{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T11:15:40Z","timestamp":1788434140125,"version":"build-2803163510"},"reference-count":98,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T00:00:00Z","timestamp":1788393600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"University of Medicine and Pharmacy Carol Davila"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Antimicrobial resistance is now documented in a substantial proportion of laboratory-confirmed bacterial infections worldwide, and although the most extreme extensively drug-resistant (XDR) and pandrug-resistant (PDR) phenotypes are concentrated among Gram-negative bacilli, resistance in Gram-positive cocci continues to rise and remains a major determinant of outcomes in severe infection. This structured comprehensive narrative review, based on a documented search of PubMed\/MEDLINE, Scopus and Web of Science to June 2026, is confined to the three Gram-positive cocci of greatest clinical importance\u2014Staphylococcus aureus, Streptococcus pneumoniae and Enterococcus faecium\u2014and summarises current global and European surveillance data for this organisms, describes the principal molecular mechanisms responsible for resistance to \u03b2-lactams, glycopeptides, fluoroquinolones, oxazolidinones, lipopeptides, tetracyclines, folate-pathway inhibitors, macrolides\u2013lincosamides\u2013streptogramins and aminoglycosides, and reviews the therapeutic options and investigational agents that may extend the treatment repertoire against multidrug-resistant (MDR) Gram-positive cocci. Surveillance indicators for the three species are compared side by side, and the agents discussed are separated according to whether they are licensed, clinically evaluated but not widely licensed, or still preclinical. Its scope is deliberately narrower than that of pan-bacterial accounts of antimicrobial resistance: it concentrates on the determinants that routine molecular confirmation does not detect, on the divergent pathogen-specific trajectories visible in recent surveillance, and on the distinction between agents supported by randomised evidence and those still at the discovery stage. Our review is structured rather than systematic; the PRISMA 2020 flow diagram is used as a reporting template only, and no claim of PRISMA compliance is made.<\/jats:p>","DOI":"10.3390\/microorganisms14091951","type":"journal-article","created":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T10:10:33Z","timestamp":1788430233000},"page":"1951","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Epidemiology of Infections Caused by Gram-Positive Cocci\u2014Staphylococcus aureus, Streptococcus pneumoniae and Enterococcus faecium: Antibiotic Resistance and Future Prospects"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7391-3394","authenticated-orcid":false,"given":"Victoria","family":"Birlutiu","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Lucian Blaga University of Sibiu, Str. Lucian Blaga, Nr. 2A, 550169 Sibiu, Romania"},{"name":"County Clinical Emergency Hospital, Bvd Corneliu Coposu, Nr. 2\u20134, 550245 Sibiu, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7400-2904","authenticated-orcid":false,"given":"Rares-Mircea","family":"Birlutiu","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, The \u201cCarol Davila\u201d University of Medicine and Pharmacy, 050474 Bucharest, Romania"},{"name":"\u201cFoisor\u201d Clinical Hospital of Orthopaedics, Traumatology and Osteoarticular TB, 021382 Bucharest, Romania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,3]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2025). Global Antibiotic Resistance Surveillance Report 2025, World Health Organization."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Birlutiu, V., and Birlutiu, R.-M. (2025). An Overview of the Epidemiology of Multidrug Resistance and Bacterial Resistance Mechanisms: What Solutions Are Available? A Comprehensive Review. Microorganisms, 13.","DOI":"10.3390\/microorganisms13092194"},{"key":"ref_3","doi-asserted-by":"crossref","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":"ref_4","doi-asserted-by":"crossref","unstructured":"Birlutiu, V., Ciprian Ion, O., and Birlutiu, R.