title: Bactericidal effect of gentamicin peak concentration provides a rationale for administration of bolus doses.
abstract: A study was made of the influence of peak gentamicin concentration (Cmax) independent of the area under the antibiotic concentration-time curve (AUC) on the bactericidal effect of gentamicin against Escherichia coli NCTC 10418. Bacteria in the lag phase were exposed to in-vitro gentamicin concentration-time profiles which modelled complete profiles determined in vivo in patients after an intravenous bolus (1 min) or infusion (30 min) regimen. An additional in-vitro profile reflected antibiotic removal 30 min after bolus dosing. Bacterial viable cell counts and gentamicin concentrations were measured before and during antibiotic exposure. Both Cmax and AUC were shown to be factors determining antibacterial activity; however Cmax independently represented some 35% of total exposure effect. These findings indicate grounds for preferring bolus intravenous gentamicin dosing with appropriate attention to potential toxicity.
authors.affiliation: Department of Clinical Pharmacology, Alfred Hospital Campus, Prahran, Victoria, Australia.
authors.forename: A J
authors.initials: AJ
authors.lastname: McLean
authors.forename: L L
authors.initials: LL
authors.lastname: IoannidesDemos
authors.forename: S C
authors.initials: SC
authors.lastname: Li
authors.forename: E B
authors.initials: EB
authors.lastname: Bastone
authors.forename: W J
authors.initials: WJ
authors.lastname: Spicer
mesh_terms: D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000187:drug effects; D005839:Gentamicins / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology*; D007275:Injections, Intravenous; D008826:Microbial Sensitivity Tests; D008954:Models, Biological
chemical_list: D005839:Gentamicins