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To investigate the clinical efficacy of this treatment in CAP caused by<jats:italic>Streptococcus pneumoniae<\/jats:italic>strains with MICs of amoxicillin \u22652 \u03bcg\/ml, we used a lethal bacteremic pneumonia model in leukopenic female Swiss mice with induced renal failure to replicate amoxicillin kinetics in humans given 1 g\/8 h orally. Amoxicillin (15 mg\/kg of body weight\/8 h subcutaneously) was given for 3 days. We used four<jats:italic>S. pneumoniae<\/jats:italic>strains with differing amoxicillin susceptibility and tolerance profiles. Rapid bacterial killing occurred with an amoxicillin-susceptible nontolerant strain: after 4 h, blood cultures were negative and lung homogenate counts under the 2 log<jats:sub>10<\/jats:sub>CFU\/ml detection threshold (6.5 log<jats:sub>10<\/jats:sub>CFU\/ml in controls,<jats:italic>P<\/jats:italic>&lt; 0.01). With an amoxicillin-intermediate nontolerant strain, significant pulmonary bacterial clearance was observed after 24 h (4.3 versus 7.9 log<jats:sub>10<\/jats:sub>CFU\/ml,<jats:italic>P<\/jats:italic>&lt; 0.01), and counts were undetectable 12 h after treatment completion. With an amoxicillin-intermediate tolerant strain, 24-h bacterial clearance was similar (5.4 versus 8.3 log<jats:sub>10<\/jats:sub>CFU\/ml,<jats:italic>P<\/jats:italic>&lt; 0.05), but 12 h after treatment completion, lung homogenates contained 3.3 log<jats:sub>10<\/jats:sub>CFU\/ml. Similar results were obtained with an amoxicillin-resistant and -tolerant strain. Day 10 survival rates were usually similar across strains. Amoxicillin with pharmacokinetics simulating 1 g\/8 h orally in humans is bactericidal in mice with pneumonia due to<jats:italic>S. pneumoniae<\/jats:italic>for which MICs were 2 to 4 \u03bcg\/ml. The killing rate depends not only on resistance but also on tolerance of the<jats:italic>S. pneumoniae<\/jats:italic>strains.<\/jats:p>","DOI":"10.1128\/aac.00004-06","type":"journal-article","created":{"date-parts":[[2006,12,20]],"date-time":"2006-12-20T18:32:51Z","timestamp":1166639571000},"page":"208-214","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":18,"title":["Amoxicillin Is Effective against Penicillin-Resistant<i>Streptococcus pneumoniae<\/i>Strains in a Mouse Pneumonia Model Simulating Human Pharmacokinetics"],"prefix":"10.1128","volume":"51","author":[{"given":"Pierre","family":"Abgueguen","sequence":"first","affiliation":[{"name":"INSERM EMI-U 9933, Faculte\u0301 de Me\u0301decine Xavier Bichat, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Esther","family":"Azoulay-Dupuis","sequence":"additional","affiliation":[{"name":"INSERM EMI-U 9933, Faculte\u0301 de Me\u0301decine Xavier Bichat, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Violaine","family":"Noel","sequence":"additional","affiliation":[{"name":"INSERM EMI-U 9933, Faculte\u0301 de Me\u0301decine Xavier Bichat, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pierre","family":"Moine","sequence":"additional","affiliation":[{"name":"INSERM EMI-U 9933, Faculte\u0301 de Me\u0301decine Xavier Bichat, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Veronique","family":"Rieux","sequence":"additional","affiliation":[{"name":"INSERM EMI-U 9933, Faculte\u0301 de Me\u0301decine Xavier Bichat, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Fantin","sequence":"additional","affiliation":[{"name":"INSERM EMI-U 9933, Faculte\u0301 de Me\u0301decine Xavier Bichat, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jean-Pierre","family":"Bedos","sequence":"additional","affiliation":[{"name":"INSERM EMI-U 9933, Faculte\u0301 de Me\u0301decine Xavier Bichat, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.9.2375"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.36.12.2825"},{"key":"e_1_3_1_4_2","first-page":"43","volume":"68","year":"1994","unstructured":"Anthony, M. 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