{"doi":"10.1128/aac.00157-18","title":"β-Lactam Combinations with Vancomycin Show Synergistic Activity against Vancomycin-Susceptible Staphylococcus aureus, Vancomycin-Intermediate S. aureus (VISA), and Heterogeneous VISA","abstract":"<jats:title>ABSTRACT</jats:title>\n          <jats:p>\n            Increasing utilization of vancomycin due to the high prevalence of methicillin-resistant\n            <jats:named-content content-type=\"genus-species\">Staphylococcus aureus</jats:named-content>\n            (MRSA) infections has led to the emergence of vancomycin-intermediate\n            <jats:named-content content-type=\"genus-species\">S. aureus</jats:named-content>\n            (VISA) and heterogeneous VISA (hVISA) strains.\n            <jats:italic>In vitro</jats:italic>\n            data suggest the potential for potent synergy between several beta-lactams and vancomycin. The objective of this study is to evaluate the synergy between beta-lactams and vancomycin against MRSA that is vancomycin susceptible, vancomycin-susceptible\n            <jats:named-content content-type=\"genus-species\">Staphylococcus aureus</jats:named-content>\n            (VSSA), hVISA, and VISA. Fifty randomly selected clinical MRSA strains with various susceptibility levels to vancomycin were evaluated for vancomycin alone and vancomycin in combination with various concentrations of cefazolin (CFZ), cefepime (FEP), ceftaroline (CPT), and nafcillin (NAF). The potential for synergy was assessed by 24-h time-kill studies. Beta-lactams reduced vancomycin MIC values against all strains (4- to 16-fold reduction). In time-kill studies against MRSA, CFZ, FEP, CPT, and NAF all demonstrated similar degrees of killing at 24 h, and all showed synergistic activity with vancomycin against VSSA, hVISA, and VISA. Each of these combinations was also superior to any single agent against isolates of all three phenotypes, and each was bactericidal (\n            <jats:italic>P</jats:italic>\n            &lt; 0.001 for all comparisons). All single-agent exposures demonstrated no activity at 24 h. The combination of vancomycin and beta-lactams significantly improved antibacterial activity against VSSA, hVISA, and VISA strains compared to the activity of any agent alone, supporting the potential use of vancomycin–beta-lactam combination therapy in infections caused by MRSA. Further clinical research is warranted to investigate the synergy of vancomycin against these\n            <jats:named-content content-type=\"genus-species\">Staphylococcus</jats:named-content>\n            strains.\n          </jats:p>","journal":"Antimicrobial Agents and Chemotherapy","year":2018,"id":643355,"datarank":0.586803450814222,"base_score":3.912023005428146,"endowment":3.912023005428146,"self_citation_contribution":0.586803450814222,"citation_network_contribution":0.0,"self_endowment_contribution":0.586803450814222,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":49,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":348336,"name":"Michael J. Rybak","orcid":"0000-0003-2220-0081","position":1,"is_corresponding":false},{"id":1673911,"name":"Nikki Tran","orcid":"0000-0002-4199-7375","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"β-Lactam Combinations with Vancomycin Show Synergistic Activity against Vancomycin-Susceptible Staphylococcus aureus, Vancomycin-Intermediate S. aureus (VISA), and Heterogeneous VISA","abstract":"<jats:title>ABSTRACT</jats:title>\n          <jats:p>\n            Increasing utilization of vancomycin due to the high prevalence of methicillin-resistant\n            <jats:named-content content-type=\"genus-species\">Staphylococcus aureus</jats:named-content>\n            (MRSA) infections has led to the emergence of vancomycin-intermediate\n            <jats:named-content content-type=\"genus-species\">S. aureus</jats:named-content>\n            (VISA) and heterogeneous VISA (hVISA) strains.