-M. (2026). Susceptibility of Staphylococcus aureus Strains Isolated from Blood Cultures Between 2024 and 2025: A Single-Center Study. Antibiotics, 15.","DOI":"10.3390\/antibiotics15070695"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2221","DOI":"10.1016\/S0140-6736(22)02185-7","article-title":"Global Mortality Associated with 33 Bacterial Pathogens in 2019: A Systematic Analysis for the Global Burden of Disease Study 2019","volume":"400","author":"Ikuta","year":"2022","journal-title":"Lancet"},{"key":"ref_6","unstructured":"World Health Organization (2024). WHO Bacterial Priority Pathogens List, 2024: Bacterial Pathogens of Public Health Importance to Guide Research, Development and Strategies to Prevent and Control Antimicrobial Resistance, World Health Organization."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1033","DOI":"10.1016\/S1473-3099(25)00118-5","article-title":"The WHO Bacterial Priority Pathogens List 2024: A Prioritisation Study to Guide Research, Development, and Public Health Strategies against Antimicrobial Resistance","volume":"25","author":"Sati","year":"2025","journal-title":"Lancet Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1038\/s43856-025-01243-5","article-title":"Third-Generation Cephalosporin Resistance in Sub-Saharan Africa: A Systematic Review and Meta-Analysis","volume":"6","author":"Guido","year":"2025","journal-title":"Commun. Med."},{"key":"ref_9","unstructured":"World Health Organization (2022). The WHO AWaRe (Access, Watch, Reserve) Antibiotic Book, World Health Organization."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1199","DOI":"10.1016\/S0140-6736(24)01867-1","article-title":"Global Burden of Bacterial Antimicrobial Resistance 1990\u20132021: A Systematic Analysis with Forecasts to 2050","volume":"404","author":"Naghavi","year":"2024","journal-title":"Lancet"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1111\/j.1469-0691.2012.03903.x","article-title":"The Changing Epidemiology of Staphylococcus aureus Bloodstream Infection: A Multinational Population-Based Surveillance Study","volume":"19","author":"Laupland","year":"2013","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_12","unstructured":"European Centre for Disease Prevention and Control (2025). Antimicrobial Resistance in the EU\/EEA (EARS-Net)\u2014Annual Epidemiological Report for 2024."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"395","DOI":"10.2217\/fmb.12.2","article-title":"Molecular Mechanisms of \u03b2-Lactam Resistance in Streptococcus pneumoniae","volume":"7","author":"Hakenbeck","year":"2012","journal-title":"Future Microbiol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1367","DOI":"10.1099\/jmm.0.000585","article-title":"Borderline Oxacillin-Resistant Staphylococcus aureus (BORSA)\u2014A More Common Problem than Expected?","volume":"66","author":"Hryniewicz","year":"2017","journal-title":"J. Med. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"323","DOI":"10.2217\/17460913.2.3.323","article-title":"Mechanisms of Antibiotic Resistance in Staphylococcus aureus","volume":"2","author":"Pantosti","year":"2007","journal-title":"Future Microbiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"9865","DOI":"10.1073\/pnas.161272898","article-title":"The Evolution of Methicillin Resistance in Staphylococcus aureus: Similarity of Genetic Backgrounds in Historically Early Methicillin-Susceptible and -Resistant Isolates and Contemporary Epidemic Clones","volume":"98","author":"Westh","year":"2001","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2497","DOI":"10.2147\/IDR.S175967","article-title":"Methicillin-Resistant Staphylococcus aureus: Livestock-Associated, Antimicrobial, and Heavy Metal Resistance","volume":"11","author":"Dweba","year":"2018","journal-title":"Infect. Drug Resist."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4352","DOI":"10.1128\/AAC.00356-10","article-title":"Origin and Molecular Evolution of the Determinant of Methicillin Resistance in Staphylococci","volume":"54","author":"Tsubakishita","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1527","DOI":"10.2174\/138955709790361557","article-title":"Mechanisms of the Resistance and Tolerance to Beta-Lactam and Glycopeptide Antibiotics in Pathogenic Gram-Positive Cocci","volume":"9","author":"Mlynarczyk","year":"2009","journal-title":"Mini-Rev. Med. Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/S1473-3099(11)70126-8","article-title":"Meticillin-Resistant Staphylococcus aureus with a Novel MecA Homologue in Human and Bovine Populations in the UK and Denmark: A Descriptive Study","volume":"11","author":"Holden","year":"2011","journal-title":"Lancet Infect. Dis."