{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,3]],"date-time":"2026-08-03T19:45:17Z","timestamp":1785786317286,"version":"3.56.0"},"reference-count":37,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,5,17]],"date-time":"2022-05-17T00:00:00Z","timestamp":1652745600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p><jats:bold>Objective:<\/jats:bold> The aim was to evaluate the efficacy and safety of vancomycin or daptomycin (VAN\/DAP), antistaphylococcal \u03b2-lactam (ASBL), trimethoprim-sulfamethoxazole (TMP-SMX), and combination therapy of VAN\/DAP + ASBL in the management of methicillin-resistant <jats:italic>Staphylococcus<\/jats:italic> aureus (MRSA).<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Databases including PubMed, Cochrane Library, Embase database, and google scholar were searched on 1 September 2021. The randomized control trials (RCTs) and comparable clinical studies of VAN\/DAP, VAN\/DAP + ASBL, ASBL, and TMP-SMX in the management of MRSA were identified. A network meta-analysis was conducted with STATA 14.0.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> Seven RCTs and two matched cohorts with 1,048 patients were included in the analysis. The pooled results showed that VAN\/DAP + ASBL had a significantly lower rate of persistent bacteremia &amp;gt;3 days than VAN\/DAP alone [OR:0.46, 95%CI (0.26, 0.81), <jats:italic>p<\/jats:italic> &amp;lt; 0.001]. No obvious differences were observed in the outcomes of all-cause mortality, relapsed bacteremia, microbiological treatment failure, embolic or metastatic infection, and total adverse events. However, the ranking results showed that VAN\/DAP + ASBL had slightly better efficacy (all-cause mortality, persistent bacteremia &amp;gt;3\u00a0days, duration of bacteremia, microbiological treatment failure, and relapsed bacteremia) but slightly higher adverse events than VAN\/DAP alone. No obvious differences in the comparisons of VAN\/DAP vs. ASBL, and VAN\/DAP vs TMP-SMX in the analyzed outcomes. The ranking results revealed that ASBL and TMP-SMX did not have better efficacy or lower adverse events compared with the treatment of VAN\/DAP.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> The efficacy of VAN\/DAP + ASBL was slightly but not significantly better than VAN\/DAP alone in the management of MRSA.<\/jats:p>","DOI":"10.3389\/fphar.2022.805966","type":"journal-article","created":{"date-parts":[[2022,5,17]],"date-time":"2022-05-17T06:32:27Z","timestamp":1652769147000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":7,"title":["Vancomycin, Daptomycin, Antistaphylococcal \u03b2-Lactam, and Trimethoprim-Sulfamethoxazole Monotherapy and Combination Therapy in the Management of Methicillin-Resistant Staphylococcus aureus: A Network Meta-Analysis"],"prefix":"10.3389","volume":"13","author":[{"given":"Xiaonan","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ni","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pan","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingzhen","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanxiao","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zirui","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2022,5,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"325","DOI":"10.1007\/s40121-020-00292-8","article-title":"Monotherapy with Vancomycin or Daptomycin versus Combination Therapy with \u03b2-Lactams in the Treatment of Methicillin-Resistant Staphylococcus Aureus Bloodstream Infections: A Retrospective Cohort Analysis","volume":"9","author":"Alosaimy","year":"2020","journal-title":"Infect. Dis. Ther."},{"key":"B2","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.ijid.2017.01.019","article-title":"Ceftaroline Fosamil Monotherapy for Methicillin-Resistant Staphylococcus Aureus Bacteremia: A Comparative Clinical Outcomes Study","volume":"57","author":"Arshad","year":"2017","journal-title":"Int. J. Infect. Dis."