Pragmatic options for dose optimization of ceftazidime/avibactam with aztreonam in complex patients
| Autor: | Marco Falcone, Antonello Di Paolo, Alessandro Leonildi, Dario Cattaneo, Sara Baldelli, Giusy Tiseo, Manjunath P. Pai, Francesco Menichetti, Valentina Galfo, Enrico Tagliaferri |
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| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Microbiology (medical) Male medicine.medical_specialty Avibactam 030106 microbiology Population Ceftazidime Aztreonam Microbial Sensitivity Tests 030226 pharmacology & pharmacy beta-Lactamases 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine Medicine Humans Pharmacology (medical) Dosing education Aged Original Research Pharmacology Volume of distribution education.field_of_study business.industry Middle Aged Ceftazidime/avibactam Anti-Bacterial Agents Drug Combinations Infectious Diseases chemistry Pharmacodynamics Female business Azabicyclo Compounds medicine.drug |
| Zdroj: | J Antimicrob Chemother |
| ISSN: | 1460-2091 |
| Popis: | Background 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. Objectives To identify a pragmatic dosing strategy for aztreonam with avibactam to maximize the probability of target attainment (PTA). Methods 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. Results 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. Conclusions Pragmatic and lower daily-dose options are predicted for aztreonam and ceftazidime/avibactam when the eGFR is |
| Databáze: | OpenAIRE |
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