specific inhibition of RNA polymerase was obtained. Clofazimine caused non-specific inhibition of DNA, RNA and protein synthesis, consistent with membrane-damaging activity that was detected in three independent assays for membrane disrupting agents. CONCLUSIONS: Clofazimine is a potent anti-staphylococcal agent. It appears to be a membrane-disrupting agent and does not inhibit RNA polymerase.
The aim of this study was to evaluate the susceptibility of methicillin-susceptible and methicillin-resistant staphylococci (MSS, MRS) to oregano essential oil, carvacrol and thymol. The commercial aerial parts of Origanum vulgare L. were hydrodistilled and the essential oil analysed by gas- chromatography/electron impact mass spectrometry. The inhibition efficacy of this essence and its major components was assayed against 26 MSS and 21 MRS, using an agar dilution method. The methicillin resistance was thoroughly typed by Epsilometer test (E-test), polymerase chain reaction for mecA gene detection and PBP2' latex agglutination test. The results clearly demonstrated that the comparison between the susceptibility of MSS and MRS to oregano oil, carvacrol and thymol showed no significant differences (Fisher's exact test, P > 0.05). The best minimum inhibitory concentration values were reported for carvacrol (0.015-0.03%, v/v) followed by thymol (0.03-0.06%, v/v) and oregano oil (0.06-0.125%, v/v).
The purpose of the present study was to compare Franz cells (FC) and microdialysis (MD) for monitoring the skin absorption of salicylic acid (SA). The influence of pH on SA flux was also assessed by these two techniques. Excised abdominal human skin was used in the experiments. SA was dissolved in phosphate buffer solutions of pH 2, 5 and 7 (2 mg/ml). SA concentrations in the receptor FC solutions and in MD samples were assessed by high performance liquid chromatography (HPLC). The results demonstrate that the flux of SA decreased with increased pH. The profiles permeation determined by Franz cells and microdialysis were similar. However, whatever the pH, the SA flux was higher with microdialysis than with Franz cells. The results showed that SA percutaneous permeation conformed to the pH partition hypothesis. The flux of SA was different when it was determined by the two techniques. The collect of SA, by these two techniques is different. The results of the two techniques are compared and discussed.