Insights and Implications on the Impact of Reduced Vancomycin Susceptibility in Clostridioides difficile

Epidemiological studies have indicated a decline in vancomycin susceptibility among clinical isolates of C difficile, leaving uncertainty regarding its effects on patient outcomes. The hypothesis suggests that reduced vancomycin susceptibility would correspond to lower rates of sustained clinical response (SCR). Diminished vancomycin susceptibility in C difficile correlated with reduced odds of achieving a 30-day SCR and lower rates of 14-day initial cure within the investigated patient cohort.

A significant proportion (34%; 102/300) of C difficile isolates exhibited diminished susceptibility to vancomycin, with Ribotype 027 being the most prevalent (77.4%; 41/53). Overall, 83% (249) of patients achieved a 30-day SCR. However, reduced vancomycin susceptibility correlated with lower rates of 30-day SCR (76%; 78/102) compared to vancomycin-susceptible strains (86%; 171/198; P = .031). Additionally, a notable reduction in the rate of 14-day initial cure was observed among patients infected with strains displaying reduced vancomycin susceptibility (89% vs. 96%; P = .04). Reduced susceptibility remained an independent predictor of 30-day SCR in multivariable modeling (odds ratio, 0.52; 95% confidence interval, 0.28–0.97; P = .04).

Main Takeaways

The study reveals a significant correlation between reduced vancomycin susceptibility in C difficile isolates and poorer treatment outcomes, with patients infected with strains showing diminished susceptibility having lower rates of SCR and initial cure compared to those with vancomycin-susceptible strains.
Approximately 34% of the C difficile isolates included in the study exhibit diminished susceptibility to vancomycin, with Ribotype 027 being the most prevalent strain associated with reduced susceptibility, indicating a concerning trend of increasing reduced vancomycin susceptibility among clinical isolates.
These findings highlight the importance of considering vancomycin susceptibility testing and strain typing in the management of C difficile infections and the need for further research to explore patient and disease-specific risk factors associated with reduced vancomycin susceptibility and the development of alternative treatment strategies in the face of antimicrobial resistance.

Researcher from this study, Taryn A. Eubank, PharmD, BCIDP, offers a comprehensive analysis of the study’s findings. As a Research Assistant Professor at the University of Houston College of Pharmacy, Eubank specializes in infectious diseases research, providing valuable insights into her study’s results.

“Reduced vancomycin susceptibility in C difficile was associated with decreased odds of 30-day SCR and lower 14-day initial cure rates in the studied patient cohort. SCR was a composite 30-day endpoint including (i) 14-day initial cure, (ii) absence of disease recurrence by day 30, and (iii) alive at day 30.”

From 2016 to 2021, the multicenter cohort study focused on adults diagnosed with C difficile infection (CDI) who underwent oral vancomycin treatment. Methodologies included agar dilution vancomycin susceptibility testing, ribotyping, and Sanger sequencing of the vancomycin resistance vanR gene.

“Reduced susceptibility to vancomycin was defined as an MIC >2 μg/mL based the CLSI epidemiological cutoff value (ECV) and the European Committee on Antimicrobial Susceptibility Testing (EUCAST) tentative epidemiological cutoff value ([T]ECOFF),” according to Eubank. “34% (102/300) of C difficile isolates included in the study exhibited reduced vancomycin susceptibility with RT 027 accounting for the highest proportion 77.4% (41/53).”

Reduced susceptibility was defined as a vancomycin minimum inhibitory concentration (MIC) exceeding 2 μg/mL. The primary endpoint was 30-day SCR, with secondary endpoints including a 14-day initial cure, 30-day recurrence, and 30-day mortality. An exploratory analysis examined the relationship between the VanR Thr115Ala polymorphism, susceptibility levels, and clinical outcomes.

This study highlights the rise in reduced vancomycin susceptibility among C difficile isolates and its impact on patient outcomes. Looking ahead, Eubank expresses,

“Further research with isolates from other areas of the US and world is needed to continue monitoring for elevated MICs and the impact on patient outcomes. Additionally, research into patient and disease-specific risk factors predicting reduced vancomycin susceptibility are imperative to help guide clinicians’ therapy decisions when C difficile antibiotic testing is not feasible or timely for clinical laboratories.”