Abstract
Purpose: Although the current widespread use of amikacin is in intra-abdominal sepsis treatment, its pharmacokinetic changes in the present setting are not yet well known. This study was aimed to evaluate the amikacin pharmacokinetic profile in critically ill patients with intraabdominal sepsis compared to pneumosepsis. Methods: Adult septic patients received amikacin therapy were studied. Patients with intraabdominal sepsis were enrolled in group 1 (n=16), and patients with pneumosepsis were enrolled in group 2 (n=13). The amikacin serum concentrations were evaluated in the first, second, fourth and sixth hours after initiating 30-minute infusion. The pharmacokinetic parameters were calculated for each patient. Results: There was no significant difference in the volume of distribution between the two groups (0.33±0.08 vs. 0.28±0.10 L/kg, P=0.193). The amikacin clearance was significantly lower in group 1 compared to group 2 (58.5±21.7 vs. 83.9±37.0 mL/min, P=0.029). There was no significant correlation between amikacin clearance and creatinine clearance estimated by Cockcroft-Gault formula in all patients (P=0.206). The half-life was significantly longer in group 1 compared to group 2 (5.3±2.8 vs. 3.4±3.2 hours, P=0.015). Conclusion: Pathophysiologic changes following intra-abdominal sepsis can affect amikacin pharmacokinetics behavior. The clearance and half-life may change, but the alteration of the volume of distribution is not significantly different in comparison with pneumosepsis. Further studies are required to evaluate the pharmacokinetic variables of amikacin in critically ill patients with intra-abdominal sepsis.
Highlights
Intra-abdominal infections (IAIs) are sepsis common causes in critically ill patients associated with a high rate of mortality and morbidity.[1]
Among thirty-seven intensive care units (ICUs) patients met the study criteria, eight patients were excluded: (i) Three patients died because of necrotizing pancreatitis, gangrenous appendicitis, and acute respiratory distress syndrome, (ii) two patients had implausible pharmacokinetics conditions, (iii) one patient developed acute renal failure, (iv) one patient discharged earlier from ICU, (v) in one patient amikacin was stopped due to an aminoglycoside resistant organism found in his blood culture
The results suggested that amikacin pharmacokinetics behavior can be affected by pathophysiological changes following abdominal involvement in sepsis
Summary
Intra-abdominal infections (IAIs) are sepsis common causes in critically ill patients associated with a high rate of mortality and morbidity.[1] According to IAI guidelines, one of the key strategies in the successful management of these infections is early initiation of optimal antimicrobial therapy.[2,3,4] Complicated IAIs often have polymicrobial nature and require a parenteral antibiotics combination for the treatment. It is necessary to select an appropriate antimicrobial agent with individualized dosage.[5,6] In cases suspected with IAI aminoglycoside therapy in combination with a beta-lactam is recommended once a day, due to multi-drug resistance gram-negative organisms. Due to the increased prevalence of mentioned microorganisms, this recommendation has been more pronounced recently.[7]
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