Exploring the Role of Macro-Level Factors and Antibiotic Consumption in MDR of E. coli and K. pneumoniae: A Multi-Method Study in European Countries
Abstract
Background: Antimicrobial resistance (AMR) is a significant global public health concern, with rising multidrug-resistant (MDR) infections. The emergence and spread of MDR bacteria result from a complex interaction of factors across individual, community, and macro levels. While considerable research has explored individual and community factors, the impact of macro-level factors, such as healthcare systems and policies, on MDR bacteria development and spread remains relatively unexplored.
Objective: To investigate the impact of community-based antimicrobial consumption as a private-factor, and broader macro-level factors such as socioeconomic and governance aspects, on the development of MDR in two commonly encountered community-acquired bacteria: E. coli and K. pneumoniae, over time and across European countries.
Methods: The authors analyzed data from sources such as the European Antimicrobial Resistance Surveillance System, World Health Organization, and World Bank. Descriptive analyses were performed on the datasets to identify their key characteristics. Two methods, Extra Tree Regressor (ETR) and Pooled Ordinary Least Squares Regression on Data-Panel (POLS), were compared to evaluate the impact of predictor variables on MDR behavior in E. coli and K. pneumoniae.
Results: Notable differences between the two approaches in determining factors influencing E. coli and K. pneumoniae. In the case of E. coli, the data-panel approach recognized the human development index (HDI) and out-of-pocket health expenses as significant factors. In contrast, the machine learning approach deemed out-of-pocket expenses the most crucial variable. For K. pneumoniae, the data-panel approach emphasized antibiotic community-level consumption as the most critical factor. In contrast, the machine learning approach highlighted the governance index as the most crucial variable.
References
- O. Ajibola, O. Omisakin, A. Eze, S. Omoleke, Self-Medication with Antibiotics, Attitude and Knowledge of Antibiotic Resistance among Community Residents and Undergraduate Students in Northwest Nigeria, Diseases. 6 (2018). https://doi.org/10.3390/diseases6020032.
- K. Zafar, M.Z. Khan, I. Amin, Z. Mukhtar, S. Yasmin, M. Arif, K. Ejaz, S. Mansoor, Precise CRISPR-Cas9 Mediated Genome Editing in Super Basmati Rice for Resistance Against Bacterial Blight by Targeting the Major Susceptibility Gene, Front Plant Sci. 11 (2020). https://doi.org/10.3389/fpls.2020.00575.
- J. Edelsberg, D. Weycker, R. Barron, X. Li, H. Wu, G. Oster, S. Badre, W.J. Langeberg, D.J. Weber, Prevalence of antibiotic resistance in US hospitals, Diagn Microbiol Infect Dis. 78 (2014). https://doi.org/10.1016/j.diagmicrobio.2013.11.011.
- R. Laxminarayan, Z.A. Bhutta, Antimicrobial resistance—a threat to neonate survival, Lancet Glob Health. 4 (2016). https://doi.org/10.1016/S2214-109X(16)30221-2.
- J. O’Neill, Tackling drug-resistant infections globally: final report and recommendations: the review on antimicrobial resistance; 2016 [Available from: https://amr-review. org, Publications. Html. (2019).
- X. Zhen, J. Chen, X. Sun, Q. Sun, S. Guo, C.S. Lundborg, Socioeconomic factors contributing to antibiotic resistance in china: A panel data analysis, Antibiotics. 10 (2021). https://doi.org/10.3390/antibiotics10080994.
- N. Allocati, M. Masulli, M.F. Alexeyev, C. Di Ilio, Escherichia coli in Europe: An overview, Int J Environ Res Public Health. 10 (2013). https://doi.org/10.3390/ijerph10126235.
- V.N. Kachalov, H. Nguyen, S. Balakrishna, L. Salazar-Vizcaya, R. Sommerstein, S.P. Kuster, A. Hauser, P.A. Zur Wiesch, E. Klein, R.D. Kouyos, Identifying the drivers of multidrug-resistant Klebsiella pneumoniae at a European level, PLoS Comput Biol. 17 (2021). https://doi.org/10.1371/JOURNAL.PCBI.1008446.
