{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T12:03:09Z","timestamp":1790251389732,"version":"4.1.0"},"reference-count":111,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T00:00:00Z","timestamp":1770336000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"The Regional Initiative of Excellence Program"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>The rapid global spread of antimicrobial resistance (AMR) has significantly reduced the effectiveness of many modern antibiotics, creating an urgent need for alternative therapeutic strategies. One promising approach is the revival and repurposing of older antimicrobial agents whose clinical potential was previously limited by toxicity concerns, pharmacokinetic challenges, or the availability of newer drugs. Recent advances in drug delivery, dosing optimization, and antimicrobial stewardship have renewed interest in these compounds as viable options for the treatment of multidrug-resistant infections. The aim of this review is to provide a comparative, clinically oriented analysis of selected \u201cold\u201d antibiotics, fosfomycin, colistin, streptomycin, and vancomycin, with emphasis on their current therapeutic roles, pharmacokinetic\/pharmacodynamic (PK\/PD) targets, toxicity mitigation strategies, resistance mechanisms, and evidence supporting combination therapies and alternative routes of administration. This narrative review was conducted using a structured PubMed search and manual reference screening, focusing on clinical, PK\/PD, and translational studies relevant to the contemporary use of legacy antibiotics. The review summarises current evidence on the re-emerging clinical applications of these agents, each discussed in the context of historical use, mechanism of action, resistance patterns, and newly identified indications. Attention is given to novel formulations, combination strategies, and alternative routes of administration that enhance efficacy while limiting toxicity, including applications in biofilm-associated infections. Overall, strategic repurposing of older antibiotics represents a valuable complementary approach in the fight against AMR and may extend the therapeutic lifespan of existing agents in an era of limited antibiotic innovation.<\/jats:p>","DOI":"10.3390\/ph19020278","type":"journal-article","created":{"date-parts":[[2026,2,6]],"date-time":"2026-02-06T16:32:59Z","timestamp":1770395579000},"page":"278","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Reviving Old Antibiotics: New Indications and Therapeutic Perspectives\u2014A Review"],"prefix":"10.3390","volume":"19","author":[{"given":"Pawe\u0142","family":"Radkowski","sequence":"first","affiliation":[{"name":"Department of Anaesthesiology and Intensive Care, School of Medicine, Collegium Medicum, University of Warmia and Mazury in Olsztyn, 10-719 Olsztyn, Poland"},{"name":"Clinical Department of Anaesthesiology and Intensive Care, Regional Specialist Hospital in Olsztyn, 10-561 Olsztyn, Poland"},{"name":"Hospital zum Heiligen Geist, 34560 Fritzlar, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-8917-8943","authenticated-orcid":false,"given":"Julia","family":"Oszytko","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Opole University, 45-758 Opole, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3404-2108","authenticated-orcid":false,"given":"Kamil","family":"Sobolewski","sequence":"additional","affiliation":[{"name":"Clinical Department of Anaesthesiology and Intensive Care, Regional Specialist Hospital in Olsztyn, 10-561 Olsztyn, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Florian","family":"Trachte","sequence":"additional","affiliation":[{"name":"Medical Sociology Unit, Hannover Medical School, 30625 Hannover, Germany"},{"name":"Doctor\u2019s Office, C. Zuleger Extertal, 32699 Extertal, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja","family":"Czerwi\u0144ska-Rogowska","sequence":"additional","affiliation":[{"name":"Department of Human Nutrition and Metabolomics, Pomeranian Medical University, 71-460 Szczecin, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7648-7511","authenticated-orcid":false,"given":"Dariusz","family":"Onichimowski","sequence":"additional","affiliation":[{"name":"Department of Anaesthesiology and Intensive Care, School of Medicine, Collegium Medicum, University of Warmia and Mazury in Olsztyn, 10-719 Olsztyn, Poland"},{"name":"Clinical Department of Anaesthesiology and Intensive Care, Regional