{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T03:43:29Z","timestamp":1779335009909,"version":"3.51.4"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"5","license":[{"start":{"date-parts":[[2022,2,24]],"date-time":"2022-02-24T00:00:00Z","timestamp":1645660800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"funder":[{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"crossref","award":["AMR\/115\/IN\/2017-ECD-II"],"award-info":[{"award-number":["AMR\/115\/IN\/2017-ECD-II"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"crossref","award":["DBT\/2015\/IIT-R\/301"],"award-info":[{"award-number":["DBT\/2015\/IIT-R\/301"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Department of Biotechnology, India","award":["IF170898"],"award-info":[{"award-number":["IF170898"]}]},{"DOI":"10.13039\/501100010892","name":"Department of Science and Technology","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100010892","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,4,27]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objectives<\/jats:title><jats:p>To evaluate the in vitro and in vivo efficacy of the FDA-approved drug disulfiram in combination with meropenem against MBL-expressing carbapenem-resistant Acinetobacter baumannii.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Chequerboard and antibiotic resistance reversal analysis were performed using 25 clinical isolates producing different MBLs. Three representative strains harbouring NDM, IMP or non-MBL genes were subjected to a time\u2013kill assay to further evaluate this synergistic interaction. Dose-dependent inhibition by disulfiram was assessed to determine IC50 for NDM-1, IMP-7, VIM-2 and KPC-2. Further, to test the efficacy of meropenem monotherapy and meropenem in combination with disulfiram against NDM- and IMP-harbouring A. baumannii, an experimental model of systemic infection and pneumonia was developed using BALB\/c female mice.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Chequerboard and antibiotic reversal assay displayed a synergistic interaction against MBL-expressing A. baumannii strains with 4- to 32-fold reduction in MICs of meropenem. In time\u2013kill analysis, meropenem and disulfiram exhibited synergy against NDM- and IMP-producing carbapenem-resistant A. baumannii (CRAb) isolates. In vitro dose-dependent inhibition analysis showed that disulfiram inhibits NDM-1 and IMP-7 with IC50 values of 1.5 \u00b1 0.6 and 16.25 \u00b1 1.6\u2005\u03bcM, respectively, with slight or no inhibition of VIM-2 (&amp;lt;20%) and KPC-2. The combination performed better in the clearance of bacterial load from the liver and spleen of mice infected with IMP-expressing CRAb. In the pneumonia model, the combination significantly decreased the bacterial burden of NDM producers compared with monotherapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These results strongly suggest that the combination of disulfiram and meropenem represents an effective treatment option for NDM- and IMP-associated CRAb infections.<\/jats:p><\/jats:sec>","DOI":"10.1093\/jac\/dkac057","type":"journal-article","created":{"date-parts":[[2022,2,18]],"date-time":"2022-02-18T20:10:10Z","timestamp":1645215010000},"page":"1313-1323","source":"Crossref","is-referenced-by-count":8,"title":["Disulfiram enhances meropenem activity against NDM- and IMP-producing carbapenem-resistant<i>Acinetobacter baumannii<\/i>infections"],"prefix":"10.1093","volume":"77","author":[{"given":"Vineet","family":"Dubey","sequence":"first","affiliation":[{"name":"Department of Biosciences and Bioengineering, Indian Institute of Technology Roorkee, Roorkee 247667, 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