Clinical Microbiology and Antimicrobial Chemotherapy. 2004; 6(1):32-50
In vitro studies and animal models have shown that clinical efficacy of β-lactams depends on the duration of time plasma drug concentration needed to exceed the minimal inhibitory concentration for causative microorganism (time above MIC). In general, time above MIC for about 50% of the dosing interval is strongly associated with successful treatment outcomes. Several clinical trials have also confirmed these data. This PK-PD parameter should be more strict for immunocompromised patients – time above 5MIC for 100% of the dosing interval. Continuous infusion of β-lactams provides adequate plasma drug concentration for 100% of the dosing interval. Clinical studies of patients with cystic fibrosis, gram-positive infections, febrile neutropenia, and gram-negative sepsis have shown that continuous infusion is at least as effective as conventional intermittent bolus infusion. Continuous infusion also permits daily dose of drug to be reduced without deterioration of treatment outcomes and increase in adverse drug reactions rate. Continuous infusion appears to have some pharmacokinetic, economic and clinical advantages compared to intermittent administration. However, benefits of this approach require further clinical investigations to be conducted.