{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T07:56:45Z","timestamp":1789977405442,"version":"4.0.1"},"reference-count":22,"publisher":"American Society for Microbiology","issue":"11","license":[{"start":{"date-parts":[[2004,11,1]],"date-time":"2004-11-01T00:00:00Z","timestamp":1099267200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2004,11]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:p>A model of mouse sepsis caused by a serotype 6B<jats:italic>Streptococcus pneumoniae<\/jats:italic>strain (amoxicillin MIC of 8 \u03bcg\/ml) was developed to investigate the therapeutic effect of an amoxicillin dose (3.12 mg\/kg of body weight three times daily for 48 h) producing, over the whole treatment period, subinhibitory concentrations in serum (peak concentration [<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>]: 6.1 \u03bcg\/ml) in animals that prior to infection had been passively immunized with a 6B or 23F hyperimmune serum (obtained by immunization with a whole-cell heat-inactivated inoculum and diluted to produce no protective effect by itself). Mortality in nonimmunized animals treated with antibiotic (3.12 mg\/kg) was 90%, and mortality in animals immunized but not treated with the antibiotic was 100%. Antibiotic treatment in immunized animals produced mortality rates \u226420% when the hyperimmune serum was used, thus showing cross-protection and synergism (defined as the situation in which there is no response to the single agents [no differences versus placebo] while the combination exhibits significant activity) with subinhibitory concentrations of the antibiotic. The presence of antipneumococcal antibodies allowed antibiotic efficacy with negligible values of pharmacodynamic parameters (<jats:italic>C<\/jats:italic><jats:sub>max<\/jats:sub>\/MIC ratio of &lt;1 and thus a null value for the time that serum levels exceed the MIC). This in vivo synergism offers a potential therapeutic strategy against resistant strains.<\/jats:p>","DOI":"10.1128\/aac.48.11.4144-4147.2004","type":"journal-article","created":{"date-parts":[[2004,10,25]],"date-time":"2004-10-25T18:09:00Z","timestamp":1098727740000},"page":"4144-4147","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":5,"title":["Effects of Amoxicillin Subinhibitory Concentrations on the Cross-Protection Developed by Pneumococcal Antibodies in Mouse Sepsis Caused by an Amoxicillin-Resistant Serotype 6B<i>Streptococcus pneumoniae<\/i>Strain"],"prefix":"10.1128","volume":"48","author":[{"given":"D.","family":"Tarrago\u0301","sequence":"first","affiliation":[{"name":"Centro Nacional de Microbiologi\u0301a, Instituto de Salud Carlos III"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"L.","family":"Aguilar","sequence":"additional","affiliation":[{"name":"Medical Department, GlaxoSmithKline, Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. 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Yuste, I. Jado, D. Tarrag\u00f3, and A. Fenoll. 2002. \u03b2-Lactam activity against resistant pneumococcal strains is enhanced by the immune system. J. Antimicrob. Chemother.50(Suppl. S2):83-86.","journal-title":"J. Antimicrob. Chemother."},{"key":"e_1_3_2_5_2","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1097\/00001432-200306000-00006","volume":"16","year":"2003","unstructured":"Casal, J., and D. Tarrag\u00f3. 2003. Immunity to Streptococcus pneumoniae: factors affecting production and efficacy. Curr. Opin. Infect. Dis.16:219-224.","journal-title":"Curr. Opin. Infect. Dis."},{"key":"e_1_3_2_6_2","first-page":"739","year":"1991","unstructured":"Cleeland, R., and E. Squires. 1991. Evaluation of new antimicrobials in vitro and in experimental animal infections, p. 739-786. In V. Lorian (ed.), Antibiotics in laboratory medicine, 3rd ed. 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