Observed concentrations of amikacin and gentamycin in the setting of burn patients with gram-negative bacterial infections: Preliminary data from a prospective study

Abstract

Critically ill populations often have shown subtherapeutic aminoglycosides' concentrations mostly because of unavoidable changes in drug volume distribution and clearance. We present a real life prospective study evaluating plasma concentrations for once-daily dosing for amikacin and gentamycin among a population of severe burn adults. We conducted a real life prospective study on the plasma observed concentrations of amikacin and gentamycin among severe burn patients, using aminoglycoside as combination therapy. Antibiotics were prescribed at the standard doses of 15-20mg/kg/day for amikacin and 3-5mg/kg/day for gentamycin. Eight patients (4 in amikacin and 4 in gentamycin groups, respectively) were enrolled in the study. All subjects were admitted for severe burns. The most common site of infection was bloodstream (5; 62.5%) and pneumonia (4; 50%). Pseudomonas aeruginosa, followed by Klebsiella pneumoniae and multi-drug resistant Acinetobacter baumannii were the most prevalent agents isolated. Amikacin and gentamycin never achieved the target peak concentration of 60mg/L and 30mg/L: in our study Cmax, for amikacin, was 33.1±15.6mg/L (SD), while for gentamycin was 14.3mg/L±9. Cmax and total body surface area have shown a strong negative correlation with borderline statistical significance (amikacin: ρ=0.922, P=0.078; gentamycin: ρ=0.937, P=0.063). At the standard dosage, the pharmacokinetic/pharmacodynamic (PK/PD) target of Cmax>8×highest MIC was reached for 8 (53.3%) out of 15 isolated pathogens. The present study found that, in a population of septic burn patients, standard doses of gentamycin and amikacin most often lead to plasma concentrations under the PK/PD target.