Kill kinetics and regrowth patterns of Escherichia coli exposed to gentamicin concentration-time profiles simulating in vivo bolus and infusion dosing

The relative influence of peak concentration (Cmax) versus the area under the antibiotic concentration-time curve (AUC) on the bactericidal effect of gentamicin against Escherichia coli NCTC 10418 was studied. Bacteria in the lag phase were exposed to an in vitro gentamicin concentration series which mirrored the concentrations determined in patients after 80-mg intravenous bolus (1 min) and 80-mg intravenous infusion (30 min) doses. Bacterial viable cell counts and gentamicin concentrations were measured before and during antibiotic exposure. Both the Cmax and AUC were shown to be factors determining antibacterial activity; however, the Cmax was an independent determinant of effect. These findings indicate that bolus intravenous dosing with gentamicin could maximize bactericidal activity. Increased efficacy could result at any given daily antibiotic dose if delivered via bolus with long intervals (12 to 24 h) between doses if appropriate precautions to avoid toxicity are taken.