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

M. Vivas, E. Force, C. Garrig??s, F. Tubau, A. C M Platteel, J. Ariza, C. Cabellos

    Research output: Contribution to journalArticleAcademicpeer-review

    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.\n\nMETHODS: 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.\n\nRESULTS: 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.\n\nCONCLUSIONS: Daptomycin at standard doses, and especially at high doses, may be a useful alternative for the treatment of penicillin- and cephalosporin-resistant pneumococcal meningitis.
    Original languageEnglish
    Pages (from-to)3020-3026
    Number of pages7
    JournalJournal of Antimicrobial Chemotherapy
    Volume69
    Issue number11
    DOIs
    Publication statusPublished - 1 Nov 2014

    Keywords

    • CNS infections
    • Lipopeptides
    • Streptococcus pneumoniae

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