The impact of duration of antibiotic exposure on bacterial resistance predictions using in vitro dynamic models.

Objectives: To explore whether the duration of in vitro simulated antibiotic exposure influences bacterial resistance, time-dependent amplification of resistant subpopulations of Staphylococcus aureus was studied in 10 day simulations in a dynamic model with daptomycin as a prototypic agent.

Methods: S. aureus ATCC 43300 was exposed to once-daily dosing of daptomycin at subtherapeutic ratios of 24 h area under the curve (AUC(24)) to the MIC (32 and 64 h).

Linezolid pharmacodynamics with Staphylococcus aureus in an in vitro dynamic model.

To describe the relationship between the ratio of the 24-h area under the concentration-time curve (AUC(24)) to minimum inhibitory concentration (MIC) as well as the effect of linezolid on Staphylococcus aureus, the killing kinetics of three S. aureus strains was studied by in vitro simulation of 5-day antibiotic dosing over a wide range of AUC(24)/MIC ratios. Similarly susceptible meticillin-resistant S.

Enrichment of resistant Staphylococcus aureus at ciprofloxacin concentrations simulated within the mutant selection window: bolus versus continuous infusion.

Enrichment of resistant mutants at antibiotic concentrations above the minimum inhibitory concentration (MIC) but below the mutant prevention concentration (MPC), i.e. within the mutant selection window (MSW), might be dependent on the shape of the pharmacokinetic profile.

Telavancin and vancomycin pharmacodynamics with Staphylococcus aureus in an in vitro dynamic model.

Objectives: The aim of this study was to compare the pharmacodynamics of telavancin (TLV) and vancomycin (VAN) with Staphylococcus aureus. Their concentrations were simulated between the MIC and the mutant prevention concentration (MPC), and above the MPC.

Methods: Two strains of S.

Enrichment of fluoroquinolone-resistant Staphylococcus aureus: oscillating ciprofloxacin concentrations simulated at the upper and lower portions of the mutant selection window.

The time inside the mutant selection window (MSW), T(MSW), appears to be less predictive of the selection of fluoroquinolone-resistant Staphylococcus aureus than is the ratio of the area under the concentration-time curve (AUC) to the MIC. This observation might be attributed to the fact that T(MSW) does not consider the actual position of simulated antibiotic concentrations inside the MSW, which also might influence the amplification of resistant mutants. To test this hypothesis, the enrichment of ciprofloxacin-resistant S.

Concentration-response relationships as a basis for choice of the optimal endpoints of the antimicrobial effect: daptomycin and vancomycin pharmacodynamics with staphylococci in an in vitro dynamic model.

The abilities of different indices of bacterial killing to ensure reasonable concentration-response relationships have been compared only in studies in vitro with fluoroquinolones. To ascertain the relevance of conclusions drawn in these studies to other antibiotic classes, five widely used indices that reflect the rate of initial killing (time to reduce the initial inoculum 10- and 100-fold-T(90%) and T(99%), respectively), the extent of killing (minimal number of surviving organisms-N(min)), and the entire antimicrobial effect (number of surviving organisms (N(t)) at the time t close to the end of the observation period (48 h in most experiments), and area between the control growth curve and the time-kill curve from zero point to t-ABBC) were examined with daptomycin (DAP)- and vancomycin (VAN)-exposed Staphylococcus aureus. To compare the pharmacodynamics of DAP and VAN and examine different parameters, killing kinetics of differentially susceptible S.

Testing the mutant selection window hypothesis with Staphylococcus aureus exposed to daptomycin and vancomycin in an in vitro dynamic model.

Objectives: To extend the mutant selection window (MSW) hypothesis to include antibiotics in addition to fluoroquinolones, the pharmacodynamics of daptomycin (DAP) and vancomycin (VAN) and their ability to prevent the selection of resistant Staphylococcus aureus were studied in an in vitro model that simulates antibiotic concentrations below the MIC, between the MIC and the mutant prevention concentration (MPC), and above the MPC.

Methods: Two clinical isolates of S. aureus, S.

Comparative pharmacodynamics of the new fluoroquinolone ABT492 and levofloxacin with Streptococcus pneumoniae in an in vitro dynamic model.

The kinetics of killing of Streptococcus pneumoniae exposed to ABT492 or levofloxacin were compared. S. pneumoniae ATCC 49619 and four ciprofloxacin-resistant clinical isolates, S.