Amikacin In Patients Research Articles

Pharmacokinetics of amikacin in intensive care unit patients.

To characterize the population pharmacokinetics of amikacin in intensive care unit (ICU) patients and to analyse whether these patients show different kinetic behaviour on the basis of their clinical diagnoses. The patient population comprised 104 medical ICU patients on amikacin treatment for several presumed or documented Gram-negative infections. Four study groups were defined according to patients' clinical diagnosis: sepsis group (n = 39), trauma group (n = 20), pneumonia group (n = 21) and 'other diagnosis' group (n = 24). The pharmacokinetic parameters for amikacin in these patients were then compared. The ICU patients were found to have increased values for the amikacin volume of distribution (0.52 +/- 0.21 litres/kg), whereas total amikacin clearance expressed as a linear function of creatinine clearance was Cl (ml/min/kg) = 0.13 +/- 0.86 ClCR, which is not significantly different from other estimations reported in the literature. However, this relationship revealed statistically significant differences among the four groups of ICU patients. Moreover, the septic and trauma patients showed higher (but not statistically significant) values for the amikacin volume of distribution. The amikacin pharmacokinetic parameters obtained should allow Bayesian individualization of amikacin doses in patients admitted to medical ICUs, on the basis of their clinical diagnoses.

Determination of plasma concentrations of amikacin in patients of an intensive care unit.

Considering the low therapeutic index of the aminoglycosides it is mandatory to monitor serum concentrations (SC) either to obtain therapeutic levels or to avoid toxic levels. The SC of amikacin (AMK) was evaluated in 24 inpatients in an intensive care unit of Hospital São João, mean age (+/- SD) 45.5 +/- 18.57 years. In 62.5% of the patients it was shown that SC (mean +/- SD, 16.87 +/- 1.62) was inferior to the therapeutic range. In 33.3% the values (SC 25.85 +/- 3.77) were within the therapeutic window (> 20 micrograms/ml; < 35 micrograms/ml). Only 1 patient attained toxic levels (> 35 micrograms/ml). In 4 of the patients with initial SC < 20 micrograms/ml, dosage was adjusted and thereafter therapeutic value was obtained (SC 24.65 +/- 3.38). The relation between the administered dose and the dosage usually recommended (weight X 15mg/day) was calculated. In the majority of our patients (the so-called "critically ill patients") the recommended dosages of AMK need to be increased in order to get the desired SC. In the population of this study a dosage of about 120% relative to the initial recommended dosage was necessary.

Amikacin serum protein binding in spinal cord injury

While changes in the disposition kinetics of aminoglycoside antibiotics have been observed in patients with spinal cord injury (SCI), the extent of binding of aminoglycoside antibiotics to serum protein has not been studied as a potential etiology. Eighty-six serum samples were obtained from 26 volunteers (9 paraplegic, 10 tetraplegic, 7 able-bodied controls) to determine the extent of amikacin binding to serum protein. Free (unbound) amikacin obtained from an ultrafiltrate of serum amikacin were quantitated over a range of serum concentrations (range 1.37 μg/mL to 73.99 μg/mL). There was no statistically significant difference demonstrated between mean amikacin serum protein binding in patients with SCI (mean ± SD, 17.63% ± 7.22%) and in able-bodied controls (18.03% ± 3.64%). The percent serum protein binding of amikacin did not covary with total amikacin concentration, and linear regression of free versus total serum amikacin concentrations was expressed by the equation, y = 0.803x + 0.350, r = 0.979. We conclude that changes in the pharmacokinetic behavior of amikacin in patients with SCI are not attributable to alterations in serum protein binding.

Gram-negative bacteremias. Analysis of factors for clinical assessment of gentamicin resistance.

We reviewed the charts of 163 patients with 183 episodes of Gram-negative bacillary bacteremia to determine a clinical profile that would select patients at high risk for experiencing gentamicin-sulfate-resistant Gram-negative bacillary bacteremia at our hospital. Gentamicin-resistant Gram-negative bacilli were only associated with institution-acquired bacteremia. Among institution-acquired episodes, urinary tract infection, diagnostic or therapeutic procedures of the lower respiratory tract or urinary tract, presence of pneumonic infiltrate on chest roentgenogram, prior therapy with gentamicin, and prior therapy with other antibiotics were significant risk factors. Because only two of the 29 gentamicin-resistant bacteria that were tested against amikacin base were resistant to amikacin, we advocate initial treatment with amikacin for patients with evidence of an institution-acquired Gram-negative bacteremic episode. Gentamicin is still our initial choice for a community-acquired episode.

