Effect of multidrug resistance-conferring mutations on the fitness and virulence of Pseudomonas aeruginosa.

Background: Multidrug resistance has become a quandary in the treatment of bacterial infections. The effect of resistance mutations and the fitness cost on the pathogenicity of Pseudomonas aeruginosa is not well established. The objective of this study was to examine the impact of multidrug resistance on the fitness and virulence of P.

Pharmacodynamic modeling of aminoglycosides against Pseudomonas aeruginosa and Acinetobacter baumannii: identifying dosing regimens to suppress resistance development.

To facilitate optimal dosing regimen design, we previously developed a mathematical model using time-kill study data to predict the responses of Pseudomonas aeruginosa to various pharmacokinetic profiles of meropenem and levofloxacin. In this study, we extended the model to predict the activities of gentamicin and amikacin exposures against P. aeruginosa and Acinetobacter baumannii, respectively.

Impact of sample size on the performance of multiple-model pharmacokinetic simulations.

Monte Carlo simulations are increasingly used to predict pharmacokinetic variability of antimicrobials in a population. We investigated the sample size necessary to provide robust pharmacokinetic predictions. To obtain reasonably robust predictions, a nonparametric model derived from a sample population size of >/=50 appears to be necessary as the input information.

Comparative performance of different stochastic methods to simulate drug exposure and variability in a population.

Monte Carlo simulations (MCSs) are increasingly being used to predict the pharmacokinetic variability of antimicrobials in a population. However, various MCS approaches may differ in the accuracy of the predictions. We compared the performance of 3 different MCS approaches using a data set with known parameter values and dispersion.

Comparative pharmacodynamics of gentamicin against Staphylococcus aureus and Pseudomonas aeruginosa.

Aminoglycosides are often used to treat severe infections with gram-positive organisms. Previous studies have shown concentration-dependent killing by aminoglycosides of gram-negative bacteria, but limited data are available for gram-positive bacteria. We compared the in vitro pharmacodynamics of gentamicin against Staphylococcus aureus and Pseudomonas aeruginosa.

Pharmacodynamics of polymyxin B against Pseudomonas aeruginosa.

Despite limited data, polymyxin B (PB) is increasingly used clinically as the last therapeutic option for multidrug-resistant (MDR) gram-negative bacterial infections. We examined the in vitro pharmacodynamics of PB against four strains of Pseudomonas aeruginosa. Clonal relatedness of the strains was assessed by random amplification of polymorphic DNA.