Individualizing beta-lactam dosing in real-world patients: lessons from a pharmacist-led programme implementation and evaluation

在真实世界中为患者个体化调整β-内酰胺类抗生素剂量:药师主导的项目实施和评估的经验教训

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Abstract

BACKGROUND: Individualized dosing of beta-lactam using serum concentrations is an emerging approach to overcome PK/PD variability in select patients. Herein, we describe a beta-lactam dose individualization programme highlighting successes and challenges. METHODS: We conducted a single-centre evaluation of a beta-lactam dose individualization using serum concentration monitoring programme. In September 2023, a pharmacist-driven protocol was implemented at an academic centre as a collaboration between Infectious Diseases, Pharmacy, and the Clinical Laboratory. De-centralized pharmacists ordered serum concentrations for cefepime, meropenem or piperacillin-tazobactam treated patients. RESULTS: Interpretation was conducted using Bayesian software. The drug monitored, treatment indication, model fitness, whether therapy was altered, whether protocols were followed and PK/PD attainment for each patient were recorded. Eighty-two beta-lactam serum levels were ordered in 47 patients between 26 September 2023 and 31 March 2024. Cefepime was most frequently monitored (70.7%). Common treatment indications in monitored patients were hospital-acquired/ventilator-associated pneumonia (25.5%), surgical prophylaxis (12.8%), bone/joint (12.8%) and central nervous system infection (12.8%). Model fitness was good or intermediate in >95% of cases. Dose or agent optimization was possible in 60% of cases, and dose adjustments were made in 34% of cases. Protocol deviations were common (57.4%). Targets of 100% fT(>1×MIC) and fT(>4×MIC) were achieved in 91.5% and 61.7% of patients, respectively. Troughs exceeding protocol safety goals occurred >20% of the time. CONCLUSION: We found that dose optimization was possible in >50% of monitored patients necessitating dose adjustments >33% of the time. Protocol deviations reinforced areas for continued pharmacist and provider education to optimize the use of this targeted intervention.

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