B-058. Daptomycin in Experimental Murine Pneumococcal Meningitis
Session: Poster Session: Therapy of Bacterial Infections in Animal Models
Saturday, October 25, 2008: 12:00 AM
Room: Hall C
Background: Daptomycin may be an alternative to vancomycin for the empirical treatment of suspected pneumococcal meningitis. We compared the activity of daptomycin with that of vancomycin in a murine model of pneumococcal meningitis. Methods: Ninety-six 25-30 g mice were inoculated intrathecally with Xen 10 (serotype 3 Streptococcus pneumoniae modified by integration of a luminescent lux operon). Sixteen hours post infection, all mice were treated (i.p.) with either 1 mg/kg dexamethasone alone or in combination with either 50 mg/kg vancomycin or 25 mg/kg daptomycin. Vancomycin-treated animals were given a second dose of vancomycin at 20 hours post infection. All animals received a second dose of dexamethasone at 22 hours post infection. Sixteen, 20 and 24 hours post infection, Lumazone (MAG biosystems, Pleasanton, CA) imaging and suboccipital puncture for cerebrospinal fluid (CSF) collection for quantitative culture, were performed.
Results: Sixteen hours post intrathecal bacterial inoculation, mean bacterial titers in cerebrospinal fluid (CSF) were 6.8 log10 cfu/ml. Amongst the animals treated 16 hours post infection with no antibiotic, vancomycin 50 mg/kg or daptomycin 25 mg/kg, mean CSF titers were 6.2, 5.8, and 4.9 log10 cfu/ml, respectively, at 20 hours post infection (p-value, 0.36 and 0.004 for vancomycin or daptomycin, respectively, versus no antibiotic). Amongst the animals given no antibiotic, vancomycin 50 mg/kg at 16 and 20 hours or daptomycin 25 mg/kg at 16 hours, mean CSF titers were 7.6, 3.4, and 3.9 log10 cfu/ml, respectively, at 24 hours post infection (p-value, <0.001 for both vancomycin or daptomycin versus no antibiotic). At 24 hours post infection there was no significant difference in bactericidal activity between the vancomycin and daptomycin groups (p-value, 0.18). In vivo imaging correlated with bacterial concentration in CSF (Pearson’s R: 0.75).
Conclusions: Daptomycin, when given in combination with dexamethasone, is active in the treatment of experimental pneumococcal meningitis.
Barry Mook-Kanamori, MD1, Cheol-In Kang, MD2, Diederik van de Beek, MD, PhD3, James Steckelberg, MD, FIDSA4, Mark Rouse, BS1, Robin Patel, MD, FIDSA1 and  B. B. Mook-Kanamori, None., (1)Mayo Clinic, Rochester, MN, (2)Samsung Medical Center, Seoul, Korea, Republic of, (3)Academic Medical Center, Amsterdam, Netherlands, (4)Department of Medicine, Division of Infectious Diseases, Mayo Clinic, Rochester, MN