title: Once-daily amikacin dosing in burn patients treated with continuous venovenous hemofiltration.
abstract: Amikacin clearance can be increased in burn injury, which is often complicated by renal insufficiency. Little is known about the impact of renal replacement therapies, such as continuous venovenous hemofiltration (CVVH), on amikacin pharmacokinetics. We retrospectively examined the clinical pharmacokinetics, bacteriology, and clinical outcomes of 60 burn patients given 15 mg/kg of body weight of amikacin in single daily doses. Twelve were treated with concurrent CVVH therapy, and 48 were not. The pharmacodynamic target of ≥10 for the maximum concentration of drug in serum divided by the MIC (C(max)/MIC) was achieved in only 8.5% of patients, with a small reduction of C(max) in patients receiving CVVH and no difference in amikacin clearance. Mortality and burn size were greater in patients who received CVVH. Overall, 172 Gram-negative isolates were recovered from the blood cultures of 39 patients, with amikacin MIC data available for 82 isolates from 24 patients. A 10,000-patient Monte Carlo simulation was conducted incorporating pharmacokinetic and MIC data from these patients. The cumulative fraction of response (CFR) was similar in CVVH and non-CVVH patients. The CFR rates were not significantly improved by a theoretical 20 mg/kg amikacin dose. Overall, CVVH did not appear to have a major impact on amikacin serum concentrations. The low pharmacodynamic target attainment appears to be primarily due to higher amikacin MICs rather than more rapid clearance of amikacin related to CVVH therapy.
authors.affiliation: Infectious Disease Service, San Antonio Military Medical Center, Brooke Army Medical Center, 3851 Roger Brooke Drive, Fort Sam Houston, TX 78234, USA.
authors.forename: Kevin S
authors.initials: KS
authors.lastname: Akers
authors.forename: Jason M
authors.initials: JM
authors.lastname: Cota
authors.forename: Christopher R
authors.initials: CR
authors.lastname: Frei
authors.forename: Kevin K
authors.initials: KK
authors.lastname: Chung
authors.forename: Katrin
authors.initials: K
authors.lastname: Mende
authors.forename: Clinton K
authors.initials: CK
authors.lastname: Murray
mesh_terms: D000293:Adolescent; D000328:Adult; D000583:Amikacin / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology; D002056:Burns / Q000150:complications / Q000401:mortality; D005260:Female; D006090:Gram-Negative Bacteria / Q000187:drug effects; D016905:Gram-Negative Bacterial Infections / Q000150:complications / Q000188:drug therapy* / Q000401:mortality / Q000628:therapy; D006440:Hemofiltration; D006801:Humans; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D000900:Anti-Bacterial Agents; D000583:Amikacin