- S.L.A.M. Bronzwaer, W. Goettsch, B. Olsson-Liljequist, M.C.J. Wale, A. Vatopoulos, M.J.W. Sprenger, European Antimicrobial Resistance Surveillance System (EARSS): objectives and organisation, Eurosurveillance. 4 (1999). https://doi.org/10.2807/esm.04.04.00066-en.
- K. Iskandar, L. Molinier, S. Hallit, M. Sartelli, T.C. Hardcastle, M. Haque, H. Lugova, S. Dhingra, P. Sharma, S. Islam, I. Mohammed, I. Naina Mohamed, P.A. Hanna, S. El Hajj, N.A.H. Jamaluddin, P. Salameh, C. Roques, Surveillance of antimicrobial resistance in low- and middle-income countries: a scattered picture, Antimicrob Resist Infect Control. 10 (2021). https://doi.org/10.1186/s13756-021-00931-w.
- J. Riaño-Moreno, J.P. Romero-Leiton, K. Prieto, Contribution of Governance and Socioeconomic Factors to the P. aeruginosa MDR in Europe, Antibiotics. 11 (2022). https://doi.org/10.3390/antibiotics11020212.
- G. Sulis, S. Sayood, S. Gandra, Antimicrobial resistance in low- and middle-income countries: current status and future directions, Expert Rev Anti Infect Ther. 20 (2022). https://doi.org/10.1080/14787210.2021.1951705.
- Y. Chong, S. Shimoda, N. Shimono, Current epidemiology, genetic evolution and clinical impact of extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae, Infection, Genetics and Evolution. 61 (2018). https://doi.org/10.1016/j.meegid.2018.04.005.
- S.J. Dunn, C. Connor, A. McNally, The evolution and transmission of multi-drug resistant Escherichia coli and Klebsiella pneumoniae: the complexity of clones and plasmids, Curr Opin Microbiol. 51 (2019). https://doi.org/10.1016/j.mib.2019.06.004.
- J.P. Romero-Leiton, jpatirom3/E.-coli-and-K.-pneumoniae-resistance: v0.2-alpha, (2023). https://doi.org/10.5281/ZENODO.7876664.
- M. Ali, PyCaret, PyCaret: An Open Source, Low-Code Machine Learning Library in Python. (2020).
- Y. Nohara, K. Matsumoto, H. Soejima, N. Nakashima, Explanation of machine learning models using shapley additive explanation and application for real data in hospital, Comput Methods Programs Biomed. 214 (2022). https://doi.org/10.1016/j.cmpb.2021.106584.
- R.J. Smith, C. Hsiao, Analysis of Panel Data., Economica. 55 (1988). https://doi.org/10.2307/2554479.
- A.I. McLeod, Kendall rank correlation and Mann-Kendall trend test, Btr0x2.Rz.Uni-Bayreuth.De. (2011).
- S. Mangalathu, S.H. Hwang, J.S. Jeon, Failure mode and effects analysis of RC members based on machine-learning-based SHapley Additive exPlanations (SHAP) approach, Eng Struct. 219 (2020). https://doi.org/10.1016/j.engstruct.2020.110927.
- A. Aminifar, M. Shokri, F. Rabbi, V.K.I. Pun, Y. Lamo, Extremely Randomized Trees with Privacy Preservation for Distributed Structured Health Data, IEEE Access. 10 (2022). https://doi.org/10.1109/ACCESS.2022.3141709.
- R.J. Smith, C. Hsiao, Analysis of Panel Data., Economica. 55 (1988). https://doi.org/10.2307/2554479.
- ECDC, European Centre for Disease Prevention and Control. Antimicrobial resistance in the EU/EEA (EARS-Net) - Annual Epidemiological Report 2019. Stockholm: ECDC; 2020, Antimicrobial Resistance in the EU/EEA (EARS-Net). 174 (2020).
