Related Experiment Videos
Linezolid against penicillin-sensitive and -resistant pneumococci in the rabbit meningitis model
P Cottagnoud1, C M Gerber, F Acosta
1Department of Internal Medicine, Inselspital, Freiburgstrasse, 3010 Berne, Switzerland. pcottagn@insel.ch
Abstract:
Linezolid, a new oxazolidinone antibiotic, showed good penetration (38+/-4%) into the meninges of rabbits with levels in the CSF ranging from 9.5 to 1.8 mg/L after two i.v. injections (20 mg/kg). Linezolid was clearly less effective than ceftriaxone against a penicillin-sensitive pneumococcal strain. Against a penicillin-resistant strain, linezolid had slightly inferior killing rates compared with the standard regimen (ceftriaxone combined with vancomycin). In vitro, linezolid was marginally bactericidal at concentrations above the MIC (5 x and 10 x MIC).
Insights
Linezolid, an oxazolidinone antibiotic, demonstrated good meningeal penetration in rabbits. However, it showed limited efficacy against pneumococcal strains compared to ceftriaxone and standard regimens.
Area of Science:
- Pharmacology
- Infectious Diseases
- Microbiology
Background:
- Linezolid is a novel oxazolidinone antibiotic with activity against Gram-positive bacteria.
- Bacterial meningitis remains a significant challenge, necessitating effective antibiotic penetration into the cerebrospinal fluid (CSF).
Purpose of the Study:
- To evaluate the penetration of linezolid into the meninges of rabbits.
- To assess the in vivo and in vitro efficacy of linezolid against Streptococcus pneumoniae.
Main Methods:
- Linezolid was administered intravenously to rabbits at 20 mg/kg.
- CSF and meningeal penetration were measured.
- Efficacy was tested against penicillin-sensitive and resistant pneumococcal strains in vivo and in vitro.
Main Results:
- Linezolid achieved good meningeal penetration (38+/-4%) with CSF concentrations ranging from 1.8 to 9.5 mg/L.
- Linezolid was less effective than ceftriaxone against penicillin-sensitive strains.
- Against penicillin-resistant strains, linezolid exhibited slightly inferior killing rates compared to ceftriaxone plus vancomycin.
- In vitro, linezolid was marginally bactericidal at 5x and 10x the minimum inhibitory concentration (MIC).
Conclusions:
- Linezolid demonstrates adequate penetration into the cerebrospinal fluid and meninges.
- Its efficacy against Streptococcus pneumoniae, particularly resistant strains, may be limited compared to established therapies.
- Further investigation into linezolid's role in treating bacterial meningitis is warranted.