Efficacy profiles of Daptomycin for treatment of Iinvasive and noninvasive pulmonary infections with treptococcus pneumoniae

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dc.contributor.authorHenken, S.
dc.contributor.authorBohling, J.
dc.contributor.authorMartens-Lobenhoffer, J.
dc.contributor.authorPaton, J.
dc.contributor.authorOgunniyi, A.
dc.contributor.authorBriles, D.
dc.contributor.authorSalisbury, V.
dc.contributor.authorWedekind, D.
dc.contributor.authorBode-Boger, S.
dc.contributor.authorWelsh, T.
dc.contributor.authorBange, F.
dc.contributor.authorWelte, T.
dc.contributor.authorMaus, U.
dc.date.issued2010
dc.description.abstractDaptomycin is a novel lipopeptide antibiotic with excellent activity against Gram-positive bacterial pathogens, but its therapeutic value for the treatment of invasive pneumococcal disease compared to that for the treatment of pneumococcal pneumonia is incompletely defined. We investigated the efficacy of daptomycin in two models of Streptococcus pneumoniae-induced lung infection, i.e., pneumococcal pneumonia and septic pneumococcal disease. Mice were infected with a bioluminescent, invasive serotype 2 S. pneumoniae strain or a less virulent serotype 19 S. pneumoniae strain and were then given semitherapeutic or therapeutic daptomycin or ceftriaxone. Readouts included survival; bacterial loads; and septic disease progression, as determined by biophotonic imaging. Semitherapeutic daptomycin treatment fully protected the mice against the progression of septic disease induced by serotype 2 S. pneumoniae, while therapeutic treatment of the mice with daptomycin or ceftriaxone led to 70% or 60% survival, respectively. In contrast, mice infected with serotype 19 S. pneumoniae developed severe pneumonia and lung leakage even in the presence of increased intra-alveolar daptomycin levels, resulting in only 40% survival, whereas the ceftriaxone-treated mice had 100% survival. Together, although daptomycin demonstrates little efficacy in the treatment of pneumococcal pneumonia, daptomycin is highly effective in preventing S. pneumoniae-induced septic death, thus possibly offering a therapeutic option for patients with life-threatening septic pneumococcal disease.
dc.description.statementofresponsibilityStefanie Henken, Jennifer Bohling, Jens Martens-Lobenhoffer, James C. Paton, A. David Ogunniyi, David E. Briles, Vyvyan C. Salisbury, Dirk Wedekind, Stefanie M. Bode-Böger, Thomas Welsh, Franz C. Bange, Tobias Welte and Ulrich A. Maus
dc.identifier.citationAntimicrobial Agents and Chemotherapy, 2010; 54(2):707-717
dc.identifier.doi10.1128/AAC.00943-09
dc.identifier.issn0066-4804
dc.identifier.issn1098-6596
dc.identifier.orcidPaton, J. [0000-0001-9807-5278]
dc.identifier.orcidOgunniyi, A. [0000-0001-9308-5629]
dc.identifier.urihttp://hdl.handle.net/2440/60637
dc.language.isoen
dc.publisherAmer Soc Microbiology
dc.rightsCopyright © 2010, American Society for Microbiology. All Rights Reserved.
dc.source.urihttps://doi.org/10.1128/aac.00943-09
dc.subjectAnimals
dc.subjectMice, Inbred C57BL
dc.subjectMice
dc.subjectStreptococcus pneumoniae
dc.subjectPneumococcal Infections
dc.subjectPneumonia, Pneumococcal
dc.subjectSepsis
dc.subjectDisease Models, Animal
dc.subjectCeftriaxone
dc.subjectDaptomycin
dc.subjectAnti-Bacterial Agents
dc.titleEfficacy profiles of Daptomycin for treatment of Iinvasive and noninvasive pulmonary infections with treptococcus pneumoniae
dc.typeJournal article
pubs.publication-statusPublished

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