{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T10:42:04Z","timestamp":1790764924566,"version":"4.1.0"},"reference-count":14,"publisher":"American Society for Microbiology","issue":"1","license":[{"start":{"date-parts":[[2004,1,1]],"date-time":"2004-01-01T00:00:00Z","timestamp":1072915200000},"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":[[2004,1]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            The efficacy of BB-83698, a novel potent peptide deformylase inhibitor, was evaluated in a mouse model of acute pneumonia. The\n            <jats:italic>Streptococcus pneumoniae<\/jats:italic>\n            isolates tested included four virulent strains (one penicillin-susceptible wild-type strain, one macrolide-resistant strain, and two quinolone-resistant mutants [a mutant carrying mutations in ParC and GyrA and an efflux mutant] isogenic to the wild type) and two poorly virulent penicillin-resistant strains. Pneumonia was induced by intratracheal inoculation of 10\n            <jats:sup>5<\/jats:sup>\n            CFU (virulent strains) into immunocompetent mice or 10\n            <jats:sup>7<\/jats:sup>\n            CFU (less virulent strains) into leukopenic mice. Animals received three or six subcutaneous injections of antibiotics at 12- or 24-h intervals, with antibiotic treatment initiated at 3, 6, 12, or 18 h postinfection (p.i.). BB-83698 showed potent in vitro activity against all strains (MICs, 0.06 to 0.25 \u03bcg\/ml). In the in vivo model, all control animals died within 2 to 5 days of infection. BB-83698 (80 mg\/kg of body weight twice daily or 160 mg\/kg once daily) protected 70 to 100% of the animals, as measured 10 days p.i., regardless of the preexisting resistance mechanisms. In contrast, the survival rates for animals treated with the comparator antibiotics were 30% for animals treated with erythromycin (100 mg\/kg) and infected with the macrolide-resistant strain, 34% for animals treated with amoxicillin (200 mg\/kg every 8 h) and infected with the penicillin-resistant strain, and 0 and 78% for animals treated with ciprofloxacin (250 mg\/kg) and infected with the ParC and GyrA mutant and the efflux mutant, respectively. At 80 mg\/kg, BB-83698 generated a peak concentration in lung tissue of 61.9 \u03bcg\/ml within 1 h and areas under the concentration-times curves of 57.4 and 229.4 \u03bcg \u00b7 h\/ml for plasma and lung tissue, respectively. The emergence of\n            <jats:italic>S. pneumoniae<\/jats:italic>\n            isolates with reduced susceptibilities to BB-83698 was not observed following treatment with a suboptimal dosing regimen. In conclusion, the potent in vitro activity of BB-83698 against\n            <jats:italic>S. pneumoniae<\/jats:italic>\n            , including resistant strains, translates into good in vivo efficacy in a mouse pneumonia model.\n          <\/jats:p>","DOI":"10.1128\/aac.48.1.80-85.2004","type":"journal-article","created":{"date-parts":[[2003,12,24]],"date-time":"2003-12-24T02:03:22Z","timestamp":1072231402000},"page":"80-85","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":29,"title":["Efficacy of BB-83698, a Novel Peptide Deformylase Inhibitor, in a Mouse Model of Pneumococcal Pneumonia"],"prefix":"10.1128","volume":"48","author":[{"given":"E.","family":"Azoulay-Dupuis","sequence":"first","affiliation":[{"name":"INSERM, EMI-9933, Faculte\u0301 de Me\u0301decine Xavier Bichat, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Mohler","sequence":"additional","affiliation":[{"name":"INSERM, EMI-9933, Faculte\u0301 de Me\u0301decine Xavier Bichat, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. P.","family":"Be\u0301dos","sequence":"additional","affiliation":[{"name":"INSERM, EMI-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":"10.1016\/S0924-8579(02)00022-5"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinids\/15.1.77"},{"key":"e_1_3_1_4_2","first-page":"1","volume":"51","year":"1996","unstructured":"Appelbaum, P. C. 1996. Emergence of resistance to antimicrobial agents in gram-positive bacteria. Pneumococci. Drugs51(Suppl. 1):1-5.","journal-title":"Pneumococci. Drugs"},{"key":"e_1_3_1_5_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.36.12.2698"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.40.4.941"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.44.6.1575-1577.2000"},{"key":"e_1_3_1_8_2","first-page":"984","volume":"39","year":"1991","unstructured":"B\u00e9dos, J. P., O. Rollin, D. H. Bouanchaud, and J. J. Pocidalo. 1991. Relation entre virulence et r\u00e9sistance aux antibiotiques des pneumocoques. Pathol. Biol.39:984-990.","journal-title":"Pathol. Biol."},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/iai.60.1.111-116.1992"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.2.563-570.2001"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.9.2432-2435.2001"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1002\/j.1460-2075.1994.tb06335.x"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.38.9.1953"},{"key":"e_1_3_1_14_2","unstructured":"National Committee for Clinical Laboratory Standards. 2000. Performance standards for antimicrobial disk susceptibility tests; approved standard 7th ed. M2-A7 vol. 20 no. 1. National Committee for Clinical Laboratory Standards Wayne Pa."},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.46.4.1117-1118.2002"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.48.1.80-85.2004","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.48.1.80-85.2004","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T18:04:21Z","timestamp":1645466661000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.48.1.80-85.2004"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,1]]},"references-count":14,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2004,1]]}},"alternative-id":["10.1128\/AAC.48.1.80-85.2004"],"URL":"https:\/\/doi.org\/10.1128\/aac.48.1.80-85.2004","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,1]]},"assertion":[{"value":"2003-03-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2003-10-06","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2004-01-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}