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Antimicrobial Agents and Chemotherapy, October 2004, p. 3928-3933, Vol. 48, No. 10
0066-4804/04/$08.00+0     DOI: 10.1128/AAC.48.10.3928-3933.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

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

Department of Internal Medicine, Inselspital,¹ Department of Internal Medicine, Spital Bern-Ziegler, Bern, Switzerland,³ Department of Laboratory Medicine and Biopharmaceutical Sciences, University of California, San Francisco, San Francisco, California²

Received 15 December 2003/ Returned for modification 29 March 2004/ Accepted 30 June 2004

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 log₁₀ CFU/ml · h in the bacterial titer of Streptococcus pneumoniae against a penicillin-resistant strain and of –0.97 ± 0.32 log₁₀ CFU/ml · h against a penicillin- and 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.

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