{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T23:02:21Z","timestamp":1791414141052,"version":"4.3.3"},"reference-count":31,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2011,4,1]],"date-time":"2011-04-01T00:00:00Z","timestamp":1301616000000},"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":[[2011,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Aminoglycosides are broad-spectrum antibiotics with particular clinical utility against life-threatening infections. As resistance to antibiotics, including aminoglycosides, continues to grow, there is a need for new and effective antimicrobial agents. ACHN-490 is a novel aminoglycoside in clinical development with activity against multidrug-resistant Gram-negative and select Gram-positive pathogens. Here we assess the\n            <jats:italic>in vivo<\/jats:italic>\n            efficacy of ACHN-490 against a variety of common pathogens in two murine models: the septicemia and neutropenic thigh models. When its activity against a gentamicin-susceptible strain of\n            <jats:italic>Escherichia coli<\/jats:italic>\n            was tested in the septicemia model, ACHN-490 improved 7-day survival with a dose-response profile similar to that of gentamicin, with 100% survival seen at doses of 1.6 mg\/kg of body weight and above. In animals infected with a gentamicin-susceptible strain of\n            <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n            , treatment with either ACHN-490 or gentamicin led to 100% survival at doses of 16 mg\/kg and above in the septicemia model. ACHN-490 was also effective in the neutropenic thigh model, reducing multidrug-resistant\n            <jats:italic>Enterobacteriaceae<\/jats:italic>\n            family and methicillin-resistant\n            <jats:italic>Staphylococcus aureus<\/jats:italic>\n            strains, as well as broadly susceptible strains, to static levels with dose-dependent activity. Against gentamicin-sensitive\n            <jats:italic>Enterobacteriaceae<\/jats:italic>\n            and methicillin-resistant\n            <jats:italic>S. aureus<\/jats:italic>\n            , the efficacy of ACHN-490 was comparable to that of gentamicin. However, gentamicin-resistant\n            <jats:italic>Enterobacteriaceae<\/jats:italic>\n            strains and those harboring the\n            <jats:italic>Klebsiella pneumoniae<\/jats:italic>\n            carbapenemase responded to ACHN-490 but not gentamicin, with static doses ranging from 12 mg\/kg to 64 mg\/kg for ACHN-490. These results suggest that ACHN-490 has the potential to become a clinically useful agent against drug-resistant pathogens, including\n            <jats:italic>Enterobacteriaceae<\/jats:italic>\n            ,\n            <jats:italic>P. aeruginosa<\/jats:italic>\n            , and methicillin-resistant\n            <jats:italic>S. aureus<\/jats:italic>\n            , and support further development of this promising novel aminoglycoside.\n          <\/jats:p>","DOI":"10.1128\/aac.00862-10","type":"journal-article","created":{"date-parts":[[2011,2,1]],"date-time":"2011-02-01T03:38:51Z","timestamp":1296531531000},"page":"1728-1733","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":35,"title":["<i>In Vivo<\/i>\n            Efficacy of the Novel Aminoglycoside ACHN-490 in Murine Infection Models"],"prefix":"10.1128","volume":"55","author":[{"given":"Noe","family":"Reyes","sequence":"first","affiliation":[{"name":"Achaogen, Inc., 7000 Shoreline Court, Suite 371, South San Francisco, California 94080"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James B.","family":"Aggen","sequence":"additional","affiliation":[{"name":"Achaogen, Inc., 7000 Shoreline Court, Suite 371, South San Francisco, California 94080"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corwin F.","family":"Kostrub","sequence":"additional","affiliation":[{"name":"Achaogen, Inc., 7000 Shoreline Court, Suite 371, South San Francisco, California 94080"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00572-10"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF01712153"},{"key":"e_1_3_2_4_2","first-page":"138","year":"1963","unstructured":"Black, J., B. Calesnick, D. Williams, and M. J. Weinstein. 1963. Pharmacology of gentamicin, a new broad-spectrum antibiotic, p. 138-147. Antimicrob. Agents Chemother. 1962.","journal-title":"Antimicrob. Agents Chemother."},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1001\/archinte.165.12.1430"},{"key":"e_1_3_2_6_2","unstructured":"Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically; approved standard 2006"},{"key":"e_1_3_2_7_2","first-page":"S55","volume":"12","year":"1993","unstructured":"Craig, W. 1993. Relevance of animal models for clinical treatment. Eur. J. Clin. Microbiol. Infect. Dis. 12(Suppl. 1):S55-S57.","journal-title":"Infect. 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Erlendsdottir. 1999. Murine thigh infection model, p. 137-144. In O. Zak and M. Sande (ed.), Handbook of animal models of infection. Academic Press, Inc., New York, NY.","journal-title":"Murine thigh infection model"},{"key":"e_1_3_2_14_2","doi-asserted-by":"publisher","DOI":"10.1086\/652237"},{"key":"e_1_3_2_15_2","unstructured":"Guide for the care and use of laboratory animals 1996"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00253-005-0279-0"},{"key":"e_1_3_2_17_2","first-page":"817","volume":"189","year":"1964","unstructured":"Jao, R. L., and G. G. Jackson. 1964. Gentamicin sulfate, new antibiotic against Gram-negative bacilli. Laboratory, pharmacological, and clinical evaluation. JAMA 189:817-822.","journal-title":"JAMA"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1378\/chest.08-1116"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1086\/313890"},{"key":"e_1_3_2_20_2","first-page":"179","volume":"74","year":"1990","unstructured":"Leggett, J. E., S. Ebert, B. Fantin, and W. A. Craig. 1990. Comparative dose-effect relations at several dosing intervals for beta-lactam, aminoglycoside and quinolone antibiotics against gram-negative bacilli in murine thigh-infection and pneumonitis models. Scand. J. Infect. Dis. Suppl. 74:179-184.","journal-title":"Scand. J. Infect. Dis. 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