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Diffusion of a new beta-lactam (LY 127935) into cerebrospinal fluid. Implications for therapy of gram-negative
Abstract:
LY 127935, a new oxa beta-lactam with an expanded gram-negative spectrum, was administered intravenously to seven patients, including two patients with documented gram-negative bacillary meningitis. In the patients receiving continuous therapy (2 g intravenously every 8 hours) cerebrospinal fluid trough levels of LY were never less than 6 micrograms/ml. Peak cerebrospinal fluid levels of LY ranged from 25 to 39 micrograms/ml and occurred approximately 2.5 hours after the intravenous administration of the drug. Cerebrospinal fluid levels of LY were 19 per cent to greater than 100 per cent of simultaneous serum levels. Cerebrospinal fluid bactericidal activity was 1:4 to 1:256. Intravenous LY, because of its expanded gram-negative spectrum and excellent cerebrospinal fluid penetration, is a potentially useful antibiotic in the treatment of gram-negative bacillary meningitis.
Insights
LY 127935, a novel oxa beta-lactam antibiotic, shows promising cerebrospinal fluid penetration and bactericidal activity. This makes it a potential treatment for gram-negative bacillary meningitis.
Area of Science:
- Pharmacology
- Infectious Diseases
- Neuroscience
Background:
- Gram-negative bacillary meningitis poses a significant therapeutic challenge.
- Novel antibiotics with enhanced Gram-negative spectrum are needed.
Observation:
- LY 127935, an oxa beta-lactam, was administered intravenously to seven patients.
- Two patients had documented Gram-negative bacillary meningitis.
Findings:
- Cerebrospinal fluid (CSF) trough levels of LY 127935 remained above 6 µg/ml.
- Peak CSF levels ranged from 25-39 µg/ml, reaching 19-100% of serum levels.
- CSF demonstrated bactericidal activity against Gram-negative bacteria (1:4 to 1:256).
Implications:
- Intravenous LY 127935 exhibits excellent CSF penetration.
- Its broad Gram-negative spectrum suggests potential efficacy in treating Gram-negative bacillary meningitis.