기계학습 방법을 활용한 Cephalosporins의 피부 이상반응 분석: KAERS DB를 활용한 약물감시 데이터 기반 연구
Analysis of Cutaneous Adverse Reactions to Cephalosporins Using Machine Learning Techniques: A Pharmacovigilance Study Based on KAERS DB Data
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
Background : Cross-reactivity and hypersensitivity to β-lactam antibiotics significantly limit their use. This study aimed to analyze cutaneous adverse reaction patterns associated with cefoxitin and cephalothin, which share R1 side chain chemical structures, using machine learning techniques applied to the Korea Adverse Event Reporting System Database (KAERS DB). The goal was to establish evidence for safer antibiotic use. Methods : We utilized KAERS DB data from January 2018 to December 2022. The dataset was divided into dermatological adverse events and others, with 2018-2019 data serving as the training set and 2020-2022 data as the test set. Eight machine learning models were developed to predict cutaneous adverse reaction risks. Model performance was evaluated using accuracy and Area under the Receiver Operating Characteristic Curve (AUC) on both training and test sets. Statistical analyses were performed using Python 3.7.6. Results : In the training dataset, most models achieved high accuracy (0.986), with Bagging Classifier and Extra Trees Classifier demonstrating excellent performance (AUC 0.974). The test dataset also showed high accuracy (0.998) across models, but AUC scores varied. AdaBoost Classifier (AUC 0.812), Random Forest Classifier (AUC 0.786), and MLP Classifier (AUC 0.736) performed particularly well. Conclusion : This study employed machine learning techniques to classify cutaneous adverse reactions associated with second-generation (cefoxitin) and first-generation (cephalothin) cephalosporins, which have relatively high adverse event risks, and to predict potential cutaneous reactions in new cases. The models incorporated cross-reactivity possibilities based on cephalosporin chemical structures and demonstrated high predictive accuracy. These findings are expected to contribute to the development of safer antibiotic use guidelines based on scientific evidence.
Abstract
Background : Cross-reactivity and hypersensitivity to β-lactam antibiotics significantly limit their use. This study aimed to analyze cutaneous adverse reaction patterns associated with cefoxitin and cephalothin, which share R1 side chain chemical structures, using machine learning techniques applied to the Korea Adverse Event Reporting System Database (KAERS DB). The goal was to establish evidence for safer antibiotic use. Methods : We utilized KAERS DB data from January 2018 to December 2022. The dataset was divided into dermatological adverse events and others, with 2018-2019 data serving as the training set and 2020-2022 data as the test set. Eight machine learning models were developed to predict cutaneous adverse reaction risks. Model performance was evaluated using accuracy and Area under the Receiver Operating Characteristic Curve (AUC) on both training and test sets. Statistical analyses were performed using Python 3.7.6. Results : In the training dataset, most models achieved high accuracy (0.986), with Bagging Classifier and Extra Trees Classifier demonstrating excellent performance (AUC 0.974). The test dataset also showed high accuracy (0.998) across models, but AUC scores varied. AdaBoost Classifier (AUC 0.812), Random Forest Classifier (AUC 0.786), and MLP Classifier (AUC 0.736) performed particularly well. Conclusion : This study employed machine learning techniques to classify cutaneous adverse reactions associated with second-generation (cefoxitin) and first-generation (cephalothin) cephalosporins, which have relatively high adverse event risks, and to predict potential cutaneous reactions in new cases. The models incorporated cross-reactivity possibilities based on cephalosporin chemical structures and demonstrated high predictive accuracy. These findings are expected to contribute to the development of safer antibiotic use guidelines based on scientific evidence.