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"242","DOI":"10.3201\/eid2402.171074","article-title":"Plasmid-Encoded Transferable MecB-Mediated Methicillin Resistance in Staphylococcus aureus","volume":"24","author":"Becker","year":"2018","journal-title":"Emerg. Infect. Dis."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"428","DOI":"10.1128\/AAC.50.2.428-438.2006","article-title":"Novel Mechanism of Antibiotic Resistance Originating in Vancomycin-Intermediate Staphylococcus aureus","volume":"50","author":"Cui","year":"2006","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"2557","DOI":"10.1128\/jb.179.8.2557-2566.1997","article-title":"Inhibition of Cell Wall Turnover and Autolysis by Vancomycin in a Highly Vancomycin-Resistant Mutant of Staphylococcus aureus","volume":"179","author":"Sieradzki","year":"1997","journal-title":"J. Bacteriol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1128\/CMR.00042-09","article-title":"Reduced Vancomycin Susceptibility in Staphylococcus aureus, Including Vancomycin-Intermediate and Heterogeneous Vancomycin-Intermediate Strains: Resistance Mechanisms, Laboratory Detection, and Clinical Implications","volume":"23","author":"Howden","year":"2010","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"781679","DOI":"10.1155\/2012\/781679","article-title":"Glycopeptide Resistance in Gram-Positive Cocci: A Review","volume":"2012","author":"Sujatha","year":"2012","journal-title":"Interdiscip. Perspect. Infect. Dis."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1078\/1438-4221-00185","article-title":"Resistance Mechanisms of Gram-Positive Bacteria","volume":"292","year":"2002","journal-title":"Int. J. Med. Microbiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1007\/s101560070010","article-title":"Mechanism of Quinolone Resistance in Staphylococcus aureus","volume":"6","author":"Tanaka","year":"2000","journal-title":"J. Infect. Chemother."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"2128","DOI":"10.1093\/nar\/gkac058","article-title":"Sal-Type ABC-F Proteins: Intrinsic and Common Mediators of Pleuromutilin Resistance by Target Protection in Staphylococci","volume":"50","author":"Mohamad","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e0018820","DOI":"10.1128\/CMR.00188-20","article-title":"Mobile Oxazolidinone Resistance Genes in Gram-Positive and Gram-Negative Bacteria","volume":"34","author":"Schwarz","year":"2021","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"430","DOI":"10.1093\/femsre\/fux007","article-title":"Antibiotic Resistance in Staphylococcus aureus. Current Status and Future Prospects","volume":"41","author":"Foster","year":"2017","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"a026997","DOI":"10.1101\/cshperspect.a026997","article-title":"Mechanism of Action and Resistance to Daptomycin in Staphylococcus aureus and Enterococci","volume":"6","author":"Miller","year":"2016","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1111\/j.1749-6632.2012.06819.x","article-title":"Mechanisms of Daptomycin Resistance in Staphylococcus aureus: Role of the Cell Membrane and Cell Wall","volume":"1277","author":"Bayer","year":"2013","journal-title":"Ann. N. Y. Acad. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/j.femsle.2005.02.034","article-title":"Update on Acquired Tetracycline Resistance Genes","volume":"245","author":"Roberts","year":"2005","journal-title":"FEMS Microbiol. Lett."},{"key":"ref_34","first-page":"76","article-title":"Distribution of Genes Encoding Tetracycline Resistance and Aminoglycoside Modifying Enzymes in Staphylococcus aureus Strains Isolated from a Burn Center","volume":"26","author":"Emaneini","year":"2013","journal-title":"Ann. Burn. Fire Disasters"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"16900","DOI":"10.1073\/pnas.1208037109","article-title":"Structural Basis for TetM-Mediated Tetracycline Resistance","volume":"109","author":"Franckenberg","year":"2012","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"161","DOI":"10.1111\/j.1365-2958.1989.tb01805.x","article-title":"Trimethoprim Resistance Transposon Tn 4003 from Staphylococcus aureus Encodes Genes for a Dihydrofolate Reductase and Thymidylate Synthetase Flanked by Three Copies of IS 257","volume":"3","author":"Rouch","year":"1989","journal-title":"Mol. Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1705","DOI":"10.1016\/j.str.2004.07.011","article-title":"Crystal Structure of 7,8-Dihydropteroate Synthase from Bacillus Anthracis","volume":"12","author":"Babaoglu","year":"2004","journal-title":"Structure"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"025","DOI":"10.4103\/0974-2727.78558","article-title":"Inducible Clindamycin Resistance in Staphylococcus aureus Isolated from Clinical Samples","volume":"3","author":"Prabhu","year":"2011","journal-title":"J. Lab. Physicians"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"a027029","DOI":"10.1101\/cshperspect.a027029","article-title":"Aminoglycosides: An Overview","volume":"6","author":"Krause","year":"2016","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Mlynarczyk-Bonikowska, B., Kowalewski, C., Krolak-Ulinska, A., and Marusza, W. (2022). Molecular Mechanisms of Drug Resistance in Staphylococcus aureus. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23158088"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1111\/j.1348-0421.2006.tb03815.x","article-title":"Unnoticed Spread of Class 1 Integrons in Gram-Positive Clinical Strains Isolated in Guangzhou, China","volume":"50","author":"Shi","year":"2006","journal-title":"Microbiol. Immunol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"264","DOI":"10.1007\/s00284-008-9187-8","article-title":"First Confirmation of Integron-Bearing Methicillin-Resistant Staphylococcus aureus","volume":"57","author":"Xu","year":"2008","journal-title":"Curr. Microbiol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"100281","DOI":"10.1016\/j.microb.2025.100281","article-title":"Current Strategies against Multidrug-Resistant Staphylococcus aureus and Advances toward Future Therapy","volume":"6","author":"Kumar","year":"2025","journal-title":"Microbe"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"127221","DOI":"10.1016\/j.micres.2022.127221","article-title":"Epidemiological Characteristics and Antibiotic Resistance Mechanisms of Streptococcus pneumoniae: An Updated Review","volume":"266","author":"Li","year":"2023","journal-title":"Microbiol. Res."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1128\/CMR.00058-15","article-title":"Biological and Epidemiological Features of Antibiotic-Resistant Streptococcus pneumoniae in Pre- and Post-Conjugate Vaccine Eras: A United States Perspective","volume":"29","author":"Kim","year":"2016","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_46","first-page":"1881","article-title":"Antibiotic-Resistant Streptococcus pneumoniae. Implications for Medical Practice","volume":"44","author":"Wang","year":"1998","journal-title":"Can. Fam. Physician"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1016\/S0002-9343(98)00351-9","article-title":"Drug-Resistant Streptococcus pneumoniae: Rational Antibiotic Choices","volume":"106","author":"Jacobs","year":"1999","journal-title":"Am. J. Med."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Schroeder, M.R., and Stephens, D.S. (2016). Macrolide Resistance in Streptococcus pneumoniae. Front. Cell. Infect. Microbiol., 6.","DOI":"10.3389\/fcimb.2016.00098"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.ijantimicag.2010.04.013","article-title":"Evolving Trends in Streptococcus pneumoniae Resistance: Implications for Therapy of Community-Acquired Bacterial Pneumonia","volume":"36","author":"Jones","year":"2010","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e450","DOI":"10.1016\/S2666-5247(21)00064-1","article-title":"Antimicrobial Resistance in Paediatric Streptococcus pneumoniae Isolates amid Global Implementation of Pneumococcal Conjugate Vaccines: A Systematic Review and Meta-Regression Analysis","volume":"2","author":"Andrejko","year":"2021","journal-title":"Lancet Microbe"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"628","DOI":"10.1128\/CMR.11.4.628","article-title":"Management of Infections Due to Antibiotic-Resistant Streptococcus pneumoniae","volume":"11","author":"Kaplan","year":"1998","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Zahari, N.I.N., Engku Abd Rahman, E.N.S., Irekeola, A.A., Ahmed, N., Rabaan, A.A., Alotaibi, J., Alqahtani, S.A., Halawi, M.Y., Alamri, I.A., and Almogbel, M.S. (2023). A Review of the Resistance Mechanisms for \u03b2-Lactams, Macrolides and Fluoroquinolones among Streptococcus pneumoniae. Medicina, 59.","DOI":"10.3390\/medicina59111927"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1038\/21202","article-title":"Emergence of Vancomycin Tolerance in Streptococcus pneumoniae","volume":"399","author":"Novak","year":"1999","journal-title":"Nature"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"552","DOI":"10.1086\/318697","article-title":"Clinical Isolates of Streptococcus pneumoniae That Exhibit Tolerance of Vancomycin","volume":"32","author":"Normark","year":"2001","journal-title":"Clin. Infect. Dis."