ArticleThe Journal of antimicrobial chemotherapy2025
Simulated achievement rate of β-lactams/nacubactam treatment in humans using instantaneous MIC-based PK/PD analysis.
Article in The Journal of antimicrobial chemotherapy, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Pharmacokinetics, safety, and tolerability of nacubactam (OP0595) after intravenous infusion: a randomized, double-blind, placebo-controlled phase I clinical trial in healthy Chinese male subjects.Clinical and experimental medicine · 2025Trial
- Cefepime 2.0: Upgrading β-Lactamase Inhibitor Use.Microorganisms · 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
- 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
- When Red Blood Cells Meet Carbon Monoxide: Yin and Yang in Medicines and Pharmaceuticals.Pharmaceuticals (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
- A Review ofInternational journal of microbiology · 2026Review
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Authors and funding
5 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNacubactam (NAC), a new diazabicyclooctane β-lactamase inhibitor, is being developed for use together with aztreonam (AZT) and cefepime (CFPM). However, the effective clinical dosages of AZT/NAC and CFPM/NAC have not yet been established. We have previously shown that free time above instantaneous MIC (fT > MICi) is a valuable pharmacokinetic (PK)/pharmacodynamic parameter for β-lactam (BL)/NAC in a mouse thigh infection model.
objectivesThis study simulated the fT > MICi (%) for AZT/NAC and CFPM/NAC against carbapenemase-producing Enterobacterales (CPE) with different MIC in humans to estimate the clinical efficacy at practically achievable combination doses of AZT/NAC and CFPM/NAC.
methodsUsing previously reported PK parameters of each drug in humans and chequerboard MIC data, we calculated the fT > MICi (%) for AZT/NAC and CFPM/NAC in 10 000 simulated patients to predict the percentages of target attainment of bacteriostatic and bactericidal efficacies at various combined doses.
resultsThe results predicted that both BL/NAC combinations could achieve 100% 2 log10-kill against CPE strains at the lowest combination dose (0.5 g/0.5 g q8h). Additionally, in MIC studies examining BLs/NAC at a 1:1 ratio, the dosage regimen for strains with MICcomb ≤ 1 mg/L was expected to offer 100% bactericidal efficacy (2 log10-kill) at 0.5 g/0.5 g q8h or higher doses. For strains with 1 mg/L < MICcomb ≤ 16 mg/L, BLs/NAC at a 2 g/2 g q8h was predicted to produce bactericidal efficacy (1 log10-kill). At MICcomb = 32 mg/L, some bacteriostatic effect was expected at high BL doses.
conclusionsAZT/NAC and CFPM/NAC are bactericidal against CPE at practically achievable dosages.
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