Evaluation of accessory gene regulator (agr) group and function in the proclivity towards vancomycin intermediate resistance in Staphylococcus aureus.
Simulated therapeutic vancomycin exposures were evaluated against agr wild-type and knockout Staphylococcus aureus groups I, II, III, and IV using an in vitro pharmacodynamic model. All agr groups developed intermediate resistance to vancomycin after subtherapeutic exposure. The free unbound fraction of the area under the concentration-time curve (fAUC/MIC) required to suppress resistance was fourfold higher (P < 0.001) in agr dysfunctional strains (112 to 169) than that in parent wild-type strains (28).
Tsuji
Brian T
BT
Anti-Infective Research Laboratory, Pharmacy Practice-4148, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, 259 Mack Avenue, Detroit, MI 48201, USA.
Rybak
Michael J
MJ
Lau
Kerry L
KL
Sakoulas
George
G
D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics; D019540:Area Under Curve; D001426:Bacterial Proteins / Q000502:physiology*; D003198:Computer Simulation; D006801:Humans; D008826:Microbial Sensitivity Tests; D013211:Staphylococcus aureus / Q000187:drug effects* / Q000235:genetics*; D015534:Trans-Activators / Q000502:physiology*; D014640:Vancomycin / Q000493:pharmacokinetics; D020713:Vancomycin Resistance / Q000235:genetics*
C095698:Agr protein, Staphylococcus aureus; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D015534:Trans-Activators; D014640:Vancomycin