Experimental study of the efficacy of linezolid alone and in combinations against experimental meningitis due to Staphylococcus aureus strains with decreased susceptibility to beta-lactams and glycopeptides

Cabellos, Carmen; Garrigós, Carmen; Taberner, Ferran; Force, E.; Pachón-Ibáñez, María Eugenia

doi:10.1016/j.jiac.2014.05.008

Cited by 14 publications

(4 citation statements)

References 28 publications

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“…However, linezolid has been reported to have a favourable pharmacokinetic profile exhibiting a large volume of distribution and a relatively low protein binding, favouring its penetration into the CNS with an area under the concentration-time curve (AUC) CSF/ AUC plasma close to 1 [25]. Animal models of MRSA meningitis have confirmed the good penetration of linezolid through the blood-brain barrier and an effective bacterial clearance from cerebrospinal fluid (CSF) at 24 h of treatment [26,27]. In humans, studies in postneurosurgical infections have reported a ratio between CSF and plasma linezolid trough concentrations between 0.66 and 1, resulting in maximum concentrations of up to 7.1 ± 2.2 mg/L in CSF at steady state after intravenous infusion of 600 mg every 12 h [28][29][30][31].…”

Section: Cerebrospinal Fluid Penetrationmentioning

confidence: 99%

Clinical Pharmacokinetics and Pharmacodynamics of Oxazolidinones

2017

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Oxazolidinones are a class of synthetic antimicrobial agents with potent activity against a wide range of multidrug-resistant Gram-positive pathogens including methicillin-resistant Staphylococcus aureus and vancomycin-resistant enterococci. Oxazolidinones exhibit their antibacterial effects by inhibiting protein synthesis acting on the ribosomal 50S subunit of the bacteria and thus preventing formation of a functional 70S initiation complex. Currently, two oxazolidinones have been approved by the US Food and Drug Administration: linezolid and more recently tedizolid. Other oxazolidinones are currently under investigation in clinical trials. These antimicrobial agents exhibit a favourable pharmacokinetic profile with an excellent bioavailability and a good tissue and organ penetration. In-vitro susceptibility studies have shown that oxazolidinones are bacteriostatic against enterococci and staphylococci, and bactericidal for the majority of strains of streptococci. In the context of emergence of resistance to glycopeptides, oxazolidinones have become an effective alternative to vancomycin treatment frequently associated with nephrotoxicity. However, oxazolidinones, and linezolid in particular, are associated with significant adverse events, myelosuppression representing the main unfavourable side effect. More recently, tedizolid has been shown to effectively treat acute bacterial skin and skin structure infections. This newer oxazolidinone offers the advantages of once-daily dosing and a better safety profile in healthy volunteer studies (fewer gastrointestinal and haematological side effects). The potential use of tedizolid for other infections that could require longer therapy warrants further studies for positioning this new oxazolidinone in the available antimicrobial armamentarium. Moreover, other oxazolidinones are currently under active investigation.

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Section: Cerebrospinal Fluid Penetrationmentioning

confidence: 99%

Clinical Pharmacokinetics and Pharmacodynamics of Oxazolidinones

2017

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“…Cabellos et al (2014) established a meningitis model induced by injecting a glycopeptide intermediate S. aureus (GISA) strain into the rabbit cisterna magna. Four treatment regimens, including a control group (saline), LZD, vancomycin, and LZD plus rifampicin, were applied.…”

Section: Introductionmentioning

confidence: 99%

Linezolid and Its Immunomodulatory Effect: In Vitro and In Vivo Evidence

et al. 2019

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Recent studies have explored the effects of some antibacterial agents on various aspects of the immune response to infection in addition to their bactericidal effects. As a synthetic oxazolidinone class of antibacterial agent, linezolid (LZD) exhibits activity against a broad range of Gram-positive bacteria. In the present review, we summarized the effects of LZD on the immune response and new approaches that can exploit such interactions for the treatment of bacterial infections. In vitro and pre-clinical evidence demonstrate that LZD suppresses the phagocytic ability, cytokine synthesis, and secretion of immune cells as well as the expressions of immune-related genes at the mRNA level under the stimulation of endotoxin or pathogens. Immunomodulatory effects of LZD can not only reduce the inflammatory damage induced by exaggerated or prolonged release of pro-inflammatory cytokines during infections but can also be applied to alleviate the symptoms of non-infectious inflammatory conditions. Further research is necessary to explore the molecular mechanisms involved and confirm these findings in clinical practice.

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“…The combination of rifampicin with linezolid has been shown to inhibit the generation of rifampicin-resistant bacteria [6], and also induces the effects of linezolid [7, 8]. However, numerous linezolid combination studies with rifampicin demonstrated that blood linezolid concentrations decreased when it was combined with rifampicin [9, 10].…”

Section: Introductionmentioning

confidence: 99%

Effects of a rifampicin pre-treatment on linezolid pharmacokinetics

et al. 2019

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Linezolid is an oxazolidinone antibiotic that effectively treats methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococci (VRE). Since rifampicin induces other antibiotic effects, it is combined with linezolid in therapeutic regimes. However, linezolid blood concentrations are reduced by this combination, which increases the risk of the emergence of antibiotic-resistant bacteria. We herein demonstrated that the combination of linezolid with rifampicin inhibited its absorption and promoted its elimination, but not through microsomal enzymes. Our results indicate that the combination of linezolid with rifampicin reduces linezolid blood concentrations via metabolic enzymes.

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Experimental study of the efficacy of linezolid alone and in combinations against experimental meningitis due to Staphylococcus aureus strains with decreased susceptibility to beta-lactams and glycopeptides

Cited by 14 publications

References 28 publications

Clinical Pharmacokinetics and Pharmacodynamics of Oxazolidinones

Clinical Pharmacokinetics and Pharmacodynamics of Oxazolidinones

Linezolid and Its Immunomodulatory Effect: In Vitro and In Vivo Evidence

Effects of a rifampicin pre-treatment on linezolid pharmacokinetics

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