Trends in vancomycin-resistant Enterococcus faecium and methicillin-resistant Staphylococcus aureus and their association with vancomycin / linezolid consumption in a tertiary hospital in China

Abstract

Background

Antimicrobial resistance is a major global public health challenge. Vancomycin-resistant Enterococcus faecium (VR-Efm) is a significant cause of healthcare-associated infections. To investigate the incidence density of VR-Efm and methicillin-resistant Staphylococcus aureus (MRSA), and to analyze their correlation with vancomycin and linezolid antimicrobial consumption (defined daily doses per 1,000 patient-days), thereby providing evidence for developing effective infection prevention and antimicrobial stewardship strategies.

Methods

A retrospective analysis was conducted to investigate the epidemiology of VR-Efm and MRSA from 2019 to the first and second quarters of 2025 (2025 Q1-Q2) in a tertiary care hospital in China. Correlation analyses were performed to assess the relationships between VR-Efm and MRSA incidence density and the consumption of vancomycin and linezolid, respectively.

Results

The vancomycin resistance rate among Enterococcus faecium isolates showed an upward trend, increasing from 1.6% in 2019 to 23.1% in 2025 Q1-Q2. Linezolid resistance was first identified during 2025 Q1–Q2, with a resistance rate of 1.9%. A significant positive correlation was observed between linezolid consumption and the incidence density of VR-Efm (ρ = 0.779, n = 7, p = 0.039). However, no significant association was found between vancomycin consumption and VR-Efm incidence density (ρ = -0.022, n = 7, p = 0.963). No significant correlation was found between MRSA incidence density and the consumption of vancomycin (ρ = -0.490, n = 7, p = 0.265) or linezolid (ρ = -0.190, n = 7, p = 0.683).

Conclusions

The increasing vancomycin resistance rate of Enterococcus faecium, along with the emergence of linezolid-resistant strains, warrants heightened attention and strategic action. Strengthened hospital infection control measures targeting VR-Efm are urgently needed, along with the rational use of linezolid as a key strategy to mitigate antimicrobial selection pressure.

Introduction

Antimicrobial resistance (AMR) is a major global public health challenge [1, 2]. It is estimated that by 2050, approximately 1.91 million deaths may be directly attributable to AMR, with a total of 8.22 million deaths associated with AMR worldwide [3]. Enterococcus is a genus of commensal bacteria commonly found in the human gastrointestinal tract, oral cavity, and vagina. Among its species, Enterococcus faecium (E. faecium) is an opportunistic pathogen that poses a considerable threat in healthcare settings [4, 5]. Notably, vancomycin-resistant enterococci (VRE) have been classified by the World Health Organization as high-priority pathogens for the research and development of new antimicrobial agents [6]. Vancomycin-resistant Enterococcus faecium (VR-Efm) is a significant cause of healthcare-associated infections, including urinary tract infections, intra-abdominal infections, and bloodstream infections [7, 8]. These infections are associated with increased mortality, prolonged hospital stays, and elevated healthcare costs [9, 10]. Understanding trends in AMR of VR-Efm is critical for informing infection control policies and guiding clinical decision-making. Surveillance of resistance patterns enables public health authorities and healthcare institutions to evaluate the effectiveness of current preventive strategies, including contact precautions, environmental cleaning protocols, and antimicrobial stewardship programs [11]. It also facilitates the identification of emerging resistance trends and potential gaps in existing practices, thereby allowing timely adjustments in prevention and control efforts.

While VR-Efm represents a rapidly emerging threat [12], we included methicillin-resistant Staphylococcus aureus (MRSA) in this analysis for comparative and strategic reasons. MRSA provides an important epidemiological benchmark due to its long-standing status as a major healthcare-associated pathogen [13]. Furthermore, both VR-Efm and MRSA are primary targets for glycopeptide antibiotics [14]. Therefore, examining trends in both pathogens in relation to vancomycin and linezolid consumption offers valuable insights for hospital-wide antimicrobial stewardship programs aimed at preserving the efficacy of these critical agents.

In this study, we conducted a retrospective analysis of the epidemiological and resistance trends of VR-Efm and MRSA in a tertiary care hospital in China, covering the period from 2019 to the first and second quarters of 2025 (2025 Q1-Q2). As an exploratory, hypothesis-generating analysis, this study had two primary objectives. Describe the temporal trends in VR-Efm and MRSA detection and resistance patterns, and assess the ecological correlations between the incidence density of these pathogens and the consumption of vancomycin and linezolid, respectively. we generally expected VR-Efm prevalence to increase over time and to potentially show a positive association with linezolid use. This study contributes to a better understanding of local AMR epidemiology and provides evidence to support infection prevention and antimicrobial stewardship strategies.

