{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T14:47:47Z","timestamp":1785422867405,"version":"3.56.0"},"reference-count":53,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T00:00:00Z","timestamp":1784851200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Spanish Ministry of Science and Innovation and Universities","award":["PID2023-146091OB-I00"],"award-info":[{"award-number":["PID2023-146091OB-I00"]}]},{"award":["PID2023-146091OB-I00"],"award-info":[{"award-number":["PID2023-146091OB-I00"]}],"id":[{"id":"https:\/\/ror.org\/05r0vyz12","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Severo Ochoa Programme for Centers of Excellence in R&D","award":["CEX2023-001286-S MICIU\/AEI\/10.13039\/501100011033"],"award-info":[{"award-number":["CEX2023-001286-S MICIU\/AEI\/10.13039\/501100011033"]}]},{"DOI":"10.13039\/501100004837","name":"Ministerio de Ciencia e Innovaci\u00f3n","doi-asserted-by":"crossref","award":["FORT23\/00028"],"award-info":[{"award-number":["FORT23\/00028"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"crossref"}]},{"award":["FORT23\/00028"],"award-info":[{"award-number":["FORT23\/00028"]}],"id":[{"id":"https:\/\/ror.org\/05r0vyz12","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004587","name":"Instituto de Salud Carlos III","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100004587","id-type":"DOI","asserted-by":"crossref"}]},{"id":[{"id":"https:\/\/ror.org\/00ca2c886","id-type":"ROR","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100010067","name":"Gobierno de Arag\u00f3n","doi-asserted-by":"crossref","award":["T67_23R"],"award-info":[{"award-number":["T67_23R"]}],"id":[{"id":"10.13039\/501100010067","id-type":"DOI","asserted-by":"crossref"}]},{"award":["T67_23R"],"award-info":[{"award-number":["T67_23R"]}],"id":[{"id":"https:\/\/ror.org\/0425pg203","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background: Antimicrobial combination therapies outperform traditional monotherapies by offering additive or synergetic effects, a broader spectrum of activity, enhanced efficacy against polymicrobial infections, and a reduced risk of resistance development and infection relapse. Methods: Herein, we have combined the chemotherapeutic antibiotic alkylating agent mitomycin C (MMC) with the wide-spectrum antiseptic octenidine hydrochloride (OCT). The non-specific mode of action via membrane disruption of the latter, together with the DNA-alkylating ability of the former, is here combined to produce bactericidal antibiotic-like mixtures against clinical isolates of Methicillin-resistant Staphylococcus aureus and uropathogenic Escherichia coli. The concentrations required for both antimicrobials to inhibit or eradicate bacterial biofilms as well as intracellular persisters are also determined here. The cytotoxicity of the selected combinations on eukaryotic cells was also evaluated in traditional 2D cultures and in 3D-fibroblast spheroids to mimic a physiologically relevant microenvironment present in topical infections. Finally, the ecotoxicity of the studied compounds was also evaluated through standardized bioassays using representative microorganisms commonly employed in environmental toxicity assessments such as Daphnia magna (D. magna) and Aliivibrio fischeri (A. fischeri). Results: Compared to monotherapy, these environmentally friendly antibiotic-like combinations at specific concentrations may achieve additive antimicrobial effects against planktonic, sessile, and intracellular pathogenic strains. However, the ecotoxicological response was bioindicator-dependent: the OCT\u2013MMC combination reduced toxicity in A. fischeri, but not in D. magna, where toxicity was comparable to OCT alone, indicating OCT as the main driver. Thus, any reduction in ecotoxicity appears species-specific. Nonetheless, the use of lower doses may help minimize selective pressure for resistance. Conclusions: Collectively, these findings demonstrate that selected MMC\u2013OCT combinations achieve antibacterial efficacy against planktonic, sessile, and intracellular pathogenic bacteria while preserving the viability of eukaryotic cells and exhibiting minimal toxicity toward standard ecotoxicological model organisms. Further studies are needed to guarantee the safe use of this combination at selected doses and to guarantee its non-systemic absorption after topical administration.