{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T06:50:27Z","timestamp":1790059827234,"version":"4.0.1"},"reference-count":34,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[1999,4,1]],"date-time":"1999-04-01T00:00:00Z","timestamp":922924800000},"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":[[1999,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    The 9-\n                    <jats:italic>t<\/jats:italic>\n                    -butylglycylamido derivative of minocycline (TBG-MINO) is a recently synthesized member of a novel group of antibiotics, the glycylcyclines. This new derivative, like the first glycylcyclines, the\n                    <jats:italic>N<\/jats:italic>\n                    ,\n                    <jats:italic>N<\/jats:italic>\n                    -dimethylglycylamido derivative of minocycline and 6-demethyl-6-deoxytetracycline, possesses activity against bacterial isolates containing the two major determinants responsible for tetracycline resistance: ribosomal protection and active efflux. The in vitro activities of TBG-MINO and the comparative agents were evaluated against strains with characterized tetracycline resistance as well as a spectrum of recent clinical aerobic and anaerobic gram-positive and gram-negative bacteria. TBG-MINO, with an MIC range of 0.25 to 0.5 \u03bcg\/ml, showed good activity against strains expressing\n                    <jats:italic>tet<\/jats:italic>\n                    (M) (ribosomal protection),\n                    <jats:italic>tet<\/jats:italic>\n                    (A),\n                    <jats:italic>tet<\/jats:italic>\n                    (B),\n                    <jats:italic>tet<\/jats:italic>\n                    (C),\n                    <jats:italic>tet<\/jats:italic>\n                    (D), and\n                    <jats:italic>tet<\/jats:italic>\n                    (K) (efflux resistance determinants). TBG-MINO exhibited similar activity against methicillin-resistant\n                    <jats:italic>Staphylococcus aureus<\/jats:italic>\n                    (MRSA), penicillin-resistant streptococci, and vancomycin-resistant enterococci (MICs at which 90% of strains are inhibited, \u22640.5 \u03bcg\/ml). TBG-MINO exhibited activity against a wide diversity of gram-negative aerobic and anaerobic bacteria, most of which were less susceptible to tetracycline and minocycline. The in vivo protective effects of TBG-MINO were examined against acute lethal infections in mice caused by\n                    <jats:italic>Escherichia coli<\/jats:italic>\n                    ,\n                    <jats:italic>S. aureus<\/jats:italic>\n                    , and\n                    <jats:italic>Streptococcus pneumoniae<\/jats:italic>\n                    isolates. TBG-MINO, administered intravenously, demonstrated efficacy against infections caused by\n                    <jats:italic>S. aureus<\/jats:italic>\n                    including MRSA strains and strains containing\n                    <jats:italic>tet<\/jats:italic>\n                    (K) or\n                    <jats:italic>tet<\/jats:italic>\n                    (M) resistance determinants (median effective doses [ED\n                    <jats:sub>50<\/jats:sub>\n                    s], 0.79 to 2.3 mg\/kg of body weight). TBG-MINO demonstrated efficacy against infections caused by tetracycline-sensitive\n                    <jats:italic>E. coli<\/jats:italic>\n                    strains as well as\n                    <jats:italic>E. coli<\/jats:italic>\n                    strains containing either\n                    <jats:italic>tet<\/jats:italic>\n                    (M) or the efflux determinant\n                    <jats:italic>tet<\/jats:italic>\n                    (A),\n                    <jats:italic>tet<\/jats:italic>\n                    (B), or\n                    <jats:italic>tet<\/jats:italic>\n                    (C) (ED\n                    <jats:sub>50<\/jats:sub>\n                    s, 1.5 to 3.5 mg\/kg). Overall, TBG-MINO shows antibacterial activity against a wide spectrum of gram-positive and gram-negative aerobic and anaerobic bacteria including strains resistant to other chemotherapeutic agents. The in vivo protective effects, especially against infections caused by resistant bacteria, corresponded with the in vitro activity of TBG-MINO.\n                  <\/jats:p>","DOI":"10.1128\/aac.43.4.738","type":"journal-article","created":{"date-parts":[[2018,10,8]],"date-time":"2018-10-08T20:34:41Z","timestamp":1539030881000},"page":"738-744","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":336,"title":["In Vitro and In Vivo Antibacterial Activities of a Novel Glycylcycline, the 9-\n                    <i>t<\/i>\n                    -Butylglycylamido Derivative of Minocycline (GAR-936)"],"prefix":"10.1128","volume":"43","author":[{"given":"P. J.","family":"Petersen","sequence":"first","affiliation":[{"name":"<!--label omitted: 1-->Infectious Disease Research Section, Wyeth-Ayerst Research, Pearl River, New York 10965"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N. V.","family":"Jacobus","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Infectious Disease Research Section, Wyeth-Ayerst Research, Pearl River, New York 10965"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"W. J.","family":"Weiss","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Infectious Disease Research Section, Wyeth-Ayerst Research, Pearl River, New York 10965"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. E.","family":"Sum","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Infectious Disease Research Section, Wyeth-Ayerst Research, Pearl River, New York 10965"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. T.","family":"Testa","sequence":"additional","affiliation":[{"name":"<!--label omitted: 1-->Infectious Disease Research Section, Wyeth-Ayerst Research, Pearl River, New York 10965"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/29.3.245"},{"key":"e_1_3_1_3_2","first-page":"689","article-title":"Tetracycline resistant determinants from groups A to D vary in their ability to confer decreased accumulation of tetracycline derivatives by Escherichia coli.","volume":"128","author":"Chopra I.","year":"1982","unstructured":"Chopra I. Shales S. Ball P. Tetracycline resistant determinants from groups A to D vary in their ability to confer decreased accumulation of tetracycline derivatives by Escherichia coli. J. Gen. Microbiol. 