},{"key":"B3","doi-asserted-by":"publisher","first-page":"Jc67","DOI":"10.7326\/acpj202006160-067","article-title":"In MRSA Bacteremia, Adding a \u03b2-lactam to Usual Care Did Not Improve a Composite Outcome at 90 Days","volume":"172","author":"Atalla","year":"2020","journal-title":"Ann. Intern. Med."},{"key":"B4","doi-asserted-by":"publisher","first-page":"889","DOI":"10.1089\/mdr.2020.0259","article-title":"What Is Driving the Epidemiology of Methicillin-Resistant Staphylococcus Aureus Infections in Europe?","volume":"27","author":"Borg","year":"2021","journal-title":"Microb. Drug Resist."},{"key":"B5","doi-asserted-by":"publisher","first-page":"1587","DOI":"10.1345\/aph.1R211","article-title":"Treatment of Methicillin-Resistant Staphylococcus aureus Infections with a Minimal Inhibitory Concentration of 2 \u03bcg\/mL to Vancomycin: Old (Trimethoprim\/sulfamethoxazole) versus New (Daptomycin or Linezolid) Agents","volume":"46","author":"Campbell","year":"2012","journal-title":"Ann. Pharmacother."},{"key":"B6","doi-asserted-by":"publisher","first-page":"130","DOI":"10.7326\/0003-4819-159-2-201307160-00008","article-title":"Conceptual and Technical Challenges in Network Meta-Analysis","volume":"159","author":"Cipriani","year":"2013","journal-title":"Ann. Intern. Med."},{"key":"B7","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1093\/cid\/civ808","article-title":"Combination of Vancomycin and \u03b2-Lactam Therapy for Methicillin-Resistant Staphylococcus aureus Bacteremia: A Pilot Multicenter Randomized Controlled Trial","volume":"62","author":"Davis","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"B8","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1128\/AAC.01204-13","article-title":"\u03b2-Lactams Enhance Vancomycin Activity against Methicillin-Resistant Staphylococcus aureus Bacteremia Compared to Vancomycin Alone","volume":"58","author":"Dilworth","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"B9","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1093\/jac\/dki294","article-title":"Experimental Study on the Efficacy of Combinations of Glycopeptides and Beta-Lactams against Staphylococcus Aureus with Reduced Susceptibility to Glycopeptides","volume":"56","author":"Domenech","year":"2005","journal-title":"J. Antimicrob. Chemother."},{"key":"B10","doi-asserted-by":"publisher","first-page":"882","DOI":"10.1093\/jac\/dkw510","article-title":"Trimethoprim\/Sulfamethoxazole versus Vancomycin in the Treatment of Healthcare\/Ventilator-Associated Mrsa Pneumonia: A Case-Control Study","volume":"72","author":"Eliakim-Raz","year":"2017","journal-title":"J. Antimicrob. Chemother."},{"key":"B11","doi-asserted-by":"publisher","first-page":"797","DOI":"10.1093\/jac\/dku455","article-title":"Ceftaroline Fosamil Salvage Therapy: An Option for Reduced-Vancomycin-Susceptible Mrsa Bacteraemia","volume":"70","author":"Espedido","year":"2015","journal-title":"J. Antimicrob. Chemother."},{"key":"B12","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1056\/NEJMoa053783","article-title":"Daptomycin versus Standard Therapy for Bacteremia and Endocarditis Caused by Staphylococcus Aureus","volume":"355","author":"Fowler","year":"2006","journal-title":"N. Engl. J. Med."},{"key":"B13","doi-asserted-by":"publisher","first-page":"2951","DOI":"10.1128\/aac.00232-06","article-title":"Successful Therapy of Experimental Endocarditis Caused by Vancomycin-Resistant Staphylococcus Aureus with a Combination of Vancomycin and Beta-Lactam Antibiotics","volume":"50","author":"Fox","year":"2006","journal-title":"Antimicrob. Agents Chemother."},{"key":"B14","doi-asserted-by":"publisher","first-page":"63","DOI":"10.1128\/AAC.02483-18","article-title":"Clinical Data on Daptomycin Plus Ceftaroline versus Standard of Care Monotherapy in the Treatment of Methicillin-Resistant Staphylococcus Aureus Bacteremia","volume":"63","author":"Geriak","year":"2019","journal-title":"Antimicrob. Agents Chemother."