• Nathalie Grace Chua, Liwen Loo, Daryl Kim Hor Hee, Tze Peng Lim, Tat Ming Ng, Grace Si Ru Hoo, Jie Lin Soong, Jasmine Chiat Ling Ong, Sarah Si Lin Tang, Yvonne Peijun Zhou, Winnie Lee, Lawrence Soon-U Lee, Matthew Cove, Li Min Ling, and Andrea Layhoon Kwa.
• Department of Pharmacy, Singapore General Hospital, Singapore.
• J Crit Care. 2022 Apr 1; 68: 107-113.

PurposeTo determine percentage of patients with sub-therapeutic beta-lactam exposure in our intensive care units (ICU) and to correlate target attainment with clinical outcomes.Materials And MethodsMulti-centre, prospective, observational study was conducted in ICUs from three hospitals in Singapore from July 2016 to May 2018. Adult patients (≥21 years) receiving meropenem or piperacillin-tazobactam were included. Four blood samples were obtained during a dosing interval to measure and determine attainment of therapeutic targets: unbound beta-lactam concentration above (i) minimum inhibitory concentration (MIC) at 40% (meropenem) or 50% (piperacillin) of dosing interval (40-50%fT > MIC) and (ii) 5 × MIC at 100% of dosing interval (100%fT > 5 × MIC). Correlation to clinical outcomes was evaluated using Cox regression.ResultsBeta-lactam levels were highly variable among 61 patients, with trough meropenem and piperacillin levels at 21.5 ± 16.8 mg/L and 101.6 ± 81.1 mg/L respectively. Among 85 sets of blood samples, current dosing practices were able to achieve 94% success for 40-50%fT > MIC and 44% for 100%fT > 5 × MIC. Failure to achieve 40-50%fT > MIC within 48 h was significantly associated with all-cause mortality (HR: 9.0, 95% CI: 1.8-45.0), after adjustment for APACHE II score. Achievement of 100%fT > 5 × MIC within 48 h was significantly associated with shorter length of hospital stay.ConclusionCurrent dosing practices may be suboptimal for ICU patients. Beta-lactam TDM may be useful.Copyright © 2022 Elsevier Inc. All rights reserved.

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