ArticleThe Journal of antimicrobial chemotherapy2021
Optimizing pharmacokinetics/pharmacodynamics of β-lactam/β-lactamase inhibitor combinations against high inocula of ESBL-producing bacteria.
Article in The Journal of antimicrobial chemotherapy, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers, 1 of them a synthesis that pooled it.
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Who cites it
17 citing papers in PubMed, 1 synthesis or guideline pooled it.
- What are the optimal pharmacokinetic/pharmacodynamic targets for β-lactamase inhibitors? A systematic review.The Journal of antimicrobial chemotherapy · 2024Pooled it
- Impact of Attaining an Aggressive Pharmacokinetic-Pharmacodynamic Target on the Clinical Efficacy of Continuous Infusion β-Lactam Therapy for Early Posttransplant Gram-Negative Infections in Critically Ill Orthotopic Liver Transplant Recipients: An Interim Analysis of a 3-Year Prospective, Observational Study.The Journal of infectious diseases · 2025Observational
- Impact of iron limitation on in vitro and in vivo activity of ceftazidime against A. baumannii.Diagnostic microbiology and infectious disease · 2025Article
- Rapid Design of Combination Antimicrobial Therapy againstComputers & chemical engineering · 2025Article
- In Vitro Dynamic Model Evaluation of Meropenem Alone and in Combination with Avibactam Against Carbapenemase-ProducingPharmaceuticals (Basel, Switzerland) · 2024Article
- Article
- Could an Optimized Joint Pharmacokinetic/Pharmacodynamic Target Attainment of Continuous Infusion Piperacillin-Tazobactam Be a Valuable Innovative Approach for Maximizing the Effectiveness of Monotherapy Even in the Treatment of Critically Ill Patients with Documented Extended-Spectrum Beta-Lactamase-ProducingAntibiotics (Basel, Switzerland) · 2023Article
- Pharmacodynamics of Doripenem Alone and in Combination with Relebactam in an In Vitro Hollow-Fiber Dynamic Model: Emergence of Resistance of Carbapenemase-ProducingAntibiotics (Basel, Switzerland) · 2023Article
- In vivo Pharmacokinetic/Pharmacodynamic Analysis of the Efficacy of the Cefepime/Nacubactam Combination Against β-Lactamase-Producing Enterobacterales based on the Instantaneous MIC Concept.Pharmaceutical research · 2023Article
- Development of an optimized and practical pharmacokinetics/pharmacodynamics analysis method for aztreonam/nacubactam against carbapenemase-producing K. pneumoniae.The Journal of antimicrobial chemotherapy · 2023Article
- A novel method to evaluate ceftazidime/avibactam therapy in patients with carbapenemase-producing Enterobactericeae (CPE) bloodstream infections.International journal of antimicrobial agents · 2023Article
- Deciphering longitudinal optical-density measurements to guide clinical dosing regimen design: A model-based approach.Computer methods and programs in biomedicine · 2022Article
- Optimal ceftazidime/avibactam dosing exposure against KPC-producing Klebsiella pneumoniae.The Journal of antimicrobial chemotherapy · 2022Article
- The Application of Hollow Fiber Cartridge in Biomedicine.Pharmaceutics · 2022Review
- Population pharmacokinetics of piperacillin/tazobactam in critically ill Korean patients and the effects of extracorporeal membrane oxygenation.The Journal of antimicrobial chemotherapy · 2022Article
- Experimental Validation of a Mathematical Framework to Simulate Antibiotics with Distinct Half-Lives Concurrently in an In Vitro Model.Antibiotics (Basel, Switzerland) · 2021Article
- MIC profiling of ceftazidime/avibactam against two carbapenemase-producing Klebsiella pneumoniae isolates.Journal of global antimicrobial resistance · 2020Article
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Authors and funding
10 authors.
Funding
Abstract
objectivesReduced in vitro β-lactam activity against a dense bacterial population is well recognized. It is commonly attributed to the presence of β-lactamase(s) and it is unknown whether the inoculum effect could be diminished by a β-lactamase inhibitor. We evaluated different β-lactam/β-lactamase inhibitor combinations in suppressing a high inoculum of ESBL-producing bacteria.
methodsThree clinical isolates expressing representative ESBLs (CTX-M-15 and SHV-12) were examined. The impact of escalating β-lactamase inhibitor (tazobactam or avibactam) concentrations on β-lactam (piperacillin or ceftazidime) MIC reduction was characterized by an inhibitory sigmoid Emax model. The effect of various dosing regimens of β-lactam/β-lactamase inhibitor combinations was predicted using %T>MICi and selected exposures were experimentally validated in a hollow-fibre infection model over 120 h. The threshold exposure to suppress bacterial regrowth was identified using recursive partitioning.
resultsA concentration-dependent reduction in β-lactam MIC was observed (r2 ≥0.93). Regrowth could be suppressed in all six experiments using %T>MICi ≥73.6%, but only one out of six experiments below the threshold (P = 0.015). The exposures to suppress regrowth might be attained using the clinical dose of avibactam, but a much higher dose than the standard dose would be needed for tazobactam.
conclusionsA dense population of ESBL-producing bacteria could be suppressed by an optimized dosing regimen of selected β-lactam/β-lactamase inhibitor combinations. The reversibility of enzyme inhibition could play an important role in diminishing the inoculum effect. In vivo investigations to validate these findings are warranted.
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