Vancomycin-Resistant Enterococci Are Climbing Worldwide, and the Environment Is Helping Them Spread

VRE is climbing worldwide, and the environment is helping it spread. A new global systematic review and meta-analysis, published in MicrobiologyOpen, has pooled data from 349 studies of Enterococcus faecium and 339 studies of Enterococcus faecalis to produce the most comprehensive picture yet of vancomycin resistance in these two clinically dominant species. The analysis integrated isolates from both clinical and environmental sources, spanning hospital wards, wastewater, animal stool, and environmental water, to estimate the global prevalence of vancomycin-resistant E. faecium (VREfm) and vancomycin-resistant E. faecalis (VREfs) and to track how resistance has changed over the past two decades.

The headline numbers are stark. Among 94,790 E. faecium isolates reported across 349 studies, 18,679 were vancomycin-resistant, yielding a pooled global prevalence of 25 percent (95% CI: 21–29 percent) for VREfm. Among 144,481 E. faecalis isolates from 339 studies, 2,960 were resistant, giving a pooled prevalence of 5 percent (95% CI: 3–6 percent) for VREfs. Because Egger’s regression test indicated significant publication bias in both datasets, the researchers applied the trim-and-fill method, which adjusted the estimates upward to 33 percent for VREfm and 8 percent for VREfs. In other words, roughly one in three E. faecium isolates worldwide may now carry vancomycin resistance once the bias in published literature is accounted for.

Temporal trends are equally alarming. The pooled prevalence of VREfs rose from 1 percent before 2000 to 12 percent during 2021–2025 (p = 0.0026), while VREfm climbed from 11 percent before 2000 to 29 percent in the same recent period (p = 0.0095). This is not a trend confined to a single region or population. Previous meta-analyses in Asia, India, and Iran have documented similar increases, and the new global analysis confirms that the rise in vancomycin resistance is a worldwide phenomenon driven by continued antimicrobial selective pressure and the persistence of healthcare-adapted resistant lineages.

Geographic patterns reveal a divided world. For VREfs, Africa had the highest continental prevalence at 13 percent (95% CI: 4–26 percent), while Oceania recorded essentially zero. For VREfm, South America topped the list at 57 percent (95% CI: 26–86 percent), whereas Africa showed the lowest at 5 percent (95% CI: 1–12 percent). Country-level analysis highlighted Greece (50 percent) and Slovakia (44 percent) as hotspots for VREfs, and Ireland (100 percent, based on 39 isolates) and Argentina (74 percent, based on 46 isolates) for VREfm. The authors caution that several of these country estimates rest on small sample sizes and high heterogeneity, so they should be interpreted as signals rather than definitive rates. Conversely, near-zero pooled prevalences with zero heterogeneity were observed for VREfm in Uganda, Tunisia, and Norway, and for VREfs in South Korea and Saudi Arabia, indicating highly consistent studies with very low or absent resistance in those settings.

The source of isolates matters enormously. For VREfs, non-clinical isolates showed a higher pooled prevalence (8 percent; 95% CI: 3–13 percent) than clinical isolates (4 percent; 95% CI: 3–6 percent), a statistically significant difference (p = 0.0267). Environmental water (26 percent) and animal stool (40 percent) emerged as particularly important reservoirs, suggesting that these non-clinical sources play a critical role in the circulation and spread of resistant clones. For VREfm, rectal swabs (76 percent; 95% CI: 38–99 percent) and hospital environmental samples (74 percent; 95% CI: 33–99 percent) had the highest prevalence, reflecting the capacity of E. faecium to colonize the gastrointestinal tract and persist on inanimate surfaces for days to months. This parallel between colonized patients and contaminated surfaces sustains VRE transmission within healthcare settings.

Infection setting analysis reinforced the hospital-centric nature of the problem. VREfm prevalence was significantly higher in hospital-acquired infections (29 percent; 95% CI: 21–38 percent) than in community-acquired infections (1 percent; 95% CI: 0–7 percent), a difference the authors attribute to antibiotic selective pressure, prolonged hospitalization, ICU stays, and extensive use of invasive medical devices. For VREfs, the difference between hospital-acquired (5 percent) and community-acquired (3 percent) infections was not statistically significant, though ICUs still showed the highest ward-level prevalence at 8 percent. Hematology wards, interestingly, showed the highest VREfm prevalence at 49 percent, likely reflecting the vulnerability of immunocompromised patients to enterococcal bacteremia.

