Abstract
Continuous infusion (CI) of beta-lactams could optimize their pharmacokinetic/pharmacodynamic indices, especially in difficult-to-treat infections.
Purpose
To validate an easy-to-use method to guide beta-lactams dosage in CI (formula).
Methods
A retrospective analysis was conducted of a prospectively collected cohort (n = 24 patients) with osteoarticular infections caused by Gram-negative bacilli (GNB) managed with beta-lactams in CI. Beta-lactams dose was calculated using a described formula (daily dose = 24 h × beta-lactam clearance × target “steady-state” concentration) to achieve concentrations above the MIC. We correlated the predicted concentration (Cpred = daily dose/24 h × beta-lactam clearance) with the patient’s observed concentration (Cobs) measured by UPLC–MS/MS (Spearman’s coefficient).
Results
The most frequent microorganism treated was P. aeruginosa (21 cases; 9 MDR). Beta-lactams in CI were ceftazidime (n = 14), aztreonam (7), and piperacillin/tazobactam (3), mainly used in combination (12 with colistin, 5 with ciprofloxacin) and administered without notable side effects. The plasma Cobs was higher overall than Cpred; the Spearman correlation between both concentrations was rho = 0.6 (IC 95%: 0.2–0.8) for all beta-lactams, and rho = 0.8 (IC 95%: 0.4–1) for those treated with ceftazidime.
Conclusions
The formula may be useful in clinical practice for planning the initial dosage of beta-lactams in CI, while we await a systematic therapeutic drug monitoring. The use of beta-lactams in CI was safe.
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Acknowledgements
We thank Michael Maudsley for helping with the English in this manuscript.
Funding
This work was supported by Ministerio de Economía y Competitividad, Instituto de Salud Carlos III—co-financed by the European Development Regional Fund ‘A way to achieve Europe’ ERDF, Spanish Network for Research in Infectious Diseases (REIPI RD12/0015). A. R. was supported by a research grant from the Bellvitge Biomedical Research Institute (IDIBELL).
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The authors declare that they have no conflict of interest.
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The research was conducted in accordance with the Declaration of Helsinki and national and institutional standards. The approval was obtained from Hospital Universitari de Bellvitge Ethics Committee, a tertiary-care hospital (Barcelona).
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Ribera, A., Soldevila, L., Rigo-Bonnin, R. et al. Beta-lactams in continuous infusion for Gram-negative bacilli osteoarticular infections: an easy method for clinical use. Infection 46, 239–244 (2018). https://doi.org/10.1007/s15010-018-1116-6
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DOI: https://doi.org/10.1007/s15010-018-1116-6