{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,31]],"date-time":"2026-01-31T11:07:44Z","timestamp":1769857664677,"version":"3.49.0"},"reference-count":25,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2021,1,14]],"date-time":"2021-01-14T00:00:00Z","timestamp":1610582400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"calScreener technology"},{"name":"European Union\u2019s Horizon 2020 research and innovation programme","award":["729076"],"award-info":[{"award-number":["729076"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,3,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Objectives<\/jats:title>\n                  <jats:p>The worldwide emergence of antibiotic resistance calls for effective exploitation of existing antibiotics. Antibiotic combinations with different modes of action can synergize for successful treatment. In the present study, we used microcalorimetry screening to identify synergistic combination treatments against clinical MDR isolates. The synergistic effects were validated in a murine infection model.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>The synergy of meropenem combined with colistin, rifampicin or amikacin was tested on 12 isolates (1 Escherichia coli, 5 Klebsiella pneumoniae, 3 Pseudomonas aeruginosa and 3 Acinetobacter baumannii) in an isothermal microcalorimeter measuring metabolic activity. One A. baumannii strain was tested with two individual pairings of antibiotic combinations. The microcalorimetric data were used to predict in vivo efficacy in a murine peritonitis\/sepsis model. NMRI mice were inoculated intraperitoneally and after 1\u2009h treated with saline, drug X, drug Y or X+Y. Bacterial load was determined by cfu in peritoneal fluid and blood after 4\u2009h.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>In vitro, of the 13 combinations tested on the 12 strains, 3 of them exhibited a synergistic reduction in MIC (23% n\u2009=\u20093\/13), 5 showed an additive effect (38.5% n\u2009=\u20095\/13) and 5 had indifferent or antagonistic effects (38.5% n\u2009=\u20095\/13). There was a significant correlation (P\u2009=\u20090.024) between microcalorimetry-screening FIC index values and the log reduction in peritoneal fluid from mice that underwent combination treatment compared with the most effective mono treatment. No such correlation could be found between chequerboard and in vivo results (P\u2009=\u20090.16).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>These data support microcalorimetic metabolic readout to predict additive or synergistic effects of combination treatment of MDR infections within hours.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1093\/jac\/dkaa543","type":"journal-article","created":{"date-parts":[[2020,12,18]],"date-time":"2020-12-18T16:59:40Z","timestamp":1608310780000},"page":"1001-1009","source":"Crossref","is-referenced-by-count":30,"title":["Effective antimicrobial combination <i>in vivo<\/i> treatment predicted with microcalorimetry screening"],"prefix":"10.1093","volume":"76","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7662-9118","authenticated-orcid":false,"given":"Kasper N\u00f8rskov","family":"Kragh","sequence":"first","affiliation":[{"name":"Department of Clinical Microbiology, Rigshospitalet, 2200 Copenhagen N, Denmark"},{"name":"Costerton Biofilm Center, University of Copenhagen, 2200 Copenhagen N, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Desiree","family":"Gij\u00f3n","sequence":"additional","affiliation":[{"name":"Servicio de Microbiolog\u00eda, Hospital Universitario Ram\u00f3n y Cajal and Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS), 28034 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ainhize","family":"Maruri","sequence":"additional","affiliation":[{"name":"Servicio de Microbiolog\u00eda, Hospital Universitario Ram\u00f3n y Cajal and Instituto Ram\u00f3n y Cajal de Investigaci\u00f3n Sanitaria (IRYCIS), 28034 Madrid, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0295-6877","authenticated-orcid":false,"given":"Alberto","family":"Antonelli","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence, 50121 Firenze, Italy"},{"name":"Clinical Microbiology and Virology Unit, Florence Careggi University Hospital, 50121 Firenze, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Coppi","sequence":"additional","affiliation":[{"name":"Department of Experimental and Clinical Medicine, University of Florence, 50121 Firenze, Italy"},{"name":"Clinical Microbiology and Virology Unit, Florence Careggi University Hospital, 50121 Firenze, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mette","family":"Kolpen","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology, Rigshospitalet, 2200 Copenhagen N, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephanie","family":"Crone","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology, Rigshospitalet, 2200 Copenhagen N, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chaitanya","family":"Tellapragada","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Karolinska Institutet, 14183 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Badrul","family":"Hasan","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Karolinska Institutet, 14183 Stockholm, Sweden"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stine","family":"Radmer","sequence":"additional","affiliation":[{"name":"Department of Clinical Microbiology, Rigshospitalet, 2200 Copenhagen N, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Corn\u00e9","family":"de Vogel","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infectious Diseases, Erasmus University, Erasmus MC, 3000CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Willem","family":"van Wamel","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infectious Diseases, Erasmus University, Erasmus MC, 3000CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Annelies","family":"Verbon","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Infectious Diseases, Erasmus University, Erasmus MC, 3000CA Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christian G","family":"Giske","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine, Karolinska Institutet, 14183 Stockholm, Sweden"},{"name":"Clinical Microbiology, Karolinska University 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