March 2026 - Issue One

Patient outcomes may depend on science that's moving faster than any of us can track. OpenBiome Foundation's monthly newsletter cuts through the noise - delivering focused conversations in Q&A format with leading researchers and clinicians on the microbiome discoveries most relevant to your practice. No jargon, no fluff. Just the insights worth your time.

Welcome to our first edition.

This issue features Dr. L. Clifford McDonald, MD, Associate Director for Science in the Division of Healthcare Quality Promotion (DHQP) at the Centers for Disease Control and Prevention (CDC), one of the foremost experts in Clostridioides difficile (C. difficile) epidemiology. Drawing on 25 years of surveillance data, Dr. McDonald offers his firsthand perspective on how C. difficile transmission patterns, treatment approaches, and prevention strategies have evolved, and what that means for clinical practice today.

Q&A 

Q: Over the past 25 years, what have been the most meaningful shifts in C. difficile epidemiology, and were there specific inflection points that tell us what truly moves population-level outcomes? 

A: Since the early 2000s, I’d say there have been three meaningful inflection points in C. difficile epidemiology. From 2000-2010, we saw marked increases in C. difficile-related hospitalizations following the emergence of an epidemic strain known as the ribotype (RT) 027 or sequence type (ST) 1. This strain was more virulent, at least in part due to its increased production of toxins. Around the same time, we saw C. difficile listed increasingly as the cause of death on death certificates, increasing from 793 in 1999 to 7483 in 2008. To better monitor and alert public health experts about this growing threat, CDC established surveillance for C. difficile infections (CDIs) in the Emerging Infections Program (EIP) and the National Healthcare Safety Network. By 2011, CDC surveillance showed that there were approximately half-a million CDIs occurring each year in the United States with about 30,000 associated deaths!  

Thankfully, from 2011-2017, due to increased awareness and stronger infection control and antibiotic stewardship, the prevalence of the epidemic strain RT 027/ST 1 decreased, mainly in hospitals (where it was more prevalent), and the number of healthcare-associated CDIs was slowly declining.  But, interestingly, CDC detected a steady number of community-associated CDIs, most likely because although we have antibiotic stewardship, we don’t know how to prevent exposure to C. difficile in the community.  Today, we continue to see RT 027/ST 1 prevalence decreasing and community-associated C. difficile continuing to dominate CDIs overall. 

Q: Long-term mortality data show higher rates among white patients and women. How should we interpret these patterns, and to what extent might they reflect differences in healthcare exposure, antibiotic use, or surveillance practices?

A: We have long observed a greater incidence of CDIs, and hence CDI-related mortality, in women than in men in CDC’s EIP surveillance data. As recently as 2023, EIP data showed the incidence of CDI was 134 per 100,000 among women versus about 100 per 100,000 among men with the difference in incidences being more pronounced in community-associated cases. Moreover, incidence was about 146 per 100,000 in White patients versus 107 in African American and 76 per 100,000 in Hispanics or Latinos across any race. It is thought that these differences are attributable to differences in access to the healthcare system and differences in exposure to antibiotic use.  

You can see differences in antibiotic exposure by sex at CDC’s Antibiotic Resistance and Patient Safety Portal (ARPSP) where in retail pharmacy data rates of prescribing appear consistently higher in women than in men. In 2024, the rate of prescribing was 905 prescriptions per 1,000 women and 596 prescriptions per 1,000 men. Other investigators have attributed higher rates of CDI in White persons due to greater access and exposure to hospitals, based upon discharge data, and still others have noted higher CDI testing rates in Whites. In addition, and somewhat counterintuitive to these findings, CDC found incidences of CDI were greater in communities with lower average socioeconomic status. Consistent with this latter finding are associations between socioeconomic status and diet that may impair the gut microbiome independent of any antibiotic use. Bottom line is that these demographic, socioeconomic, and other factors affect each other in complex ways; they might increase a person’s risk or decrease it. Future research in these and other domains will help us better understand determinants of infection and transmission. 

Q: How are severe and fulminant cases reflected in national surveillance data? Are we seeing a true decline in severe disease or are we becoming better at treating very sick patients?

A: In 2017, nearly 223,900 people in the U.S. required hospital care for C. difficile and at least 12,800 people died. So despite any improvements in surveillance or care, there’s still more work to be done for patients and their families.  

That said, in 2021-2023 in-hospital deaths occurred in 3% or less of CDIs detected in CDC surveillance; this is lower than the average 6% in-hospital death rates seen from 2011-2017.  There is no question that the RT 27/ST 1 strain is highly virulent resulting in more severe outcomes so that, given decreasing prevalence of this strain, there may have been a true overall decline in severity of disease. However, it also seems likely that, given increased attention to the clinical management of CDI over the past 25 years, that we have become better at treating very sick patients, including managing recurrent disease.   

Q: What trends are you seeing in the pediatric population, and how does the epidemiology of C. difficile in children differ from adults?

A: Population-based incidences in 1-17 year olds are the lowest of any age stratum with rates ranging from 29 to 35 cases per 100,000 population between 2017 and 2023, with no clear trend in rates (note: there was a slight decline in cases 2020-2021 because outpatient healthcare was used less frequently during the COVID-19 pandemic; cases have since rebounded). As adult patients age, their risk for severe CDI increases for many reasons, including exposure to antibiotics over their longer lifetime, comorbidities that may impact healing, and length of hospital stays, which introduces risk for additional infections. Compared to cases among adults, CDI in the pediatric population tend to reflect a higher proportion of community-associated cases and are generally milder with fewer complications. Due to very high rates of colonization – when a child has a pathogen on or in their body but doesn’t show signs of infection - routine testing for C. difficile in neonates and infants < 1 years of age is not recommended.    

Q: As microbiome-based therapies and other newer treatments enter clinical practice, what signals should we be watching in national surveillance data to understand whether we are truly changing the long-term trajectory of C. difficile, and what lessons from this 25-year arc should inform our response to the next infectious threat? 

A: One important outstanding question is whether the newest therapies, specifically the microbiome-based therapies, are being accessed by patients in whom these therapies are recommended. One recent study conducted before the availability of newer microbiome-based therapies (i.e., in the era of fecal microbiota transplant [FMT] recommended under FDA enforcement discretion) found that of all patients with 2 or more recurrences where FMT was recommended, only 12% of patients received FMT. The degree to which the newer microbiome-based therapies are being accessed by similar patients is unknown but given challenges to the access of FMT, this should be assessed. Aside from FMT or newer microbiome-based therapies there has been a history of slowed uptake of newer therapies for CDI, such as fidaxomicin, even when data supported clinical benefit from their use over older less expensive drugs. This may reflect challenges in translating evidence to clinical guidelines and practice, challenges that may extend to other infectious disease threats such as antibiotic resistance. 

While newer treatments and approaches are researched and gradually gain uptake, healthcare professionals must continue strategies that are proven to work: improving antibiotic use, infection control, and healthcare facility cleaning and disinfection. CDC provides educational materials for patients and practical clinical tools and training for healthcare professional (see below).   

CDC Tools and Resources

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