ArticleAntimicrobial agents and chemotherapy2013
Pharmacodynamics of ceftaroline against Staphylococcus aureus studied in an in vitro pharmacokinetic model of infection.
Article in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07306234 (Efficacy and Safety of Doxycycline Versus Macrolides for Mycoplasma Pneumoniae Infection in Children), which is not on this map. Cited by 20 papers, 1 of them a synthesis that pooled it.
What it found
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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.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Efficacy and Safety of Doxycycline Versus Macrolides for Mycoplasma Pneumoniae Infection in Children (DOMINO): A Protocol for a Multicenter, Randomized, Open-Label, Superiority Trial
Who cites it
20 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Systematic review of ceftaroline fosamil in the management of patients with methicillin-resistantEuropean respiratory review : an official journal of the European Respiratory Society · 2023Pooled it
- Plasma and parasternal subcutaneous tissue pharmacokinetics of ceftaroline fosamil in cardiac surgery with cardiopulmonary bypass.Frontiers in pharmacology · 2026Article
- Impact of Key Components of Intensified Ceftaroline Dosing on Pharmacokinetic/Pharmacodynamic Target Attainment.Clinical pharmacokinetics · 2024Article
- Pharmacodynamics of Flucloxacillin in a Neutropenic Murine Thigh Infection Model: A Piece of the Puzzle towards Evidence-Based Dosing.Antibiotics (Basel, Switzerland) · 2022Article
- Ceftaroline Fosamil for Treatment of Pediatric Complicated Skin and Soft Tissue Infections and Community-Acquired Pneumonia.Paediatric drugs · 2021Review
- Pharmacokinetic and Pharmacodynamic Target Attainment in Adult and Pediatric Patients Following Administration of Ceftaroline Fosamil as a 5-Minute Infusion.Clinical pharmacology in drug development · 2021Article
- One Size Fits All? Application of Susceptible-Dose-Dependent Breakpoints to Pediatric Patients and Laboratory Reporting.Journal of clinical microbiology · 2019Review
- Mechanisms of action and antimicrobial activity of ceftobiprole.Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia · 2019Review
- Ceftaroline fosamil doses and breakpoints for Staphylococcus aureus in complicated skin and soft tissue infections.The Journal of antimicrobial chemotherapy · 2019Article
- Review
- Penetration of Ceftaroline into the Epithelial Lining Fluid of Healthy Adult Subjects.Antimicrobial agents and chemotherapy · 2016Article
- Single- and Repeated-Dose Pharmacokinetics of Ceftaroline in Plasma and Soft Tissues of Healthy Volunteers for Two Different Dosing Regimens of Ceftaroline Fosamil.Antimicrobial agents and chemotherapy · 2016Article
- Suppression of Emergence of Resistance in Pathogenic Bacteria: Keeping Our Powder Dry, Part 1.Antimicrobial agents and chemotherapy · 2015Review
- A critical review on the clinical pharmacokinetics, pharmacodynamics, and clinical trials of ceftaroline.Clinical pharmacokinetics · 2015Review
- Pharmacokinetics of ceftaroline in normal body weight and obese (classes I, II, and III) healthy adult subjects.Antimicrobial agents and chemotherapy · 2015Article
- The Tipper-Strominger Hypothesis and Triggering of Allostery in Penicillin-Binding Protein 2a of Methicillin-Resistant Staphylococcus aureus (MRSA).Journal of the American Chemical Society · 2015Article
- Article
- Ceftaroline in the management of complicated skin and soft tissue infections and community acquired pneumonia.Therapeutics and clinical risk management · 2015Review
- In vitro activity of human-simulated epithelial lining fluid exposures of ceftaroline, ceftriaxone, and vancomycin against methicillin-susceptible and -resistant Staphylococcus aureus.Antimicrobial agents and chemotherapy · 2014Article
- Comparison of in vivo and in vitro pharmacodynamics of a humanized regimen of 600 milligrams of Ceftaroline Fosamil every 12 hours against Staphylococcus aureus at initial inocula of 106 and 108 CFU per milliliter.Antimicrobial agents and chemotherapy · 2014Article
Corrections and comments
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Authors and funding
4 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
An in vitro single-compartment dilutional pharmacokinetic model was used to study the pharmacodynamics of ceftaroline against Staphylococcus aureus (both methicillin-susceptible S. aureus [MSSA] and methicillin-resistant S. aureus [MRSA]). Mean serum free concentrations of ceftaroline (the active metabolite of the prodrug ceftaroline fosamil) dosed in humans at 600 mg every 12 h (q12h) were simulated, and activities against 12 S. aureus strains (3 MSSA strains and 9 MRSA strains, 3 of which had a vancomycin-intermediate phenotype) were determined. Ceftaroline produced 2.5- to 4.0-log10-unit reductions in viable counts by 24 h with all strains and a 0.5- to 4.0-log-unit drop in counts at 96 h. The antibacterial effect could not be related to the strain MIC across the ceftaroline MIC range from 0.12 to 2.0 μg/ml. In dose-ranging studies, the cumulative percentage of a 24-h period that the free drug concentration exceeded the MIC under steady-state pharmacokinetic conditions (fT(MIC)) of 24.5% ± 8.9% was associated with a 24-h bacteriostatic effect, one of 27.8% ± 9.5% was associated with a -1-log-unit drop, and one of 32.1% ± 8.1% was associated with a -2-log-unit drop. The MSSA and MRSA strains had similar fT(MIC) values. fT(MIC) values increased with increasing duration of exposure up to 96 h. Changes in ceftaroline population analysis profiles were related to fT(MIC). fT(MIC)s of <50% were associated with growth on 4× MIC recovery plates at 96 h of drug exposure. These data support the use of ceftaroline fosamil at doses of 600 mg q12h to treat S. aureus strains with MICs of ≤ 2 μg/ml. An fT(MIC) of 25 to 30% would make a suitable pharmacodynamic index target, but fTMIC values of ≥ 50% are needed to suppress the emergence of resistance and require clinical evaluation.
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