Specialist Hospital in Olsztyn, 10-561 Olsztyn, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5856-6929","authenticated-orcid":false,"given":"Marta","family":"Majewska","sequence":"additional","affiliation":[{"name":"Department of Human Physiology and Pathophysiology, School of Medicine, Collegium Medicum, University of Warmia and Mazury in Olsztyn, 10-719 Olsztyn, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,6]]},"reference":[{"key":"ref_1","first-page":"109","article-title":"\u201eNowe\u201d i \u201eStare\u201d Antybiotyki\u2014Mechanizmy Dzia\u0142ania i Strategie Poszukiwania Lek\u00f3w Przeciwbakteryjnych","volume":"66","author":"Sitkiewicz","year":"2017","journal-title":"Kosmos. Ser. A Biol. Pol. Tow. Przyr. Kopernika"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1016\/j.cmi.2015.06.007","article-title":"Use of Old Antibiotics Now and in the Future from a Pharmacokinetic\/Pharmacodynamic Perspective","volume":"21","author":"Muller","year":"2015","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"886","DOI":"10.1016\/j.cmi.2015.05.002","article-title":"Optimization of Dosing Regimens and Dosing in Special Populations","volume":"21","author":"Sime","year":"2015","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"482","DOI":"10.56434\/j.arch.esp.urol.20227506.72","article-title":"Fosfomycin: 50 Years of A Great Discovery (1969\u20132019)","volume":"75","year":"2022","journal-title":"Arch. Espa\u00f1oles Urol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.eimc.2018.10.002","article-title":"Uso Actual de La Fosfomicina: Del Laboratorio a La Pr\u00e1ctica Cl\u00ednica","volume":"37","author":"Candel","year":"2019","journal-title":"Enfermedades Infecc. Microbiol. Cl\u00ednica"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"621","DOI":"10.3390\/idr14040067","article-title":"Oral Fosfomycin Formulation in Bacterial Prostatitis: New Role for an Old Molecule-Brief Literature Review and Clinical Considerations","volume":"14","author":"Marino","year":"2022","journal-title":"Infect. Dis. Rep."},{"key":"ref_7","first-page":"8","article-title":"New Microbiological Aspects of Fosfomycin","volume":"32","year":"2019","journal-title":"Rev. Esp. Quimioter."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/j.jmii.2017.10.006","article-title":"Update on Fosfomycin-Modified Genes in Enterobacteriaceae","volume":"52","author":"Yang","year":"2019","journal-title":"J. Microbiol. Immunol. Infect."},{"key":"ref_9","first-page":"1","article-title":"New Perspectives for Reassessing Fosfomycin: Applicability in Current Clinical Practice","volume":"32","author":"Candel","year":"2019","journal-title":"Rev. Esp. Quimioter."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"607","DOI":"10.1089\/mdr.2017.0097","article-title":"The Activity of Fosfomycin Against Extended-Spectrum Beta-Lactamase-Producing Isolates of Enterobacteriaceae Recovered from Urinary Tract Infections: A Single-Center Study Over a Period of 12 Years","volume":"24","author":"Aris","year":"2018","journal-title":"Microb. Drug Resist."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1016\/S1473-3099(09)70325-1","article-title":"Fosfomycin for the Treatment of Multidrug-Resistant, Including Extended-Spectrum \u03b2-Lactamase Producing, Enterobacteriaceae Infections: A Systematic Review","volume":"10","author":"Falagas","year":"2010","journal-title":"Lancet Infect. Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1128\/CMR.00068-15","article-title":"Fosfomycin","volume":"29","author":"Falagas","year":"2016","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"765","DOI":"10.1007\/s40121-025-01125-2","article-title":"Real-World Use, Effectiveness, and Safety of Intravenous Fosfomycin: The FORTRESS Study","volume":"14","author":"Bodmann","year":"2025","journal-title":"Infect. Dis. Ther."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"853","DOI":"10.1093\/jac\/34.6.853","article-title":"Fosfomycin Trometamol","volume":"34","author":"Reeves","year":"1994","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Bavaro, D.F., Belati, A., Diella, L., Stufano, M., Romanelli, F., Scalone, L., Stolfa, S., Ronga, L., Maurmo, L., and Dell\u2019Aera, M. (2021). Cefiderocol-Based Combination Therapy for \u201cDifficult-to-Treat\u201d Gram-Negative Severe Infections: Real-Life Case Series and Future Perspectives. Antibiotics, 10.","DOI":"10.3390\/antibiotics10060652"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1128\/AAC.34.5.844","article-title":"Purification of a Glutathione S-Transferase That Mediates Fosfomycin Resistance in Bacteria","volume":"34","author":"Arca","year":"1990","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1097\/00019048-200106000-00004","article-title":"Fosfomycin: A Review","volume":"10","author":"Shrestha","year":"2001","journal-title":"Infect. Dis. Clin. Pract."