title: Bactericidal effect of gentamicin trough concentration provides a rationale for administration of bolus doses and maintenance of trough levels.
abstract: An in-vitro study was made of the influence of trough gentamicin concentrations (Cmin) on the bactericidal effect of gentamicin against Escherichia coli NCTC 10418. Lag phase bacterial cells were exposed in vitro to gentamicin concentration versus time profiles which modelled profiles in patients up to 30 min after either an 80 mg iv bolus over 1 min or a 30 min infusion. The gentamicin was removed 30 min post-dose and the cultures were reconstituted in broth containing a constant trough gentamicin concentration in the range of 0-3 mg/L. Bacterial cfu counts and gentamicin concentrations were measured before and during antibiotic exposure. It was found that antibacterial activity was not determined by AUC, but rather there was a threshold trough concentration producing a bactericidal effect which differed between bolus and infusion profiles. With the bolus profile trough concentrations required for a bactericidal effect were 0.5-1.0 mg/L, while with the infusion profile generating an identical post-distribution peak concentration, trough concentrations required for a sustained bactericidal effect were 2.5-3.0 mg/L. These findings favour bolus iv gentamicin dosing over infusion dosing, provided appropriate attention is paid to any potential toxicity associated with high peak concentrations. Trough data indicate the likely need to maintain critical trough concentrations by choice of appropriate intervals between doses.
authors.affiliation: Monash University Department of Medicine, Prahran, Victoria, Australia.
authors.forename: A J
authors.initials: AJ
authors.lastname: McLean
authors.forename: E B
authors.initials: EB
authors.lastname: Bastone
authors.forename: L L
authors.initials: LL
authors.lastname: Ioannides-Demos
authors.forename: W J
authors.initials: WJ
authors.lastname: Spicer
mesh_terms: D004926:Escherichia coli / Q000187:drug effects*; D005839:Gentamicins / Q000008:administration & dosage / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D013997:Time Factors
chemical_list: D005839:Gentamicins