Comparison of two methods to obtain a desired first isepamicin peak in intensive care patients

Abstract

A randomized multicenter study in intensive care unit (ICU) patients, evaluated the capacity of a Bayesian method to obtain an optimal first isepamicin (ISP) peak of 80 mg/L in comparison to a fixed loading dose (LD). Patients (n=236) over 18 years of age were enrolled from 6 September 1997 to 17 July 1999 and randomly assigned to received ISP in a calculated dose (CD) or a loading dose (LD) of 25 mg/kg body weight. The CD was estimated using a specific population model with Bayesian methodology implemented in the PKS program (Abbott PKS, Abbott Diagnostics, Rungis, France). The data required included age, body weight, height, gender and serum creatinine. ISP disposition is described by a one-compartment model. Blood samples were drawn 1 and 24 h after the start of infusion for fluorescence polarization immunoassay measurement of serum ISP concentrations. The predictive performance was assessed by computing bias and precision. Peak concentrations were significantly higher in CD group than the LD group (84.2 +/- 28.6 vs. 74.7 +/- 24.1 mg/L, respectively; P=0.008), but trough levels were comparable. The optimal ISP peak was attained by a significantly higher percentage of CD patients (P=0.018), and by significantly more CD patients on mechanical ventilation (P=0.025), and with simplified acute physiological scores (SAPS) > 35 (P=0.002). Pharmacokinetic parameters were similar for the two groups with large interindividual variations. Mean (+/- SD) volume of distribution of ventilated patients (72%) was significantly higher than of nonventilated patients (23.31 +/- 7.35 vs. 20.60 +/- 6.30 L, respectively; P=0.001). No relationship was found between the volume of distribution and SAPS. Total clearance was significantly correlated with estimated CLCR (creatinine clearance) (P=0.0001). Precision (RMSE) is better for CD than for LD strategy, respectively 27.96 and 28.66 mg/L. The Bayesian method was significantly more accurate and performed particularly well in ventilated patients and patients with high SAPS, compare to an LD of 25 mg/kg to obtain a first ISP peak of 80 mg/L in ICU patients. Therefore, a fixed dose of 28.5 mg/kg would be also adequate to reach a peak of 80 mg/L.

In-vitro Activity of Isepamicin against Gram-negative Bacteria in Comparison to Other Aminoglycosides Routinely used at a Teaching Hospital in Northern India

“…It is derived from gentamicin B and acts as an active agent against many bacteria including non-inducible and inducible Enterobacteriaceae microorganisms and non-fermenters not susceptible to other aminoglycoside agents. [22][23][24] Among the isolates recovered in our study K. pneumoniae, E. coli, and P. aeruginosa were identified as the most common microorganisms against which isepamicin was tested for its susceptibility along with other aminoglycosides used routinely in our clinical setting. A similar predominance of E. coli and P. aeruginosa was observed in studies conducted by Verbist et al, 25 Glupczynski et al, 26 Vincent et al, 27 Spencer et al, 28 Jarlier et al, 29 and Belgian Isepamicin Multicenter Study Group.…”

“…It is derived from gentamicin B and acts as an active agent against many bacteria including non-inducible and inducible Enterobacteriaceae microorganisms and non-fermenters not susceptible to other aminoglycoside agents. 22 23 24 …”

Old antibiotics for infections in critically ill patients

“…Its antibacterial spectrum includes Enterobacteriaceae and staphylococci. In France, isepamicin's pharmacokinetic characteristics have been studied extensively in the specific population of ICU patients [18,19]. For example, in a study of approximately 200 ICU patients treated for nosocomial pneumonia with isepamicin and a b-lactam antibiotic, isepamicin's clearance was found to be related to age, body weight and serum creatinine level, while it was independent of the dosage (15 versus 25 mg/kg) and the duration of treatment (5 versus 10 days).…”