Evaluation of a Meropenem and Piperacillin Monitoring Program in Intensive Care Unit Patients Calls for the Regular Assessment of Empirical Targets and Easy-to-Use Dosing Decision Tools

Antibiotics

Ferdinand Anton Weinelt¹  Lucas Dübel¹  Robin Michelet¹  Stefanie Hennig¹  Charlotte Kloft¹  Franz Weber¹  Frieder Pfäfflin²  Alexander Uhrig²  Agata Mikolajewska²  Stephan Achterberg²  Miriam Songa Stegemann²  Wilhelm Huisinga³  Peggy Kiessling⁴  Anja Theloe⁵ 

[1] Department of Clinical Pharmacy and Biochemistry, Institute of Pharmacy, Freie Universitaet Berlin, Kelchstr. 31, 12169 Berlin, Germany;Department of Infectious Diseases and Respiratory Medicine, Charité-Universitaetsmedizin Berlin, Corporate Member of Freie Universitaet Berlin, Humboldt-Universitaet zu Berlin, Berlin Institute of Health, 13353 Berlin, Germany;Institute of Mathematics, Universität Potsdam, Karl-Liebknecht-Str. 24-25, 14476 Potsdam, Germany;Labor Berlin—Charité Vivantes GmbH, 13353 Berlin, Germany;Pharmacy Department, Charité-Universitaetsmedizin Berlin, Corporate Member of Freie Universitaet Berlin, Humboldt-Universitaet zu Berlin, Berlin Institute of Health, 13353 Berlin, Germany;

关键词: meropenem;    piperacillin/tazobactam;    antimicrobial stewardship;    critically ill;    antibiotics;    pharmacokinetic/pharmacodynamic;   

DOI  :  10.3390/antibiotics11060758

来源: DOAJ

【 摘 要 】

The drug concentrations targeted in meropenem and piperacillin/tazobactam therapy also depend on the susceptibility of the pathogen. Yet, the pathogen is often unknown, and antibiotic therapy is guided by empirical targets. To reliably achieve the targeted concentrations, dosing needs to be adjusted for renal function. We aimed to evaluate a meropenem and piperacillin/tazobactam monitoring program in intensive care unit (ICU) patients by assessing (i) the adequacy of locally selected empirical targets, (ii) if dosing is adequately adjusted for renal function and individual target, and (iii) if dosing is adjusted in target attainment (TA) failure. In a prospective, observational clinical trial of drug concentrations, relevant patient characteristics and microbiological data (pathogen, minimum inhibitory concentration (MIC)) for patients receiving meropenem or piperacillin/tazobactam treatment were collected. If the MIC value was available, a target range of 1–5 × MIC was selected for minimum drug concentrations of both drugs. If the MIC value was not available, 8–40 mg/L and 16–80 mg/L were selected as empirical target ranges for meropenem and piperacillin, respectively. A total of 356 meropenem and 216 piperacillin samples were collected from 108 and 96 ICU patients, respectively. The vast majority of observed MIC values was lower than the empirical target (meropenem: 90.0%, piperacillin: 93.9%), suggesting empirical target value reductions. TA was found to be low (meropenem: 35.7%, piperacillin 50.5%) with the lowest TA for severely impaired renal function (meropenem: 13.9%, piperacillin: 29.2%), and observed drug concentrations did not significantly differ between patients with different targets, indicating dosing was not adequately adjusted for renal function or target. Dosing adjustments were rare for both drugs (meropenem: 6.13%, piperacillin: 4.78%) and for meropenem irrespective of TA, revealing that concentration monitoring alone was insufficient to guide dosing adjustment. Empirical targets should regularly be assessed and adjusted based on local susceptibility data. To improve TA, scientific knowledge should be translated into easy-to-use dosing strategies guiding antibiotic dosing.

【 授权许可】

Unknown