Materials and methods

Setting

This retrospective study investigated the epidemiology of VR-Efm and MRSA at the Affiliated Guangdong Second Provincial General Hospital of Jinan University, a tertiary care teaching hospital located in Guangzhou, Guangdong Province, China, with an approximate bed capacity of 1,730. Throughout the study period, key factors that could influence the observed epidemiological trends remained stable. There was no implementation of active surveillance screening for VRE or MRSA colonization. All isolates were obtained from clinical diagnostic cultures. The laboratory’s antimicrobial susceptibility testing platform, core diagnostic protocols, and interpretation criteria were consistent without major changes. Furthermore, no hospital-wide modifications were made to the antimicrobial stewardship program. In 2022 our hospital served as a designated COVID-19 treatment facility and implemented enhanced infection control measure.

Ethics approval and consent statement

All methods in this study were carried out in accordance with relevant guidelines and regulations. The study was approved by the Ethics Committee of The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, China (Approval No. 2025-KY-KZ-233-01). Due to the retrospective nature of the study and the use of a de-identified database, the Ethics Committee of The Affiliated Guangdong Second Provincial General Hospital of Jinan University waived the need of obtaining informed consent. This study was conducted in strict compliance with the Declaration of Helsinki.

Case definition

We examined clinical cultures that yielded Efm and Staphylococcus aureus (S. aureus) isolates with accompanying antimicrobial susceptibility testing (AST) results sufficient to determine susceptibility classifications—susceptible, intermediate, or resistant—for the phenotype of interest. Cultures lacking AST data were excluded, as resistance interpretation could not be determined. We included E. faecium and S. aureus isolated from clinical cultures collected within a defined timeframe: from 3 days prior to admission through 3 days after hospital discharge. Two certified clinical microbiology professionals independently reviewed all culture data to ensure accuracy and consistency. Each specimen was classified based on the anatomical site of collection—such as blood, respiratory tract, urinary tract, or other sites. In addition, specimens were categorized according to whether they were derived from normally sterile or nonsterile body sites, and whether the culture was likely collected for clinical or surveillance purposes. Clinical Cultures were defined as specimens collected from patients for diagnostic purposes when infection was suspected, in alignment with their symptoms and clinical presentation. These were obtained from standard clinical sites (e.g., blood, respiratory tract, urine). Surveillance Cultures were defined as specimens collected for non-diagnostic, monitoring purposes. Specimens collected from the inanimate environment surrounding a patient (e.g., bed rails, bedside tables, medical equipment). As noted, the purpose of such environmental monitoring in our facility is to investigate the role of microbial contamination in healthcare settings, evaluate contamination control strategies, and identify microbial species that may threaten a safe patient environment. Environmental and routine surveillance cultures were excluded from the analysis to ensure the clinical relevance of included isolates.

Antimicrobial consumption

This study analyzed the consumption of vancomycin and linezolid from 2019 to 2025 Q1–Q2, expressed as defined daily doses (DDD) per 1,000 patient-days. The DDD is defined as the assumed average maintenance dose per day for a drug used for its primary indication in adult.

Data collection

Clinical samples yielding a positive culture for either Efm and S. aureus were collected from the Hospital Intelligent Infection Management System (Shanghai Lilian Information Technology Co., Ltd.). Antimicrobial susceptibility testing was interpreted as susceptible, intermediate, or resistant according to the Clinical and Laboratory Standards Institute (CLSI) guidelines (M100, 33rd edition, 2023). All clinical isolates underwent identification using the automated VITEK 2 Compact system (bioMérieux, France). Susceptibility testing was performed using the dedicated VITEK 2 GP639 susceptibility card (bioMérieux). All AST results generated during the study were interpreted retrospectively using the unified standard of the CLSI M100, 33rd edition (2023) breakpoints. Reference strains were used as quality controls in accordance with established protocols. VR-Efm were defined as E. faecium isolates exhibiting resistance to vancomycin. To avoid duplication, only one isolate per patient per hospitalization was included. Repeat isolates of the same species from the same patient—regardless of sample source—were excluded. For patients with multiple hospitalizations within the same year, only the first isolate with available AST results was included in the analysis.