<\/jats:p>","DOI":"10.3390\/antibiotics15080721","type":"journal-article","created":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T10:38:41Z","timestamp":1784889521000},"page":"721","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Towards Antimicrobial Formulations of Repurposed Drugs and Cationic Surfactants: Efficacy, Cytotoxicity on Human Cell Lines, and Ecotoxicity in Aquatic Models"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-7603-0003","authenticated-orcid":false,"given":"Alida","family":"Monreal","sequence":"first","affiliation":[{"name":"Instituto de Nanociencia y Materiales de Arag\u00f3n (INMA), CSIC-Universidad de Zaragoza, 50009 Zaragoza, Spain"},{"name":"Aragon Health Research Institute (IIS Aragon), 50009 Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9444-6892","authenticated-orcid":false,"given":"Diego","family":"Ballestero","sequence":"additional","affiliation":[{"name":"Universidad San Jorge, Villanueva de G\u00e1llego, 50830 Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1505-498X","authenticated-orcid":false,"given":"Cristina","family":"Yus","sequence":"additional","affiliation":[{"name":"Instituto de Nanociencia y Materiales de Arag\u00f3n (INMA), CSIC-Universidad de Zaragoza, 50009 Zaragoza, Spain"},{"name":"Aragon Health Research Institute (IIS Aragon), 50009 Zaragoza, Spain"},{"name":"Department of Chemical and Environmental Engineering, University of Zaragoza, Campus R\u00edo Ebro-Edificio I+D, C\/Poeta Mariano Esquillor S\/N, 50018 Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iman","family":"Mattar","sequence":"additional","affiliation":[{"name":"Instituto de Nanociencia y Materiales de Arag\u00f3n (INMA), CSIC-Universidad de Zaragoza, 50009 Zaragoza, Spain"},{"name":"Aragon Health Research Institute (IIS Aragon), 50009 Zaragoza, Spain"},{"name":"Department of Chemical and Environmental Engineering, University of Zaragoza, Campus R\u00edo Ebro-Edificio I+D, C\/Poeta Mariano Esquillor S\/N, 50018 Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2293-363X","authenticated-orcid":false,"given":"Gracia","family":"Mendoza","sequence":"additional","affiliation":[{"name":"Aragon Health Research Institute (IIS Aragon), 50009 Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3061-2705","authenticated-orcid":false,"given":"Elisa","family":"Langa","sequence":"additional","affiliation":[{"name":"Universidad San Jorge, Villanueva de G\u00e1llego, 50830 Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3186-1722","authenticated-orcid":false,"given":"M\u00aa Rosa","family":"Pino-Ot\u00edn","sequence":"additional","affiliation":[{"name":"Universidad San Jorge, Villanueva de G\u00e1llego, 50830 Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3165-0156","authenticated-orcid":false,"given":"Manuel","family":"Arruebo","sequence":"additional","affiliation":[{"name":"Instituto de Nanociencia y Materiales de Arag\u00f3n (INMA), CSIC-Universidad de Zaragoza, 50009 Zaragoza, Spain"},{"name":"Aragon Health Research Institute (IIS Aragon), 50009 Zaragoza, Spain"},{"name":"Department of Chemical and Environmental Engineering, University of Zaragoza, Campus R\u00edo Ebro-Edificio I+D, C\/Poeta Mariano Esquillor S\/N, 50018 Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,24]]},"reference":[{"key":"ref_1","unstructured":"Sinawe, H., and Casadesus, D. (2025). Mitomycin, StatPearls."