This study was undertaken to evaluate the in vitro activities of arbekacin-based combination regimens against vancomycin hetero-intermediate Staphylococcus aureus (hetero-VISA). Combinations of arbekacin with vancomycin, rifampin, ampicillin-sulbactam, teicoplanin, or quinipristin-dalfopristin against seven hetero-VISA strains and two methicillin-resistant S. aureus strains were evaluated by the time-kill assay. The combinations of arbekacin with vancomycin, teicoplanin, or ampicillinsulbactam showed the synergistic interaction against hetero-VISA strains. Data suggest that these arbekacin-based combination regimens may be useful candidates for treatment options of hetero-VISA infections.
Virginiamycin/administration & dosage ; Vancomycin/*administration & dosage ; Teicoplanin/administration & dosage ; Sulbactam/administration & dosage ; Staphylococcus aureus/*drug effects/isolation & purification ; Staphylococcal Infections/drug therapy/microbiology ; Microbial Sensitivity Tests ; Methicillin Resistance ; Humans ; Drug Synergism ; Drug Resistance, Bacterial ; Dibekacin/administration & dosage/*analogs & derivatives ; Anti-Bacterial Agents/*administration & dosage ; Ampicillin/administration & dosage ; Aminoglycosides/*administration & dosage

PURPOSE: The present study was conducted to determine and compare the target attainment rate (TAR) between microorganism-nonspecific (Ctrough) and microorganism-specific (AUC24/MIC) targets over two weeks of teicoplanin administration according to several dose regimens for the treatment of Staphylococcus aureus in Korean patients with neutropenic fever. MATERIALS AND METHODS: One thousand virtual concentrations were obtained for each dose using the population pharmacokinetic parameters of teicoplanin adopted from a published study. Simulation of 1,000 virtual MICs was performed using the MICs of 78 clinical isolates of S. aureus collected from a hospital in Korea. Thereafter, these simulated MICs were randomly allocated to 1,000 virtual patients in whom the TARs for AUC24/MIC >125 [or 345] and Ctrough >10 [or 20] mg/L were determined. The relationship of the maintenance dose with the steady-state TAR was predicted with respect to the AUC24/MIC >125 [or 345] using logistic analysis. RESULTS: The standard dose regimen of teicoplanin showed TARs of about 70% [or 33%] and 70% [or 20%] at steady-state in cases with AUC24/MIC >125 [or 345] and Ctrough >10 [or 20] mg/L, respectively. CONCLUSION: The current standard dose regimen was predicted to be insufficient to adequately treat S. aureus in Korean patients with neutropenic fever. To assure at least an 80% TAR in this population, dose adjustment of teicoplanin should be considered.
Anti-Bacterial Agents/administration & dosage/*pharmacology/therapeutic use ; Computer Simulation ; Dose-Response Relationship, Drug ; Fever/drug therapy/microbiology ; Humans ; Microbial Sensitivity Tests ; Neutropenia/drug therapy/microbiology ; Republic of Korea ; Staphylococcal Infections/drug therapy ; Staphylococcus aureus/*drug effects ; Teicoplanin/administration & dosage/*pharmacology/therapeutic use ; Treatment Outcome