Differential effect of rpoB mutations on antibacterial activities of rifampicin and KRM-1648 against Staphylococcus aureus.
The in vitro antibacterial activities of the rifamycin derivatives rifampicin and KRM-1648 against 150 Staphylococcus aureus isolates were determined. The MICs of rifampicin and KRM-1648 for 90% of rifampicin-susceptible S. aureus isolates (n = 100) were 0.016 and 0.001 mg/L, respectively. In rifampicin-resistant S. aureus isolates (n = 50), different levels of resistance to rifamycins were associated with mutations at different sites in rpoB. Mutations at some sites were associated with high-level resistance to both rifamycins, while certain mutations were associated with the activity of KRM-1648 being < or = 100-fold better than that of rifampicin.
Wichelhaus
T
T
Institute of Medical Microbiology, University Hospital, Paul-Ehrlich-Strasse 40, 60596 Frankfurt am Main, Germany. wichelhaus@em.uni-frankfurt.de
Schäfer
V
V
Brade
V
V
Böddinghaus
B
B
D000904:Antibiotics, Antitubercular / Q000494:pharmacology*; D012321:DNA-Directed RNA Polymerases; D004352:Drug Resistance, Microbial; D005798:Genes, Bacterial / Q000187:drug effects*; D005838:Genotype; D008826:Microbial Sensitivity Tests; D009154:Mutation / Q000235:genetics*; D010940:Plant Proteins / Q000235:genetics*; D012293:Rifampin / Q000494:pharmacology*; D012294:Rifamycins / Q000494:pharmacology*; D013211:Staphylococcus aureus / Q000187:drug effects*
D000904:Antibiotics, Antitubercular; D010940:Plant Proteins; D012294:Rifamycins; C101305:RpoB protein, Oryza sativa; C068980:KRM 1648; D012321:DNA-Directed RNA Polymerases; D012293:Rifampin