},{"key":"B15","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1128\/aac.05473-11","article-title":"In Vitro pharmacodynamics of Vancomycin and Cefazolin Alone and in Combination against Methicillin-Resistant Staphylococcus aureus","volume":"56","author":"Hagihara","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"B16","doi-asserted-by":"publisher","first-page":"35","DOI":"10.2217\/fmb-2019-0332","article-title":"Ceftobiprole versus Daptomycin in Staphylococcus aureus Bacteremia: a Novel Protocol for a Double-Blind, Phase III Trial","volume":"15","author":"Hamed","year":"2020","journal-title":"Future Microbiol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"211","DOI":"10.1186\/s13054-017-1801-3","article-title":"Incidence, Prevalence, and Management of Mrsa Bacteremia across Patient Populations-A Review of Recent Developments in Mrsa Management and Treatment","volume":"21","author":"Hassoun","year":"2017","journal-title":"Crit. Care"},{"key":"B18","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1055\/s-0034-1397040","article-title":"Treatment of Methicillin-Resistant Staphylococcus Aureus: Vancomycin and beyond","volume":"36","author":"Holmes","year":"2015","journal-title":"Semin. Respir. Crit. Care Med."},{"key":"B19","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1016\/j.idc.2020.04.003","article-title":"Bacteremia Due to Methicillin-Resistant Staphylococcus Aureus: An Update on New Therapeutic Approaches","volume":"34","author":"Holubar","year":"2020","journal-title":"Infect. Dis. Clin. North. Am."},{"key":"B20","doi-asserted-by":"publisher","first-page":"106310","DOI":"10.1016\/j.ijantimicag.2021.106310","article-title":"Combination Ceftaroline and Daptomycin Salvage Therapy for Complicated Methicillin-Resistant Staphylococcus Aureus Bacteraemia Compared with Standard of Care","volume":"57","author":"Johnson","year":"2021","journal-title":"Int. J. Antimicrob. Agents"},{"key":"B21","doi-asserted-by":"publisher","first-page":"18033","DOI":"10.1038\/nrdp.2018.33","article-title":"Methicillin-Resistant Staphylococcus Aureus","volume":"4","author":"Lee","year":"2018","journal-title":"Nat. Rev. Dis. Primers"},{"key":"B22","doi-asserted-by":"publisher","first-page":"e18","DOI":"10.1093\/cid\/ciq146","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","volume":"52","author":"Liu","year":"2011","journal-title":"Clin. Infect. Dis."},{"key":"B23","doi-asserted-by":"publisher","first-page":"ofz538","DOI":"10.1093\/ofid\/ofz538","article-title":"Multicenter Cohort of Patients with Methicillin-Resistant Staphylococcus aureus Bacteremia Receiving Daptomycin Plus Ceftaroline Compared with Other MRSA Treatments","volume":"7","author":"McCreary","year":"2020","journal-title":"Open Forum Infect. Dis."},{"key":"B24","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1016\/j.drup.2013.10.002","article-title":"Reduced Glycopeptide and Lipopeptide Susceptibility in Staphylococcus Aureus and the \"Seesaw Effect\": Taking Advantage of the Back Door Left Open?","volume":"16","author":"Ortwine","year":"2013","journal-title":"Drug Resist. Updat"},{"key":"B25","doi-asserted-by":"publisher","first-page":"n71","DOI":"10.1136\/bmj.n71","article-title":"The Prisma 2020 Statement: An Updated Guideline for Reporting Systematic Reviews","volume":"372","author":"Page","year":"2021","journal-title":"BMJ"},{"key":"B26","doi-asserted-by":"publisher","first-page":"h2219","DOI":"10.1136\/bmj.h2219","article-title":"Trimethoprim-Sulfamethoxazole versus Vancomycin for Severe Infections Caused by Meticillin Resistant Staphylococcus Aureus: Randomised Controlled Trial","volume":"350","author":"Paul","year":"2015","journal-title":"BMJ"},{"key":"B27","doi-asserted-by":"publisher","first-page":"577","DOI":"10.1146\/annurev-biochem-060614-034516","article-title":"Mechanisms of Methicillin Resistance in Staphylococcus Aureus","volume":"84","author":"Peacock","year":"2015","journal-title":"Annu. Rev. Biochem."