- A. Cassini, D. Plachouras, T. Eckmanns, M. Abu Sin, H.P. Blank, T. Ducomble, S. Haller, T. Harder, A. Klingeberg, M. Sixtensson, E. Velasco, B. Weiß, P. Kramarz, D.L. Monnet, M.E. Kretzschmar, C. Suetens, Burden of Six Healthcare-Associated Infections on European Population Health: Estimating Incidence-Based Disability-Adjusted Life Years through a Population Prevalence-Based Modelling Study, PLoS Med. 13 (2016). https://doi.org/10.1371/journal.pmed.1002150.
- N. Singh, P.K. Singh, U. Singh, R. Garg, A. Jain, Fluroquinolone drug resistance among MDR-TB patients increases the risk of unfavourable interim microbiological treatment outcome: An observational study, J Glob Antimicrob Resist. 24 (2021). https://doi.org/10.1016/j.jgar.2020.11.011.
- M. Alsan, L. Schoemaker, K. Eggleston, N. Kammili, P. Kolli, J. Bhattacharya, Out-of-pocket health expenditures and antimicrobial resistance in low-income and middle-income countries: an economic analysis, Lancet Infect Dis. 15 (2015) 1203–1210. https://doi.org/10.1016/S1473-3099(15)00149-8.
- Z.J. Ou, D.F. Yu, Y.H. Liang, W.Q. He, Y.Z. Li, Y.X. Meng, H.S. Xiong, M.Y. Zhang, H. He, Y.H. Gao, F. Wu, Q. Chen, Trends in burden of multidrug-resistant tuberculosis in countries, regions, and worldwide from 1990 to 2017: results from the Global Burden of Disease study, Infect Dis Poverty. 10 (2021). https://doi.org/10.1186/s40249-021-00803-w.
- S. Khazaei, S. Rezaeian, V. Baigi, M. Saatchi, L. Molaeipoor, Z. Khazaei, Incidence and pattern of tuberculosis treatment success rates in different levels of the human development index: a global perspective, S Afr J Infect Dis. 32 (2017). https://doi.org/10.4102/sajid.v32i3.47.
- P. Conceição, Human Development Report 2020: The Next Frontier Human Development and the Anthropocene, Донну. (2020).
- S.K. Sheth, L.M.A. Bettencourt, Measuring health and human development in cities and neighborhoods in the United States, Npj Urban Sustainability. 3 (2023). https://doi.org/10.1038/s42949-023-00088-y.
- A. Balode, V. Punda-Polić, M.J. Dowzicky, Antimicrobial susceptibility of Gram-negative and Gram-positive bacteria collected from countries in Eastern Europe: Results from the Tigecycline Evaluation and Surveillance Trial (T.E.S.T.) 2004-2010, Int J Antimicrob Agents. 41 (2013). https://doi.org/10.1016/j.ijantimicag.2013.02.022.
- E. Tacconelli, M.D. Pezzani, Public health burden of antimicrobial resistance in Europe, Lancet Infect Dis. 19 (2019). https://doi.org/10.1016/S1473-3099(18)30648-0.
- R. Podschun, U. Ullmann, Klebsiella spp. as nosocomial pathogens: Epidemiology, taxonomy, typing methods, and pathogenicity factors, Clin Microbiol Rev. 11 (1998). https://doi.org/10.1128/cmr.11.4.589.
- C.G. Giske, D.L. Monnet, O. Cars, Y. Carmeli, Clinical and economic impact of common multidrug-resistant gram-negative bacilli, Antimicrob Agents Chemother. 52 (2008). https://doi.org/10.1128/AAC.01169-07.
- S. Navon-Venezia, K. Kondratyeva, A. Carattoli, Klebsiella pneumoniae: A major worldwide source and shuttle for antibiotic resistance, FEMS Microbiol Rev. 41 (2017). https://doi.org/10.1093/femsre/fux013.
- J. Boelaert, É. Ollion, The great regression machine learning, econometrics, and the future of quantitative social sciences, Rev Fr Sociol. 59 (2018). https://doi.org/10.3917/rfs.593.0475.
- D. Bzdok, N. Altman, M. Krzywinski, Statistics versus machine learning, Nat Methods. 15 (2018). https://doi.org/10.1038/nmeth.4642.