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1038\/s41579-024-01054-w","article-title":"ESKAPE Pathogens: Antimicrobial Resistance, Epidemiology, Clinical Impact and Therapeutics","volume":"22","author":"Miller","year":"2024","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.drup.2018.10.002","article-title":"Update on Prevalence and Mechanisms of Resistance to Linezolid, Tigecycline and Daptomycin in Enterococci in Europe: Towards a Common Nomenclature","volume":"40","author":"Bender","year":"2018","journal-title":"Drug Resist. Updat."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2594","DOI":"10.1128\/AAC.45.9.2594-2597.2001","article-title":"Role of Penicillin-Binding Protein 5 in Expression of Ampicillin Resistance and Peptidoglycan Structure in Enterococcus faecium","volume":"45","author":"Sifaoui","year":"2001","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"3272","DOI":"10.1128\/AAC.00099-11","article-title":"Analysis of PBP5 of Early U.S. Isolates of Enterococcus faecium: Sequence Variation Alone Does Not Explain Increasing Ampicillin Resistance over Time","volume":"55","author":"Rice","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"16490","DOI":"10.1074\/jbc.M909877199","article-title":"Novel Mechanism of \u03b2-Lactam Resistance Due to Bypass of DD-Transpeptidation in Enterococcus faecium","volume":"275","author":"Mainardi","year":"2000","journal-title":"J. Biol. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1128\/JB.186.5.1221-1228.2004","article-title":"Role of Class A Penicillin-Binding Proteins in PBP5-Mediated \u03b2-Lactam Resistance in Enterococcus Faecalis","volume":"186","author":"Arbeloa","year":"2004","journal-title":"J. Bacteriol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"3649","DOI":"10.1128\/JB.01834-08","article-title":"Role of Class A Penicillin-Binding Proteins in the Expression of \u03b2-Lactam Resistance in Enterococcus faecium","volume":"191","author":"Rice","year":"2009","journal-title":"J. Bacteriol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"7184","DOI":"10.1128\/JB.185.24.7184-7192.2003","article-title":"The CroRS Two-Component Regulatory System Is Requiredfor Intrinsic \u03b2-Lactam Resistance in Enterococcusfaecalis","volume":"185","author":"Comenge","year":"2003","journal-title":"J. Bacteriol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"7951","DOI":"10.1128\/JB.186.23.7951-7958.2004","article-title":"Systematic Inactivation and Phenotypic Characterization of Two-Component Signal Transduction Systems of Enterococcus Faecalis V583","volume":"186","author":"Hancock","year":"2004","journal-title":"J. Bacteriol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e02461-16","DOI":"10.1128\/AAC.02461-16","article-title":"Requirement of the CroRS Two-Component System for Resistance to Cell Wall-Targeting Antimicrobials in Enterococcus faecium","volume":"61","author":"Kellogg","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"e00199-11","DOI":"10.1128\/mBio.00199-11","article-title":"Reciprocal Regulation of Cephalosporin Resistance in Enterococcus Faecalis","volume":"2","author":"Kristich","year":"2011","journal-title":"mBio"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"3508","DOI":"10.1073\/pnas.0608742104","article-title":"A Eukaryotic-Type Ser\/Thr Kinase in Enterococcus Faecalis Mediates Antimicrobial Resistance and Intestinal Persistence","volume":"104","author":"Kristich","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Desbonnet, C., Tait-Kamradt, A., Garcia-Solache, M., Dunman, P., Coleman, J., Arthur, M., and Rice, L.B. (2016). Involvement of the Eukaryote-Like Kinase-Phosphatase System and a Protein That Interacts with Penicillin-Binding Protein 5 in Emergence of Cephalosporin Resistance in Cephalosporin-Sensitive Class A Penicillin-Binding Protein Mutants in Enterococcus faecium. mBio, 7.","DOI":"10.1128\/mBio.02188-15"},{"key":"ref_68","doi-asserted-by":"crossref","unstructured":"Kellogg, S.L., and Kristich, C.J. (2018). Convergence of PASTA Kinase and Two-Component Signaling in Response to Cell Wall Stress in Enterococcus Faecalis. J. Bacteriol., 200.","DOI":"10.1128\/JB.00086-18"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1586\/14787210.2014.956092","article-title":"Mechanisms of Antibiotic Resistance in Enterococci","volume":"12","author":"Miller","year":"2014","journal-title":"Expert Rev. Anti. Infect. Ther."