The influence of various concentrations (0.003-8 mg/mL) of N-acetylcysteine on the formation of biofilms by 15 strains of Staphylococcus epidermidis has been studied. A dose-related decrease in biofilm formation was observed, except with the lowest concentrations. The 'slime' index relative to the control was 63%, 55%, 46%, 34%, 26% and 26% in the presence of 0.25, 0.5, 1, 2, 4, and 8 mg/mL of N-acetylcysteine, respectively. These data are statistically significant. The inhibitory effect of 2 mg/mL of N-acetylcysteine on slime formation was also verified by electron microscopy.
Aims: The aim of this study is to determine the in vitro activity of allicin against Staphylococcus epidermidis and to evaluate the influence of allicin on biofilm formation. Methods and Results: In vitro activity of allicin (diallyl thiosulphinate) against 38 strains of S. epidermidis was investigated. The activity of allicin was similar against S. epidermidis methicillin susceptible and methicillin resistant strains [minimum inhibitory concentration (MIC) 90 ¼ 8 mg l)1 ]. In general, subinhibitory concentrations (sub-MIC) of allicin diminished biofilm formation in the five strains analysed.
Conclusion:The results confirm the antibacterial effect of allicin. Sub-MICs of allicin also diminished the biofilm formations by S. epidermidis. Significance and Impact of the Study: The present study shows that allicin is active in vitro against S. epidermidis and that sub-MICs of allicin may play a role in the prevention of adherence of this bacteria to medical devices.
Purpose: A dose-escalation, phase I study evaluated the safety, pharmacokinetics, and efficacy of a weekly 1-h regimen of kahalalide F, a cyclic depsipeptide isolated from the marine mollusk Elysia rufescens, in adult patients with advanced solid tumors and no standard treatment available.
Experimental Design: Patients received an i.v. 1-h infusion of kahalalide F once weekly until disease progression or unacceptable toxicity. The starting kahalalide F dose was 266 μg/m2, and dose escalation proceeded based on the worst toxicity found in the previous cohort.
Results: Thirty-eight patients were enrolled at three Spanish institutions and received once-weekly kahalalide F 1-h infusions at doses between 266 and 1,200 μg/m2. Dose-limiting toxicities consisted of transient grade 3/4 increases in transaminase blood levels. The maximum tolerated dose for this kahalalide F schedule was 800 μg/m2, and the recommended dose for phase II studies was 650 μg/m2. No accumulated toxicity was found. One patient with malignant melanoma had unconfirmed partial response, one patient with metastatic lung adenocarcinoma had minor response, and six patients with different types of metastatic solid tumors had stable disease for 2.8 to 12.7 months. The noncompartmental pharmacokinetics of this kahalalide F schedule was linear and showed a narrow distribution and short body residence. The transaminitis associated with kahalalide F was dose dependent.
Conclusions: The maximum tolerated dose was 800 μg/m2. Dose-limiting toxicities with weekly kahalalide F 1-h i.v. infusions were transient grade 3/4 increases in blood transaminase levels, and 650 μg/m2 was declared the recommended dose for phase II studies. This schedule showed a favorable safety profile and hints of antitumor activity.
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