Volume 6 Number 1 2025
Integrating Clinical Data and Molecular Profiling to Predict Antibiotic-Induced Anaphylaxis: A Comparative Study of Ceftriaxone and Meropenem
Md. Robiul Islam1*, Most Farhana Akter1, Md Abu Bakar Siddique2, Tufael3, Amena Khatun Manica4
Journal of Primeasia 6 (1) 1-11 https://doi.org/10.25163/primeasia.6110446
Submitted: 31 August 2025 Revised: 15 November 2025 Accepted: 20 November 2025 Published: 22 November 2025
Abstract
Background: Antibiotic-associated allergies and anaphylaxis remain a major yet preventable threat in modern medicine, often linked to inappropriate prescribing or overuse. Among β-lactam antibiotics, Ceftriaxone has been frequently reported as a leading cause of severe allergic reactions, but the underlying molecular risk factors are still poorly understood.
Objective: This study aimed to identify antibiotic-related medication errors and elucidate molecular interactions contributing to hypersensitivity, focusing on Ceftriaxone and Meropenem.
Methods: Clinical pharmacovigilance data were retrieved from the WHO VigiBase to identify antibiotics most commonly associated with anaphylaxis. Molecular docking was performed using AutoDock Vina (PyRx 0.8) to evaluate drug interactions with the IL4Rα receptor, a key mediator of allergic immune responses. Pharmacokinetic and toxicity profiles were assessed via SwissADME and ProTox-II, while protein–ligand stability was examined using iMODS.
Results: Ceftriaxone demonstrated a stronger binding affinity (-8.2 kcal/mol) to IL4Rα compared to Meropenem (-6.2 kcal/mol), forming multiple stabilizing hydrogen bonds and π-sulfur interactions. Despite its potent interaction, Ceftriaxone exhibited high polarity and poor oral bioavailability, which may influence its systemic allergenic potential. Both drugs were predicted to have low toxicity risks, and iMODS analysis confirmed complex stability. Overall, integrating clinical and molecular analyses provides valuable insight into antibiotic-induced hypersensitivity mechanisms.
Conclusion: These findings support the potential use of IL4Rα molecular profiling as a predictive tool for identifying allergy-prone antibiotics, enabling safer, precision-based prescribing.
Keywords: Antibiotic allergy, Ceftriaxone, Meropenem, IL4Rα, Molecular docking
References
Athanassiou, G., Michaleas, S., Lada-Chitiroglou, E., Tsitsa, T., & Antoniadou-Vyza, E. (2003). Antimicrobial activity of β-lactam antibiotics against clinical pathogens after molecular inclusion in several cyclodextrins. A novel approach to bacterial resistance. Journal of Pharmacy and Pharmacology, 55(3), 291–300. https://doi.org/10.1211/002235702649
Bauer, J. A., Pavlovic, J., & Bauerová-Hlinková, V. (2019). Normal Mode Analysis as a Routine Part of a Structural Investigation. Molecules, 24(18), 3293. https://doi.org/10.3390/molecules24183293
Caruso, C., Valluzzi, R. L., Colantuono, S., Gaeta, F., & Romano, A. (2021). β-Lactam Allergy and Cross-Reactivity: A Clinician’s Guide to Selecting an Alternative Antibiotic. Journal of Asthma and Allergy, Volume 14, 31–46. https://doi.org/10.2147/JAA.S242061
Cho, J., Oh, J., Park, J., Jo, H., Kim, T. H., Kim, H., Yim, Y., Park, S., Kim, K., Woo, H. G., Hwang, Y., Miligkos, M., Yon, D. K., & Papadopoulos, N. G. (2025). Global Burden of Drug-Induced Anaphylaxis Associated With 33 Classes of Antibiotics (1968–2024): A Pharmacovigilance Analysis. Clinical & Experimental Allergy. https://doi.org/10.1111/cea.70121