\n            <jats:italic>In vitro</jats:italic>\n            data suggest the potential for potent synergy between several beta-lactams and vancomycin. The objective of this study is to evaluate the synergy between beta-lactams and vancomycin against MRSA that is vancomycin susceptible, vancomycin-susceptible\n            <jats:named-content content-type=\"genus-species\">Staphylococcus aureus</jats:named-content>\n            (VSSA), hVISA, and VISA. Fifty randomly selected clinical MRSA strains with various susceptibility levels to vancomycin were evaluated for vancomycin alone and vancomycin in combination with various concentrations of cefazolin (CFZ), cefepime (FEP), ceftaroline (CPT), and nafcillin (NAF). The potential for synergy was assessed by 24-h time-kill studies. Beta-lactams reduced vancomycin MIC values against all strains (4- to 16-fold reduction). In time-kill studies against MRSA, CFZ, FEP, CPT, and NAF all demonstrated similar degrees of killing at 24 h, and all showed synergistic activity with vancomycin against VSSA, hVISA, and VISA. Each of these combinations was also superior to any single agent against isolates of all three phenotypes, and each was bactericidal (\n            <jats:italic>P</jats:italic>\n            &lt; 0.001 for all comparisons). All single-agent exposures demonstrated no activity at 24 h. The combination of vancomycin and beta-lactams significantly improved antibacterial activity against VSSA, hVISA, and VISA strains compared to the activity of any agent alone, supporting the potential use of vancomycin–beta-lactam combination therapy in infections caused by MRSA. Further clinical research is warranted to investigate the synergy of vancomycin against these\n            <jats:named-content content-type=\"genus-species\">Staphylococcus</jats:named-content>\n            strains.\n          </jats:p>","is_dataset_classified":null,"base_score":3.912023005428146,"endowment":3.912023005428146,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"29555635","pmcid":"PMC5971571","openalex_id":"https://openalex.org/W2793624603","authors":[],"funders":[{"funder_name":"NIAID NIH HHS","grant_id":"R01 AI121400","title":null}],"total_grants":1,"fwci":4.4176,"citation_percentile":0.95433471,"influential_citations":0,"citation_trend":[{"year":2018,"count":4},{"year":2019,"count":6},{"year":2020,"count":15},{"year":2021,"count":6},{"year":2022,"count":4},{"year":2023,"count":6},{"year":2024,"count":3},{"year":2025,"count":2},{"year":2026,"count":3}],"oa_status":"bronze","license":"https://journals.asm.org/non-commercial-tdm-license","oa_locations":[{"url":"https://aac.asm.org/content/aac/62/6/e00157-18.full.pdf","host_type":"journal"},{"url":"https://aac.asm.org/content/aac/62/6/e00157-18.full.pdf","host_type":"publisher"},{"url":"https://journals.asm.org/doi/pdf/10.1128/AAC.00157-18","host_type":"publisher"},{"url":"https://doi.org/10.1128/aac.00157-18","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/29555635","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/5971571","host_type":"repository"}],"fields_of_study":["Antimicrobial Resistance in Staphylococcus","Bacterial Identification and Susceptibility Testing","Antibiotics Pharmacokinetics and Efficacy","Cefazolin","Cefepime","Cephalosporins","Drug Synergism","Drug Therapy, Combination","Humans","Methicillin-Resistant Staphylococcus aureus","Microbial Sensitivity Tests","Nafcillin","Staphylococcal Infections","Vancomycin","beta-Lactams","Ceftaroline"],"mesh_terms":["Cefepime","Ceftaroline","Cefazolin","Cephalosporins","Drug Synergism","Drug Therapy, Combination","Humans","Microbial Sensitivity Tests","Nafcillin","Staphylococcal Infections","Vancomycin","beta-Lactams","Methicillin-Resistant Staphylococcus aureus"],"keywords":["Vancomycin","Staphylococcus aureus","Microbiology","Cefazolin","Methicillin-resistant Staphylococcus aureus","Nafcillin","Medicine","Antibiotics","Biology","Bacteria","Penicillin","Infection","In vitro","Combination therapy","MRSA","cefepime","Ceftaroline","Time Kill"],"sdg_mappings":[{"sdg_number":0,"sdg_label":"Good health and well-being"}],"linked_datasets":[],"clinical_trials":[],"software_tools":[],"database_accessions":[],"source":"live","citation_network_status":"fetched"},"created_at":"2026-08-08T16:01:20.857477Z","pmid":null,"pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}