ArticleAntimicrobial agents and chemotherapy2009
Development and qualification of a pharmacodynamic model for the pronounced inoculum effect of ceftazidime against Pseudomonas aeruginosa.
Article in Antimicrobial agents and chemotherapy, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
56 citing papers in PubMed.
- A mechanism-based pharmacokinetic/pharmacodynamic analysis of polymyxin B-based combination therapy against carbapenem-resistantAntimicrobial agents and chemotherapy · 2026Article
- Pharmacodynamic Evaluation of Adjuvant Targets: Low Molecular Weight PBP7/8 Effects on β-Lactam Activity Against Carbapenem-Resistant Acinetobacter Baumannii.Pharmaceuticals (Basel, Switzerland) · 2025Article
- PKPD modeling of the inoculum effect of combined ceftazidime/avibactam and colistin against KPC-3Antimicrobial agents and chemotherapy · 2025Article
- Comprehensive stability analysis of 13 β-lactams and β-lactamase inhibitors inAntimicrobial agents and chemotherapy · 2024Article
- Ceftolozane-Tazobactam against Pseudomonas aeruginosa Cystic Fibrosis Clinical Isolates in the Hollow-Fiber Infection Model: Challenges Imposed by Hypermutability and Heteroresistance.Antimicrobial agents and chemotherapy · 2023Article
- Simulated Intravenous versus Inhaled Tobramycin with or without Intravenous Ceftazidime Evaluated against Hypermutable Pseudomonas aeruginosa via a Dynamic Biofilm Model and Mechanism-Based Modeling.Antimicrobial agents and chemotherapy · 2022Article
- A New Pharmacokinetic-Pharmacodynamic Model To Characterize the Inoculum Effect of Acinetobacter baumannii on Polymyxin BAntimicrobial agents and chemotherapy · 2022Article
- In Vitro Activities of Ceftazidime-Avibactam and Aztreonam-Avibactam at Different Inoculum Sizes of Extended-Spectrum β-Lactam-Resistant Enterobacterales Blood Isolates.Antibiotics (Basel, Switzerland) · 2021Article
- Informing and Validating Translational Mechanism-Based Models for Antibiotics by Experimental and Computational Approaches.Clinical pharmacology and therapeutics · 2021Article
- Combating Multidrug-Resistant Bacteria by Integrating a Novel Target Site Penetration and Receptor Binding Assay Platform Into Translational Modeling.Clinical pharmacology and therapeutics · 2021Article
- Model-Informed Drug Development for Anti-Infectives: State of the Art and Future.Clinical pharmacology and therapeutics · 2021Review
- The Spectrum of Antimicrobial Activity of Cyadox against Pathogens Collected from Pigs, Chicken, and Fish in China.Antibiotics (Basel, Switzerland) · 2021Article
- In pursuit of the triple crown: mechanism-based pharmacodynamic modelling for the optimization of three-drug combinations against KPC-producing Klebsiella pneumoniae.Clinical microbiology and infection : the official publication of the European Society of Clinical Microbiology and Infectious Diseases · 2020Article
- Recommendations for Systemic Antimicrobial Therapy in Fracture-Related Infection: A Consensus From an International Expert Group.Journal of orthopaedic trauma · 2020Article
- Meropenem-Tobramycin Combination Regimens Combat Carbapenem-Resistant Pseudomonas aeruginosa in the Hollow-Fiber Infection Model Simulating Augmented Renal Clearance in Critically Ill Patients.Antimicrobial agents and chemotherapy · 2019Article
- Inoculum effect of β-lactam antibiotics.The Journal of antimicrobial chemotherapy · 2019Review
- Evaluation of Tobramycin and Ciprofloxacin as a Synergistic Combination Against HypermutablePharmaceutics · 2019Article
- Generating Robust and Informative NonclinicalAntimicrobial agents and chemotherapy · 2019Review
- Novel Polymyxin Combination with the Antiretroviral Zidovudine Exerts Synergistic Killing against NDM-Producing Multidrug-Resistant Klebsiella pneumoniae.Antimicrobial agents and chemotherapy · 2019Article
- Meropenem Combined with Ciprofloxacin Combats Hypermutable Pseudomonas aeruginosa from Respiratory Infections of Cystic Fibrosis Patients.Antimicrobial agents and chemotherapy · 2018Article
Corrections and comments
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Authors and funding
6 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Evidence is mounting in support of the inoculum effect (i.e., slow killing at large initial inocula [CFUo]) for numerous antimicrobials against a variety of pathogens. Our objectives were to (i) determine the impact of the CFUo of Pseudomonas aeruginosa on ceftazidime activity and (ii) to develop and validate a pharmacokinetic/pharmacodynamic (PKPD) mathematical model accommodating a range of CFUo. Time-kill experiments using ceftazidime at seven concentrations up to 128 mg/liter (MIC, 2 mg/liter) were performed in duplicate against P. aeruginosa PAO1 at five CFUo from 10(5) to 10(9) CFU/ml. Samples were collected over 24 h and fit by candidate models in NONMEM VI and S-ADAPT 1.55 (all data were comodeled). External model qualification integrated data from eight previously published studies. Ceftazidime displayed approximately 3 to 4 log(10) CFU/ml net killing at 10(6.2) CFUo and concentrations of 4 mg/liter (or higher), less than 1.6 log(10) CFU/ml killing at 10(7.3) CFUo, and no killing at 10(8.0) CFUo for concentrations up to 128 mg/liter. The proposed mechanism-based model successfully described the inoculum effect and the concentration-independent lag time of killing. The mean generation time was 28.3 min. The effect of an autolysin was assumed to inhibit successful replication. Ceftazidime concentrations of 0.294 mg/liter stimulated the autolysin effect by 50%. The model was predictive in the internal cross-validation and had excellent in silico predictive performance for published studies of P. aeruginosa ATCC 27853 for various CFUo. The proposed PKPD model successfully described and predicted the pronounced inoculum effect of ceftazidime in vitro and integrated data from eight literature studies to support translation from time-kill experiments to in vitro infection models.
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