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"3345","DOI":"10.1128\/AAC.00207-11","article-title":"Genetic Basis for Daptomycin Resistance in Enterococci","volume":"55","author":"Palmer","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"892","DOI":"10.1056\/NEJMoa1011138","article-title":"Genetic Basis for In Vivo Daptomycin Resistance in Enterococci","volume":"365","author":"Arias","year":"2011","journal-title":"N. Engl. J. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1586\/14787210.2014.870886","article-title":"Antibiotic Resistance in Enterococcus faecium Clinical Isolates","volume":"12","author":"Cattoir","year":"2014","journal-title":"Expert Rev. Anti. Infect. Ther."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"10388","DOI":"10.1073\/pnas.0701809104","article-title":"Structural Basis for Streptogramin B Resistance in Staphylococcus aureus by Virginiamycin B Lyase","volume":"104","author":"Korczynska","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1128\/AAC.44.4.967-971.2000","article-title":"Macrolide Resistance Genes in Enterococcus spp.","volume":"44","author":"Portillo","year":"2000","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"4463","DOI":"10.1128\/AAC.01030-13","article-title":"Genetic Basis for In Vitro and In Vivo Resistance to Lincosamides, Streptogramins A, and Pleuromutilins (LSAP Phenotype) in Enterococcus faecium","volume":"57","author":"Isnard","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1016\/j.jgar.2023.12.002","article-title":"The First Tigecycline Resistant Enterococcus faecium in Norway Was Related to Tigecycline Exposure","volume":"36","author":"Hegstad","year":"2024","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Dadashi, M., Sharifian, P., Bostanshirin, N., Hajikhani, B., Bostanghadiri, N., Khosravi-Dehaghi, N., van Belkum, A., and Darban-Sarokhalil, D. (2021). The Global Prevalence of Daptomycin, Tigecycline, and Linezolid-Resistant Enterococcus Faecalis and Enterococcus faecium Strains from Human Clinical Samples: A Systematic Review and Meta-Analysis. Front. Med., 8.","DOI":"10.3389\/fmed.2021.720647"},{"key":"ref_78","doi-asserted-by":"crossref","unstructured":"Duplessis, C., and Crum-Cianflone, N.F. (2011). Ceftaroline: A New Cephalosporin with Activity against Methicillin-Resistant Staphylococcus aureus (MRSA). Clin. Med. Rev. Ther., 3.","DOI":"10.4137\/CMRT.S1637"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"1390","DOI":"10.1056\/NEJMoa2300220","article-title":"Ceftobiprole for Treatment of Complicated Staphylococcus aureus Bacteremia","volume":"389","author":"Holland","year":"2023","journal-title":"N. Engl. J. Med."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"264","DOI":"10.7547\/15-218","article-title":"Tedizolid and Linezolid for Treatment of Acute Bacterial Skin and Skin Structure Infections of the Lower Extremity versus Non\u2013Lower-Extremity Infections","volume":"107","author":"Joseph","year":"2017","journal-title":"J. Am. Podiatr. Med. Assoc."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"696","DOI":"10.1016\/S1473-3099(14)70737-6","article-title":"Tedizolid for 6 Days versus Linezolid for 10 Days for Acute Bacterial Skin and Skin-Structure Infections (ESTABLISH-2): A Randomised, Double-Blind, Phase 3, Non-Inferiority Trial","volume":"14","author":"Moran","year":"2014","journal-title":"Lancet Infect. Dis."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1080\/14787210.2019.1573671","article-title":"Ozenoxacin: A Review of Preclinical and Clinical Efficacy","volume":"17","author":"Vila","year":"2019","journal-title":"Expert Rev. Anti. Infect. Ther."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1093\/jac\/dkq127","article-title":"Bactericidal Activity of Besifloxacin against Staphylococci, Streptococcus pneumoniae and Haemophilus influenzae","volume":"65","author":"Haas","year":"2010","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"215","DOI":"10.2147\/OPTH.S9604","article-title":"Besifloxacin: A Novel Anti-Infective for the Treatment of Bacterial Conjunctivitis","volume":"4","author":"Comstock","year":"2010","journal-title":"Clin. Ophthalmol."