Pharmacokinetic/pharmacodynamic target attainment in critically ill renal patients on antimicrobial usage: focus on novel beta-lactams and beta lactams/beta-lactamase inhibitors.

Milo Gatti, Federico Pea

Expert review of clinical pharmacology 2021 May

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Several novel beta-lactams (BLs) and/or beta lactams/beta-lactamase inhibitors (BL/BLIs) have been recently developed for the management of multidrug-resistant bacterial infections. Data concerning dose optimization in critically ill patients with altered renal function are scanty. This article provides a critical reappraisal of pharmacokinetic and clinical issues emerged with novel BLs and/or BL/BLIs in renal critically ill patients. Clinical and pharmacokinetic studies published in English until December 2020 were searched on the PubMed-MEDLINE database. Several issues emerged with the use of novel BLs and/or BL/BLIs in critically ill renal patients. Suboptimal clinical response rate with ceftazidime-avibactam and ceftolozane-tazobactam was reported in phase II-III trials in patients with moderate kidney injury; data on patients undergoing renal replacement therapy are limited to some case reports; dose adjustment in augmented renal clearance is provided only for cefiderocol. Implementation of altered dosing strategies (prolonged infusion and/or higher dosage) coupled with adaptive real-time therapeutic drug monitoring could represent the most effective approach in warranting optimal pharmacokinetic/pharmacodynamic targets with novel BLs and/or BL/BLIs in challenging scenarios, thus minimizing the risk of clinical failure and/or of resistance selection.

Citation

Milo Gatti, Federico Pea. Pharmacokinetic/pharmacodynamic target attainment in critically ill renal patients on antimicrobial usage: focus on novel beta-lactams and beta lactams/beta-lactamase inhibitors. Expert review of clinical pharmacology. 2021 May;14(5):583-599