Combination of daptomycin plus ceftriaxone is more active than vancomycin plus ceftriaxone in experimental meningitis after addition of dexamethasone

Abstract

We examined the cerebrospinal fluid penetration of daptomycin after the addition of dexamethasone and its bactericidal efficacy with and without ceftriaxone in an experimental rabbit model of pneumococcal meningitis. The combination of daptomycin with ceftriaxone was the most efficacious regimen for pneumococcal meningitis. The previous addition of dexamethasone affected the antibacterial activity of daptomycin only marginally, either as monotherapy or combined with ceftriaxone, although the penetration of daptomycin into inflamed meninges was significantly reduced from 6 to 2%. Daptomycin with ceftriaxone might be a potential candidate for the empirical therapy of bacterial meningitis, although the activity of this regimen against Listeria monocytogenes remains to be demonstrated.

FIG. 1.

CSF levels of daptomycin after one injection of 15 mg/kg. Daptomycin levels without the previous addition of dexamethasone (□) and daptomycin levels after the addition of dexamethasone (▪) are indicated. The points that are significantly different (P > 0.05) between the two curves are indicated by the asterisks. Each error bar represents 1 standard deviation.

FIG. 2.

Antibacterial activity of daptomycin with or without dexamethasone over 8 h. Killing activity is presented as log₁₀ CFU/ml ± SD. The broken line represents the limit of detection. The points that are significantly different (P > 0.05) between the two curves are indicated by the asterisks.

FIG. 3.

Antibacterial activity of daptomycin plus ceftriaxone with or without dexamethasone over 8 h. Killing activity is presented as log₁₀ CFU/ml ± SD. The broken line represent the limit of detection.

FIG. 4.

Antibacterial activity of ceftriaxone plus vancomycin with or without dexamethasone over 8 h. Killing activity is presented as log₁₀ CFU/ml ± SD. The broken line represent the limit of detection.