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Standard dosing of piperacillin and meropenem fail to achieve adequate plasma concentrations in ICU patients
Author(s) -
Petersson J.,
Giske C. G.,
Eliasson E.
Publication year - 2016
Publication title -
acta anaesthesiologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.738
H-Index - 107
eISSN - 1399-6576
pISSN - 0001-5172
DOI - 10.1111/aas.12808
Subject(s) - meropenem , piperacillin , medicine , dosing , renal function , piperacillin/tazobactam , tazobactam , interquartile range , renal replacement therapy , cystatin c , creatinine , intensive care , antibiotics , urology , pharmacology , microbiology and biotechnology , intensive care medicine , pseudomonas aeruginosa , antibiotic resistance , biology , genetics , bacteria
Background Controversies remain regarding optimal dosing and the need for plasma concentration measurements when treating intensive care patients with beta‐lactam antibiotics. Methods We studied ICU patients treated with either antibiotic, excluding patients on renal replacement therapy. Antibiotic concentrations were measured at the mid and end of the dosing interval, and repeated after 2–3 days when feasible. Glomerular filtration rate ( GFR ) was estimated from plasma creatinine and cystatin C, GFR calculated from cystatin C ( eGFR ) and measured creatinine clearance (CrCl). Measured concentrations were compared to the clinical susceptible breakpoints for Pseudomonas aeruginosa , 16 and 2 mg/l for piperacillin and meropenem respectively. Results We analysed 33 and 31 paired samples from 20 and 19 patients treated with piperacillin–tazobactam and meropenem respectively. Antibiotic concentrations at the mid and end of the dosing interval were for piperacillin, 27.0 (14.7–52.9) and 8.6 (2.7–30.3); and for meropenem, 7.5 (4.7–10.2) and 2.4 (1.0–3.5). All values median (interquartile range) and concentrations in mg/l. The percentage of measured concentrations below the breakpoint at the mid and end of the dosing interval were for piperacillin, 27% and 61%; and for meropenem, 6% and 48%. Lower estimates of GFR were associated with higher concentrations but concentrations varied greatly between patients with similar GFR . The correlation with terminal concentration half‐life was similar for eGFR and CrCl. Conclusions With standard doses of meropenem and piperacillin–tazobactam, plasma concentrations in ICU patients vary > 10‐fold and are suboptimal in a significant percentage of patients. The variation is large also between patients with similar renal function.