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"3901","DOI":"10.1021\/bi00435a041","article-title":"DNA Sequence Specificity of Mitomycin Cross-Linking","volume":"28","author":"Teng","year":"1989","journal-title":"Biochemistry"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"4406","DOI":"10.1111\/1462-2920.12873","article-title":"Combatting Bacterial Infections by Killing Persister Cells with Mitomycin C","volume":"17","author":"Kwan","year":"2015","journal-title":"Environ. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1016\/j.ijantimicag.2016.08.022","article-title":"Repurposing the Anticancer Drug Mitomycin C for the Treatment of Persistent Acinetobacter baumannii Infections","volume":"49","author":"Wood","year":"2017","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Domalaon, R., Ammeter, D., Brizuela, M., Gorityala, B.K., Zhanel, G.G., and Schweizer, F. (2019). Repurposed Antimicrobial Combination Therapy: Tobramycin-Ciprofloxacin Hybrid Augments Activity of the Anticancer Drug Mitomycin C Against Multidrug-Resistant Gram-Negative Bacteria. Front. Microbiol., 10.","DOI":"10.3389\/fmicb.2019.01556"},{"key":"ref_6","doi-asserted-by":"crossref","unstructured":"Pacios, O., Fern\u00e1ndez-Garc\u00eda, L., Bleriot, I., Blasco, L., Gonz\u00e1lez-Bardanca, M., L\u00f3pez, M., Fern\u00e1ndez-Cuenca, F., Oteo, J., Pascual, \u00c1., and Mart\u00ednez-Mart\u00ednez, L. (2021). Enhanced Antibacterial Activity of Repurposed Mitomycin C and Imipenem in Combination with the Lytic Phage VB_KpnM-VAC13 against Clinical Isolates of Klebsiella pneumoniae. Antimicrob. Agents Chemother., 65.","DOI":"10.1128\/AAC.00900-21"},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Svedholm, E., Bruce, B., Parcell, B.J., and Coote, P.J. (2024). Repurposing Mitomycin C in Combination with Pentamidine or Gentamicin to Treat Infections with Multi-Drug-Resistant (MDR) Pseudomonas aeruginosa. Antibiotics, 13.","DOI":"10.3390\/antibiotics13020177"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Wambaugh, M.A., Shakya, V.P.S., Lewis, A.J., Mulvey, M.A., and Brown, J.C.S. (2017). High-Throughput Identification and Rational Design of Synergistic Small-Molecule Pairs for Combating and Bypassing Antibiotic Resistance. PLoS Biol., 15.","DOI":"10.1371\/journal.pbio.2001644"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"de Carvalho, C.C.C.R. (2022). Adaptation of Bacteria to Antineoplastic Agents Involves Persister Cells and Increases Resistance to Antibiotics. Bioengineering, 9.","DOI":"10.3390\/bioengineering9080355"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1038\/nature02241","article-title":"SOS Response Promotes Horizontal Dissemination of Antibiotic Resistance Genes","volume":"427","author":"Beaber","year":"2004","journal-title":"Nature"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1572","DOI":"10.1093\/jac\/dkz070","article-title":"Enhanced Emergence of Antibiotic-Resistant Pathogenic Bacteria After In Vitro Induction with Cancer Chemotherapy Drugs","volume":"74","author":"Meunier","year":"2019","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1016\/j.jgar.2021.05.010","article-title":"Challenges in the Management of Chronic Wound Infections","volume":"26","author":"Falcone","year":"2021","journal-title":"J. Glob. Antimicrob. Resist."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e23","DOI":"10.1016\/j.jhin.2018.03.037","article-title":"Pseudomonas aeruginosa Adapts to Octenidine in the Laboratory and a Simulated Clinical Setting, Leading to Increased Tolerance to Chlorhexidine and Other Biocides","volume":"100","author":"Shepherd","year":"2018","journal-title":"J. Hosp. Infect."