128 1982 689 692","journal-title":"J. Gen. Microbiol."},{"key":"e_1_3_1_4_2","unstructured":"Cleeland\n              R.\n              Squires\n              E.\n          Evaluation of new antimicrobials in vitro and in experimental animal infections\n          Antibiotics in laboratory medicine\n          3rd ed.\n              Lorian\n              V.\n          1991\n          752\n          783\n          The Williams & Wilkins Co.\n          Baltimore Md"},{"key":"e_1_3_1_5_2","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1111\/j.1749-6632.1948.tb27262.x","article-title":"Aureomycin: a product of the continuing search for new antibiotics.","volume":"51","author":"Duggar B. M.","year":"1948","unstructured":"Duggar B. M. Aureomycin: a product of the continuing search for new antibiotics. Ann. N. Y. Acad. Sci. 51 1948 177 181","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.38.3.534"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.27.4.731-734.1989"},{"key":"e_1_3_1_8_2","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/cpt19741513","article-title":"Twenty-fifth anniversary of the discovery of aureomycin: the place of the tetracyclines in antimicrobial therapy.","volume":"15","author":"Finland M.","year":"1974","unstructured":"Finland M. Twenty-fifth anniversary of the discovery of aureomycin: the place of the tetracyclines in antimicrobial therapy. Clin. Pharmacol. Ther. 15 1974 3 8","journal-title":"Clin. Pharmacol. Ther."},{"key":"e_1_3_1_9_2","unstructured":"Finney\n              D. J.\n          Probit analysis\n          3rd ed.\n          1971\n           Cambridge University Press\n          London United Kingdom"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.38.9.2218"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.35.11.2180"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/clind\/16.6.750"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.38.11.2628"},{"key":"e_1_3_1_14_2","doi-asserted-by":"crossref","unstructured":"Levy\n              S. B.\n          Resistance to the tetracyclines\n          Antimicrobial drug resistance.\n              Bryan\n              L. 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L.\n          Principles and practice of infectious diseases.\n          1993\n          Churchill Livingston Inc.\n          New York N.Y"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.36.8.1703"},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(93)90063-U"},{"key":"e_1_3_1_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.3.1.46"},{"key":"e_1_3_1_21_2","unstructured":"National Committee for Clinical Laboratory Standards\n          Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically. Approved standard M7-A4 vol. 17 no. 2.\n          1997\n          National Committee for Clinical Laboratory Standards\n          Wayne Pa"},{"key":"e_1_3_1_22_2","unstructured":"National Committee for Clinical Laboratory Standards\n          Methods for antimicrobial susceptibility testing of anaerobic bacteria. Approved standard M11-A4 vol. 17 no. 22.\n          1997\n          National Committee for Clinical Laboratory Standards\n          Wayne Pa"},{"key":"e_1_3_1_23_2","doi-asserted-by":"crossref","first-page":"784","DOI":"10.1007\/BF02098471","article-title":"In vitro activity of DMG-Mino and DMG-Dmdot, two new glycylcyclines, against anaerobic bacteria.","volume":"12","author":"Nord C.","year":"1993","unstructured":"Nord C. Lindmark A. Persson I. In vitro activity of DMG-Mino and DMG-Dmdot, two new glycylcyclines, against anaerobic bacteria. Eur. J. Clin. Microbiol. Infect. Dis. 12 1993 784 786","journal-title":"Eur. J. Clin. Microbiol. Infect. Dis."},{"key":"e_1_3_1_24_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.33.9.1588"},{"key":"e_1_3_1_25_2","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1111\/j.1365-2958.1990.tb02025.x","article-title":"New perspectives on tetracycline resistance.","volume":"4","author":"Salyers A. A.","year":"1990","unstructured":"Salyers A. 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Chem. 37 1993 184 188","journal-title":"J. Med. Chem."},{"key":"e_1_3_1_31_2","unstructured":"Sutter\n              V. L.\n              Citron\n              D. M.\n              Edelstein\n              M. A. C.\n              Finegold\n              S. M.\n          Wadsworth anaerobic bacteriology manual\n          4th ed.\n          1985\n          Star Publishing Co.\n          Belmont Calif"},{"key":"e_1_3_1_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.37.11.2270"},{"key":"e_1_3_1_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(88)91037-9"},{"key":"e_1_3_1_34_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.38.10.2513"},{"key":"e_1_3_1_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.38.5.1096"}],"container-title":["Antimicrobial Agents and Chemotherapy"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.43.4.738","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.asm.org\/doi\/pdf\/10.1128\/AAC.43.4.738","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,2,21]],"date-time":"2022-02-21T11:04:36Z","timestamp":1645441476000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.asm.org\/doi\/10.1128\/AAC.43.4.738"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1999,4]]},"references-count":34,"journal-issue":{"issue":"4","published-print":{"date-parts":[[1999,4]]}},"alternative-id":["10.1128\/AAC.43.4.738"],"URL":"https:\/\/doi.org\/10.1128\/aac.43.4.738","relation":{},"ISSN":["0066-4804","1098-6596"],"issn-type":[{"value":"0066-4804","type":"print"},{"value":"1098-6596","type":"electronic"}],"subject":[],"published":{"date-parts":[[1999,4]]},"assertion":[{"value":"1998-08-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"1999-01-02","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"1999-04-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}