Statistical analyses

All statistical analyses were performed using IBM SPSS statistical software (version 29.0). Counted data were described by the number of cases, and the Kolmogorov-Smirnov test was used to verify the normality of the data. Correlation analyses were performed to assess the relationships between the prevalence of VR-Efm and MRSA and the consumption of vancomycin and linezolid. The Spearman’s rank correlation coefficient (ρ) and the number of time points (n) were used to evaluate the strength and direction of these associations. All statistical analyses were evaluated at the statistical significance level of p < 0.05 (two-sided).

Results

Antibiotic resistance in Enterococcus faecium and Staphylococcus aureus

The vancomycin resistance rate in E. faecium increased markedly from 1.6% in 2019 to 23.1% in the the first and second quarters of 2025 (2025 Q1-Q2). Linezolid resistance was first detected in 2025 Q1–Q2, with 1 isolate resistant among 52 E. faecium isolates tested (1.9%). Similarly, teicoplanin resistance exhibited an upward trend, rising from 0% in 2019 to 20% in 2025 Q1-Q2. In contrast, S. aureus maintained a 0% resistance rate to both linezolid and vancomycin throughout the study period. Oxacillin resistance in S. aureus fluctuated between approximately 30% and 40%. These findings are illustrated in Fig. 1. Distribution and resistance of Enterococcus faecium isolates, as shown in Table 1.

Fig. 1.

Antibiotic resistance in E. faecium and S. aureus. A: Resistance rates in Enterococcus faecium. B: Resistance rates in Staphylococcus aureus. Q: quarter

Table 1.

Distribution and resistance of Enterococcus faecium isolates

Year/Period	Total E. faecium Isolates (N)	Number of VR-Efm Isolates (n)	Vancomycin Resistance Rate (%)
2019	61	1	1.6
2020	86	1	1.2
2021	75	2	2.7
2022	64	4	6.3
2023	99	16	16.2
2024	111	15	13.5
2025 Q1-Q2	52	12	23.1

VR-Efm: Vancomycin-resistant Enterococcus faecium. Q: quarter

Incidence density of VR-Efm and MRSA

The number of VR-Efm cases per 100,000 patient days gradually increased from 0.18 in 2019 to 5.17 in 2025 Q1-Q2. For MRSA, the number per 100,000 patient-days rose from 35.01 in 2019 to 57.09 in 2021, then declined to 33.59 in 2022 and 27.40 in 2023, followed by an increase to 43.72 in 2024 and 46.13 in 2025 Q1-Q2. The incidence density of VR-Efm and MRSA is illustrated in Table 2; Fig. 2.

Table 2.

Incidence density of VR-Efm and MRSA

Year/Period	Total patient-days	Number of VR-Efm Isolates (n)	Cases of VR-Efm per 100,000 patient days	Number of MRSA Isolates (n)	Cases of MRSA per 100,000 patient days
2019	559,794	1	0.18	196	35.01
2020	432,063	1	0.23	224	51.84
2021	479,973	2	0.42	274	57.09
2022	431,681	4	0.93	145	33.59
2023	551,141	16	2.90	151	27.40
2024	592,464	15	2.53	259	43.72
2025 Q1-Q2	231,946	12	5.17	107	46.13

VR-Efm: vancomycin-resistant Enterococcus faecium. MRSA: methicillin-resistant Staphylococcus aureus. Q: quarter

Fig. 2.

Incidence density of VR-Efm and MRSA from 2019 to 2025 Q1-Q2. A: Cases of VR-Efm cases per 100,000 patient days. B: Cases of MRSA cases per 100,000 patient days. VR-Efm: vancomycin-resistant Enterococcus faecium. MRSA: methicillin-resistant Staphylococcus aureus. Q: quarter

Defined daily dose of vancomycin and linezolid per 1,000 patient days

The DDD of vancomycin per 1,000 patient days decreased from 7.15 in 2019 to 4.72 in 2021. However, it peaked at 10.10 in 2022, followed by a stabilization trend, with values ranging from 5.31 in 2023 to 6.66 in 2025 Q1-Q2. In contrast, the DDD of linezolid per 1,000 patient days showed a continuous upward trend, increasing from 4.63 in 2019 to 9.41 in 2025 Q1-Q2. Notably, a marked increase was observed in 2022, reaching 8.23. Trends in the DDD of vancomycin and linezolid per 1,000 patient days from 2019 to 2025 Q1-Q2 are illustrated in Fig. 3. Antimicrobial consumption from 2019 to 2025 Q1-Q2 are illustrated in Table 3.

Fig. 3.

DDD of vancomycin and linezolid per 1,000 patient days from 2019 to 2025 Q1-Q2. A: DDD of vancomycin per 1,000 patient days. B: DDD of linezolid per 1,000 patient days. DDD: Defined daily dose. Q: quarter

Table 3.