Cirauqui Diaz, N., Frezza, E., & Martin, J. (2021). Using normal mode analysis on protein structural models. How far can we go on our predictions? Proteins: Structure, Function, and Bioinformatics, 89(5), 531–543. https://doi.org/10.1002/prot.26037
Dabhi, M., Patel, R., Shah, V., Soni, R., Saraf, M., Rawal, R., & Goswami, D. (2024). Penicillin-binding proteins: the master builders and breakers of bacterial cell walls and its interaction with β-lactam antibiotics. Journal of Proteins and Proteomics, 15(2), 215–232. https://doi.org/10.1007/s42485-024-00135-x
Eslamloo, K., Kumar, S., Xue, X., Parrish, K. S., Purcell, S. L., Fast, M. D., & Rise, M. L. (2022). Global gene expression responses of Atlantic salmon skin to Moritella viscosa. Scientific Reports, 12(1), 4622. https://doi.org/10.1038/s41598-022-08341-7
Gaspard, I., Guinnepain, M.-T., Laurent, J., Bachot, N., Kerdine, S., Bertoglio, J., Pallardy, M., & Lebrec, H. (2000). IL-4 and IFN-γ mRNA Induction in Human Peripheral Lymphocytes Specific for β-Lactam Antibiotics in Immediate or Delayed Hypersensitivity Reactions. Journal of Clinical Immunology, 20(2), 107–116. https://doi.org/10.1023/A:1006682413834
Gatti, M., & Pea, F. (2024). Pharmacokinetic/pharmacodynamic issues for optimizing treatment with beta-lactams of Gram-negative infections in critically ill orthotopic liver transplant recipients: a comprehensive review. Frontiers in Antibiotics, 3. https://doi.org/10.3389/frabi.2024.1426753
Gayvert, K. M., Madhukar, N. S., & Elemento, O. (2016). A Data-Driven Approach to Predicting Successes and Failures of Clinical Trials. Cell Chemical Biology, 23(10), 1294–1301. https://doi.org/10.1016/j.chembiol.2016.07.023
Guglielmi, L., Fontaine, C., Gougat, C., Avinens, O., Eliaou, J. -F., Guglielmi, P., & Demoly, P. (2006). IL-10 promoter and IL4-R α gene SNPs are associated with immediate β -lactam allergy in atopic women. Allergy, 61(8), 921–927. https://doi.org/10.1111/j.1398-9995.2006.01067.x
Han, X., Corson, N., Wade-Mercer, P., Gelein, R., Jiang, J., Sahu, M., Biswas, P., Finkelstein, J. N., Elder, A., & Oberdörster, G. (2012). Assessing the relevance of in vitro studies in nanotoxicology by examining correlations between in vitro and in vivo data. Toxicology, 297(1–3), 1–9. https://doi.org/10.1016/j.tox.2012.03.006
Heeb, L. E. M., Egholm, C., & Boyman, O. (2020). Evolution and function of interleukin-4 receptor signaling in adaptive immunity and neutrophils. Genes & Immunity, 21(3), 143–149. https://doi.org/10.1038/s41435-020-0095-7
Jiang, H., Harris, M. B., & Rothman, P. (2000). IL-4/IL-13 signaling beyond JAK/STAT. Journal of Allergy and Clinical Immunology, 105(6), 1063–1070. https://doi.org/10.1067/mai.2000.107604
Krivitskaya, A. V., & Khrenova, M. G. (2022). Evolution of Ceftriaxone Resistance of Penicillin-Binding Proteins 2 Revealed by Molecular Modeling. International Journal of Molecular Sciences, 24(1), 176. https://doi.org/10.3390/ijms24010176
Lagacé-Wiens, P., & Rubinstein, E. (2012). Adverse reactions to β-lactam antimicrobials. Expert Opinion on Drug Safety, 11(3), 381–399. https://doi.org/10.1517/14740338.2012.643866
Le, L., Hao, C., & Rongfei, Z. (2025). Advancements in understanding anaphylaxis: From triggers to therapeutic strategies. Allergy Medicine, 5, 100034. https://doi.org/10.1016/j.allmed.2025.100034
Martin, J. F., Alvarez-Alvarez, R., & Liras, P. (2022). Penicillin-Binding Proteins, β-Lactamases, and β-Lactamase Inhibitors in β-Lactam-Producing Actinobacteria: Self-Resistance Mechanisms. International Journal of Molecular Sciences, 23(10), 5662. https://doi.org/10.3390/ijms23105662
