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Prevention of brain injury by the nonbacteriolytic antibiotic daptomycin in experimental pneumococcal meningitis

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cris.virtual.author-orcid#PLACEHOLDER_PARENT_METADATA_VALUE#
cris.virtual.author-orcid0000-0002-1792-1768
cris.virtual.author-orcid#PLACEHOLDER_PARENT_METADATA_VALUE#
cris.virtual.author-orcid0000-0002-1106-6123
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cris.virtualsource.author-orcid217ef6c3-316d-4292-bc57-20c5412ff98c
cris.virtualsource.author-orcid349d9e04-9f5b-4e5e-9263-d584b4006dac
cris.virtualsource.author-orcid1b54a387-db97-41f4-bae6-ad365f708868
dc.contributor.authorGrandgirard, Denis
dc.contributor.authorSchürch, Christian
dc.contributor.authorCottagnoud, Philippe
dc.contributor.authorLeib, Stephen
dc.date.accessioned2024-10-13T17:36:37Z
dc.date.available2024-10-13T17:36:37Z
dc.date.issued2007
dc.description.abstractBacteriolytic 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, antibiotic therapy with nonbacteriolytic daptomycin was compared with that of bacteriolytic ceftriaxone in experimental pneumococcal meningitis, and the treatments were evaluated for their effects on inflammation and brain injury. Eleven-day-old rats were injected intracisternally with 1.3 x 10(4) +/- 0.5 x 10(4) CFU of Streptococcus pneumoniae serotype 3 and randomized to therapy with ceftriaxone (100 mg/kg of body weight subcutaneously [s.c.]; n = 55) or daptomycin (50 mg/kg s.c.; n = 56) starting at 18 h after infection. The cerebrospinal fluid (CSF) was assessed for bacterial counts, matrix metalloproteinase-9 levels, and tumor necrosis factor alpha levels at different time intervals after infection. Cortical brain damage was evaluated at 40 h after infection. Daptomycin cleared the bacteria more efficiently from the CSF than ceftriaxone within 2 h after the initiation of therapy (log(10) 3.6 +/- 1.0 and log(10) 6.3 +/- 1.4 CFU/ml, respectively; P < 0.02); reduced the inflammatory host reaction, as assessed by the matrix metalloproteinase-9 concentration in CSF 40 h after infection (P < 0.005); and prevented the development of cortical injury (cortical injury present in 0/30 and 7/28 animals, respectively; P < 0.004). Compared to ceftriaxone, daptomycin cleared the bacteria from the CSF more rapidly 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 nonbacteriolytic antibiotic therapy with daptomycin represents an advantageous alternative over current bacteriolytic antibiotic therapies for the treatment of pneumococcal meningitis.
dc.description.numberOfPages6
dc.description.sponsorshipDepartement Klinische Forschung (DKF)
dc.description.sponsorshipUniversitätsklinik für Allgemeine Innere Medizin
dc.description.sponsorshipInstitut für Infektionskrankheiten
dc.identifier.doi10.7892/boris.23931
dc.identifier.isi000246991400041
dc.identifier.pmid17371820
dc.identifier.publisherDOI10.1128/AAC.01014-06
dc.identifier.urihttps://boris-portal.unibe.ch/handle/20.500.12422/97561
dc.language.isoen
dc.publisherAmerican Society for Microbiology
dc.publisher.placeWashington, D.C.
dc.relation.isbn17371820
dc.relation.ispartofAntimicrobial agents and chemotherapy
dc.relation.issn0066-4804
dc.relation.organizationDCD5A442BD18E17DE0405C82790C4DE2
dc.relation.organizationDCD5A442C058E17DE0405C82790C4DE2
dc.relation.organizationDCD5A442BD12E17DE0405C82790C4DE2
dc.subject.ddc600 - Technology::610 - Medicine & health
dc.titlePrevention of brain injury by the nonbacteriolytic antibiotic daptomycin in experimental pneumococcal meningitis
dc.typearticle
dspace.entity.typePublication
dspace.file.typetext
oaire.citation.endPage2178
oaire.citation.issue6
oaire.citation.startPage2173
oaire.citation.volume51
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oairecerif.author.affiliationDepartement Klinische Forschung (DKF)
oairecerif.author.affiliationUniversitätsklinik für Allgemeine Innere Medizin
oairecerif.author.affiliationInstitut für Infektionskrankheiten
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unibe.eprints.legacyId23931
unibe.journal.abbrevTitleANTIMICROB AGENTS CH
unibe.refereedTRUE
unibe.subtype.articlejournal

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