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"2605","DOI":"10.1093\/jac\/dkaa209","article-title":"Delafloxacin Activity against Staphylococcus aureus with Reduced Susceptibility or Resistance to Methicillin, Vancomycin, Daptomycin or Linezolid","volume":"75","author":"Saravolatz","year":"2020","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"e33092","DOI":"10.1097\/MD.0000000000033092","article-title":"Evaluation of Efficacy and Safety of Lascufloxacin for Nursing and Healthcare Associated Pneumonia: Single-Arm, Open-Label Clinical Trial: A Study Protocol","volume":"102","author":"Hosogaya","year":"2023","journal-title":"Medicine"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"4351","DOI":"10.2147\/DDDT.S229882","article-title":"Levonadifloxacin, a Novel Broad-Spectrum Anti-MRSA Benzoquinolizine Quinolone Agent: Review of Current Evidence","volume":"13","author":"Bhagwat","year":"2019","journal-title":"Drug Des. Devel. Ther."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"S6","DOI":"10.1093\/cid\/ciz395","article-title":"Microbiology and Preclinical Review of Omadacycline","volume":"69","author":"Karlowsky","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1001\/jama.2025.12543","article-title":"Dalbavancin for Treatment of Staphylococcus aureus Bacteremia","volume":"334","author":"Turner","year":"2025","journal-title":"JAMA"},{"key":"ref_90","doi-asserted-by":"crossref","unstructured":"Birlutiu, R.-M., and Birlutiu, V. (2025). Oritavancin a Therapeutic Option for Periprosthetic Joint Infections in Selected Cases: A Comprehensive Review. Pharmaceuticals, 18.","DOI":"10.3390\/ph18081217"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1038\/nature14098","article-title":"A New Antibiotic Kills Pathogens without Detectable Resistance","volume":"517","author":"Ling","year":"2015","journal-title":"Nature"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1038\/s41564-018-0110-1","article-title":"Culture-Independent Discovery of the Malacidins as Calcium-Dependent Antibiotics with Activity against Multidrug-Resistant Gram-Positive Pathogens","volume":"3","author":"Hover","year":"2018","journal-title":"Nat. Microbiol."},{"key":"ref_93","doi-asserted-by":"crossref","unstructured":"Matyjewicz, A., Krakowska, A., M\u0171ller, D., Krakowski, J., Paczosa-Bator, B., and Skalski, T. (2026). Synergistic Action of Antimicrobial Peptides and Antibiotics. Int. J. Mol. Sci., 27.","DOI":"10.3390\/ijms27104553"},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Karaman, R., Jubeh, B., and Breijyeh, Z. (2020). Resistance of Gram-Positive Bacteria to Current Antibacterial Agents and Overcoming Approaches. Molecules, 25.","DOI":"10.3390\/molecules25122888"},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"11322","DOI":"10.1021\/ja302542j","article-title":"DCAP: A Broad-Spectrum Antibiotic That Targets the Cytoplasmic Membrane of Bacteria","volume":"134","author":"Eun","year":"2012","journal-title":"J. Am. Chem. Soc."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1016\/j.molcel.2018.03.001","article-title":"Odilorhabdins, Antibacterial Agents That Cause Miscoding by Binding at a New Ribosomal Site","volume":"70","author":"Pantel","year":"2018","journal-title":"Mol. Cell"},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Kumaran, D., Taha, M., Yi, Q., Ramirez-Arcos, S., Diallo, J.-S., Carli, A., and Abdelbary, H. (2018). Does Treatment Order Matter? Investigating the Ability of Bacteriophage to Augment Antibiotic Activity against Staphylococcus aureus Biofilms. Front. Microbiol., 9.","DOI":"10.3389\/fmicb.2018.00127"},{"key":"ref_98","unstructured":"World Health Organization (2025). Analysis of Antibacterial Agents in Clinical and Preclinical Development: Overview and Analysis 2025, World Health Organization."}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/14\/9\/1951\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T10:27:22Z","timestamp":1788431242000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/14\/9\/1951"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,3]]},"references-count":98,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["microorganisms14091951"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms14091951","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,3]]}}}