The Journal of antimicrobial chemotherapy · 2014
Experimental study of the efficacy of daptomycin for the treatment of cephalosporin-resistant pneumococcal meningitis.
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Vivas M, Force E, Garrigós C, Tubau F, Platteel A C M, Ariza J, Cabellos C
Аннотация
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.
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.