The Burden of Clostridioides difficile Infection

By Carol A. Kemper, MD, FIDSA

Medical Director, Infection Prevention, El Camino Hospital, Palo Alto Medical Foundation, Palo Alto, CA

SOURCE: Feuerstadt P, et al. The burden of CDI in the United States: A multifactorial challenge. BMC Infec Dis 2023;23:132.

This article outlines the clinical, social, and economic burden of Clostridioides difficile infection (CDI) in the United States and its shifting epidemiology. CDI is no longer an infection exclusive to healthcare facilities. As I reviewed this article, I reflected on the recent experience of an acquaintance, vacationing in Mexico, who required hospitalization for three days with severe dehydration and incapacitating diarrhea and was diagnosed with CDI. She had taken no antibiotics. She was told this infection was “acquired only in hospitals.” Not true.

We are all familiar with the rough statistics of CDI, especially in hospitalized patients, resulting in extended hospital stays, increased costs, and substantial morbidity and mortality. CDI represents at least 1% of all hospital admissions. But were you aware that about 500,000 cases of CDI are reported annually in the United States, resulting in roughly 30,000 deaths? Annual CDI-associated mortality often is greater than mortality from influenza in this country. Recent Veterans Administration data showed that 30-day mortality from CDI ranged from 6% to 11%, but the associated annual mortality, considering relapsed infection over the course of a year, may be as high as 25%. At least 8% of severe hospital infections result in colectomy.

Traditionally, CDI has been regarded as a nosocomial infection. However, the burden of healthcare-associated infection has been steadily decreasing by 36% from 2011 to 2017. This is likely the result of improved testing paradigms, more aggressive infection prevention practices, and antimicrobial stewardship. At the same time, community-associated CDI has doubled, with up to 63.3 cases/100,000 persons, and now outweighs the incidence of CDI associated with hospital admission. Overuse of antibacterials in the community must be a contributing factor. But, of interest, community-associated CDI cases tend to be younger, and 40% have no reported antibiotic exposure within the previous four months. The reasons behind this shifting epidemiology and risk factors for community infection are not well understood. But I suspect it has much to do with an increased burden of intestinal colonization in the community. Our hospital data suggest that 11% to 12% of skilled nursing facility/long-term care patients and 32% of dialysis patients are colonized; patients with a history of CDI also are at increased risk for persistent colonization. This increasing reservoir must create a risk for the community.

Beyond the clinical burden, CDI has significant impact on quality of life, with possible long-lasting emotional and social scars, as well as significant professional impact — which is likely under-appreciated. One survey of outpatient CDI cases reported that 47% had to stop working because of active diarrhea — but another 26% had to stop working even after the acute diarrhea resolved. Other data show that patients with CDI were unable to perform their usual work duties for an average of 118 days. In Silicon Valley, it is not uncommon to have highly educated, highly paid professionals laid low by this illness, bewildered and desperate to get back to work; their careers — and sometimes their companies — depend on their ability to work. The more vulnerable, especially those with lower paying or unskilled jobs, are financially devastated. Based on my own experience with severe gastroenteritis for just three days over Christmas — I could not work, let alone risk getting in the car to retrieve my own stool kit. Imagine weeks of diarrhea, unable to eat normal foods, unable to socialize, afraid to have friends or family over for dinner or share a meal, not counting the fear of relapse.

Financially, healthcare costs for hospital-associated CDI are estimated at ~ $5 billion annually, with the first episode costing $39,000 and relapsing/recurrent episodes costing the healthcare system $49,000. However, direct medical costs may be much greater, starting at $72,000 for the first episode and up to $132,000 for the first recurrence. However, these costs do not adequately reflect the revenue loss to hospitals. Further, the Centers for Medicare and Medicaid Services may now reduce overall Medicare payments to hospitals that rank in the worst-performing quartile of all hospitals on hospital-acquired conditions, such as hospital-onset CDI, adding further financial burden to hospitals challenged with increased hospital-onset C. difficile rates.

However, we seldom consider outpatient treatment costs for individuals afflicted by CDI. One survey suggested that an initial episode costs $8,695 in out-of-pocket expenses, including costs for one course of CDI treatment, while the cost of a relapse is $4,355. Those costs could be devastating for more vulnerable individuals. The updated 2021 Infectious Diseases Society of America CDI treatment guidelines, which recommended fidaxomicin as first-line therapy, likely added to this burden of expense — the cost for the drug alone ranges from $3,845 to $5,245 for a 10-day supply. Many patients simply cannot afford the cost of fidaxomicin — and treatment may be delayed, while pharmacies, insurance companies, and physician offices negotiate what treatment may be provided. And I can tell you, a recent gastrointestinal profile panel (using the BioFire PCR Platform) cost me $1,405 out of pocket (my health insurance refused to cover the cost).

COMMENTARY

Over the last few years, there has been a great deal of focus on hospital-associated CDI and interventions to reduce the risk in the hospital and improve outcomes. More research is needed to understand the reasons for the shifting epidemiology of this infection into the community, and into more vulnerable populations, and how to improve treatment outcomes.