{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T22:20:27Z","timestamp":1792189227979,"version":"4.4.0"},"reference-count":49,"publisher":"American Society for Microbiology","issue":"12","license":[{"start":{"date-parts":[[2012,12,1]],"date-time":"2012-12-01T00:00:00Z","timestamp":1354320000000},"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":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2012,12]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Methicillin-resistant\n                    <jats:named-content xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" content-type=\"genus-species\" xlink:type=\"simple\">Staphylococcus aureus<\/jats:named-content>\n                    (MRSA) has emerged to be one of the most important pathogens both in health care and in community-onset infections. Daptomycin (DAP) is a cyclic anionic lipopeptide recommended for treatment of skin infections, bacteremia, and right-sided endocarditis caused by MRSA. Resistance to DAP (DAP\n                    <jats:sup>r<\/jats:sup>\n                    ) has been reported in MRSA and is mostly accompanied by a parallel decrease in oxacillin resistance, a process known as the \u201cseesaw effect.\u201d Our study provides evidence that the seesaw effect applies to other \u03b2-lactams and carbapenems of clinical use, including nafcillin (NAF), cefotaxime (CTX), amoxicillin-clavulanic (AMC), and imipenem (IMP), in heterogeneous DAP\n                    <jats:sup>r<\/jats:sup>\n                    MRSA strains but not in MRSA strains expressing homogeneous \u03b2-lactam resistance. The antibacterial efficacy of DAP in combination with \u03b2-lactams was evaluated in isogenic DAP-susceptible (DAP\n                    <jats:sup>s<\/jats:sup>\n                    )\/Dap\n                    <jats:sup>r<\/jats:sup>\n                    MRSA strains originally obtained from patients that failed DAP monotherapy. Both\n                    <jats:italic>in vitro<\/jats:italic>\n                    (MIC, synergy-kill curve) and\n                    <jats:italic>in vivo<\/jats:italic>\n                    (wax worm model) approaches were used. In these models, DAP and a \u03b2-lactam proved to be highly synergistic against both heterogeneous and homogeneous clinical DAP\n                    <jats:sup>r<\/jats:sup>\n                    MRSA strains. Mechanistically, \u03b2-lactams induced a reduction in the cell net positive surface charge, reverting the increased repulsion provoked by DAP alone, an effect that may favor the binding of DAP to the cell surface. The ease of\n                    <jats:italic>in vitro<\/jats:italic>\n                    mutant selection was observed when DAP\n                    <jats:sup>s<\/jats:sup>\n                    MRSA strains were exposed to DAP. Importantly, the combination of DAP and a \u03b2-lactam prevented the selection of DAP\n                    <jats:sup>r<\/jats:sup>\n                    variants. In summary, our data show that the DAP\u2013\u03b2-lactam combination may significantly enhance both the\n                    <jats:italic>in vitro<\/jats:italic>\n                    and\n                    <jats:italic>in vivo<\/jats:italic>\n                    efficacy of anti-MRSA therapeutic options against DAP\n                    <jats:sup>r<\/jats:sup>\n                    MRSA infections and represent an option in preventing DAP\n                    <jats:sup>r<\/jats:sup>\n                    selection in persistent or refractory MRSA infections.\n                  <\/jats:p>","DOI":"10.1128\/aac.01525-12","type":"journal-article","created":{"date-parts":[[2012,9,18]],"date-time":"2012-09-18T01:02:59Z","timestamp":1347930179000},"page":"6192-6200","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":133,"title":["\u03b2-Lactams Increase the Antibacterial Activity of Daptomycin against Clinical Methicillin-Resistant Staphylococcus aureus Strains and Prevent Selection of Daptomycin-Resistant Derivatives"],"prefix":"10.1128","volume":"56","author":[{"given":"Shrenik","family":"Mehta","sequence":"first","affiliation":[{"name":"Department of Pathology and Genomic Medicine, Center for Molecular and Translational Human Infectious Diseases Research, The Methodist Hospital Research Institute, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher","family":"Singh","sequence":"additional","affiliation":[{"name":"Department of Pathology and Genomic Medicine, Center for Molecular and Translational Human Infectious Diseases Research, The Methodist Hospital Research Institute, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Konrad B.","family":"Plata","sequence":"additional","affiliation":[{"name":"Department of Pathology and Genomic Medicine, Center for Molecular and Translational Human Infectious Diseases Research, The Methodist Hospital Research Institute, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Palas K.","family":"Chanda","sequence":"additional","affiliation":[{"name":"Department of Pathology and Genomic Medicine, Center for Molecular and Translational Human Infectious Diseases Research, The Methodist Hospital Research Institute, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arundhati","family":"Paul","sequence":"additional","affiliation":[{"name":"Department of Pathology and Genomic Medicine, Center for Molecular and Translational Human Infectious Diseases Research, The Methodist Hospital Research Institute, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarah","family":"Riosa","sequence":"additional","affiliation":[{"name":"Department of Pathology and Genomic Medicine, Center for Molecular and Translational Human Infectious Diseases Research, The Methodist Hospital Research Institute, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto R.","family":"Rosato","sequence":"additional","affiliation":[{"name":"Department of Pathology and Genomic Medicine, Center for Molecular and Translational Human Infectious Diseases Research, The Methodist Hospital Research Institute, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adriana E.","family":"Rosato","sequence":"additional","affiliation":[{"name":"Department of Pathology and Genomic Medicine, Center for Molecular and Translational Human Infectious Diseases Research, The Methodist Hospital Research Institute, Houston, Texas, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.45.2.454-459.2001"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1086\/420818"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpa.2009.02.031"},{"key":"e_1_3_3_5_2","doi-asserted-by":"publisher","DOI":"10.1039\/b416648p"},{"key":"e_1_3_3_6_2","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.33.3.551-555.1995"},{"key":"e_1_3_3_7_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00247-06"},{"key":"e_1_3_3_8_2","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkp164"},{"key":"e_1_3_3_9_2","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1016\/j.hrtlng.2007.02.012","article-title":"E. faecalis vancomycin-sensitive enterococcal bacteremia unresponsive to a vancomycin tolerant strain successfully treated with high-dose daptomycin","volume":"36","author":"Cunha BA","year":"2007","unstructured":"CunhaBA MickailN EisensteinL. 2007. 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