ArticleThe Journal of antimicrobial chemotherapy2023
Development of an optimized and practical pharmacokinetics/pharmacodynamics analysis method for aztreonam/nacubactam against carbapenemase-producing K. pneumoniae.
Article in The Journal of antimicrobial chemotherapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 13 citations in OpenAlex.
- The global epidemiology and treatment of metallo-β-lactamase-producing gram-negative pathogens.JAC-antimicrobial resistance · 2026Review
- Preclinical Pharmacokinetics and Pharmacodynamics of Antibiotic Adjuvants.ACS infectious diseases · 2026Review
- Evidence of intrapulmonary penetration of nacubactam, a novel β-lactamase inhibitor, following coadministration of nacubactam with meropenem in healthy adults.Antimicrobial agents and chemotherapy · 2026Article
- Pharmacokinetic analysis of nacubactam, a novel β-lactamase inhibitor, co-administered with meropenem in patients with a complicated urinary tract infection.JAC-antimicrobial resistance · 2026Article
- Nacubactam: a review on mechanistic insights and therapeutic promise for combating β-lactam resistance among multidrug-resistant Gram-negative pathogens.Annals of medicine and surgery (2012) · 2026Review
- Clinically Significant Carbapenemases in Gram-Negative Pathogens: Molecular Diversity and Advances in β-Lactamase Inhibitor Therapy.Antibiotics (Basel, Switzerland) · 2026Review
- Restoration of β-lactam activity by nacubactam combinations against extensively drug-resistant K. pneumoniae harbouring diverse carbapenem resistance gene.World journal of microbiology & biotechnology · 2026Article
- The global resistance problem and the clinical antibacterial pipeline.Nature reviews. Microbiology · 2025Review
- Clinical efficacy, safety and pharmacokinetics of novel β-lactam/β-lactamase inhibitor combinations: a systematic review.JAC-antimicrobial resistance · 2025Review
- In vitro activity and resistance mechanisms of novel antimicrobial agents against metallo-β-lactamase producers.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2025Review
- Simulated achievement rate of β-lactams/nacubactam treatment in humans using instantaneous MIC-based PK/PD analysis.The Journal of antimicrobial chemotherapy · 2025Article
- New Agents Are Coming, and So Is the Resistance.Antibiotics (Basel, Switzerland) · 2024Review
- Revisiting the Checkerboard to Inform Development of β-Lactam/β-Lactamase Inhibitor Combinations.Antibiotics (Basel, Switzerland) · 2024Article
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNacubactam, a new β-lactamase inhibitor with antibacterial activity, is being developed as a single drug to be co-administered with cefepime or aztreonam. However, determining pharmacokinetics/pharmacodynamics (PK/PD) parameters in β-lactam/β-lactamase inhibitor combinations remains challenging. We aimed to establish a practical PK/PD analysis method for aztreonam/nacubactam that incorporates instantaneous MIC (MICi).
methodsBased on chequerboard MIC measurements, MICi of aztreonam against carbapenemase-producing Klebsiella pneumoniae in the presence of nacubactam was simulated.
resultsThe mean change in the bacterial count of thigh-infected mice in an in vivo PD study was plotted based on %fT>MICi and analysed using the inhibitory effect sigmoid Imax model. fT>MICi calculated from the PK experiments showed a high correlation with the in vivo bactericidal effect, suggesting that fT>MICi is the optimal PK/PD parameter for aztreonam/nacubactam. The target values of fT>MICi achieving growth inhibition, 1 log10 kill and 2 log10 kill, were 22, 38% and 75%, respectively.
conclusionsThe PK/PD analysis method proposed in this study is promising for determining practical PK/PD parameters in combination therapy. In addition, this is the first report of aztreonam/nacubactam showing a potent in vivo therapeutic effect against NDM-producing K. pneumoniae.
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