ArticleJAC-antimicrobial resistance2025
A model-based evaluation of the pharmacokinetics-pharmacodynamics (PKPD) of avibactam in combination with ceftazidime.
Article in JAC-antimicrobial resistance, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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Who cites it
1 citing paper in PubMed.
- Optimization of meropenem dosing regimens in critically ill patients with augmented renal clearance.Frontiers in medicine · 2025Article
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Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: The emergence of β-lactamase-producing bacteria limits the effectiveness of β-lactam (BL) antibiotics, and the combination with a β-lactamase inhibitor (BLI) aims to counteract this resistance. However, existing guidelines primarily focus on optimizing the dosing of BLs and do not adequately address the interaction between BLs and BLIs, leading to uncertain pharmacokinetic/pharmacodynamic (PK/PD) targets and potentially suboptimal dosing strategies. Objectives: To investigate optimal PK/PD targets and dosing strategies for avibactam (BLI) combined with ceftazidime (BL) using mechanism-based PKPD models. Methods: PK models for ceftazidime and avibactam were integrated with mechanism-based PKPD models for Gram-negative bacteria. Simulations explored dose regimens in mice and humans, evaluating PK/PD indices and computing the PTA for diverse dosing strategies and infusion modes. Results: Conclusion: The PK/PD indices predictive of avibactam efficacy varied by species (mice and humans), bacterial strains, and mode of infusion. Dosing simulations suggest that increasing avibactam relative to ceftazidime and using continuous infusion regimens may enhance bacterial killing. These findings highlight the importance of refining dosing strategies for both components of the combination therapy.
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Registered trials
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