Experimental study of the efficacy of daptomycin for the treatment of cephalosporin-resistant pneumococcal meningitis.

Abstract

OBJECTIVES:

To determine the efficacy of daptomycin for the treatment of penicillin- and cephalosporin-resistant pneumococcal meningitis using in vitro and in vivo methods.

METHODS:

In vitro killing curves were determined with clinically achievable CSF antibiotic concentrations. In a rabbit model of pneumococcal meningitis, we studied the efficacy (Δ cfu/mL) of daptomycin used at 15 and 25 mg/kg, comparing it with ceftriaxone 100 mg/kg/24 h and ceftriaxone plus vancomycin 30 mg/kg/24 h over a 26 h period against two different strains: HUB 2349 and ATCC 51916, with MICs of 2 and 32 mg/L of cefotaxime/ceftriaxone, respectively.

RESULTS:

The penetration of daptomycin into CSF ranged between 9% and 11%. Daptomycin therapy achieved an excellent response, being bactericidal within 2 h of antibiotic administration. Against strain HUB 2349, daptomycin at both doses was as effective as ceftriaxone plus vancomycin. Against the highly resistant strain, daptomycin 25 mg/kg was significantly better than ceftriaxone plus vancomycin at 2 and 6 h.

CONCLUSIONS:

Daptomycin at standard doses, and especially at high doses, may be a useful alternative for the treatment of penicillin- and cephalosporin-resistant pneumococcal meningitis.

• Authors: M Vivas, E Force, C Garrigós, F Tubau, A C M Platteel, J Ariza, C Cabellos
• Journal: The Journal of antimicrobial chemotherapy (J Antimicrob Chemother) Vol. 69 Issue 11 Pg. 3020-6 (Nov 2014) ISSN: 1460-2091 [Electronic] England
• PMID: 24962033 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author 2014. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: [email protected].

Chemical References

• Cephalosporins
• Daptomycin

Topics

• Animals
• Cephalosporin Resistance (drug effects)
• Cephalosporins (pharmacology, therapeutic use)
• Daptomycin (pharmacology, therapeutic use)
• Female
• Meningitis, Pneumococcal (cerebrospinal fluid, drug therapy)
• Rabbits
• Treatment Outcome