Antimicrobial consumption from 2019 to 2025 Q1-Q2

Year/Period	Total patient-days	DDD of Vancomycin	Vancomycin DDD per 1,000 Patient-Days	DDD of Linezolid	Linezolid DDD per 1,000 Patient-Days
2019	559,794	4000.75	7.15	2593.00	4.63
2020	432,063	2248.83	5.20	1911.30	4.42
2021	479,973	2264.55	4.72	2462.04	5.13
2022	431,681	4361.41	10.10	3554.30	8.23
2023	551,141	2926.31	5.31	3370.27	6.12
2024	592,464	3838.93	6.48	4432.27	7.48
2025 Q1-Q2	231,946	1545.59	6.66	2183.64	9.41

DDD: defined daily dose. Q: quarter

Correlation analysis of VR-Efm and MRSA with vancomycin and linezolid

Correlation analysis showed that increased vancomycin consumption was not associated with the incidence density of VR-Efm (ρ = -0.022, n = 7, p = 0.963). However, a significant positive correlation was observed between linezolid consumption and the incidence density of VR-Efm (ρ = 0.779, n = 7, p = 0.039). No significant correlation was found between MRSA incidence density and the consumption of vancomycin (ρ = -0.490, n = 7, p = 0.265) or linezolid (ρ = -0.190, n = 7, p = 0.683). The correlation analysis of VR-Efm and MRSA with vancomycin and linezolid consumption is presented in Fig. 4.

Fig. 4.

Correlation analysis of VR-Efm and MRSA with vancomycin and linezolid

Discussion

Our study revealed a significant upward trend in the epidemiology of VR-Efm, with it’s vancomycin resistance rate rising from 1.6% in 2019 to 23.1% in 2025 Q1-Q2 at a tertiary care hospital in Guangzhou, Guangdong, China. Consistent with our findings, recent years have witnessed a marked increase in VRE prevalence in Guangdong Province, with the detection rate of VR-Efm rising sharply from 1.4% in 2019 to 21.3% in 2023.

The observed surge in VR-Efm aligns with regional surveillance reports indicating a rising prevalence of VR-Efm in Guangdong Province during a similar timeframe [15]. The specific clonal lineages contributing to this increase in our hospital setting warrant future molecular epidemiological investigation. ST80 VR-Efm has been recognized as a high-risk clone responsible for nosocomial outbreaks in America, Australia, and Europe [16, 17]. Notably, studies have indicated that this epidemic clone is now also emerging as a significant threat within China, presenting substantial challenges to hospital infection prevention and control [18–21]. In 2022, our hospital operated as a designated COVID-19 treatment facility and implemented strengthened infection control measures. These enhancements included increased mask usage, improved hand hygiene compliance, and the establishment of an infection control observer system [22]. During this period of heightened infection control vigilance, we observed a concurrent decline in MRSA detection rates. Although this ecological association aligns with the anticipated effects of such interventions, our study design precludes causal inference. Future investigations incorporating detailed compliance monitoring are necessary to evaluate the causal impact of these measures on pathogen transmission dynamics. In contrast, we documented a paradoxical rise in VR-Efm prevalence during the same interval. This divergent trend may be better attributed to the continuous evolutionary adaptation of dominant VR-Efm clones with enhanced transmissibility, rather than to deficiencies in infection control protocols.

The rapid rise in VR-Efm detection rates has significantly increased the burden on hospital infection prevention systems. To effectively control VR-Efm transmission in healthcare settings, we recommend strict adherence to hand hygiene, prompt patient isolation, rigorous environmental disinfection, and thorough medical equipment sterilization. These measures are especially critical in intensive care units, where transmission risk is highest [23].

Treatment options for VRE infections remain limited, with linezolid serving as the primary last-line antibiotic in clinical practice [24, 25]. Linezolid resistance is increasingly reported worldwide, with a systematic review of 84 studies (2004–2021) demonstrating a 3.3% global resistance rate among enterococci [26]. Although our study found the incidence density of linezolid-resistant enterococci to be below 2%, consistent with previous reports from China [27, 28], we identified linezolid-resistant E. faecium in 2025 Q1-Q2. This finding underscores the urgent need for targeted infection control strategies, as the clinical management of VR-Efm bacteremia presents significant challenges due to limited therapeutic options. Of particular concern is the emergence of linezolid resistance, an association that aligns with the established mechanism of antimicrobial selective pressure [29–32]. Furthermore, our study suggests that the rising prevalence of VR-Efm may be associated with increased linezolid utilization. It has been reported that resistance to linezolid in VRE is increasing in parallel with rising linezolid consumption [33], highlighting the need for enhanced antimicrobial stewardship of this critical antibiotic. These findings highlights the importance of antimicrobial stewardship, including the judicious use of agents such as linezolid, as a key strategy in efforts to mitigate the selection pressure that may contribute to resistance development and spread.