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"22","DOI":"10.1016\/j.ijantimicag.2018.09.013","article-title":"Resistance to Fosfomycin: Mechanisms, Frequency and Clinical Consequences","volume":"53","author":"Falagas","year":"2019","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"106106","DOI":"10.1016\/j.ijantimicag.2020.106106","article-title":"Fosfomycin for Bacterial Prostatitis: A Review","volume":"56","author":"Kwan","year":"2020","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Dijkmans, A.C., Zacar\u00edas, N.V.O., Burggraaf, J., Mouton, J.W., Wilms, E., Van Nieuwkoop, C., Touw, D.J., Stevens, J., and Kamerling, I.M.C. (2017). Fosfomycin: Pharmacological, Clinical and Future Perspectives. Antibiotics, 6.","DOI":"10.3390\/antibiotics6040024"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Fan, L., Shang, X., Zhu, J., Ma, B., and Zhang, Q. (2018). Pharmacodynamic and Pharmacokinetic Studies and Prostatic Tissue Distribution of Fosfomycin Tromethamine in Bacterial Prostatitis or Normal Rats. Andrologia, 50.","DOI":"10.1111\/and.13021"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Bouiller, K., Zayet, S., Lalloz, P.-E., Potron, A., Gendrin, V., Chirouze, C., and Klopfenstein, T. (2022). Efficacy and Safety of Oral Fosfomycin-Trometamol in Male Urinary Tract Infections with Multidrug-Resistant Enterobacterales. Antibiotics, 11.","DOI":"10.3390\/antibiotics11020198"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1141","DOI":"10.1093\/cid\/civ436","article-title":"Fosfomycin for Treatment of Prostatitis: New Tricks for Old Dogs","volume":"61","author":"Grayson","year":"2015","journal-title":"Clin. Infect. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"368","DOI":"10.1097\/00019048-200009090-00004","article-title":"Treatment of a Complicated Vancomycin-Resistant Enterococcal Urinary Tract Infection with Fosfomycin","volume":"9","author":"Shrestha","year":"2000","journal-title":"Infect. Dis. Clin. Pract."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"227","DOI":"10.4081\/aiua.2018.4.227","article-title":"Multidisciplinary Approach to Prostatitis","volume":"90","author":"Magri","year":"2018","journal-title":"Arch. Ital. Urol. Androl."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3948","DOI":"10.1093\/eurheartj\/ehad193","article-title":"2023 ESC Guidelines for the Management of Endocarditis","volume":"44","author":"Marsan","year":"2023","journal-title":"Eur. Heart J."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1","DOI":"10.51585\/gjm.2024.1.0028","article-title":"Fosfomycin in the Treatment of New Delhi Metallo-\u03b2-Lactamase-5 (blaNDM-5)-Producing Escherichia coli Infection","volume":"4","author":"Tozluyur","year":"2024","journal-title":"Ger. J. Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3042","DOI":"10.1093\/jac\/dkv221","article-title":"In Vitro Pharmacodynamics of Fosfomycin against Clinical Isolates of Pseudomonas aeruginosa","volume":"70","author":"Walsh","year":"2015","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e732","DOI":"10.1016\/j.ijid.2011.07.007","article-title":"The Revival of Fosfomycin","volume":"15","author":"Michalopoulos","year":"2011","journal-title":"Int. J. Infect. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1038\/s44259-024-00046-3","article-title":"Mechanisms of Antimicrobial Resistance in Biofilms","volume":"2","author":"Liu","year":"2024","journal-title":"npj Antimicrob. Resist."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"522","DOI":"10.1080\/21505594.2017.1313372","article-title":"Strategies for Combating Bacterial Biofilms: A Focus on Anti-Biofilm Agents and Their Mechanisms of Action","volume":"9","author":"Roy","year":"2017","journal-title":"Virulence"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Wang, L., Di Luca, M., Tkhilaishvili, T., Trampuz, A., and Gonzalez Moreno, M. (2019). Synergistic Activity of Fosfomycin, Ciprofloxacin, and Gentamicin Against Escherichia coli and Pseudomonas aeruginosa Biofilms. Front. Microbiol., 10.","DOI":"10.3389\/fmicb.2019.02522"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1111\/2049-632X.12015","article-title":"Eradication of Pseudomonas aeruginosa Biofilms on Cultured Airway Cells by a Fosfomycin\/Tobramycin Antibiotic Combination","volume":"67","author":"Anderson","year":"2013","journal-title":"Pathog. Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e01650-17","DOI":"10.1128\/AAC.01650-17","article-title":"Use of Calgary and Microfluidic BioFlux Systems to Test the Activity of Fosfomycin and Tobramycin Alone and in Combination against Cystic Fibrosis Pseudomonas aeruginosa Biofilms","volume":"62","author":"Morosini","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"626","DOI":"10.1097\/QCO.0b013e328358afe5","article-title":"\u2018Old\u2019 Antibiotics for Emerging Multidrug-Resistant Bacteria","volume":"25","author":"Bergen","year":"2012","journal-title":"Curr. Opin. Infect. Dis."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"e01424-17","DOI":"10.1128\/AAC.01424-17","article-title":"Inhibition of Fosfomycin Resistance Protein FosA by Phosphonoformate (Foscarnet) in Multidrug-Resistant Gram-Negative Pathogens","volume":"61","author":"Ito","year":"2017","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"549","DOI":"10.1128\/jb.54.5.549-556.1947","article-title":"Studies on Polymyxin: Isolation and Identification of Bacillus polymyxa and Differentiation of Polymyxin from Certain Known Antibiotics","volume":"54","author":"Stansly","year":"1947","journal-title":"J. Bacteriol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/j.ijantimicag.2016.06.023","article-title":"Molecular Mechanisms of Polymyxin Resistance: Knowns and Unknowns","volume":"48","author":"Baron","year":"2016","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Hamel, M., Rolain, J.-M., and Baron, S.A. (2021). The History of Colistin Resistance Mechanisms in Bacteria: Progress and Challenges. Microorganisms, 9.","DOI":"10.3390\/microorganisms9020442"},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Andrade, F.F., Silva, D., Rodrigues, A., and Pina-Vaz, C. (2020). Colistin Update on Its Mechanism of Action and Resistance, Present and Future Challenges. Microorganisms, 8.","DOI":"10.3390\/microorganisms8111716"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1016\/j.drudis.2018.07.004","article-title":"MCR-1: A Promising Target for Structure-Based Design of Inhibitors to Tackle Polymyxin Resistance","volume":"24","author":"Son","year":"2019","journal-title":"Drug Discov. Today"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1016\/j.idc.2016.02.005","article-title":"Agents of Last Resort: Polymyxin Resistance","volume":"30","author":"Kaye","year":"2016","journal-title":"Infect. Dis. Clin. N. Am."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1093\/cid\/ciw839","article-title":"Dosing Guidance for Intravenous Colistin in Critically-Ill Patients","volume":"64","author":"Nation","year":"2017","journal-title":"Clin. Infect. Dis."},{"key":"ref_44","doi-asserted-by":"crossref","unstructured":"Aslan, A.T., and Akova, M. (2022). The Role of Colistin in the Era of New \u03b2-Lactam\/\u03b2-Lactamase Inhibitor Combinations. Antibiotics, 11.","DOI":"10.3390\/antibiotics11020277"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Haseeb, A., Faidah, H.S., Alghamdi, S., Alotaibi, A.F., Elrggal, M.E., Mahrous, A.J., Almarzoky Abuhussain, S.S., Obaid, N.A., Algethamy, M., and AlQarni, A. (2021). Dose Optimization of Colistin: A Systematic Review. Antibiotics, 10.","DOI":"10.3390\/antibiotics10121454"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1080\/22221751.2020.1754133","article-title":"Colistin and Its Role in the Era of Antibiotic Resistance: An Extended Review (2000\u20132019)","volume":"9","author":"Zhong","year":"2020","journal-title":"Emerg. Microbes Infect."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.ijantimicag.2004.10.001","article-title":"Evaluation of Colistin as an Agent against Multi-Resistant Gram-Negative Bacteria","volume":"25","author":"Li","year":"2005","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1038\/ja.2013.111","article-title":"A Secondary Mode of Action of Polymyxins against Gram-Negative Bacteria Involves the Inhibition of NADH-Quinone Oxidoreductase Activity","volume":"67","author":"Deris","year":"2014","journal-title":"J. Antibiot."