Darji, Siddhi A.Siddhi A.DarjiRaulji, AvaniAvaniRauljiPatel, AxitaAxitaPatelPandya, HimanshuHimanshuPandyaPatel, RupalRupalPatelPatel, ChiragChiragPatelDatta, BhaskarBhaskarDattaBanerjee, DevjaniDevjaniBanerjee2026-02-252026-02-252026-01-010021-882010.1038/s41429-026-00896-12-s2.0-105030331515https://repository.iitgn.ac.in/handle/IITG2025/34669Antimicrobial resistance (AMR) in Escherichia coli (E.coli) poses a significant global threat to public health due to increasing resistance against antibiotics. This study explored a novel combination therapy by investigating the synergistic potential of three distinct antibiotics to combat AMR in E. coli isolates. Multi drug resistant (MDR), extensive drug resistant (XDR), and pan drug resistant (PDR) E. coli isolates were confirmed using the automated system Vitek followed by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). Dual and triple combinations of meropenem, ceftazidime, and polymyxin B were evaluated using a checkerboard assay and were further corroborated using field emission scanning electron microscopy (FE-SEM). Checkerboard assays demonstrated significant bactericidal activity up to 24 h for all MDR, XDR, and PDR isolates treated with combinations of meropenem + polymyxin B; ceftazidime + polymyxin B and meropenem + ceftazidime + polymyxin B. Notably, few of the XDR and PDR isolates showed no bacterial growth for up to 96 h with meropenem + polymyxin B; ceftazidime + polymyxin B; and meropenem + ceftazidime + polymyxin B combinations. FE-SEM images supported these findings, revealing significant plasmolysis with meropenem + polymyxin B; ceftazidime + polymyxin B; and meropenem + ceftazidime + polymyxin B treatments compared to the control. Dual and triple combination regimens were found to be effective for treating MDR, XDR, and PDR isolates. The present study suggested a promising strategy in in vitro conditions, but its effectiveness still requires further in vivo validation considering pharmacokinetics/pharmacodynamics (PK-PD) modeling and dynamic dosing regimens.en-USAntibioticsAntimicrobial resistanceMetagenomicsArticle18811469ArticleArticleWOS:001692572900001