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https://hdl.handle.net/2440/60637
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Type: | Journal article |
Title: | Efficacy profiles of Daptomycin for treatment of Iinvasive and noninvasive pulmonary infections with treptococcus pneumoniae |
Author: | Henken, S. Bohling, J. Martens-Lobenhoffer, J. Paton, J. Ogunniyi, A. Briles, D. Salisbury, V. Wedekind, D. Bode-Boger, S. Welsh, T. Bange, F. Welte, T. Maus, U. |
Citation: | Antimicrobial Agents and Chemotherapy, 2010; 54(2):707-717 |
Publisher: | Amer Soc Microbiology |
Issue Date: | 2010 |
ISSN: | 0066-4804 1098-6596 |
Statement of Responsibility: | Stefanie 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 |
Abstract: | Daptomycin 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. |
Keywords: | Animals Mice, Inbred C57BL Mice Streptococcus pneumoniae Pneumococcal Infections Pneumonia, Pneumococcal Sepsis Disease Models, Animal Ceftriaxone Daptomycin Anti-Bacterial Agents |
Rights: | Copyright © 2010, American Society for Microbiology. All Rights Reserved. |
DOI: | 10.1128/AAC.00943-09 |
Published version: | http://dx.doi.org/10.1128/aac.00943-09 |
Appears in Collections: | Aurora harvest 5 Molecular and Biomedical Science publications |
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