Gram-Negative Bacteremias

• We reviewed the charts of 163 patients with 183 episodes of Gram-negative bacillary bacteremia to determine a clinical profile that would select patients at high risk for experiencing gentamicin-sulfate-resistant Gram-negative bacillary bacteremia at our hospital. Gentamicin-resistant Gram-negative bacilli were only associated with institution-acquired bacteremia. Among institution-acquired episodes, urinary tract infection, diagnostic or therapeutic procedures of the lower respiratory tract or urinary tract, presence of pneumonic infiltrate on chest roentgenogram, prior therapy with gentamicin, and prior therapy with other antibiotics were significant risk factors. Because only two of the 29 gentamicin-resistant bacteria that were tested against amikacin base were resistant to amikacin, we advocate initial treatment with amikacin for patients with evidence of an institution-acquired Gram-negative bacteremic episode. Gentamicin is still our initial choice for a community-acquired episode. (<i>Arch Intern Med</i>1981;141:582-586)

Pharmacokinetics of amikacin in patients with impaired renal function.

Pharmacokinetic parameters were determined after a single intramuscular injection of 7.5 mg of amikacin/kg to 10 volunteers with impaired renal function (creatinine clearance rate, 2.2-65ml/min per 1.73 m2) and to six volunteers with normal renal function. The mean peak concentrations of amikacin in sera of the two groups did not differ significantly from each other and exceeded by two to five times the reported in vitro minimal inhibitory concentrations for the majority of Pseudomonas aeruginosa and Enterobacteriaceae strains. There was a significant linear relation between the elimination rate constant of amikacin and the rate of creatinine clearance; there was a significant nonlinear relation between the half-life of amikacin and the serum creatinine concentration. Knowledge of these relations may aid in adjustment of the dosage of amikacin in patients with impaired renal function, especially when such information is used in conjunction with serum assays of amikacin.

Pharmacokinetics of amikacin in patients with renal insufficiency: relation of half-life and creatinine clearance.

The half-life of amikacin after a single intramuscular injection was determined in patients with severe renal failure who received 3.75 mg of drug/kg and in patients with various degrees of renal function who received 7.5 mg of drug/kg. The relation of the half-life of amikacin to levels of serum creatinine is practically identical to that of kanamycin. However, although concentrations of serum creatinine remained practically unchanged, rates of creatinine clearance may by considerably decreased in older subjects. This decrease may result in overestimation of the rate of glomerular filtration and subsequent overdosage. Therefore, the half-life of amikacin should be derived from values of rates of creatinine clearance or be predicted with use of a nomogram. The calculated half-life values may be used for development of appropriate dosage schedules for patients with various degrees of renal function. Such schedules would ensure therapeutic levels of drug and avoid potentially toxic accumulation of antibiotic.

Pharmacokinetics of amikacin in patients with normal or impaired renal function: radioenzymatic acetylation assay.

The acetylating radioenzymatic assay was used for determination of levels of amikacin in serum and urine. Because of an inhibitor present in various amounts in urine, assay of amikacin in urine by this method requires added internal standards and thus is less precise than the assay in serum. Determination of the rate of plasma clearance, half-life, and volume of distribution of amikacin in 10 patients with normal renal function, four patients undergoing dialysis, and five patients with end-stage renal diseases have shown a relation of half-life (t1/2 in hr) to rate of clearance of serum creatinine (Cer) of t1/2 = 3 X Cer, the same relation as found for kanamycin and gentamicin. The apparent steady-state volume of distribution of amikacin in patients with diminished renal function is slightly, but not significantly, larger than that in normal patients; the values were 0.28 +/- 0.10 and 0.21 +/- 0.10, respectively. In normal patients, 87% of the drug is excreted by the kidney.