},{"key":"B28","doi-asserted-by":"publisher","first-page":"673","DOI":"10.1016\/j.cmi.2018.01.010","article-title":"Efficacy and Safety of Fosfomycin Plus Imipenem versus Vancomycin for Complicated Bacteraemia and Endocarditis Due to Methicillin-Resistant Staphylococcus Aureus: A Randomized Clinical Trial","volume":"24","author":"Peric\u00e0s","year":"2018","journal-title":"Clin. Microbiol. Infect."},{"key":"B29","doi-asserted-by":"publisher","first-page":"S35","DOI":"10.1086\/491712","article-title":"The Pharmacokinetic and Pharmacodynamic Properties of Vancomycin","volume":"42","author":"Rybak","year":"2006","journal-title":"Clin. Infect. Dis."},{"key":"B30","doi-asserted-by":"publisher","first-page":"2053","DOI":"10.1093\/jac\/dkv076","article-title":"Activity of Ceftaroline and Comparator Agents Tested against Staphylococcus Aureus from Patients with Bloodstream Infections in Us Medical Centres (2009-13)","volume":"70","author":"Sader","year":"2015","journal-title":"J. Antimicrob. Chemother."},{"key":"B31","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1039\/c6md00585c","article-title":"A Review on Cell Wall Synthesis Inhibitors with an Emphasis on Glycopeptide Antibiotics","volume":"8","author":"Sarkar","year":"2017","journal-title":"Medchemcomm"},{"key":"B32","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1089\/mdr.2015.0226","article-title":"Comparative Fitness and Determinants for the Characteristic Drug Resistance of St239-Mrsa-Iii-T030 and St239-Mrsa-Iii-T037 Strains Isolated in China","volume":"22","author":"Shang","year":"2016","journal-title":"Microb. Drug Resist."},{"key":"B33","doi-asserted-by":"publisher","first-page":"143","DOI":"10.1016\/j.ijantimicag.2019.06.006","article-title":"High-Dose Trimethoprim-Sulfamethoxazole and Clindamycin for Staphylococcus Aureus Endocarditis","volume":"54","author":"Tissot-Dupont","year":"2019","journal-title":"Int. J. Antimicrob. Agents"},{"key":"B34","doi-asserted-by":"publisher","first-page":"527","DOI":"10.1001\/jama.2020.0103","article-title":"Effect of Vancomycin or Daptomycin with vs without an Antistaphylococcal \u03b2-Lactam on Mortality, Bacteremia, Relapse, or Treatment Failure in Patients with MRSA Bacteremia: A Randomized Clinical Trial","volume":"323","author":"Tong","year":"2020","journal-title":"JAMA"},{"key":"B35","doi-asserted-by":"publisher","first-page":"1413","DOI":"10.1093\/cid\/ciz995","article-title":"Cefazolin and Ertapenem Salvage Therapy Rapidly Clears Persistent Methicillin-Susceptible Staphylococcus Aureus Bacteremia","volume":"71","author":"Ulloa","year":"2020","journal-title":"Clin. Infect. Dis."},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1128\/microbiolspec.GPP3-0057-2018","article-title":"Antibiotic Resistance and the Mrsa Problem","volume":"7","author":"Vestergaard","year":"2019","journal-title":"Microbiol. Spectr."},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1128\/aac.01377-20","article-title":"Adjuvant \u03b2-Lactam Therapy Combined with Vancomycin or Daptomycin for Methicillin-Resistant Staphylococcus aureus Bacteremia: a Systematic Review and Meta-Analysis","volume":"64","author":"Wang","year":"2020","journal-title":"Antimicrob. Agents Chemother."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.805966\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,5,17]],"date-time":"2022-05-17T06:32:29Z","timestamp":1652769149000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2022.805966\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,17]]},"references-count":37,"alternative-id":["10.3389\/fphar.2022.805966"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2022.805966","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,5,17]]},"article-number":"805966"}}