참고문헌 (33)
- Zakhour J, "Metallo-beta-lactamases: Mechanisms, treatment challenges, and future prospects", Expert Rev. Anti Infect. Ther, 22(4), pp.189~201 (2024)
- Del Pozzo-Magaña BR, "Drugs and the skin: A concise review of cutaneous adverse drug reactions", Br. J. Clin. Pharmacol, pp.1~18 (2022)
- Ariza A, "Hypersensitivity reactions to β-lactams:relevance of hapten-protein conjugates", 25(1), pp.12~25 (2015)
- Goh SJ, "The complexity of T cell–mediated penicillin hypersensitivity reactions", Allergy, 76(1), pp.150~167 (2021)
- Ponvert C, "Allergy to betalactam antibiotics in children: results of a 20-year study based on clinical history, skin and challenge tests", Pediatr. Allergy Immunol, 22(4), pp.411~418 (2011)
- Gastaminza G, "Palmar exfoliative exanthema to amoxicillin", Allergy, 55(5), pp.510~514 (2000)
- Papay J, "Spontaneous adverse event reports of Stevens–Johnson syndrome", toxic epidermal necrolysis : detecting associations with medications, 2012, pp.21(3), 289~296
- Kardaun S, "Drug reaction with eosinophilia and systemic symptoms (DRESS): an original multisystem adverse drug reaction. Results from the prospective RegiSCAR study", Br. J. Dermatol, 169(5), pp.1071~1080 (2013)
- Lin Y-F, "Severe cutaneous adverse reactions related to systemic antibiotics", Clin. Infect. Dis, 58(10), pp.1377~1385 (2014)
- Pichichero M, "Comparison of European and US results for cephalosporin versus penicillin treatment of group A streptococcal tonsillopharyngitis", Eur. J. Clin. Microbiol. Infect. Dis, 25, pp.354~364 (2006)
- Khan DA, "Cephalosporin allergy : current understanding and future challenges", The Journal of Allergy and Clinical Immunology : In Practice, 7(7), pp.2105~2114 (2019)
- Macy E, "Self-reported antibiotic allergy incidence and prevalence : age and sex effects", The American journal of medicine, 122(8), pp.778~ (2009)
- Yuson C, "Immediate cephalosporin allergy", Intern. Med. J, 49(8), pp.985~993 (2019)
- MacFadden DR, "Impact of reported beta-lactam allergy on inpatient outcomes: a multicenter prospective cohort study", Clin. Infect. Dis, 63(7), pp.904~910 (2016)
- Zavaleta-Monestel E, "Management and Implications of Beta-Lactam Allergies", Cureus, 16(5), pp.1~11 (2024)
- Chaudhry SB, "Cephalosporins : a focus on side chains and β-lactam cross-reactivity", Pharmacy, 7(3), pp.103~ (2019)
- Zagursky RJ, "Cross-reactivity in β-lactam allergy", The Journal of Allergy and Clinical Immunology : In Practice, 6(1), pp.72~81 (2018)
- Shin JY, "New initiatives for pharmacovigilance in South Korea : introducing the Korea Institute of Drug Safety and risk management(KIDS)", pharmacoepidemiology and drug safety, 23(11), pp.1115~1122 (2014)
- Brockow K, "Skin tests in the diagnosis of drug hypersensitivity reactions", Curr. Pharm. Des, 14(27), pp.2778~2791 (2008)
- Geer MI, "Frequency, types, severity, preventability and costs of Adverse Drug Reactions at a tertiary care hospital", Journal of pharmacological and toxicological methods, 81, pp.323~334 (2016)
- Lee A-Y, "Immunological Mechanisms in Cutaneous Adverse Drug Reactions", Biomol. Ther. (Seoul), 32(1), pp.1~12 (2024)
- Campagna JD, "The use of cephalosporins in penicillin-allergic patients : a literature review", The Journal of emergency medicine, 42(5), pp.612~620 (2012)
- Sacco K, "Clinical outcomes following inpatient penicillin allergy testing : a systematic review and meta-analysis", Allergy, 72(9), pp.1288~1296 (2017)
- Picard M, "Cross-reactivity to cephalosporins and carbapenems in penicillin-allergic patients : two systematic reviews and meta-analyses", The Journal of Allergy and Clinical Immunology : In Practice, 7(8), pp.2722~2738 (2019)
- Sexton ME, "Management of Penicillin Allergy in the Perioperative Setting", Antibiotics, 13(2), pp.157~169 (2024)
- Chung WH, "Severe cutaneous adverse drug reactions", The Journal of Dermatology, 43(7), pp.758~766 (2016)
- Rodilla EM, "Immunological aspects of nonimmediate reactions to β-lactam antibiotics", Expert Rev. Clin. Immunol, 6(5), pp.789~800 (2010)
- Torres MJ, "T lymphocytes as tools in diagnostics and Immunotoxicology", pp.165~184 (2014)
- Fernandez TD, "Evolution of diagnostic approaches in betalactam hypersensitivity", Expert Rev. Clin. Pharmacol, 10(6), pp.671~683 (2017)
- Romano A, "Non-immediate cutaneous reactions to beta-lactams: approach to diagnosis", Curr. Allergy Asthma Rep, 17(4), pp.23~32 (2017)
- Chow AW, "IDSA clinical practice guideline for acute bacterial rhinosinusitis in children and adults", Clin. Infect. Dis, 54(8), pp.e72~e112 (2012)
- Habib G, "2015 ESC Guidelines for the management of infective endocarditis", Rev. Esp. Cardiol, 69(1), pp.7~10 (2016)
- Drug Allergy: Diagnosis and Management of Drug Allergy in Adults, Children and Young People, "UK NCGC", 1~167 (2014)