Prevention of Brain Injury by the Non Bacteriolytic Antibiotic Daptomycin in Experimental Pneumococcal Meningitis.

Author(s): Grandgirard D, Schurch C, Cottagnoud P, Leib SL

Affiliation(s): Institute for Infectious Diseases, University of Bern, Switzerland, Department of Internal Medicine; and Clinic for Infectious Diseases, University Hospital, Inselspital, Bern, Switzerland.

Publication date & source: 2007-03-19, Antimicrob Agents Chemother., [Epub ahead of print]

Publication type:

Background: Bacteriolytic antibiotics cause the release of bacterial components that augment the host inflammatory response which in turn contributes to the pathophysiology of brain injury in bacterial meningitis. In the present study in experimental pneumococcal meningitis, antibiotic therapy with non-bacteriolytic daptomycin vs. bacteriolytic ceftriaxone was evaluated for an effect on inflammation and brain injury. Methods: Eleven day old rats were injected intracisternally with 1.3 +/- 0.5 x 10(4) colony forming units (cfu) of Streptococcus pneumoniae serotype 3 and randomized for therapy with ceftriaxone (100 mg/kg s.c., n=55) or daptomycin (50 mg/kg s.c., n=56) starting at 18 h after infection. Cerebrospinal fluid was assessed for bacterial count, matrix metalloprotease-9 and TNF-alpha at different time intervals after infection. Cortical brain damage was evaluated at 40 h after infection. Results: Daptomycin vs. ceftriaxone cleared bacteria more efficiently from the CSF within two hours after initiation of therapy (log10 3.6+/-1.0 vs. log10 6.3+/-1.4 cfu/ml, P<0.02), reduced the inflammatory host reaction assessed by concentration of matrix metalloprotease-9 in CSF at 40 hours after infection (P<0.005), and prevented the development of cortical injury (cortical injury present in 0/30 vs. 7/28 animals, P<0.004). Conclusion: Compared to ceftriaxone, daptomycin cleared bacteria more rapidly from the CSF and caused less CSF inflammation. This combined effect provides an explanation for the observation that daptomycin prevented the development of cortical brain injury in experimental pneumococcal meningitis. Further research is needed to investigate whether non-bacteriolytic antibiotic therapy with Daptomycin represents an advantageous alternative over current bacteriolytic antibiotics for the therapy of pneumococcal meningitis.