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.
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).
- 5.McKinnon PS, Paladino JA, Schentag JJ. Evaluation of area under the inhibitory curve (AUIC) and time above the minimum inhibitory concentration (T > MIC) as predictors of outcome for cefepime and ceftazidime in serious bacterial infections. Int J Antimicrob Agents. 2008;31:345–51.CrossRefPubMedGoogle Scholar
- 10.Cappelletty DM, Kang SL, Palmer SM, Rybak MJ. Pharmacodynamics of ceftazidime administered as continuous infusion or intermittent bolus alone and in combination with single daily-dose amikacin against Pseudomonas aeruginosa in an in vitro infection model. Antimicrob Agents Chemother. 1995;39:1797–801.CrossRefPubMedPubMedCentralGoogle Scholar
- 17.Moriyama B, Henning SA, Childs R, Holland SM, Anderson VL, Morris JC, et al. High-dose continuous infusion beta-lactam antibiotics for the treatment of resistant Pseudomonas aeruginosa infections in immunocompromised patients. Ann Pharmacother. 2010;44:929–35.CrossRefPubMedPubMedCentralGoogle Scholar
- 19.Georges B, Conil J-M, Seguin T, Ruiz S, Minville V, Cougot P, et al. Population pharmacokinetics of ceftazidime in intensive care unit patients: influence of glomerular filtration rate, mechanical ventilation, and reason for admission. Antimicrob Agents Chemother. 2009;53:4483–9.CrossRefPubMedPubMedCentralGoogle Scholar
- 21.Magiorakos A-P, Srinivasan A, Carey RB, Carmeli Y, Falagas ME, Giske CG, et al. Multidrug-resistant, extensively drug-resistant and pandrug-resistant bacteria: an international expert proposal for interim standard definitions for acquired resistance. Clin Microbiol Infect. 2012;18:268–81.CrossRefPubMedGoogle Scholar
- 27.Rigo-Bonnin R, Cobo-Sacristán S, Padullés A, Ribera A, Arbiol-Roca A, Murillo Ó, et al. Measurement of ceftazidime concentration in human plasma by ultra-performance liquid chromatography-tandem mass spectrometry. Application to critically ill patients and patients with osteoarticular infections. Biomed Chromatogr. 2016;30:410–8.CrossRefPubMedGoogle Scholar
- 28.Rigo-Bonnin R, Ribera A, Arbiol-Roca A, Cobo-Sacristán S, Padullés A, Murillo Ò, et al. Development and validation of a measurement procedure based on ultra-high performance liquid chromatography-tandem mass spectrometry for simultaneous measurement of β-lactam antibiotic concentration in human plasma. Clin Chim Acta. 2017;468:215–24.CrossRefPubMedGoogle Scholar