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Updated: Jul 23, 2026
07:47
Experimental Human Pneumococcal Carriage
Published on: February 15, 2013
BMS-284756 in experimental cephalosporin-resistant pneumococcal meningitis
V Rodriguez-Cerrato1, F Ghaffar, J Saavedra
1Department of Pediatrics, The University of Texas Southwestern Medical Center, Dallas, Texas 75390-9063, USA. rodriguez_cerrato@yahoo.com
Antimicrobial Agents and Chemotherapy
|October 16, 2001
Summary
BMS-284756 demonstrates potent activity against resistant Streptococcus pneumoniae meningitis in rabbits. This novel quinolone achieved efficacy comparable to standard therapies, highlighting its potential for treating serious bacterial infections.
Area of Science:
- Pharmacology
- Infectious Diseases
- Microbiology
Background:
- Emergence of antibiotic resistance in Streptococcus pneumoniae poses a significant therapeutic challenge.
- Penicillin- and cephalosporin-resistant S. pneumoniae (CRSP) strains are associated with severe infections like meningitis.
- Novel antimicrobial agents are crucial for combating resistant bacterial pathogens.
Purpose of the Study:
- To evaluate the pharmacodynamic profile of BMS-284756 in experimental meningitis.
- To assess the effectiveness of BMS-284756 against CRSP meningitis in a rabbit model.
- To determine the cerebrospinal fluid (CSF) penetration and bactericidal activity of BMS-284756.
Main Methods:
- Experimental meningitis induced in rabbits via intracisternal inoculation of CRSP.
- Intravenous administration of BMS-284756 at various single and divided doses.
- Measurement of BMS-284756 concentrations in CSF and plasma.
- Determination of Minimum Inhibitory Concentrations (MICs) and Minimum Bactericidal Concentrations (MBCs).
- Calculation of CSF bacterial killing rates (BKR) and assessment of drug penetration.
Main Results:
- BMS-284756 exhibited low MICs (0.06 microg/ml) against CRSP.
- CSF concentrations of BMS-284756 increased with dose, with an elimination half-life of 4.5-6.3 hours.
- Bactericidal effect in CSF was concentration-dependent, with significant bacterial killing rates observed.
- Penetration into purulent CSF ranged from 14% to 25% relative to plasma.
- A 30 mg/kg dose of BMS-284756 showed efficacy comparable to vancomycin and ceftriaxone.
Conclusions:
- BMS-284756 possesses significant bactericidal activity against CRSP in the CSF.
- The drug's effectiveness is concentration-dependent and comparable to standard therapies at optimal doses.
- BMS-284756 shows promise as a therapeutic option for meningitis caused by resistant S. pneumoniae.
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