},{"key":"ref_49","first-page":"1","article-title":"Colistin in Critically Ill Patients: A Critical Review","volume":"4","year":"2016","journal-title":"Int. Arab. J. Antimicrob. Agents"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1093\/cid\/ciu213","article-title":"Colistin and Polymyxin B: Peas in a Pod, or Chalk and Cheese?","volume":"59","author":"Nation","year":"2014","journal-title":"Clin. Infect. Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1086\/429323","article-title":"Colistin: The Revival of Polymyxins for the Management of Multidrug-Resistant Gram-Negative Bacterial Infections","volume":"40","author":"Falagas","year":"2005","journal-title":"Clin. Infect. Dis."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1111\/j.1469-0691.2011.03734.x","article-title":"Colistin: New Lessons on an Old Antibiotic","volume":"18","author":"Yahav","year":"2012","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1007\/s00228-015-1865-4","article-title":"A Review on Colistin Nephrotoxicity","volume":"71","author":"Shokouhi","year":"2015","journal-title":"Eur. J. Clin. Pharmacol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1007\/s40262-017-0561-1","article-title":"Clinical Pharmacokinetics and Pharmacodynamics of Colistin","volume":"56","author":"Marchand","year":"2017","journal-title":"Clin. Pharmacokinet."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"128","DOI":"10.1111\/bcpt.13482","article-title":"Steady-State Pharmacokinetic and Pharmacodynamic Profiling of Colistin in Critically Ill Patients with Multi-Drug\u2013Resistant Gram-Negative Bacterial Infections, along with Differences in Clinical, Microbiological and Safety Outcome","volume":"128","author":"Ram","year":"2021","journal-title":"Basic Clin. Pharmacol. Toxicol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"7331","DOI":"10.1128\/AAC.03510-14","article-title":"Comparison of Intrapulmonary and Systemic Pharmacokinetics of Colistin Methanesulfonate (CMS) and Colistin after Aerosol Delivery and Intravenous Administration of CMS in Critically Ill Patients","volume":"58","author":"Boisson","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_57","doi-asserted-by":"crossref","unstructured":"Lee, D.-H., Kim, S.-Y., Kim, Y.-K., Jung, S.-Y., Jang, J.-H., Jang, H.-J., and Lee, J.-H. (2024). Intrapulmonary and Systemic Pharmacokinetics of Colistin Following Nebulization of Low-Dose Colistimethate Sodium in Patients with Ventilator-Associated Pneumonia Caused by Carbapenem-Resistant Acinetobacter baumannii. Antibiotics, 13.","DOI":"10.3390\/antibiotics13030258"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"2570","DOI":"10.1128\/AAC.01705-13","article-title":"Pulmonary and Systemic Pharmacokinetics of Inhaled and Intravenous Colistin Methanesulfonate in Cystic Fibrosis Patients: Targeting Advantage of Inhalational Administration","volume":"58","author":"Li","year":"2014","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1177\/2049936113476284","article-title":"Clinical Management of Infections Caused by Multidrug-Resistant Enterobacteriaceae","volume":"1","author":"Pascual","year":"2013","journal-title":"Ther. Adv. Infect."},{"key":"ref_60","first-page":"157","article-title":"Colistin: An Antibiotic and Its Role in Multiresistant Gram-Negative Infections","volume":"47","author":"Loho","year":"2015","journal-title":"Acta Med. Indones."},{"key":"ref_61","doi-asserted-by":"crossref","unstructured":"Liang, L., Zhong, L.-L., Wang, L., Zhou, D., Li, Y., Li, J., Chen, Y., Liang, W., Wei, W., and Zhang, C. (2023). A New Variant of the Colistin Resistance Gene MCR-1 with Co-Resistance to \u03b2-Lactam Antibiotics Reveals a Potential Novel Antimicrobial Peptide. PLoS Biol., 21.","DOI":"10.1371\/journal.pbio.3002433"},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"5925","DOI":"10.1128\/AAC.00808-15","article-title":"Mucin Binding Reduces Colistin Antimicrobial Activity","volume":"59","author":"Huang","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"603","DOI":"10.1016\/j.ijantimicag.2015.09.011","article-title":"Intravenous Combined with Aerosolised Polymyxin versus Intravenous Polymyxin Alone in the Treatment of Pneumonia Caused by Multidrug-Resistant Pathogens: A Systematic Review and Meta-Analysis","volume":"46","author":"Liu","year":"2015","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1465","DOI":"10.1016\/j.cmi.2021.01.020","article-title":"Efficacy of Adjunctive Nebulized Colistin in Critically Ill Patients with Nosocomial Carbapenem-Resistant Gram-Negative Bacterial Pneumonia: A Multi-Centre Observational Study","volume":"27","author":"Feng","year":"2021","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s40560-015-0072-9","article-title":"Colistin for Lung Infection: An Update","volume":"3","author":"Gurjar","year":"2015","journal-title":"J. Intensive Care"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1007\/s40121-015-0093-7","article-title":"Optimizing Polymyxin Combinations Against Resistant Gram-Negative Bacteria","volume":"4","author":"Bergen","year":"2015","journal-title":"Infect. Dis. Ther."