Abstract
Gentamicin is still widely used in the treatment of patients in an intensive care unit (ICU). The efficacy of aminoglycosides correlates with the peak serum concentration (Cmax), and the toxicity with the minimum serum concentration (Cmin). The aim of this study was to determine Cmax and Cmin in serum of cerebral coma ICU patients when a dosage of gentamicin of 5 mg/kg body weight was administered once daily; to evaluate the rationality of mentioned dose; and to identify factors associated with these concentrations. Material and METHODS. A total of 24 ICU patients suffering from cerebral coma were included into this analysis. A dosage of gentamicin of 5 mg/kg body weight was administered once a day. Gentamicin concentrations were tested twice after the first dose infusion (immediately and 5 hours after 1-hour infusion). Cmax, Cmin, volume of distribution (Vd), and elimination half-life (T1/2) were obtained. RESULTS. The mean Cmax was 17.96 (SD, 4.31) µg/mL (range, 10.30-27.87 µg/mL). The desirable Cmax (≥ 20 µg/mL) was reached only in 6 patients (25%). Cmin was calculated using a special pharmacokinetic program "Kinetica." Cmin of 0.5 µg/mL was not exceeded in any patient. A correlative analysis indicated a significant inverse direct correlation between Cmax and Vd and between Cmax and treatment duration in the ICU. An inverse correlation was observed between Cmin and T1/2, evaluation of coma according to the Glasgow coma scale, and creatinine clearance. CONCLUSIONS. A dosage of 5 mg/kg body weight once a day was not sufficient in cerebral coma ICU patients. This dose was not associated with the nephrotoxic effect of gentamicin (additional risk factors were absent). It is recommended to obtain gentamicin concentration at two time points following administration of the first dose (e.g., immediately after 1-hour infusion and 5 hours later), and using a special pharmacokinetic software, to calculate a necessary dose and interval of administration.
Highlights
Aminoglycosides, including gentamicin, are still widely used for the treatment of patients in intensive care units (ICUs) despite the fact that a number of more advanced and possibly safer antibiotics have been introduced
A dosage of 5 mg/kg body weight once a day was not sufficient in cerebral coma ICU patients. This dose was not associated with the nephrotoxic effect of gentamicin
As toxic effects correlate with serum Cmin, efficacy correlates with serum Cmax, and pharmacokinetic parameters vary widely in ICU patients, the monitoring of aminoglycoside serum concentrations followed by the dose correction is highly recommended [4, 26,27,28,29]
Summary
Aminoglycosides, including gentamicin, are still widely used for the treatment of patients in intensive care units (ICUs) despite the fact that a number of more advanced and possibly safer antibiotics have been introduced. This is caused by several factors: concentration-dependent bactericidal effect, concentration-dependent postantibiotic effect, rare occurrence of resistance, low price, synergisms with other beta-lactam antibiotics [1], and increased frequency of resistance of gram-negative pathogens to beta-lactam antibiotics and fluoroquinolones [2]. The frequency of nephrotoxic effect caused by aminoglycosides used once a day reported in various sources varies from 0%–5% [4,5,6] to 14% [7]. The inconsistency of data can be related to differences in the characteristics of patients (including the presence of other factors increasing the risk of nephrotoxicity), different dosing, and modification of doses regarding the pharmacokinetic parameters calculated.
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