Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004610 (bacteremia)
 13,199 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Staphylococcus aureus, coagulase-negative staphylococci, and Enterococcus spp. represent the most frequently recovered organisms from bloodstream infections. As a treatment option, daptomycin has been recently approved for the treatment of S. aureus bacteremia and right-sided endocarditis. We evaluated the spectrum of activity and potency of daptomycin and other antibiotics against 142 linezolid-nonsusceptible clinical strains. The isolates were tested for susceptibility by reference broth microdilution methods utilizing physiologic free calcium ions levels (50 mg/L) when testing daptomycin. Staphylococcus spp. and Enterococcus spp. were selected and screened for 23S rRNA, L4 and L22 mutations, and the cfr gene. Daptomycin was potent against all linezolid-nonsusceptible staphylococci (minimal inhibitory concentrations [MIC](90), 0.5 microg/ml) and enterococci (MIC(90), 1 microg/ml) isolates at the respective breakpoints of <or=1 microg/ml and <or=4 microg/ml. The majority of the isolates (84.5%) showed ribosomal target-site alterations, mainly G2576T, and five isolates (two S. aureus and three Staphylococcus epidermidis) had the mobile cfr element. In conclusion, daptomycin was the most active agent tested against this collection of gram-positive clinical organisms and ribosomal target mutations comprised the main resistance mechanism against linezolid.
 ...
PMID:Daptomycin activity tested against linezolid-nonsusceptible gram-positive clinical isolates. 1985 29

Fifty-six Staphylococcus epidermidis clinical isolates, showing high-level linezolid resistance and causing bacteremia in critically ill patients, were studied. All isolates belonged to ST22 clone and carried the T2504A and C2534T mutations in gene coding for 23SrRNA as well as the C189A, G208A, C209T and G384C missense mutations in L3 protein which resulted in Asp159Tyr, Gly152Asp and Leu94Val substitutions. Other silent mutations were also detected in genes coding for ribosomal proteins L3 and L22. In silico analysis of missense mutations showed that although L3 protein retained the sequence of secondary motifs, the tertiary structure was influenced. The observed alteration in L3 protein folding provides an indication on the putative role of L3-coding gene mutations in high-level linezolid resistance. Furthermore, linezolid pressure in health care settings where linezolid consumption is of high rates might lead to the selection of resistant mutants possessing L3 mutations that might confer high-level linezolid resistance.
 ...
PMID:Accumulation of multiple mutations in linezolid-resistant Staphylococcus epidermidis causing bloodstream infections; in silico analysis of L3 amino acid substitutions that might confer high-level linezolid resistance. 2707 30