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1186\/1752-1947-6-426","article-title":"Intravesical Colistin Irrigation to Treat Multidrug-Resistant Acinetobacter baumannii Urinary Tract Infection: A Case Report","volume":"6","year":"2012","journal-title":"J. Med. Case Rep."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.ccc.2007.12.003","article-title":"Colistin and Polymyxin B in Critical Care","volume":"24","author":"Michalopoulos","year":"2008","journal-title":"Crit. Care Clin."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1856","DOI":"10.1093\/jac\/dku065","article-title":"In Vitro Activity and Post-Antibiotic Effects of Colistin in Combination with Other Antimicrobials against Colistin-Resistant KPC-Producing Klebsiella pneumoniae Bloodstream Isolates","volume":"69","author":"Gaibani","year":"2014","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Diani, E., Bianco, G., Gatti, M., Gibellini, D., and Gaibani, P. (2024). Colistin: Lights and Shadows of an Older Antibiotic. Molecules, 29.","DOI":"10.20944\/preprints202405.2049.v1"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"1749","DOI":"10.1513\/AnnalsATS.201509-632PS","article-title":"Treatment of Tuberculosis. A Historical Perspective","volume":"12","author":"Murray","year":"2015","journal-title":"Ann. Am. Thorac. Soc."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Zwick, E.D., and Pepperell, C.S. (2020). Tuberculosis Sanatorium Treatment at the Advent of the Chemotherapy Era. BMC Infect. Dis., 20.","DOI":"10.1186\/s12879-020-05539-w"},{"key":"ref_73","unstructured":"Waters, M., and Tadi, P. (2025). Streptomycin. StatPearls, StatPearls Publishing."},{"key":"ref_74","unstructured":"World Health Organization (2022). WHO Operational Handbook on Tuberculosis. Module 4: Treatment\u2014Drug-Resistant Tuberculosis Treatment, 2022 Update, World Health Organization. [1st ed.]."},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Goutelle, S., and Maire, P. (2017). Individualizing Tuberculosis Therapy. Individualized Drug Therapy for Patients, Academic Press.","DOI":"10.1016\/B978-0-12-803348-7.00015-0"},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Doughty, L.A., and Linden, P. (2003). Antimicrobial Choices and Dosing Strategies to Maximize Efficacy and Minimize the Development of Bacterial Resistance. Immunology and Infectious Disease, Springer.","DOI":"10.1007\/978-1-4615-0245-6"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1000214","DOI":"10.4172\/2153-2435.1000214","article-title":"Optimizing Antibiotic Pharmacodynamics for Clinical Practice","volume":"4","author":"Connors","year":"2013","journal-title":"Pharm. Anal. Acta"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1538","DOI":"10.1086\/420742","article-title":"Aminoglycoside Toxicity: Daily versus Thrice-Weekly Dosing for Treatment of Mycobacterial Diseases","volume":"38","author":"Peloquin","year":"2004","journal-title":"Clin. Infect. Dis."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"e84702","DOI":"10.7554\/eLife.84702","article-title":"Teaching Old Drugs New Tricks","volume":"11","author":"Faille","year":"2022","journal-title":"eLife"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"570","DOI":"10.1016\/j.chembiol.2025.03.008","article-title":"Streptomycin Targets Tumor-Initiating Cells by Disrupting Oxidative Phosphorylation","volume":"32","author":"Guillorit","year":"2025","journal-title":"Cell Chem. Biol."},{"key":"ref_81","doi-asserted-by":"crossref","unstructured":"Serio, A., Magalh\u00e3es, M., Blanchard, J., and Connolly, L. (2017). Aminoglycosides: Mechanisms of Action and Resistance. Antimicrobial Drug Resistance: Mechanisms of Drug Resistance, Springer.","DOI":"10.1007\/978-3-319-46718-4_14"},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Rocha, D.M.G.C., Magalh\u00e3es, C., C\u00e1, B., Ramos, A., Carvalho, T., Comas, I., Guimar\u00e3es, J.T., Bastos, H.N., Saraiva, M., and Os\u00f3rio, N.S. (2021). Heterogeneous Streptomycin Resistance Level Among Mycobacterium tuberculosis Strains from the Same Transmission Cluster. Front. Microbiol., 12.","DOI":"10.3389\/fmicb.2021.659545"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1038\/s41467-020-15832-6","article-title":"Mycobacterium tuberculosis Associated with Severe Tuberculosis Evades Cytosolic Surveillance Systems and Modulates IL-1\u03b2 Production","volume":"11","author":"Sousa","year":"2020","journal-title":"Nat. Commun."