The present study has several limitations that should be acknowledged. First, as a single-center investigation conducted in a tertiary hospital setting, the findings may have limited generalizability to other healthcare facilities with different patient populations, antibiotic stewardship programs. Second, the retrospective longitudinal ecological analysis of the study design precluded assessment of temporal trends in pathogen prevalence and resistance patterns, which may vary due to seasonal factors, changes in antibiotic prescribing practices. Third, the relatively small sample size of certain resistant isolates, particularly VR-Efm, may have reduced statistical power for some subgroup analyses. Fourth, while a significant correlation was observed between linezolid consumption and VR-Efm prevalence, our study design cannot establish causality. This association may be confounded by unmeasured variables, such as patient comorbidities, the use of other antibiotics, and temporal changes in infection control practices, which were not fully adjusted for in the analysis. Fifth, the study utilized phenotypic antimicrobial susceptibility testing without molecular characterization of resistance mechanisms, which could provide more comprehensive insights into resistance patterns and transmission dynamics. Sixth, the correlation analysis of aggregated time-series data using Spearman’s rank correlation has inherent limitations, including susceptibility to autocorrelation and limited power due to the small number of observational points (n = 7). The findings represent exploratory associations that require validation through more sophisticated longitudinal analyses (e.g., interrupted time-series, regression models controlling for autocorrelation) in larger datasets. Finally, Potential changes in specimen submission practices and diagnostic intensity may independently influence pathogen detection rates. Temporal variations in patient case-mix—such as the proportion of critically ill patients and length of hospital stay—could act as confounders for trends in resistant pathogen prevalence. Additionally, the selective pressure exerted by antibiotics other than vancomycin and linezolid (e.g., cephalosporins, carbapenems) was not accounted for in our analysis. The absence of colonization pressure metrics, such as the prevalence of VRE/MRSA colonization upon admission, further limits the completeness of our transmission dynamics assessment. These limitations highlight the need for caution when interpreting the results and suggest directions for future multicenter prospective studies incorporating genomic epidemiology and standardized clinical data collection.

Conclusion

Our analysis of key pathogen resistance trends from 2019 to 2025 Q1-Q2 in a tertiary hospital in China yielded several critical findings. The vancomycin resistance rate among E. faecium isolates demonstrated a consistent upward trajectory, rising from 1.6% in 2019 to 23.1% in 2025 Q1-Q2. Furthermore, linezolid-resistant E. faecium was first detected during this period, exhibiting a resistance rate of 1.9%. A significant positive correlation was observed between linezolid consumption and the incidence density of VR-Efm (ρ = 0.779, n = 7, p = 0.039). The escalating incidence density of VR-Efm presents a mounting challenge for infection prevention and control. This underscores the urgent need for reinforced hospital infection control measures specifically targeting VR-Efm, as a key strategy in efforts to mitigate the selection pressure that may contribute to resistance development and spread.

Author contributions

ZL: Investigation, Writing - original draft, Formal analysis, Data curation. TW: Data curation, Writing - original draft, Formal analysis. BL: Writing - original draft, Formal analysis, Data curation. CF: Data curation, Writing - original draft, Formal analysis. ML: Data curation, Writing - original draft, Formal analysis. YZ: Data curation, Writing - original draft, Formal analysis. GL: Project administration, Conceptualization, Methodology, Writing - review & editing, Supervision, Investigation, Resources. All authors read and approved the final manuscript.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Data availability

The original contributions presented in the study are included in the article/Supplementary material, further inquiries can be directed to the corresponding author.

Declarations

Ethics approval and consent to participate

All methods in this study were carried out in accordance with relevant guidelines and regulations. The study was approved by the Ethics Committee of The Affiliated Guangdong Second Provincial General Hospital of Jinan University, Guangzhou, China (Approval No. 2025-KY-KZ-233-01). Due to the retrospective nature of the study and the use of a de-identified database, the Ethics Committee of The Affiliated Guangdong Second Provincial General Hospital of Jinan University waived the need of obtaining informed consent. This study was conducted in strict compliance with the Declaration of Helsinki.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.