ArticleAntimicrobial agents and chemotherapy2013
Evaluation of ceftaroline activity against heteroresistant vancomycin-intermediate Staphylococcus aureus and vancomycin-intermediate methicillin-resistant S. aureus strains in an in vitro pharmacokinetic/pharmacodynamic model: exploring the "seesaw effect".
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. Cited by 30 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
30 citing papers in PubMed, 1 synthesis or guideline pooled it, 63 citations in OpenAlex.
- Global trends and research profile of antibiotic heteroresistance: a bibliometric and visual analysis.Frontiers in microbiology · 2026Pooled it
- Trial
- Early initiation of ceftaroline-based combination therapy for methicillin-resistant Staphylococcus aureus bacteremia.Annals of clinical microbiology and antimicrobials · 2025Article
- Navigating collateral sensitivity: insights into the mechanisms and applications of antibiotic resistance trade-offs.Frontiers in microbiology · 2024Review
- Knockout ofJournal of bacteriology · 2022Article
- Nemonoxacin Enhances Antibacterial Activity and Anti-Resistance Mutation Ability of Vancomycin against Methicillin-Resistant Staphylococcus aureus in anAntimicrobial agents and chemotherapy · 2022Article
- MRSA compendium of epidemiology, transmission, pathophysiology, treatment, and prevention within one health framework.Frontiers in microbiology · 2022Review
- Synergy Between Beta-Lactams and Lipo-, Glyco-, and Lipoglycopeptides, Is Independent of the Seesaw Effect in Methicillin-ResistantFrontiers in molecular biosciences · 2021Article
- The Emerging Role of β-Lactams in the Treatment of Methicillin-Resistant Staphylococcus aureus Bloodstream Infections.Antimicrobial agents and chemotherapy · 2020Review
- Occurrence of cross-resistance and β-lactam seesaw effect in glycopeptide-, lipopeptide- and lipoglycopeptide-resistant MRSA correlates with membrane phosphatidylglycerol levels.The Journal of antimicrobial chemotherapy · 2020Article
- Impact of Daptomycin Dose Exposure Alone or in Combination with β-Lactams or Rifampin against Vancomycin-Resistant Enterococci in anAntimicrobial agents and chemotherapy · 2020Article
- Multicenter Cohort of Patients With Methicillin-ResistantOpen forum infectious diseases · 2020Article
- Dalbavancin Alone and in Combination with Ceftaroline against Four Different Phenotypes ofAntimicrobial agents and chemotherapy · 2019Article
- Novel single-nucleotide variations associated with vancomycin resistance in vancomycin-intermediateInfection and drug resistance · 2018Article
- Fosfomycin Enhances the Activity of Daptomycin against Vancomycin-Resistant Enterococci in an In Vitro Pharmacokinetic-Pharmacodynamic Model.Antimicrobial agents and chemotherapy · 2016Article
- Review
- Mechanisms of drug resistance: daptomycin resistance.Annals of the New York Academy of Sciences · 2015Review
- Telavancin demonstrates activity against methicillin-resistant Staphylococcus aureus isolates with reduced susceptibility to vancomycin, daptomycin, and linezolid in broth microdilution MIC and one-compartment pharmacokinetic/pharmacodynamic models.Antimicrobial agents and chemotherapy · 2015Article
- Evaluation of Ceftaroline Alone and in Combination against Biofilm-Producing Methicillin-Resistant Staphylococcus aureus with Reduced Susceptibility to Daptomycin and Vancomycin in an In Vitro Pharmacokinetic/Pharmacodynamic Model.Antimicrobial agents and chemotherapy · 2015Article
- Missense mutations in PBP2A Affecting ceftaroline susceptibility detected in epidemic hospital-acquired methicillin-resistant Staphylococcus aureus clonotypes ST228 and ST247 in Western Switzerland archived since 1998.Antimicrobial agents and chemotherapy · 2015Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
Abstract
A "seesaw effect" in methicillin-resistant Staphylococcus aureus (MRSA) has been demonstrated, whereby susceptibility to β-lactam antimicrobials increases as glyco- and lipopeptide susceptibility decreases. We investigated this effect by evaluating the activity of the anti-MRSA cephalosporin ceftaroline against isogenic pairs of MRSA strains with various susceptibilities to vancomycin in an in vitro pharmacokinetic/pharmacodynamic (PK/PD) model. The activities of ceftaroline at 600 mg every 12 h (q12h) (targeted free maximum concentration of drug in serum [fC(max)], 15.2 μg/ml; half-life [t(1/2)], 2.3 h) and vancomycin at 1 g q12h (targeted fC(max), 18 μg/ml; t(1/2), 6 h) were evaluated against 3 pairs of isogenic clinical strains of MRSA that developed increased MICs to vancomycin in patients while on therapy using a two-compartment hollow-fiber PK/PD model with a starting inoculum of ~10(7) CFU/ml over a 96-h period. Bacterial killing and development of resistance were evaluated. Expression of penicillin-binding proteins (PBPs) 2 and 4 was evaluated by reverse transcription (RT)-PCR. The achieved pharmacokinetic parameters were 98 to 119% of the targeted values. Ceftaroline and vancomycin were bactericidal against 5/6 and 1/6 strains, respectively, at 96 h. Ceftaroline was more active against the mutant strains than the parent strains, with this difference being statistically significant for 2/3 strain pairs at 96 h. The level of PBP2 expression was 4.4× higher in the vancomycin-intermediate S. aureus (VISA) strain in 1/3 pairs. The levels of PBP2 and PBP4 expression were otherwise similar between the parent and mutant strains. These data support the seesaw hypothesis that ceftaroline, like traditional β-lactams, is more active against strains that are less susceptible to vancomycin even when the ceftaroline MICs are identical. Further research to explore these unique findings is warranted.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.