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Objectives: To develop a population model to describe the pharmacokinetics (PK) of intravenous meropenem in adult patients with severe burns and investigate potential relationships between dosage regimens and antimicrobial efficacy., Patients and Methods: A dose of 1 g every 8 h was administered to adult patients with total body surface area burns of ≥15%. Doses for subsequent courses were determined using results from the initial course and the patient's clinical condition. Five plasma meropenem concentrations were typically measured over the dosage interval on one to four occasions. An open, two-compartment PK model was fitted to the meropenem concentrations using NONMEM and the effect of covariates on meropenem PK was investigated. Monte Carlo simulations investigated dosage regimens to achieve a target T>MIC for ≥40%, ≥60% or ≥80% of the dose interval., Results: Data comprised 113 meropenem concentration measurements from 20 dosage intervals in 12 patients. The parameters were CL (L/h) = 0.196 L/h/kg × [1 - 0.023 × (age - 46)] × [1 - 0.049 × (albumin - 15)], V1 = 0.273 L/kg × [1 - 0.049 × (albumin - 15)], Q = 0.199 L/h/kg and V2 = 0.309 L/kg × [1 - 0.049 × (albumin - 15)]. For a target of ≥80% T>MIC, the breakpoint was 8 mg/L for doses of 1 g every 4 h and 2 g every 8 h given over 3 h, but only 4 mg/L if given over 5 min., Conclusions: Although 1 g 8 hourly should be effective against Escherichia coli and CoNS, higher doses, ideally with a longer infusion time, would be more appropriate for empirical therapy, mixed infections and bacteria with MIC values ≥4 mg/L., (© The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Altered pharmacokinetics in patients with major burns may result in serum antibiotic concentrations below those required to be effective against the common pathogens encountered in burns patients. The major changes in the fluid volumes of key body compartments, which occur with a large burn, may increase the apparent volume of distribution of a drug, thereby lowering its concentration when a standard dose is given. In addition, the observed increase in renal blood flow reported in burns patients, because of the change in cardiac output, may result in a higher drug clearance and a shorter elimination half-life. As a consequence, studies have recommended higher doses or more frequent dosing or both for some antibiotics in patients with major burns, but data are lacking for many of the antibiotics reserved for treatment of life-threatening infections. The authors measured serum concentrations of two antibiotics, linezolid and meropenem, in an immunosuppressed patient who presented with a severe burn to determine whether therapeutic concentrations were achieved, thereby improving the likelihood of infection control.