Balsacone C, a new antibiotic targeting bacterial cell membranes, inhibits clinical isolates of methicillin-resistant staphylococcus aureus (MRSA) without inducing resistance

New options are urgently needed for the treatment of methicillin-resistant Staphylococcus aureus (MRSA) infections. Balsacone C is a new dihydrochalcone extracted from Populus balsamifera that has been reported previously as being active against Staphylococcus aureus. Here, we evaluate the antibacterial activity of balsacone C against MRSA. Thirty-four (34) MRSA isolates were obtained from hospitalized patients; these isolates were then characterized for their resistance. Most of these MRSA (>85%) were resistant to penicillin, amoxicillin/clavulanic acid, ciprofloxacin, moxifloxacin, levofloxacin, clindamycin, erythromycin, and cefoxitin as well as being sensitive to linezolid, trimethoprim/sulfamethoxazole, rifampicin, and gentamicin. When tested against all MRSA isolates and various gram-positive bacteria, the antibacterial activity of balsacone C produced a MIC of 3–11.6 mg/mL. We observed no resistant isolates of MRSA (against balsacone C) even after 30 passages. Microscopy fluorescence showed that bacteria cell membrane integrity was compromised by low concentrations of balsacone C. Scanning electron microscope (SEM) confirmed balsacone C–provoked changes in the bacterial cell membrane and we find a dose-dependent release of DNA and proteins. This loss of cellular integrity leads to cell death and suggests a low potential for the development of spontaneous resistance

A randomized trial of tigecycline versus ampicillin-sulbactam or amoxicillin-clavulanate for the treatment of complicated skin and skin structure infections

Background: Complicated skin and skin structure infections (cSSSIs) frequently result in hospitalization with significant morbidity and mortality.Methods: In this phase 3b/4 parallel, randomized, open-label, comparative study, 531 subjects with cSSSI received tigecycline (100 mg initial dose, then 50 mg intravenously every 12 hrs) or ampicillin-sulbactam 1.5-3 g IV every 6 hrs or amoxicillin-clavulanate 1.2 g IV every 6-8 hrs. Vancomycin could be added at the discretion of the investigator to the comparator arm if methicillin-resistant Staphylococcus aureus (MRSA) was confirmed or suspected within 72 hrs of enrollment. The primary endpoint was clinical response in the clinically evaluable (CE) population at the test-of-cure (TOC) visit. Microbiologic response and safety were also assessed. The modified intent-to-treat (mITT) population comprised 531 subjects (tigecycline, n = 268; comparator, n = 263) and 405 were clinically evaluable (tigecycline, n = 209; comparator, n = 196).Results: In the CE population, 162/209 (77.5%) tigecycline-treated subjects and 152/196 (77.6%) comparator-treated subjects were clinically cured (difference 0.0; 95% confidence interval [CI]: -8.7, 8.6). The eradication rates at the subject level for the microbiologically evaluable (ME) population were 79.2% in the tigecycline treatment group and 76.8% in the comparator treatment group (difference 2.4; 95% CI: -9.6, 14.4) at the TOC assessment. Nausea, vomiting, and diarrhea rates were higher in the tigecycline group.Conclusions: Tigecycline was generally safe and effective in the treatment of cSSSIs.Trial registration: ClinicalTrials.gov NCT00368537. © 2012 Matthews et al.; licensee BioMed Central Ltd