title: Effect of dexamethasone on the efficacy of daptomycin in the therapy of experimental pneumococcal meningitis.
abstract: This study aimed to determine the effect of dexamethasone in combination with low-dose or high-dose daptomycin for the treatment of penicillin- and cephalosporin-resistant pneumococcal meningitis. Efficacy (ΔCFU/mL) and cerebrospinal fluid (CSF) levels of daptomycin at 15mg/kg and 25mg/kg were studied in a rabbit model of pneumococcal meningitis, comparing them with the same doses in combination with dexamethasone at 0.125mg/kg every 12h over a 26-h period against two different Streptococcus pneumoniae strains, HUB 2349 and ATCC 51916 with daptomycin minimum inhibitory concentrations (MICs) of 0.09mg/L and 0.19mg/L, respectively. Daptomycin levels in CSF were lower when dexamethasone was given concurrently. Against strain HUB 2349, therapeutic failure occurred with daptomycin 15mg/kg+dexamethasone; daptomycin 25mg/kg+dexamethasone was better at reducing bacterial counts than the lower dose throughout treatment. Against the highly cephalosporin-resistant ATCC 51916 strain, daptomycin 15mg/kg+dexamethasone achieved a lower bacterial decrease than daptomycin 15mg/kg alone, and therapeutic failure at 24h occurred in the daptomycin 15mg/kg+dexamethasone group. Addition of dexamethasone to a 25mg/kg daptomycin dose did not affect the efficacy of daptomycin: it remained bactericidal throughout treatment. In conclusion, against the studied strains, low-dose (15mg/kg/day) daptomycin is affected by concomitant use of dexamethasone: CSF levels are reduced and its bacterial efficacy is affected. At a higher daptomycin dose (25mg/kg/day), however, the use of dexamethasone does not alter efficacy; the combination appears to be a good choice for the treatment of 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. Electronic address: 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: 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: C
authors: C
authors: El Haj
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; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D058491:Bacterial Load; D002555:Cerebrospinal Fluid / Q000737:chemistry; D017576:Daptomycin / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D003907:Dexamethasone / Q000494:pharmacology / Q000627:therapeutic use*; D024881:Drug Resistance, Bacterial; D004359:Drug Therapy, Combination; D008586:Meningitis, Pneumococcal / Q000188:drug therapy*; D008826:Microbial Sensitivity Tests; D011817:Rabbits; D013296:Streptococcus pneumoniae; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D003907:Dexamethasone; D017576:Daptomycin
keywords: CNS infection; Lipopeptide; Steroids; Streptococcus pneumoniae