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Rocha, D.M.G.C., Viveiros, M., Saraiva, M., and Os\u00f3rio, N.S. (2021). The Neglected Contribution of Streptomycin to the Tuberculosis Drug Resistance Problem. Genes, 12.","DOI":"10.3390\/genes12122003"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Ektefaie, Y., Dixit, A., Freschi, L., and Farhat, M. (2019). Tuberculosis Resistance Acquisition in Space and Time: An Analysis of Globally Diverse M. tuberculosis Whole Genome Sequences. bioRxiv.","DOI":"10.1101\/837096"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"114966","DOI":"10.1016\/j.bcp.2022.114966","article-title":"Targeting Cancer Stem Cells with Antibiotics Inducing Mitochondrial Dysfunction as an Alternative Anticancer Therapy","volume":"198","author":"Karp","year":"2022","journal-title":"Biochem. Pharmacol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"e77460","DOI":"10.7554\/eLife.77460","article-title":"Structure of the Mitoribosomal Small Subunit with Streptomycin Reveals Fe-S Clusters and Physiological Molecules","volume":"11","author":"Itoh","year":"2022","journal-title":"eLife"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"114116","DOI":"10.1016\/j.biopha.2022.114116","article-title":"Use of the Quantum Dot-Labeled Solid Lipid Nanoparticles for Delivery of Streptomycin and Hydroxychloroquine: A New Therapeutic Approach for Treatment of Intracellular Brucella abortus Infection","volume":"158","author":"Karimitabar","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"21503","DOI":"10.1038\/s41598-022-25769-z","article-title":"Delivery of Streptomycin to the Rat Colon by Use of Electrospun Nanofibers","volume":"12","author":"Guerra","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1080\/08830185.2020.1762597","article-title":"Triggering Receptor Expressed on Myeloid Cells-1 (TREM-1) as a Therapeutic Target in Infectious and Noninfectious Disease: A Critical Review","volume":"39","author":"Dantas","year":"2020","journal-title":"Int. Rev. Immunol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"3277","DOI":"10.1021\/acs.jcim.0c00179","article-title":"Fast Identification of Possible Drug Treatment of Coronavirus Disease-19 (COVID-19) through Computational Drug Repurposing Study","volume":"60","author":"Wang","year":"2020","journal-title":"J. Chem. Inf. Model."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1002\/pro.3819","article-title":"Molecular Mechanisms of Vancomycin Resistance","volume":"29","author":"Stogios","year":"2020","journal-title":"Protein Sci."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1016\/j.ijpharm.2006.03.014","article-title":"Characterization of Biodegradable Chitosan Microspheres Containing Vancomycin and Treatment of Experimental Osteomyelitis Caused by Methicillin-Resistant Staphylococcus Aureus with Prepared Microspheres","volume":"317","author":"Cevher","year":"2006","journal-title":"Int. J. Pharm."},{"key":"ref_94","doi-asserted-by":"crossref","unstructured":"Elrggal, M.E., Haseeb, A., AlGethamy, M., Ahsan, U., Saleem, Z., Althaqafi, A.S., Alshuail, S.S., Alsiddiqi, Z.A., Iqbal, M.S., and Alzahrani, A.F. (2023). Dose Optimization of Vancomycin in Obese Patients: A Systematic Review. Front. Pharmacol., 14.","DOI":"10.3389\/fphar.2023.965284"},{"key":"ref_95","first-page":"694","article-title":"The Use of Vancomycin with Its Therapeutic and Adverse Effects: A Review","volume":"19","author":"Bruniera","year":"2015","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"111975","DOI":"10.1016\/j.msec.2021.111975","article-title":"Dual Drug Delivery of Vancomycin and Imipenem\/Cilastatin by Coaxial Nanofibers for Treatment of Diabetic Foot Ulcer Infections","volume":"123","author":"Davani","year":"2021","journal-title":"Mater. Sci. Eng. C Mater. Biol. Appl."