The Prevalence and Determinants of Fusidic Acid Resistance Among Methicillin-Resistant Staphylococcus aureus Clinical Isolates in China

Huilin Zhao; Xinyi Wang; Bingjie Wang; Yanlei Xu; Lulin Rao; Baoshan Wan; Yinjuan Guo; Xiaocui Wu; Jingyi Yu; Liang Chen; Meilan Li; Fangyou Yu

doi:10.3389/fmed.2021.761894

The Prevalence and Determinants of Fusidic Acid Resistance Among Methicillin-Resistant Staphylococcus aureus Clinical Isolates in China

Front Med (Lausanne). 2021 Nov 30:8:761894. doi: 10.3389/fmed.2021.761894. eCollection 2021.

Authors

Huilin Zhao¹, Xinyi Wang¹, Bingjie Wang¹, Yanlei Xu², Lulin Rao³, Baoshan Wan¹, Yinjuan Guo¹, Xiaocui Wu¹, Jingyi Yu¹, Liang Chen^{4

5}, Meilan Li⁶, Fangyou Yu^{1

3}

Affiliations

¹ Department of Clinical Laboratory, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.
² Jiangxi Provincial Key Laboratory of Preventive Medicine, School of Public Health, Nanchang University, Nanchang, China.
³ Department of Laboratory Medicine, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
⁴ Center for Discovery and Innovation, Hackensack Meridian Health, Nutley, NJ, United States.
⁵ Department of Medical Sciences, Hackensack Meridian School of Medicine, Nutley, NJ, United States.
⁶ Respiratory Intensive Care Unit, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai, China.

Abstract

The significant increase in resistance of methicillin-resistant Staphylococcus aureus (MRSA) to fusidic acid (FA) is a worrying public concern. However, the data on the prevalence of FA-resistant MRSA isolates in China is still limited. This study aims to investigate the prevalence of FA resistance and resistance determinants among MRSA isolates from six tertiary hospitals in different regions of China between 2016 and 2020. The antimicrobial susceptibility of MRSA isolates was performed by disk diffusion test and broth microdilution method. Whole-genome sequencing was conducted to evaluate the determinants of FA resistance and molecular characterization of FA-resistant MRSA isolates. In this study, a total of 74 (74/457, 16.2%) isolates were identified to be FA-resistant among 457 non-duplicate MRSA isolates. The prevalence of 74 FA-resistant isolates was as follows: Hubei (28/70, 40%), Shanghai (18/84, 21.4%), Jiangxi (7/58, 12.1%), Inner Mongolia Autonomous Region (6/38, 15.8%), Guangdong (12/112, 10.7%), and Sichuan (3/95, 3.2%). The mutations in fusA were present in 79.7% (59/74) of FA-resistant MRSA isolates, with 54 (54/74, 73%) having L461K mutation and conferring high-level resistance [Minimum Inhibitory Concentration (MIC)>128 μg/ml]. Acquired gene, fusB, with low-level resistance (MIC <16 μg/ml) was found in 20.3% (15/74) FA-resistant MRSA isolates. ST5-MRSA-II-t2460 was the most prevalence clone with high-level resistance, accounting for 51.4% (38/74), which was distributed in Hubei (24/28, 85.7%), Inner Mongolia Autonomous Region (4/6, 66.7%), Shanghai (7/18, 38.9%), and Guangdong (3/12, 25%). ST630-t4549 MRSA isolates with low-level resistance were the most common in Jiangxi (3/7, 42.9%) and Sichuan (2/3, 66.7%). In brief, the prevalence of FA resistance among MRSA isolates in China was relatively high with geographic differences. High-level FA resistance was associated mostly with fusA mutations, especially the L461K mutation, whereas fusB usually conferred the low-level resistance to FA. The spread of ST5-MRSA-II-t2460 clone with high-level resistance to FA contributed greatly to the increase of FA-resistant MRSA isolates in most regions, especially in Hubei.

Keywords: determinants; fusidic acid; methicillin-resistant Staphylococcus aureus; molecular characteristic; prevalence.