{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T11:38:32Z","timestamp":1785411512629,"version":"3.56.0"},"reference-count":29,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2023-00219399"],"award-info":[{"award-number":["RS-2023-00219399"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["RS-2025-00559904"],"award-info":[{"award-number":["RS-2025-00559904"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"award":["RS-2023-00219399"],"award-info":[{"award-number":["RS-2023-00219399"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"publisher"}]},{"award":["RS-2025-00559904"],"award-info":[{"award-number":["RS-2025-00559904"]}],"id":[{"id":"https:\/\/ror.org\/013aysd81","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background\/Objectives: Imipenem, known as a carbapenem, is widely used in combination with Cilastatin to treat severe bacterial infections. Imipenem is a \u03b2-lactam antibiotic with potent antibacterial activity but a relatively unstable chemical structure. Due to these structural characteristics, it may degrade or undergo structural changes over time in aqueous solutions. Methods: In this study, Imipenem was investigated for its structural stability over time in aqueous solution at 37 \u00b0C. Structural changes in the Imipenem\/Cilastatin solution were confirmed by HPLC-DAD at the maximum absorbance wavelength. Results: Imipenem undergone progressive degradation and structural transformation for the dimerization, while Cilastatin remained stable under the same conditions. LC-Q-TOF\/MS confirmed the formation of a dimeric Imipenem species after prolonged incubation. Antibacterial activity showed that Imipenem was effective against P. carotovorum regardless of the dissolution times. However, Imipenem solution after 24 h with chemical degradation exhibited significantly decreased effects against E. coli and P. aeruginosa. Conclusions: Accordingly, the patterns of metabolite changes in Imipenem and Cilastatin were characterized according to concentration and dissolution time, and the corresponding antibacterial activities against different bacterial strains were compared.<\/jats:p>","DOI":"10.3390\/antibiotics15070704","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T10:44:02Z","timestamp":1784544242000},"page":"704","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Time-Dependent Degradation of Imipenem in Aqueous Solution and Its Impact on Antibacterial Activity"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-5811-0638","authenticated-orcid":false,"given":"Gu Hae","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Engineering, Institute of Agricultural and Life Science (IALS), Anti-Aging Bio Cell Factory Regional Leading Research Center (ABC-RLRC), Gyeongsang National University, Jinju 52828, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-2740-6514","authenticated-orcid":false,"given":"Na Rae","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Engineering, Institute of Agricultural and Life Science (IALS), Anti-Aging Bio Cell Factory Regional Leading Research Center (ABC-RLRC), Gyeongsang National University, Jinju 52828, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-0083-0999","authenticated-orcid":false,"given":"Jisoo","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Engineering, Institute of Agricultural and Life Science (IALS), Anti-Aging Bio Cell Factory Regional Leading Research Center (ABC-RLRC), Gyeongsang National University, Jinju 52828, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-5709-8048","authenticated-orcid":false,"given":"Seungjae","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Engineering, Institute of Agricultural and Life Science (IALS), Anti-Aging Bio Cell Factory Regional Leading Research Center (ABC-RLRC), Gyeongsang National University, Jinju 52828, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-5199-8680","authenticated-orcid":false,"given":"Seungyu","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Engineering, Institute of Agricultural and Life Science (IALS), Anti-Aging Bio Cell Factory Regional Leading Research Center (ABC-RLRC), Gyeongsang National University, Jinju 52828, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7402-7298","authenticated-orcid":false,"given":"Dawon","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Physiology, College of Medicine, Gyeongsang National University, Jinju 52727, Republic of Korea"},{"name":"Department of Convergence Medical Science and Institute of Medical Sciences, Gyeongsang National University, Jinju 52727, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1943-6467","authenticated-orcid":false,"given":"Jeong Yoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Engineering, Institute of Agricultural and Life Science (IALS), Anti-Aging Bio Cell Factory Regional Leading Research Center (ABC-RLRC), Gyeongsang National University, Jinju 52828, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1016\/S0025-6196(12)61732-7","article-title":"Imipenem","volume":"66","author":"Hellinger","year":"1991","journal-title":"Mayo Clin. Proc."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1016\/S0025-7125(16)30759-3","article-title":"Imipenem: A New Carbapenem Antibiotic","volume":"72","author":"Lipman","year":"1988","journal-title":"Med. Clin. N. Am."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e4471","DOI":"10.1002\/bmc.4471","article-title":"Stability and Degradation Products of Imipenem Applying High-Resolution Mass Spectrometry: An Analytical Study Focused on Solutions for Infusion","volume":"33","author":"Tsao","year":"2019","journal-title":"Biomed. Chromatogr."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1002\/jps.2600790816","article-title":"Stability and Kinetics of Degradation of Imipenem in Aqueous Solution","volume":"79","author":"Smith","year":"1990","journal-title":"J. Pharm. Sci."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"99","DOI":"10.2165\/00003495-199651010-00008","article-title":"Imipenem\/Cilastatin: An Update of Its Antibacterial Activity, Pharmacokinetics and Therapeutic Efficacy in the Treatment of Serious Infections","volume":"51","author":"Balfour","year":"1996","journal-title":"Drugs"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1016\/S0025-7125(16)30037-2","article-title":"Carbapenems","volume":"79","author":"Norrby","year":"1995","journal-title":"Med. Clin. N. Am."