A pharmacokinetic-pharmacodynamic (PKPD) model-based analysis of tedizolid against enterococci using the hollow-fibre infection model

Iqbal, Khalid; Rohde, Holger; Huang, Jia-Bin; Tikiso, T.; Amann, Lisa F; Zeitlinger, Markus; Wicha, Sebastian G.

doi:10.1093/jac/dkac183

Cited by 5 publications

(3 citation statements)

References 41 publications

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“…The authors concluded that the recommended dose of 200 mg/day was insufficient to suppress bacterial growth in the system, indicating that additional factors may contribute to the clinical effect of the drug. These results corroborate to the precaution of using tedizolid in immunocompromised patients [ 78 ].…”

Section: The Use Of Pop Pk/pd Modelssupporting

confidence: 87%

Pharmacokinetic/Pharmacodynamic Modeling and Application in Antibacterial and Antifungal Pharmacotherapy: A Narrative Review

et al. 2022

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Pharmacokinetics and pharmacodynamics are areas in pharmacology related to different themes in the pharmaceutical sciences, including therapeutic drug monitoring and different stages of drug development. Although the knowledge of these disciplines is essential, they have historically been treated separately. While pharmacokinetics was limited to describing the time course of plasma concentrations after administering a drug-dose, pharmacodynamics describes the intensity of the response to these concentrations. In the last decades, the concept of pharmacokinetic/pharmacodynamic modeling (PK/PD) emerged, which seeks to establish mathematical models to describe the complete time course of the dose-response relationship. The integration of these two fields has had applications in optimizing dose regimens in treating antibacterial and antifungals. The anti-infective PK/PD models predict the relationship between different dosing regimens and their pharmacological activity. The reviewed studies show that PK/PD modeling is an essential and efficient tool for a better understanding of the pharmacological activity of antibacterial and antifungal agents.

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Section: The Use Of Pop Pk/pd Modelssupporting

confidence: 87%

Pharmacokinetic/Pharmacodynamic Modeling and Application in Antibacterial and Antifungal Pharmacotherapy: A Narrative Review

et al. 2022

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“…Gastrointestinal disorders and myelotoxicity are less frequent with tedizolid, and a favorable action against MRSA IE have been reported in experimental models (rats and rabbits). Against VRE tedizolid has a fourfold lower MIC when compared to linezolid and has activity against linezolid-resistant strains with a cfr mutation, probably due to additional interactions with the ribosomal [ 95 , 96 , 145 , 146 , 147 ]. Thus, compared to linezolid, tedizolid has the potential to be a first-line agent for the treatment of serious VRE infections, but until now, no clinical data have been published in patients with IE.…”

Section: Therapeutic Choicesmentioning

confidence: 99%

Treatment of Enterococcus faecalis Infective Endocarditis: A Continuing Challenge

et al. 2023

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Today, Enterococcus faecalis is one of the main causes of infective endocarditis in the world, generally affecting an elderly and fragile population, with a high mortality rate. Enterococci are partially resistant to many commonly used antimicrobial agents such as penicillin and ampicillin, as well as high-level resistance to most cephalosporins and sometimes carbapenems, because of low-affinity penicillin-binding proteins, that lead to an unacceptable number of therapeutic failures with monotherapy. For many years, the synergistic combination of penicillins and aminoglycosides has been the cornerstone of treatment, but the emergence of strains with high resistance to aminoglycosides led to the search for new alternatives, like dual beta-lactam therapy. The development of multi-drug resistant strains of Enterococcus faecium is a matter of considerable concern due to its probable spread to E. faecalis and have necessitated the search of new guidelines with the combination of daptomycin, fosfomycin or tigecycline. Some of them have scarce clinical experience and others are still under investigation and will be analyzed in this review. In addition, the need for prolonged treatment (6–8 weeks) to avoid relapses has forced to the consideration of other viable options as outpatient parenteral strategies, long-acting administrations with the new lipoglycopeptides (dalbavancin or oritavancin), and sequential oral treatments, which will also be discussed.

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“…Gastrointestinal disorders and myelotoxicity are less frequent with tedizolid, and a favorable action against MRSA IE have been reported in experimental models (rats and rabbits). Against VRE tedizolid has a fourfold lower MIC when compared to linezolid and has activity against linezolid-resistant strains with a cfr mutation, probably due to additional interactions with the ribosomal [126][127][128][129][130][131] . Thus, compared to linezolid, tedizolid has the potential to be a first-line agent for the treatment of serious VRE infections, but until now, no clinical data have been published in patients with IE.…”

Section: Linezolid and Tedizolidmentioning

confidence: 99%

Treatment of <em>Enterococcus faecalis</em> Infective Endocarditis: A Continuing Challenge

Herrero-Hidalgo¹,

Fernández-Rubio²,

Luque‐Márquez³

et al. 2023

Preprint

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Today, enterococci (mainly Enterococcus faecalis) are one of the main causes of infective endocarditis in the world, generally affecting an elderly and fragile population, with a high mortality rate. enterococci are intrinsically resistant to many commonly used antimicrobial agents. All enterococci exhibit decreased susceptibility to penicillin and ampicillin, as well as high-level resistance to most cephalosporins and all semi-synthetic penicillins, as the result of expression of low-affinity penicillin-binding proteins, that precludes an unacceptable number of therapeutic failures with monotherapy with these drugs. For years, the synergistic combination of penicillins and aminoglycosides was the cornerstone of treatment, but the emergence of strains with high resistance to aminoglycosides led to the search for new alternatives, such as dual beta-lactam therapy. The development of multi-drug resistant strains of Enterococcus faecium is a matter of considerable concern due to its probable spread to E. faecalis and have forced the search of new alternatives with the combination of daptomycin, fosfomycin or tigecycline. Some of them have scarce clinical experience and others are still under investigation and will be analyzed in this review. In addition, the need for prolonged treatment (6-8 weeks) to avoid relapses has led to the consideration of viable options such as outpatient parenteral therapies or long-acting administrations with the new lipoglycopeptides (dalbavancin or oritavancin), and sequential oral treatments, which will also be discussed.

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A pharmacokinetic-pharmacodynamic (PKPD) model-based analysis of tedizolid against enterococci using the hollow-fibre infection model

Cited by 5 publications

References 41 publications

Pharmacokinetic/Pharmacodynamic Modeling and Application in Antibacterial and Antifungal Pharmacotherapy: A Narrative Review

Pharmacokinetic/Pharmacodynamic Modeling and Application in Antibacterial and Antifungal Pharmacotherapy: A Narrative Review

Treatment of Enterococcus faecalis Infective Endocarditis: A Continuing Challenge

Treatment of <em>Enterococcus faecalis</em> Infective Endocarditis: A Continuing Challenge

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