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1280","DOI":"10.1093\/jac\/dkm092","article-title":"Low-Level Exposure of MRSA to Octenidine Dihydrochloride Does Not Select for Resistance","volume":"59","author":"Gemmell","year":"2007","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"3868","DOI":"10.1021\/acsinfecdis.4c00433","article-title":"Highly Effective Biocides against Pseudomonas aeruginosa Reveal New Mechanistic Insights Across Gram-Negative Bacteria","volume":"10","author":"Sanchez","year":"2024","journal-title":"ACS Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Lescat, M., Magnan, M., Kenmoe, S., Nordmann, P., and Poirel, L. (2022). Co-Lateral Effect of Octenidine, Chlorhexidine and Colistin Selective Pressures on Four Enterobacterial Species: A Comparative Genomic Analysis. Antibiotics, 11.","DOI":"10.3390\/antibiotics11010050"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"P33","DOI":"10.1186\/2047-2994-4-S1-P33","article-title":"Residual Antiseptic Efficacy of Octenidine Dihydrochloride Versus Chlorhexidine Gluconate in Alcoholic Solutions","volume":"4","author":"Brill","year":"2015","journal-title":"Antimicrob. Resist. Infect. Control"},{"key":"ref_18","first-page":"1","article-title":"Residual Antimicrobial Effect of Chlorhexidine Digluconate and Octenidine Dihydrochloride on Reconstructed Human Epidermis","volume":"27","author":"Langer","year":"2014","journal-title":"Ski. Pharmacol. Physiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/S0195-6701(03)00260-3","article-title":"A Standardized Test to Assess the Impact of Different Organic Challenges on the Antimicrobial Activity of Antiseptics","volume":"55","author":"Pitten","year":"2003","journal-title":"J. Hosp. Infect."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1038\/s41598-020-79378-9","article-title":"Octenidine-Based Hydrogel Shows Anti-Inflammatory and Protease-Inhibitory Capacities in Wounded Human Skin","volume":"11","author":"Seiser","year":"2021","journal-title":"Sci. Rep."},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Mart\u00edn Bueno, J., Camacho-Mu\u00f1oz, M., Santos, J., Aparicio, I., and Alonso, E. (2014). Occurrence and Ecotoxicological Risk Assessment of 14 Cytostatic Drugs in Wastewater. Water, 225.","DOI":"10.1007\/s11270-014-1896-y"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1016\/j.scitotenv.2012.12.061","article-title":"Removal of Cytostatic Drugs from Aquatic Environment: A Review","volume":"445\u2013446","author":"Zhang","year":"2013","journal-title":"Sci. Total Environ."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"167","DOI":"10.1016\/j.jhydrol.2007.09.054","article-title":"Do Cytotoxic Chemotherapy Drugs Discharged into Rivers Pose a Risk to the Environment and Human Health? An Overview and UK Case Study","volume":"348","author":"Johnson","year":"2008","journal-title":"J. Hydrol."},{"key":"ref_24","first-page":"100538","article-title":"Bibliometric Analysis of Emerging Contaminants and Cytostatic Compounds: Understanding the Current Challenges","volume":"17","author":"Corpa","year":"2025","journal-title":"J. Hazard. Mater. Adv."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"e00210-21","DOI":"10.1128\/AEM.00210-21","article-title":"Long-Term Exposure to Octenidine in a Simulated Sink Trap Environment Results in Selection of Pseudomonas aeruginosa, Citrobacter, and Enterobacter Isolates with Mutations in Efflux Pump Regulators","volume":"87","author":"Garratt","year":"2021","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Kl\u00e1tyik, S., Bohus, P., Darvas, B., and Sz\u00e9k\u00e1cs, A. (2017). Authorization and Toxicity of Veterinary Drugs and Plant Protection Products: Residues of the Active Ingredients in Food and Feed and Toxicity Problems Related to Adjuvants. Front. Vet. Sci., 4.","DOI":"10.3389\/fvets.2017.00146"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.jmb.2006.05.017","article-title":"The Mitomycin C (MMC)-Binding Protein from MMC-Producing Microorganisms Protects from the Lethal Effect of Bleomycin: Crystallographic Analysis to Elucidate the Binding Mode of the Antibiotic to the Protein","volume":"360","author":"Danshiitsoodol","year":"2006","journal-title":"J. Mol. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1016\/j.bbamem.2017.11.007","article-title":"Modification of Membrane Properties and Fatty Acids Biosynthesis-Related Genes in Escherichia coli and Staphylococcus aureus: Implications for the Antibacterial Mechanism of Naringenin","volume":"1860","author":"Wang","year":"2018","journal-title":"Biochim. Biophys. Acta BBA Biomembr."