Maurya, R., Vikal, A., Patel, P., Narang, R. K., & Kurmi, B. Das. (2024). “Enhancing Oral Drug Absorption: Overcoming Physiological and Pharmaceutical Barriers for Improved Bioavailability.” AAPS PharmSciTech, 25(7), 228. https://doi.org/10.1208/s12249-024-02940-5
Md Sakil Amin, & Md Jabir Rashid. (2025). Probiotics as Emerging Neurotherapeutics in Spinal Cord Injury: Modulating Inflammation, Infection, and Regeneration. Microbial Bioactives, 8(1), 1–11. https://doi.org/10.25163/microbbioacts.8110290
Minaldi, E., Phillips, E. J., & Norton, A. (2021). Immediate and Delayed Hypersensitivity Reactions to Beta-Lactam Antibiotics. Clinical Reviews in Allergy & Immunology, 62(3), 449–462. https://doi.org/10.1007/s12016-021-08903-z
Montañez, M. I., Mayorga, C., Bogas, G., Barrionuevo, E., Fernandez-Santamaria, R., Martin-Serrano, A., Laguna, J. J., Torres, M. J., Fernandez, T. D., & Doña, I. (2017). Epidemiology, Mechanisms, and Diagnosis of Drug-Induced Anaphylaxis. Frontiers in Immunology, 8. https://doi.org/10.3389/fimmu.2017.00614
Mvondo, J. G. M., Matondo, A., Mawete, D. T., Bambi, S.-M. N., Mbala, B. M., & Lohohola, P. O. (2021). In Silico ADME/T Properties of Quinine Derivatives using SwissADME and pkCSM Webservers. International Journal of TROPICAL DISEASE & Health, 1–12. https://doi.org/10.9734/ijtdh/2021/v42i1130492
Nguyen, S. M. T., Rupprecht, C. P., Haque, A., Pattanaik, D., Yusin, J., & Krishnaswamy, G. (2021). Mechanisms Governing Anaphylaxis: Inflammatory Cells, Mediators, Endothelial Gap Junctions and Beyond. International Journal of Molecular Sciences, 22(15), 7785. https://doi.org/10.3390/ijms22157785
Nicoletti, P., Carr, D. F., Barrett, S., McEvoy, L., Friedmann, P. S., Shear, N. H., Nelson, M. R., Chiriac, A. M., Blanca-López, N., Cornejo-García, J. A., Gaeta, F., Nakonechna, A., Torres, M. J., Caruso, C., Valluzzi, R. L., Floratos, A., Shen, Y., Pavlos, R. K., Phillips, E. J., … Pirmohamed, M. (2021). Beta-lactam-induced immediate hypersensitivity reactions: A genome-wide association study of a deeply phenotyped cohort. Journal of Allergy and Clinical Immunology, 147(5), 1830-1837.e15. https://doi.org/10.1016/j.jaci.2020.10.004
Oner, E., Al-Khafaji, K., Mezher, M. H., Demirhan, I., Suhail Wadi, J., Belge Kurutas, E., Yalin, S., & Choowongkomon, K. (2023). Investigation of berberine and its derivatives in Sars Cov-2 main protease structure by molecular docking, PROTOX-II and ADMET methods: in machine learning and in silico study. Journal of Biomolecular Structure and Dynamics, 41(19), 9366–9381. https://doi.org/10.1080/07391102.2022.2142848
Peña-Mendizabal, E., Morais, S., & Maquieira, Á. (2020). Neo-antigens for the serological diagnosis of IgE-mediated drug allergic reactions to antibiotics cephalosporin, carbapenem and monobactam. Scientific Reports, 10(1), 16037. https://doi.org/10.1038/s41598-020-73109-w
Pichler, W. J. (2022). The important role of non-covalent drug-protein interactions in drug hypersensitivity reactions. Allergy, 77(2), 404–415. https://doi.org/10.1111/all.14962
Poulsen, L. K., & Hummelshoj, L. (2007). Triggers of IgE class switching and allergy development. Annals of Medicine, 39(6), 440–456. https://doi.org/10.1080/07853890701449354
