{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T15:17:41Z","timestamp":1785165461546,"version":"3.55.0"},"reference-count":35,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2019,10,14]],"date-time":"2019-10-14T00:00:00Z","timestamp":1571011200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>This study assesses the synergistic effect of the combination of cephalosporins and sulbactam with daptomycin against daptomycin-nonsusceptible, vancomycin-intermediate resistant Staphylococcus aureus (VISA) or heterogeneous vancomycin-intermediate S. aureus (h-VISA) isolates. The in vitro activity of daptomycin against daptomycin-nonsusceptible VISA\/h-VISA isolates after adding cephalosporins with or without sulbactam was evaluated. The MIC of daptomycin against the VISA\/h-VISA isolates was reduced after adding cephalosporins to daptomycin. Except for one VISA and two h-VISA isolates, the other VISA\/h-VISA isolates became daptomycin-susceptible (MICs \u2264 1 mg\/L). After adding sulbactam to each daptomycin\/cephalosporin combination, the MIC of daptomycin against the VISA\/h-VISA isolates decreased for 5 (33.3%), 6 (40.0%), 6 (40.0%), and 6 (40.0%) isolates with the cefazolin, cefmetazole, cefotaxime, and cefepime combinations, respectively. Synergism using the checkerboard method was noted in 100% of cefazolin and cefotaxime combinations and 87% and 80% of cefmetazole and cefepime combinations for all the VISA and h-VISA isolates. With the addition of sulbactam, synergism was noted in 100% of cefazolin, cefmetazole, and cefotaxime combinations and 93% of the cefepime combinations for all the VISA and h-VISA isolates. Almost all the FICs for the three-drug combinations were lower than those for the two-drug combinations. Using time-killing methods, a synergistic effect against five h-VISA isolates was observed. A synergistic effect of daptomycin, sulbactam, and each cephalosporin was observed for all VISA isolates. In conclusion, the activity of daptomycin against daptomycin-nonsusceptible VISA\/h-VISA isolates can be enhanced by adding cephalosporins, and partially further promoted by sulbactam.<\/jats:p>","DOI":"10.3390\/antibiotics8040184","type":"journal-article","created":{"date-parts":[[2019,10,14]],"date-time":"2019-10-14T12:14:05Z","timestamp":1571055245000},"page":"184","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["The Potential Role of Sulbactam and Cephalosporins Plus Daptomycin Against Daptomycin-Nonsusceptible VISA and H-VISA Isolates: An In Vitro Study"],"prefix":"10.3390","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6334-2388","authenticated-orcid":false,"given":"Chih-Cheng","family":"Lai","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Kaohsiung Veterans General Hospital, Tainan Branch, Tainan 71051, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chi-Chung","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medical Research; Chi Mei Medical Center; Tainan 71004, Taiwan"},{"name":"Department of Food Science, National Chiayi University, Chiayi 60004, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying-Chen","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Food Science, National Chiayi University, Chiayi 60004, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tsuey-Pin","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Health and Nutrition, Chia-Nan University of Pharmacy and Science, Tainan 71710, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung-Jui","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medicine, Chi Mei Medical Center, Tainan 71004, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bo-An","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Medicine, Chi Mei Medical Center, Tainan 71004, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien-Ming","family":"Chao","sequence":"additional","affiliation":[{"name":"Department of Intensive Care Medicine, Chi Mei Medical Center, Liouying, Tainan 73657, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yin-Ching","family":"Chuang","sequence":"additional","affiliation":[{"name":"Department of Medical Research; Chi Mei Medical Center; Tainan 71004, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung-Jen","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Health and Nutrition, Chia-Nan University of Pharmacy and Science, Tainan 71710, Taiwan"},{"name":"Department of Medicine, Chi Mei Medical Center, Tainan 71004, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,10,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1093\/cid\/cir034","article-title":"Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children: Executive summary","volume":"52","author":"Liu","year":"2011","journal-title":"Clin. 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