551. Higher than recommended amikacin loading doses achieve pharmacokinetic targets without associated toxicity
- Author
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Gálvez, Ricardo, Luengo, Cecilia, Cornejo, Rodrigo, Kosche, Johann, Romero, Carlos, Tobar, Eduardo, Illanes, Victor, Llanos, Osvaldo, and Castro, José
- Subjects
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ANTIBIOTICS , *PHARMACOKINETICS , *DRUG dosage , *DRUG toxicity , *AMINOGLYCOSIDES , *NOSOCOMIAL infections , *SEPSIS , *CRITICALLY ill , *NEPHROTOXICOLOGY - Abstract
Abstract: Antibiotic therapy improves the outcome of severe sepsis and septic shock, however pharmacokinetic properties are altered in this scenario. Amikacin (AMK) is an option to treat community or nosocomial infections, although standard doses might be insufficient in critically ill patients. The aim of this study was to evaluate two AMK dosage regimens in comparison with standard therapy with regard to efficacy in achieving adequate plasma levels as well as safety. In total, 99 patients with severe sepsis or septic shock were randomised to different AMK dose protocols: Group 1, 25mg/kg/day; Group 2, 30mg/kg/day; and Group 3, historical standard dose (15mg/kg/day). Peak plasma concentrations at 1h (C max) were determined. Pharmacokinetics was determined and renal function was monitored to evaluate toxicity. Groups were compared using bilateral T-test. Demographic characteristics of the three groups were comparable. AMK C max values were 57.4±9.8, 72.1±18.4 and 35.2±9.4μg/mL, respectively (P <0.001 between Groups 1 and 2 versus Group 3, and P <0.01 between Group 1 versus Group 2). A C max >60μg/mL was reached by 39%, 76% and 0% of patients in Groups 1, 2 and 3, respectively (P <0.001) and creatinine clearance at Day 28 was 95.6±47.4, 89.7±26.6 and 56.4±18.4mL/min, respectively. In conclusion, a 30mg/kg daily dose of AMK presents significantly higher C max compared with the other groups, with 76% of patients reaching recommended peak plasma levels with no association with higher nephrotoxicity. Standard doses are insufficient in critically ill patients to reach the recommended C max. [Copyright &y& Elsevier]
- Published
- 2011
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