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"5128","DOI":"10.1021\/acsami.6b14912","article-title":"Sustainable Release of Vancomycin from Silk Fibroin Nanoparticles for Treating Severe Bone Infection in Rat Tibia Osteomyelitis Model","volume":"9","author":"Mottaghitalab","year":"2017","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"1077","DOI":"10.1080\/19490976.2020.1743492","article-title":"Vancomycin Prevents Fermentable Fiber-Induced Liver Cancer in Mice with Dysbiotic Gut Microbiota","volume":"11","author":"Singh","year":"2020","journal-title":"Gut Microbes"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1093\/ajhp\/zxaa036","article-title":"Therapeutic Monitoring of Vancomycin for Serious Methicillin-Resistant Staphylococcus aureus Infections: A Revised Consensus Guideline and Review by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists","volume":"77","author":"Rybak","year":"2020","journal-title":"Am. J. Health Syst. Pharm."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1056\/NEJM198807213190307","article-title":"Plasmid-Mediated Resistance to Vancomycin and Teicoplanin in Enterococcus faecium","volume":"319","author":"Leclercq","year":"1988","journal-title":"N. Engl. J. Med."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"3991","DOI":"10.2147\/IJN.S443051","article-title":"Innovative Vancomycin-Loaded Hydrogel-Based Systems\u2014New Opportunities for the Antibiotic Therapy","volume":"19","author":"Florczyk","year":"2024","journal-title":"Int. J. Nanomed."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"1435","DOI":"10.1161\/CIR.0000000000000296","article-title":"Infective Endocarditis in Adults: Diagnosis, Antimicrobial Therapy, and Management of Complications: A Scientific Statement for Healthcare Professionals From the American Heart Association","volume":"132","author":"Baddour","year":"2015","journal-title":"Circulation"},{"key":"ref_103","doi-asserted-by":"crossref","unstructured":"Save, J., Que, Y.-A., Entenza, J., and Resch, G. (2022). Subtherapeutic Doses of Vancomycin Synergize with Bacteriophages for Treatment of Experimental Methicillin-Resistant Staphylococcus aureus Infective Endocarditis. Viruses, 14.","DOI":"10.1101\/2022.06.02.494631"},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"21676","DOI":"10.1038\/s41598-021-01052-5","article-title":"Novel Colistin-EDTA Combination for Successful Eradication of Colistin-Resistant Klebsiella pneumoniae Catheter-Related Biofilm Infections","volume":"11","author":"Shein","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"1259","DOI":"10.2147\/IDR.S438576","article-title":"The Potentiation Activity of Azithromycin in Combination with Colistin or Levofloxacin Against Pseudomonas aeruginosa Biofilm Infection","volume":"17","author":"Wang","year":"2024","journal-title":"Infect. Drug Resist."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1093\/jac\/dkr535","article-title":"In Vitro Efficacy of Fosfomycin-Containing Regimens against Methicillin-Resistant Staphylococcus aureus in Biofilms","volume":"67","author":"Tang","year":"2012","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"6413982","DOI":"10.1155\/2016\/6413982","article-title":"Efficacy of Linezolid and Fosfomycin in Catheter-Related Biofilm Infection Caused by Methicillin-Resistant Staphylococcus aureus","volume":"2016","author":"Chai","year":"2016","journal-title":"BioMed Res. Int."},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"859","DOI":"10.1128\/AAC.04246-14","article-title":"Daptomycin plus Fosfomycin, a Synergistic Combination in Experimental Implant-Associated Osteomyelitis Due to Methicillin-Resistant Staphylococcus aureus in Rats","volume":"59","author":"Lingscheid","year":"2015","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"5080","DOI":"10.1128\/AAC.00702-13","article-title":"Vancomycin-Rifampin Combination Therapy Has Enhanced Efficacy against an Experimental Staphylococcus aureus Prosthetic Joint Infection","volume":"57","author":"Niska","year":"2013","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"3880","DOI":"10.1128\/AAC.00134-09","article-title":"Activities of Daptomycin and Vancomycin Alone and in Combination with Rifampin and Gentamicin against Biofilm-Forming Methicillin-Resistant Staphylococcus aureus Isolates in an Experimental Model of Endocarditis","volume":"53","author":"LaPlante","year":"2009","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_111","doi-asserted-by":"crossref","unstructured":"Herrera-Hidalgo, L., Fern\u00e1ndez-Rubio, B., Luque-M\u00e1rquez, R., L\u00f3pez-Cort\u00e9s, L.E., Gil-Navarro, M.V., and de Alarc\u00f3n, A. (2023). Treatment of Enterococcus faecalis Infective Endocarditis: A Continuing Challenge. 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