Dosing problems of gentamicin in critically ill patients.

Twenty critically ill patients with a diagnosis of possible or documented Gram-negative sepsis received gentamicin sulphate by i.v. short infusion (30 min). The same daily dose was administered in a variable frequency regimen (ten were treated by an 8 h frequency regimen and ten by a 12 h frequency regimen). Repeated measurements of gentamicin plasma levels and of serum creatinine, albumin, total proteins and haematocrit were performed simultaneously, with measurements of tubular casts, alkaline phosphatase, leucine aminopeptidase and gamma-glutamyl-transpeptidase activity in urine. There was a considerable variation in plasma gentamicin concentrations among individuals patients and in the same patient from day to day with each dosage regimen. Despite the daily administration of at least 5 mg/kg/day of gentamicin, nephrotoxicity occurred in only one patient. The mean duration of therapy was about ten days. Although the series of patients was small, no significant difference was reported in either the 8 or 12 h dosage regimen in respect to favourable response to treatment among the patients. Probably a high peak concentration greatly exceeding the minimal inhibitory concentration (MIC) for a short duration, kills Gram-negative bacteria as effectively as a long concentration exceeding the MIC for a longer period of time. The reported half-lives and area under curve values for gentamicin in our patients varied widely even in the same patient.