VRE Colonization Linked to Higher Mortality in Sepsis Patients

A recent study in Infection Prevention in Practice found that colonization with vancomycin-resistant enterococci (VRE) is associated with significantly higher mortality in patients who develop sepsis. The study analyzed data from over 7,000 septic patients to determine whether colonization with drug-resistant organisms—including VRE, methicillin-resistant Staphylococcus aureus (MRSA), and Clostridioides difficile, influences sepsis outcomes such as mortality, mechanical ventilation, and renal replacement therapy (RRT).

The results showed that VRE colonization was linked to a 7% higher mortality rate (26% vs. 19%) compared to non-colonized patients, with the difference being statistically significant (p < 0.001). VRE-colonized patients were also more likely to require mechanical ventilation (odds ratio = 1.179) and RRT (odds ratio = 1.36). In contrast, MRSA colonization showed a smaller impact on mortality (4% higher, 24% vs. 20%, p = .014), while C diff colonization did not significantly affect mortality (3% difference, 21% vs. 18%, p = .052).

Multivariable analysis further confirmed that VRE colonization was significantly associated with increased hospital mortality (odds ratio = 1.273, 95% CI: 1.099-1.475, p = .001). VRE was also linked to an increased likelihood of requiring mechanical ventilation and RRT, suggesting that colonization with VRE worsens outcomes in septic patients.

The investigators chose to study VRE, MRSA, and C diff due to their clinical relevance and the existing gap in research regarding their role in sepsis outcomes. As the investigators point out, “Studies that have evaluated the association of colonization of VRE, MRSA, and C diff on mortality or critical care outcomes are limited by their small sizes. In nursing home patients, MRSA+ has been shown to be associated with increased mortality, while in the general US population MRSA+ was not associated with long-term mortality.” This observation reflects the need for further investigation into how these organisms specifically impact sepsis outcomes.

The investigators go on to highlight additional limitations in the current literature, stating, “A Canadian study of 745 patients hospitalized with MRSA infection or colonization showed no increased mortality compared to a control population of general medicine patients, 8% v 7%, p=0.328. The study was limited by not separating infected from colonized patients and for not controlling for severity of illness. A small study of 150 patients hospitalized with MRSA infection or colonization found no difference in mortality. In addition to also not separating colonized from infected patients, the study was underpowered to find a clinically significant 70% increase in mortality.” This further underscores the challenges in drawing definitive conclusions from prior research.

These gaps, along with issues like small sample sizes and the lack of distinction between colonized and infected patients, highlight the importance of studying the impact of MRSA, VRE, and C diff on sepsis outcomes.

Additional limitations included the conduction at a single hospital, its findings may not be applicable to other institutions with different infection patterns. Additionally, isolating the effects of contact precautions from disease severity was difficult, and missing data (<6%) could introduce bias. The source of colonization—whether from antibiotics or patient-to-patient transmission—remains unclear and requires further exploration.

At IDWeek 2024, we spoke with Matthew J Ziegler, MD MSCE about findings from the STOP-CDI trial, which focused on prophylactic oral vancomycin to prevent hospital-onset C difficile infections (HO-CDI) in high-risk hospitalized patients, particularly those undergoing immunosuppressive treatments. The trial found that C difficile colonization screening and vancomycin prophylaxis significantly reduced HO-CDI rates, particularly among oncology patients, where HO-CDI rates dropped from 7.5% to 1%. The study also noted improvements in hospital stay and stool output, but no changes in mortality or VRE infections.²

Both studies emphasize the importance of early screening and targeted interventions to manage drug-resistant organisms in vulnerable patient populations. While the VRE study highlighted the need for managing VRE colonization to improve sepsis outcomes, the STOP-CDI trial showed that prophylactic vancomycin could effectively reduce C difficile infections. Both studies underscore the importance of antibiotic stewardship to reduce infection risks without exacerbating resistance, demonstrating the benefits of strategic antibiotic use to manage infections in high-risk settings.

In conclusion, the findings from both studies reinforce the critical role of managing drug-resistant organisms like VRE and C difficile in preventing severe outcomes, particularly in patients undergoing immunosuppressive therapies. Identifying and managing colonization with VRE and other resistant pathogens is crucial to improving patient outcomes and minimizing the need for aggressive interventions like mechanical ventilation and RRT.

Watch our full interview here: Targeted Prophylaxis Reduces Hospital-Onset C difficile Infections in High-Risk Patients

References

1. Sigakis MJG, Posluszny J, Maile MD, et. al. Is there an association between colonization of vancomycin-resistant Enterococci, methicillin-resistant Staphylococcus aureus, or Clostridioides difficile and mortality in sepsis? Infect Prev Pract. 2024;6(4):100413. doi:10.1016/j.infpip.2024.100413

2. Ziegler M, et. al. Screening and Targeted Prophylaxis for Clostridioides Difficile Infection: STOP-CDI. Presentation #203 presented at IDWeek 2024. October 16-19, 2024. Los Angeles, CA.