A risk assessment framework for multidrug-resistant Staphylococcus aureus using machine learning and mass spectrometry technology

Author:

Wang Zhuo1ORCID,Pang Yuxuan12ORCID,Chung Chia-Ru3ORCID,Wang Hsin-Yao4ORCID,Cui Haiyan5,Chiang Ying-Chih67,Horng Jorng-Tzong38,Lu Jang-Jih491011,Lee Tzong-Yi1213ORCID

Affiliation:

1. Warshel Institute for Computational Biology, School of Medicine, The Chinese University of Hong Kong, Shenzhen , Shenzhen, Guangdong 518172 , China

2. School of Science and Engineering, The Chinese University of Hong Kong , Shenzhen, Shenzhen, Guangdong 518172 , China

3. Department of Computer Science and Information Engineering, National Central University , Taoyuan 32001 , Taiwan

4. Department of Laboratory Medicine, Chang Gung Memorial Hospital at Linkou , Taoyuan 333423 , Taiwan

5. Department of Clinical Laboratory, Longgang District People's Hospital of Shenzhen & The Second Affiliated Hospital of the Chinese University of Hong Kong , Shenzhen , China

6. Kobilka Institute of Innovative Drug Discovery , School of Medicine, , Shenzhen, Shenzhen, Guangdong, 518172 , China

7. The Chinese University of Hong Kong , School of Medicine, , Shenzhen, Shenzhen, Guangdong, 518172 , China

8. Department of Bioinformatics and Medical Engineering, Asia University , Taichung 41354 , Taiwan

9. Department of Medical Biotechnology and Laboratory Science, Chang Gung University , Taoyuan 33303 , Taiwan

10. Department of Medicine , College of Medicine, , Taoyuan 33303 , Taiwan

11. Chang Gung University , College of Medicine, , Taoyuan 33303 , Taiwan

12. Institute of Bioinformatics and Systems Biology, National Yang Ming Chiao Tung University , Hsinchu 300093 , Taiwan

13. Center for Intelligent Drug Systems and Smart Bio-devices (IDS2B), National Yang Ming Chiao Tung University , Hsinchu 300093 , Taiwan

Abstract

Abstract The emergence of multidrug-resistant bacteria is a critical global crisis that poses a serious threat to public health, particularly with the rise of multidrug-resistant Staphylococcus aureus. Accurate assessment of drug resistance is essential for appropriate treatment and prevention of transmission of these deadly pathogens. Early detection of drug resistance in patients is critical for providing timely treatment and reducing the spread of multidrug-resistant bacteria. This study aims to develop a novel risk assessment framework for S. aureus that can accurately determine the resistance to multiple antibiotics. The comprehensive 7-year study involved ˃20 000 isolates with susceptibility testing profiles of six antibiotics. By incorporating mass spectrometry and machine learning, the study was able to predict the susceptibility to four different antibiotics with high accuracy. To validate the accuracy of our models, we externally tested on an independent cohort and achieved impressive results with an area under the receiver operating characteristic curve of 0. 94, 0.90, 0.86 and 0.91, and an area under the precision–recall curve of 0.93, 0.87, 0.87 and 0.81, respectively, for oxacillin, clindamycin, erythromycin and trimethoprim-sulfamethoxazole. In addition, the framework evaluated the level of multidrug resistance of the isolates by using the predicted drug resistance probabilities, interpreting them in the context of a multidrug resistance risk score and analyzing the performance contribution of different sample groups. The results of this study provide an efficient method for early antibiotic decision-making and a better understanding of the multidrug resistance risk of S. aureus.

Funder

Guangdong Province Basic and Applied Basic Research Fund

National Natural Science Foundation of China

Chang Gung Memorial Hospital

Natural Science Foundation of Guangdong

Warshel Institute for Computational Biology, School of Medicine

The Chinese University of Hong Kong

Center for Intelligent Drug Systems and Smart Bio-devices

The Featured Areas Research Center Program

Higher Education Sprout Project

Yushan Young Fellow Program

Ministry of Education

National Science and Technology Council

Publisher

Oxford University Press (OUP)

Subject

Molecular Biology,Information Systems

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