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Zander, Johannes; Döbbeler, Gundula; Nagel, Dorothea; Scharf, Christina; Huseyn-Zada, Mikayil; Jung, Jette; Frey, Lorenz; Vogeser, Michael; Zoller, Michael (2016): Variability of piperacillin concentrations in relation to tazobactam concentrations in critically ill patients. In: International Journal of Antimicrobial Agents, Vol. 48, No. 4: pp. 435-439
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Abstract

Therapeutic drug monitoring for critically ill patients receiving piperacillin/tazobactam is described as a useful tool. However, the minimum inhibitory concentration of piperacillin depends on a sufficiently high concentration of tazobactam in case of beta-lactamase-producing strains. Therefore, the relationship between piperacillin and tazobactam concentrations was assessed in a heterogeneous group of critically ill patients. Sixty patients with severe infections receiving 4.5 g of piperacillin/tazobactam 2-3 times daily by intermittent infusion were included in this prospective observational study (NCT01793012). Over 4 days, multiple serum samples were obtained to determine the total piperacillin and tazobactam concentrations. The target ranges were defined as trough levels > 16 mg/L (> 22.5 mg/L) and > 4 mg/L (> 5.7 mg/L) for the calculated unbound concentrations (measured total concentrations) of piperacillin and tazobactam, respectively. Despite a high correlation coefficient (r = 0.93) comparing piperacillin and tazobactam trough levels, the piperacillin/tazobactam quotients varied between ca. 1 and 10. From linear regression analysis of piperacillin versus tazobactam values, it follows that a piperacillin trough level of 22.5 mg/L might be associated with tazobactam trough levels ranging from 1.5 mg/L to 10.1 mg/L. A 70 mg/L threshold for total piperacillin trough levels would be necessary to ensure that tazobactam concentrations are > 5.7 mg/L. Because of the observed variability of piperacillin/tazobactam quotients, defining the total piperacillin target range >= 70 mg/L might be useful to ensure that tazobactam concentrations do not fall below 5.7 mg/L. Further studies are necessary to confirm that the used therapeutic ranges are associated with optimal outcomes in critically ill patients. (C) 2016 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.