Background and importance Exposure to beta-lactam antibiotics due to their hydrophilic properties is widely known to be influenced by the typical pharmacokinetic alterations in critical patients, such as increased volume of distribution and increased clearance. For instance, subtherapeutic plasma concentrations are a concern.
Aim and objectives The objective of this work was to determine if the current dosage of meropenem and piperacillin strategies in clinical practice are enough to achieve pharmacokinetic/pharmacodynamic targets (minimum 100% fT once above MIC, optimal 4–6 times above MIC).
Material and methods A prospective study was conducted from February to June 2019 of serum levels of meropenem and piperacillin in an intensive care unit in the south of Spain. In all patients, the initial dose was chosen by the prescribing intensivist (extended infusions, high doses and adjustments for renal impairment were also included). A predose sample (100% fT >MIC) of the target antibiotics within the first 48 hours was included. As the majority of treatments were empirical, the CMI target was defined by EUCAST PK/PD break points (MIC >16 µg/mL for suspected Pseudomonas aeruginosa in the case of piperacillin and >2 µg/mL in the case of meropenem)
Results Twenty-eight patients were included. Median age was 64 years (IQR 48–78 years), median APACHE II score was 15 (IQR 14–24) and 18/28 patients were men. Of the 28 patients treated, 10 did not reach 100% fT >MIC, mostly in the piperacillin group (6/9) and 4/9 in the meropenem group; 100% fT> 4–6×MIC was not achieved in 8/9 patients in the piperacillin group and in 12/19 in the meropenem group.
Conclusion and relevance Over 5 months, thanks to the active surveillance of patients who were candidates for beta-lactam therapeutic drug monitoring and the request for determination of plasma levels by the hospital pharmacist, more than 30% of meropenem and piperacillin prescriptions were found to be subtherapeutic and 70% were optimisable.
References and/or acknowledgements 1. Roberts JA, Paul SK, Akova M, et al. DALI: defining antibiotic levels in intensive care unit patients: are current beta-lactam antibiotic doses sufficient for critically ill patients?Clin Infect Dis 2014;58:1072–1083.
2. Abdulaziz S Alobaid, María Núñez-Núñez, Roberts JA. 10 Key references in the pharmacokinetics/pharmacodynamics and b-lactam antibiotics.
3. Craig WA. Pharmacokinetic/pharmacodynamic parameters: rationale for antibacterial dosing of mice and men. Clin Infect Dis 1998;26:1–10.
No conflict of interest.
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