Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Oct 25;82(12):578.
doi: 10.1007/s00284-025-04543-0.

Evaluating Antibacterial Efficacy of Cefiderocol and Cefepime/Taniborbactam Against OXA-48-Like and NDM-Expressing Enterobacterales: An In-Vitro and In-Silico Approach

Mohanraj Gopikrishnan  1 , Sriroopreddy Ramireddy  1 , Yamuna Devi Bakathavatchalam  2 , Rinku Polachirakkal Varghese  1 , D Thirumal Kumar  3 , Binesh Lal  2 , Abi Manesh  4 , Kamini Walia  5 , Balaji Veeraraghavan  6 , C George Priya Doss  7
Affiliations

Evaluating Antibacterial Efficacy of Cefiderocol and Cefepime/Taniborbactam Against OXA-48-Like and NDM-Expressing Enterobacterales: An In-Vitro and In-Silico Approach

Mohanraj Gopikrishnan et al. Curr Microbiol. .

Abstract

New Delhi metallo-β-lactamase (NDM)-producing enterobacterales infections pose significant challenges due to limited treatment options. Recently, a triple combination of ceftazidime/avibactam and aztreonam has been utilized to combat these infections. However, a four-amino-acid insertion in PBP3 and/or the ampC β-lactamase has been linked to the development of resistance to this triple combination in several recent investigations. To evaluate the effectiveness of cefiderocol and cefepime/tazobactam using both in-vitro and in-silico methods, this study examines current non-duplicate isolates of carbapenem-resistant E. coli (n = 40) and carbapenem-resistant K. pneumoniae (n = 40) derived from blood cultures. The MIC of cefepime/taniborbactam and cefiderocol was ascertained using the micro-broth dilution technique. Additionally, computational analysis was performed using molecular docking with AutoDock tools and dynamic simulation with GROMACS, followed by MM-PBSA analysis for a duration of 50 ns. In MIC assays, cefiderocol and cefepime/taniborbactam showed minimal effectiveness against NDM-producing K. pneumoniae and E. coli that possessed OXA-48-like traits. However, both antibiotics showed strong affinity against OXA-48-like producers. Docking studies varied from -4.3 to -8.1 kcal/mol, indicating a higher binding affinity and stronger hydrogen bond formation in OXA-48-like compared to NDM producers. All complexes exhibited stable conformational states, as indicated by analyses of the RMSD, RMSF, Rg, SASA, and hydrogen bond trajectories. Further evidence supports stable BL/BLI interactions within binding sites, mediated by PCA, FEL, and DCCM, as indicated by the binding free energy. Computational studies confirmed better binding affinity for both OXA-48-like and NDM. However, in-vitro studies demonstrated that cefepime/taniborbactam and cefiderocol represent viable alternative options, specifically for OXA-48-like producers, as their effectiveness is significantly compromised in the presence of NDM.

PubMed Disclaimer

Conflict of interest statement

Declarations. Conflicts of interest: The authors declare that they have no competing interests. Consent to Participate: Not applicable. This was an in-vitro and in-silico study involving bacterial isolates without the involvement of human participants. Consent for Publication: Not applicable. This study did not involve individual participants, and hence, consent for publication is not required. All authors have reviewed and approved the final version of the manuscript for publication. Ethics Approval: The study was approved by the Institutional Review Board and Ethical Committee, Christian Medical College, Vellore, India (IRB No.: 12945 dated 24-06-2020).

References

    1. Barbadoro P, Bencardino D, Carloni E et al (2021) Carriage of carbapenem-resistant enterobacterales in adult patients admitted to a university hospital in Italy. Antibiotics (Basel) 10:61. https://doi.org/10.3390/antibiotics10010061 - DOI - PubMed
    1. Bakthavatchalam YD, Routray A, Mane A et al (2022) In vitro activity of ceftazidime–avibactam and its comparators against carbapenem resistant enterobacterales collected across india: results from ATLAS surveillance 2018 to 2019. Diagn Microbiol Infect Dis 103:115652. https://doi.org/10.1016/j.diagmicrobio.2022.115652 - DOI - PubMed
    1. Soman R, Bakthavatchalam YD, Nadarajan A et al (2021) Is it time to move away from polymyxins? Evidence and alternatives. Eur J Clin Microbiol Infect Dis 40:461–475. https://doi.org/10.1007/s10096-020-04053-w - DOI - PubMed
    1. Veeraraghavan B, Bakthavatchalam YD, Soman R et al (2021) Management of serious infections caused by metallo β-lactamases with or without OXA-48-like expressing enterobacterales with aztreonam and ceftazidime/avibactam combination: dosing strategy for better clinical outcome. Indian J Med Microbiol 39:286–288. https://doi.org/10.1016/j.ijmmb.2021.04.002 - DOI - PubMed
    1. Wu W, Feng Y, Tang G et al (2019) NDM metallo-β-lactamases and their bacterial producers in health care settings. Clin Microbiol Rev. https://doi.org/10.1128/cmr.00115-18 - DOI - PubMed - PMC

MeSH terms

LinkOut - more resources