ArticleAntimicrobial agents and chemotherapy2010
In vivo pharmacodynamic activity of tomopenem (formerly CS-023) against Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus in a murine thigh infection model.
Article in Antimicrobial agents and chemotherapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Systematic review of antimicrobial pharmacokinetic/pharmacodynamic indices in murine thigh and hollow fibre dose fractionation studies analysed with a standard method.The Journal of antimicrobial chemotherapy · 2026Pooled it
- Pharmacokinetic-pharmacodynamic modeling to evaluate the relative impact of immune response and meropenem on bacterial killingAntimicrobial agents and chemotherapy · 2026Article
- Simulation-based evaluation of the impact of dose fractionation study design on antibiotic PKPD analyses.JAC-antimicrobial resistance · 2025Article
- Pharmacodynamics of Flucloxacillin in a Neutropenic Murine Thigh Infection Model: A Piece of the Puzzle towards Evidence-Based Dosing.Antibiotics (Basel, Switzerland) · 2022Article
- Limitations of Antibiotic MIC-Based PK-PD Metrics: Looking Back to Move Forward.Frontiers in pharmacology · 2021Review
- Article
- Simulation-Based Evaluation of PK/PD Indices for Meropenem Across Patient Groups and Experimental Designs.Pharmaceutical research · 2016Article
- Development of novel antibacterial drugs to combat multiple resistant organisms.Langenbeck's archives of surgery · 2015Review
- Advances in MRSA drug discovery: where are we and where do we need to be?Expert opinion on drug discovery · 2013Review
- New antibiotics for bad bugs: where are we?Annals of clinical microbiology and antimicrobials · 2013Review
- Comparative in vivo efficacies of epithelial lining fluid exposures of tedizolid, linezolid, and vancomycin for methicillin-resistant Staphylococcus aureus in a mouse pneumonia model.Antimicrobial agents and chemotherapy · 2012Article
- Efficacy of human-simulated exposures of tomopenem (formerly CS-023) in a murine model of Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus infection.Antimicrobial agents and chemotherapy · 2011Article
- Pharmacodynamics of razupenem (PZ601) studied in an in vitro pharmacokinetic model of infection.Antimicrobial agents and chemotherapy · 2011Article
- In vivo pharmacodynamic activity of tomopenem (formerly CS-023) against Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus in a murine thigh infection model.Antimicrobial agents and chemotherapy · 2010Article
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11 authors.
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No grant is acknowledged in the PubMed record.
Abstract
Tomopenem (formerly CS-023) is a novel carbapenem with broad-spectrum activities against diverse hospital pathogens, including Pseudomonas aeruginosa and methicillin-resistant Staphylococcus aureus (MRSA). We examined the in vivo pharmacodynamic characteristics of tomopenem against P. aeruginosa and MRSA by using a neutropenic murine thigh infection model with P. aeruginosa 12467 (MIC, 1 μg/ml) and MRSA 12372 (MIC, 2 μg/ml). The mice had 10(6) to 10(7) CFU/thigh of each strain 2 h after inoculation and were treated for 24 h with a fractionated administration of tomopenem given at intervals of 3, 6, 12, and 24 h. The serum protein binding of tomopenem was 17.4%. The efficacy of tomopenem in both infection models was enhanced by frequent dosing, which indicates that the efficacy is driven by the time above MIC (T(MIC)). In a sigmoid model, the cumulative percentages of the 24-h period that the concentrations of free, unbound fractions of the drug exceeded the MIC under steady-state pharmacokinetic conditions (f%T(MIC)s) were best correlated with efficacy when R(2) was 0.79 and 0.86 against P. aeruginosa and MRSA, respectively. Other pharmacokinetic and pharmacodynamic (PK-PD) indexes for the free, unbound fractions, the area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC/MIC) and the maximum concentration of the drug in serum divided by the MIC (C(max)/MIC), showed poor correlation with efficacy when R(2) was ≤0.42. The f%T(MIC) values required for a static effect, 1-log kill, and 2-log kill against P. aeruginosa were 29, 39, and 51, respectively, which were similar to those for meropenem, for which the values were 24, 33, and 45, respectively. Against MRSA, the values for tomopenem were 27, 35, and 47. In conclusion, the pharmacodynamic characteristics of tomopenem were similar to those of meropenem against P. aeruginosa, and there was no difference between the target values for P. aeruginosa and MRSA required for efficacy in this study.
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