{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,27]],"date-time":"2026-04-27T20:24:05Z","timestamp":1777321445215,"version":"3.51.4"},"reference-count":47,"publisher":"American Society for Microbiology","issue":"8","license":[{"start":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T00:00:00Z","timestamp":1722902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,8,6]],"date-time":"2024-08-06T00:00:00Z","timestamp":1722902400000},"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":["Microbiol Spectr"],"published-print":{"date-parts":[[2024,8,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:sec>\n            <jats:title\/>\n            <jats:p>\n              Methicillin-resistant\n              <jats:italic>Staphylococcus aureus<\/jats:italic>\n              (MRSA) bacteremia is a serious clinical challenge with high mortality rates. Antibiotic combination therapy is currently used in cases of persistent infection; however, the limited development of new antibiotics will likely increase the need for combination therapy, and better methods are needed for identifying effective combinations for treating persistent bacteremia. To identify pairwise combinations with the most consistent potential for benefit compared to monotherapy with a primary anti-MRSA agent, we conducted a systematic study with an\n              <jats:italic>in vitro<\/jats:italic>\n              high-throughput methodology. We tested daptomycin and vancomycin each in combination with gentamicin, rifampicin, cefazolin, and oxacillin, and ceftaroline with daptomycin, gentamicin, and rifampicin. Combining cefazolin with daptomycin lowered the daptomycin concentration required to reach 95% growth inhibition (IC\n              <jats:sub>95<\/jats:sub>\n              ) for all isolates tested and lowered daptomycin IC\n              <jats:sub>95<\/jats:sub>\n              below the sensitivity breakpoint for five out of six isolates that had daptomycin minimum inhibitory concentrations at or above the sensitivity breakpoint. Similarly, vancomycin IC\n              <jats:sub>95<\/jats:sub>\n              s were decreased when vancomycin was combined with cefazolin for 86.7% of the isolates tested. This was a higher percentage than was achieved by adding any other secondary antibiotic to vancomycin. Adding rifampicin to daptomycin or vancomycin did not always reduce IC\n              <jats:sub>95<\/jats:sub>\n              s and failed to produce synergistic interaction in any of the isolates tested; the addition of rifampicin to ceftaroline was frequently synergistic and always lowered the amount of ceftaroline required to reach the IC\n              <jats:sub>95<\/jats:sub>\n              . These analyses rationalize further\n              <jats:italic>in vivo<\/jats:italic>\n              evaluation of three drug pairs for MRSA bacteremia: daptomycin+cefazolin, vancomycin+cefazolin, and ceftaroline+rifampicin.\n            <\/jats:p>\n            <jats:sec>\n              <jats:title>IMPORTANCE<\/jats:title>\n              <jats:p>\n                Bloodstream infections caused by methicillin-resistant\n                <jats:italic>Staphylococcus aureus<\/jats:italic>\n                (MRSA) have a high mortality rate despite the availability of vancomycin, daptomycin, and newer antibiotics including ceftaroline. With the slow output of the antibiotic pipeline and the serious clinical challenge posed by persistent MRSA infections, better strategies for utilizing combination therapy are becoming increasingly necessary. We demonstrated the value of a systematic high-throughput approach, adapted from prior work testing antibiotic combinations against tuberculosis and other mycobacteria, by using this approach to test antibiotic pairs against a panel of MRSA isolates with diverse patterns of antibiotic susceptibility. We identified three antibiotic pairs\u2014daptomycin+cefazolin, vancomycin+cefazolin, and ceftaroline+rifampicin\u2014where the addition of the second antibiotic improved the potency of the first antibiotic across all or most isolates tested. Our results indicate that these pairs warrant further evaluation in the clinical setting.\n              <\/jats:p>\n            <\/jats:sec>\n          <\/jats:sec>","DOI":"10.1128\/spectrum.00976-24","type":"journal-article","created":{"date-parts":[[2024,6,25]],"date-time":"2024-06-25T13:01:46Z","timestamp":1719320506000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":5,"title":["<i>In vitro<\/i>\n            identification of underutilized \u03b2-lactam combinations against methicillin-resistant\n            <i>Staphylococcus aureus<\/i>\n            bacteremia isolates"],"prefix":"10.1128","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3034-2162","authenticated-orcid":false,"given":"Kathleen P.","family":"Davis","sequence":"first","affiliation":[{"name":"Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, USA"},{"name":"The Stuart B. Levy Center for Integrated Management of Antimicrobial Resistance, Tufts University School of Medicine, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laura A.","family":"McDermott","sequence":"additional","affiliation":[{"name":"Division of Geographic Medicine and Infectious Diseases, Department of Medicine, Tufts Medical Center, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0119-3978","authenticated-orcid":false,"given":"David R.","family":"Snydman","sequence":"additional","affiliation":[{"name":"The Stuart B. Levy Center for Integrated Management of Antimicrobial Resistance, Tufts University School of Medicine, Boston, Massachusetts, USA"},{"name":"Division of Geographic Medicine and Infectious Diseases, Department of Medicine, Tufts Medical Center, Boston, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2236-1424","authenticated-orcid":false,"given":"Bree B.","family":"Aldridge","sequence":"additional","affiliation":[{"name":"Department of Molecular Biology and Microbiology, Tufts University School of Medicine, Boston, Massachusetts, USA"},{"name":"The Stuart B. Levy Center for Integrated Management of Antimicrobial Resistance, Tufts University School of Medicine, Boston, Massachusetts, USA"},{"name":"Department of Biomedical Engineering, Tufts University School of Engineering, Medford, Massachusetts, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"235","reference":[{"key":"e_1_3_5_2_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciw828"},{"key":"e_1_3_5_3_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1914433"},{"key":"e_1_3_5_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.lana.2023.100561"},{"key":"e_1_3_5_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjmed.2022.09.017"},{"key":"e_1_3_5_6_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cir034"},{"key":"e_1_3_5_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2017.01.019"},{"key":"e_1_3_5_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofx084"},{"key":"e_1_3_5_9_2","doi-asserted-by":"publisher","DOI":"10.1002\/phar.1596"},{"key":"e_1_3_5_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02483-18"},{"key":"e_1_3_5_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofz538"},{"key":"e_1_3_5_12_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.02015-16"},{"key":"e_1_3_5_13_2","doi-asserted-by":"publisher","DOI":"10.1093\/ofid\/ofab606"},{"key":"e_1_3_5_14_2","doi-asserted-by":"publisher","DOI":"10.1086\/428616"},{"key":"e_1_3_5_15_2","doi-asserted-by":"publisher","DOI":"10.1093\/jpids\/piad032"},{"key":"e_1_3_5_16_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cix287"},{"key":"e_1_3_5_17_2","volume-title":"The Sanford guide to antimicrobial therapy","author":"Gilbert DN, Chambers HF, Saag MS, Pavia AT, Black D, Boucher HW, Freedman DO, Kim K, Schwartz BS","year":"2020","unstructured":"Gilbert DN, Chambers HF, Saag MS, Pavia AT, Black D, Boucher HW, Freedman DO, Kim K, Schwartz BS. 2020. 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