Laboratory methods also shape reported resistance rates. Studies combining biochemical tests with multiplex PCR or PCR reported the highest prevalence estimates for both species, suggesting that combined phenotypic and molecular approaches improve diagnostic accuracy. For antimicrobial susceptibility testing, disc diffusion combined with E-test methods yielded the highest VREfs prevalence (21 percent), while the E-test alone reported the highest VREfm prevalence (64 percent). Interpretive guidelines influenced results as well: CLSI criteria produced the highest VREfs estimate (5 percent), while EUCAST criteria produced the highest VREfm estimate (36 percent). These differences in breakpoints and susceptibility categorization mean that reported vancomycin resistance rates may depend as much on the laboratory method as on the biology of the pathogen itself.

The clinical implications are serious. E. faecium is classified as one of the ESKAPE pathogens because of its ability to acquire multidrug resistance determinants and persist in healthcare settings, and it accounts for approximately 77 percent of vancomycin-resistant enterococcal bacteremia cases, with E. faecalis contributing 9 percent. Rising VRE prevalence reduces the effectiveness of glycopeptide therapy and increases reliance on last-resort agents such as linezolid, daptomycin, and tigecycline. Comparative clinical data for these alternatives remain limited, and therapy choice is influenced by resistance patterns, infection site, and patient factors, making accurate surveillance of resistance trends essential for guiding empiric treatment.

The authors argue that their integrated approach, combining clinical and environmental isolates within a single analytical framework, overcomes limitations of previous reviews that focused mainly on clinical sources. Environmental enterococci may serve as reservoirs of vancomycin resistance determinants and contribute to the transmission of resistance genes to hospital-associated populations, a dynamic that clinical-only surveillance systematically underestimates. The findings support One Health surveillance strategies that integrate clinical, environmental, and animal sampling to improve infection prevention, antimicrobial stewardship, and public health responses to VRE dissemination.

Despite substantial heterogeneity across studies and uneven geographic representation, the analysis provides a robust foundation for targeted interventions. The authors call for standardized antimicrobial susceptibility testing methods and interpretive criteria, incorporation of whole-genome sequencing to characterize resistance determinants and distinguish clonal transmission from gene dissemination, and future multicenter prospective studies spanning the One Health continuum. Frameworks such as the WHO Global Antimicrobial Resistance and Use Surveillance System (GLASS) can improve data consistency and quality, particularly in regions with limited surveillance capacity. As vancomycin resistance continues its upward trajectory, the message from this global synthesis is clear: the battle against resistant enterococci cannot be won in hospital wards alone, because the environment is an active partner in the spread of resistance.

Subject of Research: Global prevalence and temporal trends of vancomycin-resistant Enterococcus faecium and Enterococcus faecalis from clinical and environmental sources

Article Title: Global Prevalence of Vancomycin‐Resistant Enterococcus faecium and Enterococcus faecalis Isolated From Clinical and Environmental Sources: A Systematic Review and Meta‐Analysis

Article References: Narimisa, N., Navidifar, T., Hameed, T. T., Mohammadzadeh, R., Abdoli, F., Ghamari, M., Nourollahi, D., Ansari, F., Ansari, A., & Bostanghadiri, N. (2026). Global Prevalence of Vancomycin‐Resistant Enterococcus faecium and Enterococcus faecalis Isolated From Clinical and Environmental Sources: A Systematic Review and Meta‐Analysis. MicrobiologyOpen, 15(5), Article e70434. https://doi.org/10.1002/mbo3.70434

Image Credits: AI Generated

DOI: 10.1002/mbo3.70434

Keywords: antimicrobial resistance, vancomycin-resistant enterococci, VRE, Enterococcus faecium, Enterococcus faecalis, systematic review, meta-analysis, One Health, hospital-acquired infections, public health, Global, Prevalence