Activity of delafloxacin against methicillin-resistant Staphylococcus aureus: resistance selection and characterization.

OBJECTIVES: To determine the potential for delafloxacin to select for resistant mutants in methicillin-resistant Staphylococcus aureus (MRSA), including isolates with existing mutations in the quinolone resistance determining region (QRDR). METHODS: Susceptibility testing by broth microdilution was performed on 30 MRSA clinical isolates. For four of these isolates, the presence or absence of mutations in the QRDR was characterized. Resistance selection was performed on these four isolates by spreading cells on drug-containing agar plates followed by incubation for 48 h. Resistance frequencies and mutant prevention concentrations (MPCs) were calculated for each; PCR amplification and sequencing were performed using standard methods to characterize mutations in the QRDR. Growth rate analysis was performed and relative fitness was determined. RESULTS: Delafloxacin demonstrated potent in vitro activity against this set of MRSA isolates, with MICs of 0.008-1 mg/L and an MIC(50) and MIC(90) of 0.03 and 0.5 mg/L, respectively. Spontaneous delafloxacin resistance frequencies for the MRSA strains were 2 × 10(-9) to <9.5 × 10(-11). Delafloxacin MPCs were one to four times the MIC for any isolate, lower than those of comparator quinolones. Some delafloxacin-selected mutants showed a fitness cost when co-cultured with the parent strain. CONCLUSIONS: Delafloxacin demonstrates excellent antibacterial potency and exhibits a low probability for the selection of resistant mutants in MRSA. Although mutants can be selected at low frequencies in vitro from quinolone-resistant isolates, delafloxacin MICs and MPCs remain low and a fitness cost can be observed. Consequently delafloxacin warrants further investigation for the potential treatment of drug-resistant MRSA infections.

Ultrafine particle exposure during fire suppression--is it an important contributory factor for coronary heart disease in firefighters?

OBJECTIVE: Coronary heart disease (CHD) is the primary cause of death among US firefighters during fire suppression. In other populations, exposure to respirable particles, including ultrafine particles, has been widely implicated as a risk factor for CHD. This study is the first to report detailed characterization of respirable particles released by combustion of an automobile and model residential structures under firefighter exposure conditions. METHODS: Characterization was performed when feasible during knockdown and routinely during overhaul. RESULTS: Ultrafines accounted for >70% of particles in all fire suppression stages, occurring in concentrations exceeding background by factors between 2 (automobile) and 400 (bedroom), consistent among all structures. CONCLUSIONS: Exposure to ultrafine particles during fire suppression should be considered a potential contributing factor for CHD in firefighters. Of major significance is their predominance during overhaul, where firefighters frequently remove respiratory protection.

Bioactive saponins from Acacia tenuifolia from the suriname rainforest.

Bioassay-guided fractionation of the MeOH extract of Acacia tenuifolia using the engineered yeast strains 1138, 1140, 1353, and Sc7 as the bioassay tool resulted in the isolation of the three new saponins 3, 5, and 6 and the three known saponins 1, 2, and 4. The structures of the new compounds were established on the basis of HRMS, 1D and 2D NMR spectral data on the intact saponins, and GC-MS analyses of the sugars. Compounds 1,2 and 5,6 showed cytotoxicity against mammalian cell lines.