Understanding Clostridioides difficile Infections and Antibiotic Stewardship

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In a 17-year study across 2 Québec hospitals, researchers explored the relationship between antibiotic use and healthcare-associated Clostridioides difficile infections.

Doctors typically wear protective suites when caring for patients with Clostridioides difficile infection to prevent transmission of the bacteria.

Doctors typically wear protective suites when caring for patients with Clostridioides difficile infection to prevent transmission of the bacteria.

Image credits: Unsplash

New long-term data from 2 hospitals in Québec, Cananda, recently assessed the relationship between antibiotic use and healthcare-associated Clostridioides difficile infections. The study aimed to characterize the epidemiology of healthcare-associated Clostridioides difficile infection (HA-CDI) following the 2003 epidemic and to evaluate how antibiotic stewardship affected HA-CDI incidence and the prevalence of the NAP1/027 strain. Reductions in fluoroquinolone usage in these hospitals corresponded with decreased HA-CDI rates and a shift in genotype from NAP1/027 to non-NAP1/027 strains.

  • NAP1/027 strain: This genotype, ribotype 027, is associated with increased virulence and resistance to fluoroquinolone antibiotics. It has been implicated in more severe and recurrent cases of CDI.
  • Non-NAP1/027 strains are C difficile strains that do not belong to the NAP1/027 genotype. They may vary in virulence factors, and susceptibility to antibiotics compared to the NAP1/027 strain.

Between 2003 and 2020, cases dropped from 26.5 per 10,000 patient days in 2003 to 4.9 cases per 10,000 patient days in 2020, respectively. Throughout the 17-year study period, there was an increase in the use of third-generation cephalosporins, accompanied by decreases using fluoroquinolones and clindamycin. The reduction in fluoroquinolone use was correlated with a significant decrease in HA-CDI incidence and a decrease in the NAP1/027 strain by approximately 80% in both hospitals.

“This decline occurred while total antibiotic consumption was increasing, but the use of certain high-risk antibiotics—fluoroquinolones, second-generation cephalosporins, and clindamycin—was decreasing,” explains investigators. "In the later years of our study, we observed a significant decrease over time in the C difficile NAP1/027 strain which is inherently resistant to fluoroquinolones. There was a parallel significant decrease in fluoroquinolone utilization at one of the two hospitals.”1

3 Key Takeaways

  1. Findings underscore the importance of antibiotic stewardship in controlling HA-CDI rates and managing resistant strains, emphasizing the need for strategic antibiotic use in hospital settings.
  2. Decreased use of fluoroquinolones coincided with a significant decline in HA-CDI cases from 26.5 to 4.9 per 10,000 patient-days between 2003 and 2020.
  3. The decrease in fluoroquinolone usage also led to an approximate 80% reduction in the prevalence of the hypervirulent NAP1/027 strain in both hospitals.

From 2003 to 2020, the incidence of HA-CDI and antibiotic usage were examined alongside available C difficile isolates. The effect of antibiotic usage on HA-CDI incidence was assessed using a dynamic regression time-series model. Antibiotic utilization and the percentage of NAP1/027 strains were biannually compared for isolates available from 2010 to 2020.

“Our findings demonstrated an association between a decrease in fluoroquinolone utilization and a decrease in total C difficile incidence. We were further able to demonstrate that a significant decrease in the incidence of the NAP1/027 strain was concomitant with a decrease in fluoroquinolone utilization at one of our two hospital sites in the final years of the study,” according to investigators.1

According to a recent announcement by WHO addressing challenges in the antibacterial pipeline, they are developing products targeting C difficile and H pylori. This includes 5 antibiotics and 9 non-traditional antibacterial treatments for C difficile, and 1 antibiotic and 1 non-traditional therapy for H pylori. This proves the development of antibacterial agents remains relevant to ensure effective treatment for patients battling these diseases.2

This study has limitations such as only having data from 2 hospitals, warranting broader data collection across multiple institutions to determine the impact of reduced fluoroquinolone use on HA-CDI and the NAP1/027 strain across countries. Various infection control interventions during the study period may confound assessments of antibiotic impacts on HA-CDI. The study did not separately analyze the effects of individual antibiotic classes. Retrospective data access limited a full evaluation of antibiotic effects on NAP1/027 strain dynamics. Reduced fluoroquinolone use correlated with decreased NAP1/027 isolates in both hospitals studied.

According to investigators, “Another possible contributor to the decline in HA-CDI incidence was the move to a single-room facility for the RVH site in 2015. A previous time-series analysis conducted at our institution did not demonstrate an association of HA-CDI incidence and housing patients in single rooms.”1

The decline in HA-CDI in two Montreal hospitals was linked to reduced use of high-risk antibiotics, notably fluoroquinolones. Decreased fluoroquinolone use correlated with significant reductions in both HA-CDI incidence and the proportion of NAP1/027 C difficile strains at one study site. These findings highlight the critical role of antibiotic stewardship in controlling HA-CDI rates and mitigating hypervirulent strains within hospital settings.

References
  1. Couture S, Frenette C, Schiller I, et. Al. The changing epidemiology of Clostridioides difficile infection and the NAP1/027 strain in two Québec hospitals: a 17-year time-series study. CambridgeCore. Published June 4, 2024. Accessed June 19, 2024. https://www.cambridge.org/core/journals/antimicrobial-stewardship-and-healthcare-epidemiology/article/changing-epidemiology-of-clostridioides-difficile-infection-and-the-nap1027-strain-in-two-quebec-hospitals-a-17year-timeseries-study/717C3C12762A3EBFD6418690957915AB
  2. Abene, S. WHO Analysis Highlights Antibacterial Pipeline Challenges and Progress. ContagionLive. Published June 18, 2024. Accessed June 19, 2024. https://www.contagionlive.com/view/who-analysis-highlights-antibacterial-pipeline-challenges-and-progress
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