{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T04:56:46Z","timestamp":1761541006830},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2010,8,3]],"date-time":"2010-08-03T00:00:00Z","timestamp":1280793600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"},{"start":{"date-parts":[[2010,8,3]],"date-time":"2010-08-03T00:00:00Z","timestamp":1280793600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/2.0\/"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Crit Care"],"abstract":"<jats:title>Abstract<\/jats:title><jats:sec>\n                        <jats:title>Introduction<\/jats:title>\n                        <jats:p><jats:italic>Streptococcus (S.) pneumoniae<\/jats:italic> is the most common cause of community-acquired pneumonia. The factor V Leiden (FVL) mutation results in resistance of activated FV to inactivation by activated protein C and thereby in a prothrombotic phenotype. Human heterozygous FVL carriers have been reported to be relatively protected against sepsis-related mortality. We here determined the effect of the FVL mutation on coagulation, inflammation, bacterial outgrowth and outcome in murine pneumococcal pneumonia.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Methods<\/jats:title>\n                        <jats:p>Wild-type mice and mice heterozygous or homozygous for the FVL mutation were infected intranasally with 2*10<jats:sup>6<\/jats:sup> colony forming units of viable <jats:italic>S. pneumoniae<\/jats:italic>. Mice were euthanized after 24 or 48 hours or observed in a survival study. In separate experiments mice were treated with ceftriaxone intraperitoneally 24 hours after infection and euthanized after 48 hours or observed in a survival study.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Results<\/jats:title>\n                        <jats:p>The FVL mutation had no consistent effect on activation of coagulation in either the presence or absence of ceftriaxone therapy, as reflected by comparable lung and plasma levels of thrombin-antithrombin complexes and fibrin degradation products. Moreover, the FVL mutation had no effect on lung histopathology, neutrophil influx, cytokine and chemokine levels or bacterial outgrowth. Remarkably, homozygous FVL mice were strongly protected against death due to pneumococcal pneumonia when treated with ceftriaxone, which was associated with more pronounced FXIII depletion; this protective effect was not observed in the absence of antibiotic therapy.<\/jats:p>\n                     <\/jats:sec><jats:sec>\n                        <jats:title>Conclusions<\/jats:title>\n                        <jats:p>Homozygosity for the FVL mutation protects against lethality due to pneumococcal pneumonia in mice treated with antibiotics.<\/jats:p>\n                     <\/jats:sec>","DOI":"10.1186\/cc9213","type":"journal-article","created":{"date-parts":[[2010,8,3]],"date-time":"2010-08-03T19:02:56Z","timestamp":1280862176000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Impact of the factor V Leiden mutation on the outcome of pneumococcal pneumonia: a controlled laboratory study"],"prefix":"10.1186","volume":"14","author":[{"given":"Marcel","family":"Schouten","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cornelis","family":"van't Veer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joris JTH","family":"Roelofs","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcel","family":"Levi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tom","family":"van der Poll","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2010,8,3]]},"reference":[{"key":"8620_CR1","doi-asserted-by":"publisher","first-page":"S27","DOI":"10.1086\/511159","volume":"44","author":"LA Mandell","year":"2007","unstructured":"Mandell LA, Wunderink RG, Anzueto A, Bartlett JG, Campbell GD, Dean NC, Dowell SF, File TM, Musher DM, Niederman MS, Torres A, Whitney CG: Infectious Diseases Society of America\/American Thoracic Society consensus guidelines on the management of community-acquired pneumonia in adults.\n                           Clin Infect Dis 2007, 44: S27-S72. 10.1086\/511159","journal-title":"Clin Infect Dis"},{"key":"8620_CR2","doi-asserted-by":"publisher","first-page":"952","DOI":"10.1097\/01.CCM.0000162381.24074.D7","volume":"33","author":"PF Laterre","year":"2005","unstructured":"Laterre PF, Garber G, Levy H, Wunderink R, Kinasewitz GT, Sollet JP, Maki DG, Bates B, Yan SCB, Dhainaut JF: Severe community-acquired pneumonia as a cause of severe sepsis: Data from the PROWESS study.\n                           Crit Care Med 2005, 33: 952-961. 10.1097\/01.CCM.0000162381.24074.D7","journal-title":"Crit Care Med"},{"key":"8620_CR3","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1007\/s15010-008-8128-6","volume":"37","author":"GM Vail","year":"2009","unstructured":"Vail GM, Xie YJ, Haney DJ, Barnes CJ: Biomarkers of thrombosis, fibrinolysis, and inflammation in patients with severe sepsis due to community-acquired pneumonia with and without Streptococcus pneumoniae.\n                           Infection 2009, 37: 358-364. 10.1007\/s15010-008-8128-6","journal-title":"Infection"},{"key":"8620_CR4","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1086\/313954","volume":"31","author":"JG Bartlett","year":"2000","unstructured":"Bartlett JG, Dowell SF, Mandell LA, File TM Jr, Musher DM, Fine MJ: Practice guidelines for the management of community-acquired pneumonia in adults. 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