{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T23:11:05Z","timestamp":1787008265940,"version":"build-2736575974"},"reference-count":40,"publisher":"SAGE Publications","issue":"9","license":[{"start":{"date-parts":[[2020,9,1]],"date-time":"2020-09-01T00:00:00Z","timestamp":1598918400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Microbial Drug Resistance"],"published-print":{"date-parts":[[2020,9,1]]},"abstract":"<jats:p>\n                    With the stagnancy of antibiotics development, polymyxins have become the last defense for treatment of multidrug-resistant (MDR) Gram-negative bacteria, whereas the effect of polymyxin monotherapy is limited by resistance. The objective of this study was to evaluate the effects of polymyxin B (PMNB)-vorinostat (SAHA) combination therapy against Gram-negative pathogens\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    and\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    . The antibacterial activities of PMNB and SAHA were evaluated by susceptibility testing. The synergistic effect was assessed by checkerboard tests and time-killing kinetics experiments. Cellular morphology studies and reactive oxygen species (ROS) assay were conducted to explore potential mechanisms. Also,\n                    <jats:italic toggle=\"yes\">Galleria mellonella<\/jats:italic>\n                    models were made to evaluate the antibacterial effects\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    . PMNB-SAHA had the synergistic effect against all tested isolates, reducing &gt;2 log\n                    <jats:sub>10<\/jats:sub>\n                    colony-forming units (CFU)\/mL at 40 minutes, and showed more powerful antibacterial effects than PMNB alone in the 24-hour window. Cellular morphology study showed the change of membrane and disruption of integrity. ROS assay showed more oxidative stress in combination than PMNB or SAHA monotherapy. In animal models, PMNB-SAHA showed a higher survival rate than that of monotherapy. This study is the first to report the synergistic antibacterial effect of PMNB-SAHA therapy against MDR Gram-negative bacteria. Further clinical research is needed to confirm the results.\n                  <\/jats:p>","DOI":"10.1089\/mdr.2019.0309","type":"journal-article","created":{"date-parts":[[2020,4,29]],"date-time":"2020-04-29T20:27:32Z","timestamp":1588192052000},"page":"1108-1119","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":6,"title":["<i>In Vitro<\/i>\n                    and\n                    <i>In Vivo<\/i>\n                    Effects of the Polymyxin-Vorinostat Combination Therapy Against Multidrug-Resistant Gram-Negative Pathogens"],"prefix":"10.1177","volume":"26","author":[{"given":"Haoran","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Infectious Disease, The First Affiliated Hospital of Anhui Medical University, Hefei, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongru","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Neurology, Xiangya Hospital Central South University, Changsha, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhou","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, The First Affiliated Hospital of Anhui Medical University, Hefei, China."},{"name":"Department of Clinical Laboratory, The Second Hospital of Anhui Medical University, Hefei, China."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiabin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, The First Affiliated Hospital of Anhui Medical University, Hefei, China."},{"name":"Department of Molecular Biology, Anhui Center for Surveillance of Bacterial Resistance, Hefei, China."},{"name":"Department of Infectious Diseases, Chaohu Hospital of Anhui Medical University, Hefei, China."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2020,9,9]]},"reference":[{"key":"e_1_3_6_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cit152"},{"key":"e_1_3_6_3_2","first-page":"848","volume":"41","author":"Gaynes R.","year":"2005","unstructured":"Gaynes R., , and Edwards J.R.. 2005. Overview of nosocomial infections caused by Gram-negative bacilli. Clin. Infect. Dis. 41:848\u2013854.","journal-title":"Overview of nosocomial infections caused by Gram-negative bacilli. Clin. Infect. Dis"},{"key":"e_1_3_6_4_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-0691.2010.03420.x"},{"key":"e_1_3_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(14)70850-3"},{"key":"e_1_3_6_6_2","first-page":"43","article-title":"Polymyxin: a new chemotherapeutic agent","volume":"81","author":"Stansly P.G.","year":"1947","unstructured":"Stansly P.G., , Shepherd R.G, , and White H.J.. 1947. Polymyxin: a new chemotherapeutic agent. Bull. Johns Hopkins Hosp. 81:43\u201354.","journal-title":"Bull. Johns Hopkins Hosp"},{"key":"e_1_3_6_7_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi00587a024"},{"key":"e_1_3_6_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00256-11"},{"key":"e_1_3_6_9_2","first-page":"2311","article-title":"Pharmacokinetics of four different brands of colistimethate and formed colistin in rats","volume":"68","author":"He H.","year":"2013","unstructured":"He H., , Li J.C, , Nation R.L, , Jacob J., , Chen G., , Lee H.J, , Tsuji B.T, , Thompson P.E, , Roberts K., , Velkov T., , and Li J.. 2013. Pharmacokinetics of four different brands of colistimethate and formed colistin in rats. J. Antimicrob. Chemother. 