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- Title
Pragmatic options for dose optimization of ceftazidime/avibactam with aztreonam in complex patients.
- Authors
Falcone, Marco; Menichetti, Francesco; Cattaneo, Dario; Tiseo, Giusy; Baldelli, Sara; Galfo, Valentina; Leonildi, Alessandro; Tagliaferri, Enrico; Paolo, Antonello Di; Pai, Manjunath P; Di Paolo, Antonello
- Abstract
<bold>Background: </bold>Avibactam is a β-lactamase inhibitor that is combined with aztreonam against Enterobacterales co-expressing serine- and metallo-β-lactamases (MBL). Optimal dosing of aztreonam with avibactam is not well-defined in critically ill patients and contingent on ceftazidime/avibactam product labelling.<bold>Objectives: </bold>To identify a pragmatic dosing strategy for aztreonam with avibactam to maximize the probability of target attainment (PTA).<bold>Methods: </bold>We conducted a prospective observational pharmacokinetic study. Five blood samples were collected around the fourth dose of aztreonam or ceftazidime/avibactam and assayed for all three drugs. Population pharmacokinetic (PK) analysis coupled with Monte Carlo simulations were used to create a dosing nomogram for aztreonam and ceftazidime/avibactam based on drug-specific pharmacodynamic (PD) targets.<bold>Results: </bold>A total of 41 participants (59% male) median age of 75 years (IQR 63-79 years) were enrolled. They were critically ill (46%) with multiple comorbidities and complications including burns (20%). Population PK analysis identified higher volume of distribution and lower clearance (CL) compared with typical value expectations for aztreonam and ceftazidime/avibactam. Estimated glomerular filtration (eGFR) rate using the CKD-EPI equation predicted CL for all three drugs. The need for high doses of aztreonam and ceftazidime/avibactam above those in the existing product labels are not predicted by this analysis with the exception of ceftazidime/avibactam for patients with eGFR of 6-15 mL/min, in whom suboptimal PTA of ≤71% is predicted.<bold>Conclusions: </bold>Pragmatic and lower daily-dose options are predicted for aztreonam and ceftazidime/avibactam when the eGFR is <90 mL/min. These options should be tested prospectively.
- Subjects
CEFTAZIDIME; AZTREONAM; EPIDERMAL growth factor receptors; MONTE Carlo method
- Publication
Journal of Antimicrobial Chemotherapy (JAC), 2021, Vol 76, Issue 4, p1025
- ISSN
0305-7453
- Publication type
journal article
- DOI
10.1093/jac/dkaa549