Experience in Monitoring Gentamicin Therapy during Treatment of Serious Gram-Negative Sepsis

Abstract

SummaryThis paper reports our experience in monitoring gentamicin therapy during the treatment of 68 episodes of serious Gramnegative sepsis in 65 hospital patients. Most of the patients had major underlying disease. Of those who were adequately treated (peak serum concentrations of 5 ,ug/ml or more in 72 hours for septicaemia, urinary tract infection, and wound infection; and 8 ,ug/ml or more at some time during the course of treatment for pneumonia) B4% (46 out of 55) were cured. These serum concentrations could be achieved only by starting with a regimen of 5 mg/kg/day in three divided doses in ali adult patients, subsequent dosage being determined by the results of rapid serum assay. The incidence of nephrotoxicity and symptomatic ototoxicity was no greater than in previous series. The main reason for assaying serum gentamicin is to ensure that an adequate dosage is achieved as soon as possible. In patients with impaired renal function or receiving prolonged high dosage assays also serve to guard against an excessive accumulation of gentamicin and an increased risk of toxicity.

Individualised aminoglycoside dosage based on pharmacokinetic analysis is superior to dosage based on physician intuition at achieving target plasma drug concentrations [see comments]

“…A favourable outcome was also demonstrated in patients with gram-negative pneumonia who achieved maximum peak concentrations of gentamicin or tobramycin of > 7mg 1' or mean peak concentrations of > 6 mg l- (Moore et al, 1984b). Other studies support these findings and suggest that peak concentrations should not be < 5 mg 1-1, and preferably much higher (Noone et al, 1974, Moore et al, 1987.…”

Comparison of Sawchuk‐Zaske and Bayesian forecasting for aminoglycosides in seriously ill patients.

“…Frequently the doses required initially are 1.5 to 3 times the normal recommended dosage (Zaske et al, 1982a;Denaro & Ravenscroft, 1987). Retrospective studies have suggested an improved survival with such a stratagem (Noone et al, 1974;Zaske et al, 1982b;Moore et al, 1984a,b).…”

“…Aminoglycoside pharmacokinetic parameters may be greatly changed in patients who are seriously ill with septicaemia and/or have large fluctuations in their extra-cellular fluid volume (Pennington et al, 1975;Zaske et al, 1976;Denaro & Ravenscroft, 1987;Lacarelle et al, 1987). The importance of the correlation between peak serum aminoglycoside concentrations and clinical outcome is now widely accepted (Jackson & Riff, 1971;Noone et al, 1974;Moore et al, 1984a,b). Methods used to individualize therapy must (1) accurately estimate volume of distribution (V) and clearance (CL), so that desired peak drug concentrations are attained, (2) have the ability to predict changes in aminoglycoside pharmacokinetic parameters that occur with disease, (3) be easily implemented and (4) be cost effective.…”

A bioactive sol‐gel glass implant for in vivo gentamicin release. Experimental model in Rabbit

“…Therapeutic gentamicin concentrations in humans were been established by Barza et al 12 and Noone et al 13 as 5-10 mg/mL. Persistent concentrations higher than 10 mg/mL lead to alterations in the VIII craneal nerve and nephrotoxicity, although lower levels may also be associated with toxic effects.…”