68:2311\u20132317.","journal-title":"J. Antimicrob. Chemother"},{"key":"e_1_3_6_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dks437"},{"key":"e_1_3_6_11_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02319-16"},{"key":"e_1_3_6_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/35106079"},{"key":"e_1_3_6_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2016.36"},{"key":"e_1_3_6_14_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1210620"},{"key":"e_1_3_6_15_2","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0020987"},{"key":"e_1_3_6_16_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1013754107"},{"key":"e_1_3_6_17_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1008522107"},{"key":"e_1_3_6_18_2","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2009.013870"},{"key":"e_1_3_6_19_2","doi-asserted-by":"publisher","DOI":"10.1517\/13543784.2011.542750"},{"key":"e_1_3_6_20_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02574-18"},{"key":"e_1_3_6_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41429-019-0186-8"},{"key":"e_1_3_6_22_2","author":"Cheah S.E.","year":"2016","unstructured":"Cheah S.E., , Li J., , Tsuji B.T, , Forrest A., , Bulitta J.B, , and Nation R.L.. 2016. Colistin and polymyxin B dosage regimens against Acinetobacter baumannii: differences in activity and the emergence of resistance. Antimicrob. Agents. Chemother. 60:AAC.02927-15.","journal-title":"Acinetobacter baumannii"},{"key":"e_1_3_6_23_2","doi-asserted-by":"publisher","DOI":"10.1097\/QAD.0000000000001442"},{"key":"e_1_3_6_24_2","first-page":"961","volume":"55","author":"Marfurt J.","year":"2011","unstructured":"Marfurt J., , Chalfein F., , Prayoga P., , Wabiser F., , Kenangalem E., , Piera K.A, , Fairlie D.P, , Tjitra E., , Anstey N.M, , Andrews K.T, , and Price R.N.. 2011. Ex vivo activity of histone deacetylase inhibitors against multidrug-resistant clinical isolates of Plasmodium falciparum and P. vivax. Antimicrob. Agents. Chemother. 55:961\u2013966.","journal-title":"Ex vivo activity of histone deacetylase inhibitors against multidrug-resistant clinical isolates of Plasmodium falciparum and P. vivax. Antimicrob. Agents. Chemother"},{"key":"e_1_3_6_25_2","first-page":"119","article-title":"Possible involvement of ROS generation in vorinostat pretreatment induced enhancement of the antibacterial activity of ciprofloxacin","volume":"9","author":"Masadeh M.M.","year":"2017","unstructured":"Masadeh M.M., , K.H. Alzoubi S.I., , Al-azzam, and Al-buhairan A.H.. 2017. Possible involvement of ROS generation in vorinostat pretreatment induced enhancement of the antibacterial activity of ciprofloxacin. Clin. Pharmacol. 9:119\u2013124.","journal-title":"Clin. Pharmacol"},{"key":"e_1_3_6_26_2","unstructured":"Wayne P.A. 2018. Performance Standards for Antimicrobial Susceptibility Testing. 28th ed. Clinical and Laboratory Standards Institute (CLSI) Document M100. Wayne PA: CLSI."},{"key":"e_1_3_6_27_2","unstructured":"The European Committee on Antimicrobial Susceptibility Testing (EUCAST). 2019. Breakpoint Tables for Interpretation of MICs and Zone Diameters. Version 9.0. Available at www.eucast.org (accessed February1 2020)."},{"key":"e_1_3_6_28_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkg301"},{"key":"e_1_3_6_29_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00981-16"},{"key":"e_1_3_6_30_2","doi-asserted-by":"publisher","DOI":"10.1038\/ja.2015.127"},{"key":"e_1_3_6_31_2","first-page":"e00073","volume":"61","author":"Huang D.","year":"2017","unstructured":"Huang D., , Yu B., , Diep J.K, , Sharma R., , Dudley M., , Monteiro J., , Kaye K.S, , Pogue J.M, , Abboud C.S, , and Rao G.G.. 2017. In vitro assessment of combined polymyxin B and minocycline therapy against Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae. Antimicrob. Agents Chemother. 61:e00073-00017.","journal-title":"In vitro assessment of combined polymyxin B and minocycline therapy against Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae. Antimicrob. Agents Chemother"},{"key":"e_1_3_6_32_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.03003-15"},{"key":"e_1_3_6_33_2","doi-asserted-by":"publisher","DOI":"10.1038\/msb4100135"},{"key":"e_1_3_6_34_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.78.2.1001"},{"key":"e_1_3_6_35_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00756-12"},{"key":"e_1_3_6_36_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01533-08"},{"key":"e_1_3_6_37_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2007.06.049"},{"key":"e_1_3_6_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jgar.2017.09.011"},{"key":"e_1_3_6_39_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-017-02736-7"},{"key":"e_1_3_6_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(17)30753-3"},{"key":"e_1_3_6_41_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dku476"}],"container-title":["Microbial Drug Resistance"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/mdr.2019.0309","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/mdr.2019.0309","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/mdr.2019.0309","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T20:36:32Z","timestamp":1777667792000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/10.1089\/mdr.2019.0309"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,9,1]]},"references-count":40,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2020,9,1]]}},"alternative-id":["10.1089\/mdr.2019.0309"],"URL":"https:\/\/doi.org\/10.1089\/mdr.2019.0309","relation":{},"ISSN":["1076-6294","1931-8448"],"issn-type":[{"value":"1076-6294","type":"print"},{"value":"1931-8448","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,9,1]]}}}