An environmental survey and a cohort study were done to analyze an outbreak of infections in a burn unit caused by a serotype O:11 and a multidrug-resistant serotype O:12 Pseudomonas aeruginosa. The P. aeruginosa O:11 outbreak was controlled by eradicating an environmental source, contaminated hydrotherapy equipment. To assess risk factors for infections caused by P. aeruginosa O:12, 15 infected burn patients were compared with 32 noninfected burn patients hospitalized during the outbreak. Patients had similar extent, severity, location, and care of burn injuries, exposure to invasive procedures, and past history of P. aeruginosa infection. Prior treatment with ceftazidime (3 g/day) was the only independent risk factor for P. aeruginosa O:12 infection. The outbreak was controlled by increasing the daily administration of ceftazidime from 3 to 6 g and by a reinforcement of isolation precautions.

The interindividual variability of imipenem pharmacokinetic parameters in burn patients suggest that these parameters have to be estimated with a large number of patients. The aim of this study is (i) to estimate these parameters with a population pharmacokinetic approach, and (ii) to test the influence of factors on pharmacokinetics parameters. Data are provided by therapeutic drug monitoring (n = 47,118 samples) and analysed by a nonlinear mixed effect modelling method. Among the tested covariates (age, gender, body weight, height, size of burn and creatinine plasma level) creatinine plasma level affects imipenem pharmacokinetic parameters substantially. The best fit is obtained with a two-compartment model integrating a linear-inverse relationship between imipenem clearance and creatinine plasma level. The estimates of imipenem clearance (16.37 +/- 0.204 L/h) and of the distribution volume of the central compartment (0.376 +/- 0.039 L/kg) are higher in the population of burn patients than the estimates in healthy subjects. This result is connected with high values of glomerule filtration rate and confirms the interest of therapeutic drug monitoring of imipenem in burn patients and particularly for patients with extreme values of creatinine clearance.

Aim The aim of this study was to characterize, via a population pharmacokinetic approach, the pharmacokinetics of ceftazidime in burn patients who were not in the acute post-injury phase. Methods The development of the pharmacokinetic model was based on data from therapeutic drug monitoring (41 patients, 94 samples). The estimation of population pharmacokinetic parameters and the selection of covariates (age, gender, body weight, size of burn and creatinine plasma concentration) that could affect the pharmacokinetics were performed with a nonlinear mixed effect modelling method. Results No relationship between covariates and the pharmacokinetic parameters was established with the exception of an inverse-linear relationship between creatinine plasma concentration and ceftazidime total clearance. The total clearance of ceftazidime was 2.72 l h -1 [coefficient variation (CV) = 56.3%] and the distribution volume of the central compartment was 0.28 l kg -1 (CV = 13.2%) The transfer rate constants (k12, k 21) between the central and peripheral compartments were 0.06718 h -1 (CV = 87.2%) and 0.001823 h -1 (CV = 82.7%), respectively. From these parameters, the total ceftazidime volume of distribution (10.64 l kg -1 ) was calculated. Conclusion The population parameters were different from those obtained in a previous study performed in fewer patients and in the early period after burn injury. In our study, the lower ceftazidime clearance could be explained by the relative decrease in ceftazidime elimination in relation to the burn area, and the higher ceftazidime volume of distribution in the presence of interstitial oedema, which could act as a reservoir from which ceftazidime returns slowly to the circulation.

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