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Previous studies have shown that the high dose of gentamicin (8 mg/kg) rarely achieves the desired peak plasma concentration (Cmax) of ≥30 mg/l in patients with severe sepsis or septic shock. The aim of this study was to determine the first dose of gentamicin needed to achieve a Cmax ≥ 30 mg/l. We conducted a prospective observational cohort study in one intensive care unit. All consecutive patients hospitalized for severe sepsis or septic shock and treated with a first dose of gentamicin >6 mg/kg were evaluated. During the study period, 15 of the 57 patients (26.3 %) treated with gentamicin had a Cmax ≥ 30 mg/l. The median dose of gentamicin administered was 8.9 [7.8-9.9] mg/kg. Independent factors in the multivariate analysis associated with a Cmax ≥ 30 mg/l were higher body mass index (per kg/m increment) (OR: 1.173, 95%CI: 1.015-1.356, P = 0.03) and higher first dose of gentamicin (per mg/kg increment) (OR: 2.343, 95%CI: 1.346-4.08, P = 0.003). The optimal first dose to achieve a Cmax ≥ 30 mg/l was 11 mg/kg, with a specificity and a sensitivity of 100 % and 53.3 % respectively. These results suggest that a first dose of gentamicin >11 mg/kg is needed to achieve a Cmax ≥ 30 mg/l in most patients. [ABSTRACT FROM AUTHOR]