title: Experimental study of the efficacy of daptomycin for the treatment of cephalosporin-resistant pneumococcal meningitis.
abstract: OBJECTIVE
  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: Laboratory of Experimental Infection, Infectious Diseases Department, IDIBELL-Hospital Universitari de Bellvitge, Feixa Llarga s/n 08907 L'Hospitalet de Llobregat, Barcelona, Spain mireiavivas@gmail.com.
authors: M
authors: M
authors: Vivas
authors: Laboratory of Experimental Infection, Infectious Diseases Department, IDIBELL-Hospital Universitari de Bellvitge, Feixa Llarga s/n 08907 L'Hospitalet de Llobregat, Barcelona, Spain.
authors: E
authors: E
authors: Force
authors: Laboratory of Experimental Infection, Infectious Diseases Department, IDIBELL-Hospital Universitari de Bellvitge, Feixa Llarga s/n 08907 L'Hospitalet de Llobregat, Barcelona, Spain.
authors: C
authors: C
authors: Garrigós
authors: Microbiology Department, IDIBELL-Hospital Universitari de Bellvitge and CIBERES ISCIII, Feixa Llarga s/n 08907 L'Hospitalet de Llobregat, Barcelona, Spain.
authors: F
authors: F
authors: Tubau
authors: Laboratory of Experimental Infection, Infectious Diseases Department, IDIBELL-Hospital Universitari de Bellvitge, Feixa Llarga s/n 08907 L'Hospitalet de Llobregat, Barcelona, Spain.
authors: A C M
authors: AC
authors: Platteel
authors: Laboratory of Experimental Infection, Infectious Diseases Department, IDIBELL-Hospital Universitari de Bellvitge, Feixa Llarga s/n 08907 L'Hospitalet de Llobregat, Barcelona, Spain.
authors: J
authors: J
authors: Ariza
authors: Laboratory of Experimental Infection, Infectious Diseases Department, IDIBELL-Hospital Universitari de Bellvitge, Feixa Llarga s/n 08907 L'Hospitalet de Llobregat, Barcelona, Spain.
authors: C
authors: C
authors: Cabellos
mesh_terms: D000818:Animals; D018550:Cephalosporin Resistance / Q000187:drug effects*; D002511:Cephalosporins / Q000494:pharmacology / Q000627:therapeutic use*; D017576:Daptomycin / Q000494:pharmacology / Q000627:therapeutic use*; D005260:Female; D008586:Meningitis, Pneumococcal / Q000134:cerebrospinal fluid / Q000188:drug therapy*; D011817:Rabbits; D016896:Treatment Outcome
chemical_list: D002511:Cephalosporins; D017576:Daptomycin
keywords: CNS infections; Streptococcus pneumoniae; lipopeptides