Monte Carlo simulation in the evaluation of susceptibility breakpoints: predicting the future: insights from the society of infectious diseases pharmacists.
Appropriate treatment with antimicrobials involves factors we cannot control. Factors such as interpatient variability in drug exposure, the minimum inhibitory concentration (MIC) of the infecting pathogen, and the patient's clinical status clearly affect the therapeutic response. Despite these uncertainties, we can estimate the probability of attaining a successful therapeutic outcome in the context of factors that are within our control. Chief among these are drug, dose, and the dosing interval. One way to predict the probability of a positive therapeutic outcome is through the use of an integrated pharmacokinetic-pharmacodynamic stochastic model. Pharmacokinetic-pharmacodynamic target attainment analyses using Monte Carlo simulation to integrate interpatient variability in drug exposure, drug potency, and in vivo exposure targets predictive of positive therapeutic outcomes are influencing antibacterial susceptibility breakpoints at home and abroad. The consequences of this paradigm shift are far reaching, affecting the commercial concerns of drug and susceptibility testing device manufacturers, perceptions about antimicrobial resistance, and ultimately patient care decisions.
Ambrose
Paul G
PG
Institute for Clinical Pharmacodynamics, Ordway Research Institute, 150 New Scotland Avenue, Albany, NY 12208, USA. PAmbrose-ICPD@OrdwayResearch.org
D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D002439:Cefotaxime / Q000494:pharmacology / Q000627:therapeutic use; D002443:Ceftriaxone / Q000494:pharmacology / Q000627:therapeutic use; D024881:Drug Resistance, Bacterial; D006801:Humans; D015233:Models, Statistical; D009010:Monte Carlo Method; D011008:Pneumococcal Infections / Q000188:drug therapy* / Q000382:microbiology; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000201:enzymology; D001618:beta-Lactamases / Q000378:metabolism
D000900:Anti-Bacterial Agents; D002443:Ceftriaxone; D001618:beta-Lactamases; D002439:Cefotaxime