Biomedical subjects
Publications and source records attributed to Angela M Nilius.
A novel series of antimicrobials of the oxazolidinone class is disclosed. These compounds are characterized relative to previously described analogues by a 'halostilbene-derived' pharmacophore and demonstrate enhanced antimicrobial activity against key Gram-positive pathogens when compared to Linezolid.
Community-acquired methicillin-resistant Staphylococcus aureus (MRSA) infections are increasing. Since most published data are on nosocomial MRSA, our goal was to identify the antimicrobial susceptibility profile and resistance mechanisms of pretreatment MRSA isolates obtained from adult subjects participating in recent clinical treatment trials of community respiratory infections. Out of 465 S. aureus isolates, 43 were identified as MRSA. Antimicrobial susceptibility testing indicated susceptibility rates to: vancomycin (100%), gentamicin (86%), clindamycin (39%), quinolones (49%), and erythromycin (12%). Among our MRSA isolates, the MLS constitutive phenotype and ermA were more prevalent than the MLS inducible phenotype and ermC. No isolates had ermB or msrA. All ciprofloxacin resistant isolates had an amino acid change in GyrA and GrlA. The relatedness of our MRSA strains was assessed by ribotyping. Our results indicate that MRSA from adult subjects with community respiratory infections have similar antimicrobial susceptibility profiles and resistance mechanisms as nosocomial MRSA, and represent a genetically diverse group.
The prevalence of antibiotic resistance in bacterial pathogens associated with community-acquired respiratory tract infections is increasing. Ketolides, semi-synthetic derivatives of erythromycin, overcome the macrolide resistance mechanisms found in Streptococcus pneumoniae and Streptococcus pyogenes, two key pathogens. They also have improved potency and longer post-antibiotic effects, while maintaining the antibacterial spectrum of the macrolide class. The new ketolides cethromycin (ABT-773) and telithromycin have overall antibacterial properties that suggest they will be clinically useful new antibiotics and are undergoing clinical development and regulatory review.
Attempts were made to select mutants on agar media containing the new ketolide ABT-773, erythromycin or rifampicin, at concentrations above the MICs, from Staphylococcus aureus, Streptococcus pneumoniae, Streptococcus pyogenes and Haemophilus influenzae, including erythromycin-resistant strains. ABT-773 did not select for mutants in four strains, whereas in eight strains the frequencies at 72 h were < or = 10(-9). ABT-773 MICs were 0.015-4 mg/L for mutants, except those selected from inducible Erm(A) S. aureus. Mutants selected on ABT-773 or erythromycin were cross-resistant to ABT-773, erythromycin and, sometimes, clindamycin. The susceptibility profiles indicate that different mutations were selected and that ABT-773 and erythromycin may interact with the ribosome differently.