Radkowski, P., Derkaczew, M., Mazuchowski, M., Moussa, A., Podhorodecka, K., Dawidowska-Fidrych, J., Braczkowska-Skibinska, M., Synia, D., Sliwa, K., Wiszpolska, M., & Majewska, M. (2024). Antibiotic–Drug Interactions in the Intensive Care Unit: A Literature Review. Antibiotics, 13(6), 503. https://doi.org/10.3390/antibiotics13060503
Rahman, S. S., Klamrak, A., Mahat, N. C., Rahat, R. H., Nopkuesuk, N., Kamruzzaman, M., Janpan, P., Saengkun, Y., Nabnueangsap, J., Soonkum, T., Sangkudruea, P., Jangpromma, N., Kulchat, S., Patramanon, R., Chaveerach, A., Daduang, J., & Daduang, S. (2025). Thyroid Stimulatory Activity of Houttuynia cordata Thunb. Ethanolic Extract in 6-Propyl-Thiouracil-Induced Hypothyroid and STZ Induced Diabetes Rats: In Vivo and In Silico Studies. Nutrients, 17(3), 594. https://doi.org/10.3390/nu17030594
Rubio, I., Osuchowski, M. F., Shankar-Hari, M., Skirecki, T., Winkler, M. S., Lachmann, G., La Rosée, P., Monneret, G., Venet, F., Bauer, M., Brunkhorst, F. M., Kox, M., Cavaillon, J.-M., Uhle, F., Weigand, M. A., Flohé, S. B., Wiersinga, W. J., Martin-Fernandez, M., Almansa, R., … Bermejo-Martín, J. F. (2019). Current gaps in sepsis immunology: new opportunities for translational research. The Lancet Infectious Diseases, 19(12), e422–e436. https://doi.org/10.1016/S1473-3099(19)30567-5
Ruzza, P., Vitale, R. M., Hussain, R., Montini, A., Honisch, C., Pozzebon, A., Hughes, C. S., Biondi, B., Amodeo, P., Sechi, G., & Siligardi, G. (2018). Chaperone-like effect of ceftriaxone on HEWL aggregation: A spectroscopic and computational study. Biochimica et Biophysica Acta (BBA) - General Subjects, 1862(6), 1317–1326. https://doi.org/10.1016/j.bbagen.2018.02.014
Schnyder, B., & Brockow, K. (2015). Pathogenesis of drug allergy – current concepts and recent insights. Clinical & Experimental Allergy, 45(9), 1376–1383. https://doi.org/10.1111/cea.12591
Siddique, S. A., Mohamed, S. K., Sarfraz, M., Bakhite, E. A., Marae, I. S., Soliman, A. A. E., Khamies, E., Selim, A. F., Qahtan, M. Q. M., Abuelizz, H. A., Al-Salahi, R., Mague, J. T., & El Bakri, Y. (2025). Synthesis, investigation of the crystal structure, DFT and in silico medicinal potential of nicotinonitrile substituted quinazolindione as potential anticancer scaffold. Molecular Physics, 123(16). https://doi.org/10.1080/00268976.2024.2448566
Simons, F. E. R. (2009). Anaphylaxis: Recent advances in assessment and treatment. Journal of Allergy and Clinical Immunology, 124(4), 625–636. https://doi.org/10.1016/j.jaci.2009.08.025
Tolomeo, M., & Cascio, A. (2024). STAT4 and STAT6, their role in cellular and humoral immunity and in diverse human diseases. International Reviews of Immunology, 43(6), 394–418. https://doi.org/10.1080/08830185.2024.2395274
Vardakas, K. Z., Kalimeris, G. D., Triarides, N. A., & Falagas, M. E. (2018). An update on adverse drug reactions related to β-lactam antibiotics. Expert Opinion on Drug Safety, 17(5), 499–508. https://doi.org/10.1080/14740338.2018.1462334
Vashishat, A., Patel, P., Das Gupta, G., & Das Kurmi, B. (2024). Alternatives of Animal Models for Biomedical Research: a Comprehensive Review of Modern Approaches. Stem Cell Reviews and Reports, 20(4), 881–899. https://doi.org/10.1007/s12015-024-10701-x
Walters, W. P. (2012). Going further than Lipinski’s rule in drug design. Expert Opinion on Drug Discovery, 7(2), 99–107. https://doi.org/10.1517/17460441.2012.648612
Wilke, M. S., Lovering, A. L., & Strynadka, N. C. (2005). β-Lactam antibiotic resistance: a current structural perspective. Current Opinion in Microbiology, 8(5), 525–533. https://doi.org/10.1016/j.mib.2005.08.016