The decisive study: defining beta-lactam concentration in Intensive care unit patients.

Summary of Research Findings: 1. Patients age, estimated CLcr and recent surgery significantly predicted the Vd and CL of both beta-lactams. Piperacillin and meropenem concentrations were highly-variable with coefficient of variation (COV) of ≥67.7%. Forty-nine patients (58.3%) achieved the PK/PD target and they tend to be older, with slower CLcr and receiving continuous infusion. Based on the most parsimonious logistic regression model, higher CLcr and intermittent infusion were significant predictors of sub-optimal PK/PD target attainment. 2. Malaysian physicians are receptive to PK/PD approach in antibiotic optimization among ICU patients. Nonetheless, there is still a gap in the knowledge of antibiotic PK/PD as well as its application in the critically ill, especially for β-lactams. We also found variable compliance to guidelines for antibiotic choice, as well as antibiotic dosing, for commonly encountered infections in ICU. This warrants further study and interventions in order to improve guideline compliance among local physician. 3. Early and appropriate administration of antimicrobial therapy remains the most important intervention in managing sepsis. To achieve favourable outcomes, the goal is to achieve effective drug concentrations at the site of infection. In critically ill patients, development of organ failure may complicate antibiotic dosing. Two pharmacokinetic parameters that vary with greatest significance in patients with MODS are Vd and drug CL. In presence of AKI, antibiotic dose adjustments in patients with reduced clearance are commonly applied to avoid adverse effects. Augmented renal clearance is another important phenomenon which is a manifestation of enhanced renal function. Early recognition of patients at risk of ARC allows further intervention to prevent antibiotic failure. In patients with ARC, higher doses of renal eliminated antibiotics are recommended or administration of non-renally eliminated drugs should be considered