{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T23:54:37Z","timestamp":1790380477243,"version":"4.1.0"},"reference-count":55,"publisher":"American Society for Microbiology","issue":"4","license":[{"start":{"date-parts":[[2024,4,2]],"date-time":"2024-04-02T00:00:00Z","timestamp":1712016000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2024,4,2]],"date-time":"2024-04-02T00:00:00Z","timestamp":1712016000000},"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":[[2024,4,2]]},"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) causes biofilm-related medical device infections. Phage-antibiotic combinations offer potential therapy due to proven\n                      <jats:italic>in vitro<\/jats:italic>\n                      antibiofilm efficacy. We evaluated phage-antibiotic synergy against biofilms using modified checkerboard and 24-h time-kill assays. Humanized-simulated daptomycin (DAP) (10, 8, and 6 mg\/kg q24h) and ceftaroline (CPT) (600 mg q12h) were combined with Intesti13, Sb-1, and Romulus phages (tMOI 1, q12h). Assays were conducted in 168-h biofilm reactor models against DAP non-susceptible (DNS) vancomycin intermediate\n                      <jats:italic>S. aureus<\/jats:italic>\n                      (VISA) MRSA D712 and DAP-susceptible MRSA 8014. Synergistic activity and bactericidal activity were defined as \u22652log\n                      <jats:sub>10<\/jats:sub>\n                      CFU\/mL reduction from antibiotic-only regimens and \u22653log\n                      <jats:sub>10<\/jats:sub>\n                      CFU\/mL decrease from baseline at 24 h. Differences were analyzed by one-way analysis of variance with Tukey\u2019s\n                      <jats:italic>post hoc<\/jats:italic>\n                      test (\n                      <jats:italic>P<\/jats:italic>\n                      \u2264 0.05 is considered significant). Surviving bacteria were examined for antibiotic minimum biofilm inhibitory concentration (MBIC) changes and phage susceptibility. In 168-h biofilm models, humanized DAP 10 mg\/kg + CPT, combined with a 2-phage cocktail (Intesti13 + Sb-1) against D712, and a 3-phage cocktail (Intesti13 + Sb-1 + Romulus) against 8014, demonstrated synergistic bactericidal activity. At 168 h, bacteria were minimally detectable [2log\n                      <jats:sub>10<\/jats:sub>\n                      CFU\/cm\n                      <jats:sup>2<\/jats:sup>\n                      (\u2212\u03944.23 and \u2212\u03944.42 log\n                      <jats:sub>10<\/jats:sub>\n                      CFU\/cm\n                      <jats:sup>2<\/jats:sup>\n                      ; both\n                      <jats:italic>P<\/jats:italic>\n                      &lt; 0.001)]. Antibiotic MBIC remained unchanged compared to baseline across various time points. None of the tested bacteria at 168 h exhibited complete phage resistance. This study reveals bactericidal efficacy of DAP + CPT with 2-phage and 3-phage cocktails against DNS VISA and MRSA isolates (D712 and 8014) in biofilm models, maintaining susceptibility. Further research is needed for diverse strains and durations, aligning with infection care.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>IMPORTANCE<\/jats:title>\n                    <jats:p>\n                      The prevalence of biofilm-associated medical device infections caused by methicillin-resistant\n                      <jats:italic>Staphylococcus aureus<\/jats:italic>\n                      (MRSA) presents a pressing medical challenge. The latest research demonstrates the potential of phage-antibiotic combinations (PACs) as a promising solution, notably\n                      <jats:italic>in vitro<\/jats:italic>\n                      antibiofilm efficacy. By adopting modified checkerboard and 24-h time-kill assays, the study investigated the synergistic action of phages combined with humanized-simulated doses of daptomycin (DAP) and ceftaroline (CPT). The results were promising: a combination of DAP, CPT, and either a 2-phage or 3-phage cocktail effectively exhibited bactericidal activity against both DAP non-susceptible vancomycin intermediate\n                      <jats:italic>S. aureus<\/jats:italic>\n                      MRSA and DAP-susceptible MRSA strains within 168-h biofilm models. Moreover, post-treatment evaluations revealed no discernible rise in antibiotic resistance or complete phage resistance. This pioneering work suggests the potential of PACs in addressing MRSA biofilm infections, setting the stage for further expansive research tailored to diverse bacterial strains and treatment durations.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1128\/spectrum.03212-23","type":"journal-article","created":{"date-parts":[[2024,2,27]],"date-time":"2024-02-27T09:02:05Z","timestamp":1709024525000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":33,"title":["Synergistic bactericidal effects of phage-enhanced antibiotic therapy against MRSA biofilms"],"prefix":"10.1128","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4891-8625","authenticated-orcid":false,"given":"Ashlan J.","family":"Kunz Coyne","sequence":"first","affiliation":[{"name":"Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle","family":"Stamper","sequence":"additional","affiliation":[{"name":"Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Callan","family":"Bleick","sequence":"additional","affiliation":[{"name":"Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Razieh","family":"Kebriaei","sequence":"additional","affiliation":[{"name":"Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan M.","family":"Lehman","sequence":"additional","affiliation":[{"name":"Center for Biologics Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2220-0081","authenticated-orcid":true,"given":"Michael J.","family":"Rybak","sequence":"additional","affiliation":[{"name":"Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, Michigan, USA"},{"name":"Department of Pharmacy Services, Detroit Receiving Hospital, Detroit Medical Center, Detroit, Michigan, USA"},{"name":"Department of Medicine, Division of Infectious Diseases, Wayne State University, Detroit, Michigan, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcma.2017.07.012"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.2147\/IDR.S379502"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.idc.2018.06.009"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1111\/lam.13144"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.15.2.167-193.2002"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.2174\/1874285801711010053"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1128\/CMR.00134-14"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.DMIH2-0004-2015"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1111\/1574-6976.12072"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-019-1894-8"},{"key":"e_1_3_2_12_2","unstructured":"Lytic infection of Escherichia coli biofilms by bacteriophage T4. 2023. 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