Daptomycin Is Highly Efficacious against Penicillin-Resistant and Penicillin- and Quinolone-Resistant Pneumococci in Experimental Meningitis

Abstract

The penetration of daptomycin, a new lipopeptide antibiotic, into inflamed meninges ranged between 4.37 and 7.53% (mean, 5.97%). Daptomycin was very efficacious in the treatment of experimental pneumococcal meningitis, producing a decrease of ؊1.20 ؎ 0.32 ⌬log 10 CFU/ml ⅐ h in the bacterial titer of Streptococcus pneumoniae against a penicillin-resistant strain and of ؊0.97 ؎ 0.32 ⌬log 10 CFU/ml ⅐ h against a penicillinand quinolone-resistant strain found in cerebrospinal fluid (CSF). For both strains, daptomycin was significantly superior to the standard regimen of a combination of ceftriaxone with vancomycin, sterilizing 9 of 10 CSF samples after 4 h. In vitro, daptomycin produced highly bactericidal activity in concentrations above the MIC.

Daptomycin Produces an Enhanced Bactericidal Activity Compared to Ceftriaxone, Measured by [ 3 H]Choline Release in the Cerebrospinal Fluid, in Experimental Meningitis Due to a Penicillin-Resistant Pneumococcal Strain without Lysing Its Cell Wall

“…None of the CSF samples from the ceftriaxone group were sterile at the end of the treatment period. The data confirmed the efficacy of daptomycin in experimental meningitis, as demonstrated in previous studies (2,6). We are aware that the standard regimen for pneumococcal meningitis due to penicillin-resistant strains consists of a combination of ceftriaxone plus vancomycin and not of ceftriaxone monotherapy, but the aim of this study was to compare a bacteriolytic with a nonbacteriolytic regimen.…”

Penetration of Drugs through the Blood-Cerebrospinal Fluid/Blood-Brain Barrier for Treatment of Central Nervous System Infections

“…In an animal model of meningitis, the mean CSF penetration was 6%, and the compound was rapidly bactericidal (36). Daptomycin was successfully used to treat meningitis caused by methicillin-resistant staphylococci in a 41-year-old woman (119).…”

Pathogenesis and Pathophysiology of Pneumococcal Meningitis

“…Daptomycin, a lipopeptide antibiotic, has been shown to effectively clear S. pneumoniae in experimental rat, mouse, and rabbit meningitis models (100,177). Treatment with daptomycin led to lower levels of inflammatory cytokines and possibly to less cortical brain damage and neuronal apoptosis than those for treatment with ceftriaxone alone (176,177).…”