Beta-lactams in continuous infusion for Gram-negative bacilli osteoarticular infections: an easy method for clinical use
Continuous infusion (CI) of beta-lactams could optimize their pharmacokinetic/pharmacodynamic indices, especially in difficult-to-treat infections.
To validate an easy-to-use method to guide beta-lactams dosage in CI (formula).
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).
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.
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.
KeywordsBeta-lactams Continuous infusion Biofilm-related infections Osteoarticular infections Gram-negative bacilli Antibiotic plasma levels
We thank Michael Maudsley for helping with the English in this manuscript.
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).
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical approval and informed consent
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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