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Denkel, L.A., Kramer, T.S., Schwab, F., Golembus, J., Wolke, S., Gastmeier, P., and Geffers, C. (2022). Chlorhexidine and Octenidine Susceptibility of Bacterial Isolates from Clinical Samples in a Three-Armed Cluster Randomised Decolonisation Trial. PLoS ONE, 17.","DOI":"10.1371\/journal.pone.0278569"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1111\/mmi.14699","article-title":"Friends or Enemies? The Complicated Relationship Between Pseudomonas aeruginosa and Staphylococcus aureus","volume":"116","author":"Yung","year":"2021","journal-title":"Mol. Microbiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"27877","DOI":"10.1038\/s41598-024-79573-y","article-title":"Impact of Mixed Staphylococcus aureus-Pseudomonas aeruginosa Biofilm on Susceptibility to Antimicrobial Treatments in a 3D In Vitro Model","volume":"14","author":"Landa","year":"2024","journal-title":"Sci. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"44S","DOI":"10.1016\/j.amjsurg.2003.10.008","article-title":"An Evidence-Based Approach to Diabetic Foot Infections","volume":"186","author":"Frykberg","year":"2003","journal-title":"Am. J. Surg."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e13688","DOI":"10.1111\/eci.13688","article-title":"The Skin Microbiome of Infected Pressure Ulcers: A Review and Implications for Health Professionals","volume":"52","author":"Gomes","year":"2022","journal-title":"Eur. J. Clin. Investig."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"404","DOI":"10.3390\/pathogens3020404","article-title":"Antibiofilm Effect of Octenidine Hydrochloride on Staphylococcus aureus, MRSA and VRSA","volume":"3","author":"Amalaradjou","year":"2014","journal-title":"Pathogens"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"e0228121","DOI":"10.1128\/mBio.02281-21","article-title":"Synergism Versus Additivity: Defining the Interactions between Common Disinfectants","volume":"12","author":"Noel","year":"2021","journal-title":"MBio"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3392","DOI":"10.1016\/j.bpj.2021.06.027","article-title":"Unraveling the Mechanism of Octenidine and Chlorhexidine on Membranes: Does Electrostatics Matter?","volume":"120","author":"Rzycki","year":"2021","journal-title":"Biophys. J."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"e00180-22","DOI":"10.1128\/aem.00180-22","article-title":"Disruption of the Cytoplasmic Membrane Structure and Barrier Function Underlies the Potent Antiseptic Activity of Octenidine in Gram-Positive Bacteria","volume":"88","author":"Malanovic","year":"2022","journal-title":"Appl. Environ. Microbiol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3576","DOI":"10.1093\/jac\/dkaa346","article-title":"Octenidine\/Carbenicillin GUMBOS as Potential Treatment for Oropharyngeal Gonorrhoea","volume":"75","author":"Lopez","year":"2020","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Kwiatkowski, P., \u0141opusiewicz, \u0141., Kostek, M., Droz\u0142owska, E., Pruss, A., Wojciuk, B., Sienkiewicz, M., Zieli\u0144ska-Bli\u017aniewska, H., and Do\u0142\u0119gowska, B. (2020). The Antibacterial Activity of Lavender Essential Oil Alone and In Combination with Octenidine Dihydrochloride Against MRSA Strains. Molecules, 25.","DOI":"10.3390\/molecules25010095"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/j.ijantimicag.2016.05.008","article-title":"Synergistic Antibiofilm Efficacy of Various Commercial Antiseptics, Enzymes and EDTA: A Study of Pseudomonas aeruginosa and Staphylococcus aureus Biofilms","volume":"48","author":"Lefebvre","year":"2016","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Van de Vliet, L., Vackier, T., Thevissen, K., Decoster, D., and Steenackers, H.P. (2024). Imidazoles and Quaternary Ammonium Compounds as Effective Therapies against (Multidrug-Resistant) Bacterial Wound Infections. Antibiotics, 13.","DOI":"10.3390\/antibiotics13100949"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"372","DOI":"10.1016\/j.jbiotec.2005.12.021","article-title":"Culture of Skin Cells in 3D Rather than 2D Improves Their Ability to Survive Exposure to Cytotoxic Agents","volume":"122","author":"Sun","year":"2006","journal-title":"J. Biotechnol."