ArticleAntimicrobial agents and chemotherapy2007
Pharmacokinetic/pharmacodynamic factors influencing emergence of resistance to linezolid in an in vitro model.
Article in Antimicrobial agents and chemotherapy, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 63 citations in OpenAlex.
- Applying pharmacokinetic/pharmacodynamic measurements for linezolid in critically ill patients: optimizing efficacy and reducing resistance occurrence.European journal of clinical pharmacology · 2022Trial
- The emergence of linezolid resistance among Enterococci in intestinal microbiota of treated patients is unrelated to individual pharmacokinetic characteristics.Antimicrobial agents and chemotherapy · 2014Trial
- Comparison of the pharmacokinetics of two dosage regimens of linezolid in multidrug-resistant and extensively drug-resistant tuberculosis patients.Clinical pharmacokinetics · 2010Trial
- Pharmacokinetics of linezolid in septic patients with and without extended dialysis.European journal of clinical pharmacology · 2010Trial
- Therapeutic approach to difficult-to-treat multidrug-resistant enterococcal infections.Antimicrobial agents and chemotherapy · 2025Review
- Enhanced efficacy of sequential administration of fosfomycin and linezolid againstFrontiers in microbiology · 2025Article
- Antimicrobial Pharmacokinetics and Pharmacodynamics in Critical Care: Adjusting the Dose in Extracorporeal Circulation and to Prevent the Genesis of Multiresistant Bacteria.Antibiotics (Basel, Switzerland) · 2023Review
- Assessing the Emergence of Resistance in vitro and Invivo: Linezolid Combined with Fosfomycin Against Fosfomycin-Sensitive and ResistantInfection and drug resistance · 2022Article
- Dose Optimization of Combined Linezolid and Fosfomycin againstMicrobiology spectrum · 2021Article
- Optimization of Linezolid Dosing Regimens for Treatment of Vancomycin-Resistant Enterococci Infection.Infection & chemotherapy · 2021Article
- Development and Validation of an HPLC-UV Method for Quantitation of Linezolid: Application to Resistance Study Using in vitro PK/PD Model.Infection and drug resistance · 2021Article
- Determining therapeutic trough ranges for linezolid.Saudi pharmaceutical journal : SPJ : the official publication of the Saudi Pharmaceutical Society · 2019Article
- Impact of erythrocytes on bacterial growth and antimicrobial activity of selected antibiotics.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2019Article
- Pharmacokinetics and pharmacodynamics of Linezolid in burn patients.Annals of burns and fire disasters · 2018Article
- Review
- Observed Antagonistic Effect of Linezolid on Daptomycin or Vancomycin Activity against Biofilm-Forming Methicillin-Resistant Staphylococcus aureus in an In Vitro Pharmacodynamic Model.Antimicrobial agents and chemotherapy · 2015Article
- In vitro resistance studies with bacteria that exhibit low mutation frequencies: prediction of "antimutant" linezolid concentrations using a mixed inoculum containing both susceptible and resistant Staphylococcus aureus.Antimicrobial agents and chemotherapy · 2015Article
- In vitro simulation of in vivo pharmacokinetic model with intravenous administration via flow rate modulation.Journal of pharmacokinetics and pharmacodynamics · 2015Article
- Pharmacokinetics and pharmacodynamics of nemonoxacin against Streptococcus pneumoniae in an in vitro infection model.Antimicrobial agents and chemotherapy · 2013Article
- Emergence of linezolid-resistant Staphylococcus aureus after prolonged treatment of cystic fibrosis patients in Cleveland, Ohio.Antimicrobial agents and chemotherapy · 2011Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Emerging resistance threatens the usefulness of linezolid for the treatment of severe infections caused by multidrug-resistant gram-positive bacteria. Optimal pharmacokinetic (PK)/pharmacodynamic (PD) indices have been described for the antimicrobial efficacy of linezolid (area under the concentration-time curve over 24 h at steady state divided by the MIC, >100; the cumulative percentage of a 24-h period that the drug concentration exceeds the MIC under steady-state PK conditions, >85). The aim of this study was to investigate the influence of these PK/PD indices on the development of resistance to linezolid by using an in vitro PK/PD model. Four dosage regimens were simulated over 72 h (two intermittent bolus regimens of 600 mg every 12 h [q12h] and 120 mg q12h and two continuous-infusion regimens of 120 mg/24 h and 30 mg/24 h) against four reference strains: methicillin-resistant Staphylococcus aureus (MRSA), heteroresistant vancomycin-intermediate S. aureus (hVISA), vancomycin-intermediate S. aureus (VISA), and vancomycin-resistant Enterococcus faecium (VRE). Linezolid concentrations were measured by high-performance liquid chromatography. Changes in susceptibility were characterized by pre- and posttreatment MIC measurements and population analysis profiles (PAPs). The linezolid concentrations that were achieved closely matched those that were targeted. The simulation with 600 mg q12h provided a >3-log10 reduction in the number of CFU/ml for all four strains, as did the 120-mg-q12h regimen for hVISA and VISA and the 30-mg/24-h continuous infusion for VRE and VISA. After 72 h of exposure to the 120-mg/24-h continuous-infusion simulation, the area under the PAP curve for all strains increased substantially (40 to 178%); increases in the MICs for the MRSA and hVISA strains were observed. The results demonstrate that PK/PD considerations are important in optimizing both antibacterial activity and the development of resistance to linezolid. The potential for resistance development appears to be higher when a constant concentration is maintained in the vicinity of the MIC of the bacteria.
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