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1016\/0002-9343(85)90099-3","article-title":"Carbapenems: Special Properties Contributing to Their Activity","volume":"78","author":"Neu","year":"1985","journal-title":"Am. J. Med."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Codjoe, F.S., and Donkor, E.S. (2017). Carbapenem Resistance: A Review. Med. Sci., 6.","DOI":"10.3390\/medsci6010001"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4943","DOI":"10.1128\/AAC.00296-11","article-title":"Carbapenems: Past, Present, and Future","volume":"55","author":"Endimiani","year":"2011","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"129","DOI":"10.1093\/jac\/30.2.129","article-title":"Inactivation of New Carbapenem Antibiotics by Dehydropeptidase-I from Porcine and Human Renal Cortex","volume":"30","author":"Hikida","year":"1992","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1093\/jac\/18.Supplement_E.79","article-title":"An Overview of the Pharmacology of Imipenem\/Cilastatin","volume":"18","author":"Drusano","year":"1986","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"15593258211059325","DOI":"10.1177\/15593258211059325","article-title":"Influence of Concentration and Temperature on Stability of Imipenem Focused on Solutions for Extended Infusion","volume":"19","author":"Sornsuvit","year":"2021","journal-title":"Dose-Response"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1007\/s40265-021-01471-8","article-title":"Imipenem\/Cilastatin\/Relebactam: A Review in Gram-Negative Bacterial Infections","volume":"81","author":"Heo","year":"2021","journal-title":"Drugs"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1080\/14740338.2020.1796967","article-title":"Cilastatin as a Protective Agent against Drug-Induced Nephrotoxicity: A Literature Review","volume":"19","author":"Shayan","year":"2020","journal-title":"Expert Opin. Drug Saf."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"408","DOI":"10.2165\/00003495-199244030-00008","article-title":"Imipenem\/Cilastatin","volume":"44","author":"Buckley","year":"1992","journal-title":"Drugs"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1016\/j.tox.2018.05.011","article-title":"Exposure to Imipenem\/Cilastatin Causes Nephrotoxicity and Even Urolithiasis in Wistar Rats","volume":"404\u2013405","author":"Tahri","year":"2018","journal-title":"Toxicology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1016\/0002-9343(85)90102-0","article-title":"Imipenem\/Cilastatin: Pharmacokinetic Profile in Renal Insufficiency","volume":"78","author":"Gibson","year":"1985","journal-title":"Am. J. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1128\/AAC.29.2.188","article-title":"Imipenem Pharmacokinetics and Body Fluid Concentrations in Patients Receiving High-Dose Treatment for Serious Infections","volume":"29","author":"MacGregor","year":"1986","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1027","DOI":"10.2165\/00003495-200767070-00006","article-title":"Comparative Review of the Carbapenems","volume":"67","author":"Zhanel","year":"2012","journal-title":"Drugs"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"183","DOI":"10.2165\/00003495-198733030-00001","article-title":"Imipenem\/Cilastatin. A Review of Its Antibacterial Activity, Pharmacokinetic Properties and Therapeutic Efficacy","volume":"33","author":"Clissold","year":"1987","journal-title":"Drugs"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"230","DOI":"10.1177\/0885066609335660","article-title":"The Use of Carbapenems in the Treatment of Serious Infections","volume":"24","author":"Baughman","year":"2009","journal-title":"J. Intensive Care Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/S0924-8579(98)00094-6","article-title":"Carbapenems in Clinical Practice: A Guide to Their Use in Serious Infection","volume":"11","author":"Bradley","year":"1999","journal-title":"Int. J. Antimicrob. Agents"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/jac\/12.suppl_D.1","article-title":"Thienamycin: Development of Imipenem-Cilastatin","volume":"12","author":"Kahan","year":"1983","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"14900","DOI":"10.1038\/s41598-018-33148-w","article-title":"A Natural Deep Eutectic Solvent Formulated to Stabilize \u03b2-Lactam Antibiotics","volume":"8","author":"Olivares","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1128\/AAC.29.5.936","article-title":"Degradation kinetics of imipenem in normal saline and in human serum","volume":"29","author":"Swanson","year":"1986","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e0139923","DOI":"10.1128\/aac.01399-23","article-title":"Dosing Strategy To Mitigate Thermal Drug Degradation","volume":"68","author":"Zhou","year":"2024","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"134896","DOI":"10.1016\/j.colsurfa.2024.134896","article-title":"Particle Behaviors of Imipenem\/Cilastatin in Various Liquids Investigated by Chemical Structures and Temporal Microscope Observations","volume":"701","author":"Zhang","year":"2024","journal-title":"Colloids Surf. A Physicochem. Eng. Asp."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e0093822","DOI":"10.1128\/spectrum.00938-22","article-title":"Direct Colorimetry of Imipenem Decomposition as a Novel Cost-Effective Method for Detecting Carbapenemase-Producing Enterobacteria","volume":"10","author":"Kotsakis","year":"2022","journal-title":"Microbiol. Spectr."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"9199","DOI":"10.1016\/S0040-4020(01)00905-X","article-title":"A Tentative Rationalization of Microwave Effects in Organic Synthesis According to the Reaction Medium, and Mechanistic Considerations","volume":"57","author":"Perreux","year":"2001","journal-title":"Tetrahedron"}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/15\/7\/704\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T11:24:50Z","timestamp":1784546690000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/15\/7\/704"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,20]]},"references-count":29,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2026,7]]}},"alternative-id":["antibiotics15070704"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics15070704","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,20]]}}}