},{"key":"ref_43","doi-asserted-by":"crossref","unstructured":"Chelmu\u0219-Burlacu, A., Tang, E., and Pieptu, D. (2023). Phenotypic Modulation of Adipose-Derived Stem Cells and Fibroblasts Treated with Povidone\u2013Iodine and Chlorhexidine in Mono and Coculture Models. Biomedicines, 11.","DOI":"10.3390\/biomedicines11071855"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"327","DOI":"10.1007\/s00405-009-1151-0","article-title":"Topical Use of MMC in the Upper Aerodigestive Tract: A Review on the Side Effects","volume":"267","author":"Veen","year":"2010","journal-title":"Eur. Arch. Oto-Rhino-Laryngol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.otohns.2006.02.024","article-title":"The Effects of Intradermal and Topical Mitomycin C on Wound Healing","volume":"135","author":"Porter","year":"2006","journal-title":"Otolaryngol.-Head Neck Surg."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"660","DOI":"10.1080\/02713683.2023.2189636","article-title":"Analysis of the Systemic Exposure of Mitomycin C Used in Glaucoma Filtering Surgery Among Women in the Reproductive Age Group","volume":"48","author":"Angmo","year":"2023","journal-title":"Curr. Eye Res."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"295","DOI":"10.1038\/nrmicro1384","article-title":"Small Colony Variants: A Pathogenic Form of Bacteria That Facilitates Persistent and Recurrent Infections","volume":"4","author":"Proctor","year":"2006","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Butucel, E., Balta, I., Ahmadi, M., Dumitrescu, G., Morariu, F., Pet, I., Stef, L., and Corcionivoschi, N. (2022). Biocides as Biomedicines against Foodborne Pathogenic Bacteria. Biomedicines, 10.","DOI":"10.3390\/biomedicines10020379"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1295","DOI":"10.1016\/j.scitotenv.2018.01.066","article-title":"Vibrio fischeri Bioluminescence Inhibition Assay for Ecotoxicity Assessment: A Review","volume":"626","author":"Abbas","year":"2018","journal-title":"Sci. Total Environ."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"17006","DOI":"10.1038\/s41598-017-17191-7","article-title":"Feeding Type and Development Drive the Ingestion of Microplastics by Freshwater Invertebrates","volume":"7","author":"Scherer","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"26977","DOI":"10.1007\/s11356-021-17928-y","article-title":"Mixture Toxicity of Six Pharmaceuticals Towards Aliivibrio fischeri, Daphnia magna, and Lemna minor","volume":"29","author":"Grabarczyk","year":"2022","journal-title":"Environ. Sci. Pollut. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1716","DOI":"10.1002\/etc.198","article-title":"Toxicity of Three Binary Mixtures to Daphnia magna: Comparing Chemical Modes of Action and Deviations from Conceptual Models","volume":"29","author":"Loureiro","year":"2010","journal-title":"Environ. Toxicol. Chem."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"143038","DOI":"10.1016\/j.scitotenv.2020.143038","article-title":"Daphnia magna Model in the Toxicity Assessment of Pharmaceuticals: A Review","volume":"763","author":"Tkaczyk","year":"2021","journal-title":"Sci. Total Environ."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/15\/8\/721\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,26]],"date-time":"2026-07-26T04:18:59Z","timestamp":1785039539000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/15\/8\/721"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,24]]},"references-count":53,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["antibiotics15080721"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics15080721","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,24]]}}}