The burden of Clostridioides difficile infections in the United States

By Pooja Toshniwal PahariaReviewed by Benedette Cuffari, M.Sc.Mar 13 2023

In a recent review published in BMC Infectious Diseases, researchers reviewed existing data on Clostridioides difficile infections (CDI) among United States residents.

Study: The burden of CDI in the United States: a multifactorial challenge.  Image Credit: AnaLysiSStudiO / Shutterstock.com

What are CDIs?

CDIs have caused considerable mortality in the U.S. and have notable psychological, clinical, economic, and social implications.

Healthcare-related CDI incidence has reduced, whereas that of community-onset CDIs has increased. Notably, CDIs have recurred secondary to intestinal dysbiosis in several patients, with detrimental impacts on the quality of life of affected individuals.

In the present review, researchers describe the evolving epidemiology, recurrence, risk factors, clinical presentations, and complications of CDIs.

CDI epidemiology and recurrence

The U.S. Centers for Disease Control and Prevention (CDC) has identified CDIs as an urgent global threat, underscoring that immediate and aggressive actions are required to prevent CDI-associated complications and C. difficile reinfections. Currently, CDIs are not considered nosocomial infections.

CDI incidence is estimated to be eight cases among 10,000 individual days, whereas crude incidence rates of 121 CDI among 100,000 individuals have been reported.

CDI burden was reportedly reduced by 24% between 2011 and 2017 and further declined during coronavirus disease 2019 (COVID-19), likely because of reduced testing and strict implementation of infection control and prevention measures.

According to CDC reports, the incidence of healthcare-related CDIs, which describe disease onset in healthcare facilities or those attributed to recent hospitalizations, is 58 cases among 100,000 individuals. These rates were 53% in 2012 and reduced by 36% by 2017 and 47% in 2019. Comparatively, community-onset CDI incidence doubled in the previous decade, with the estimated incidence being 63 cases among 100,000 individuals.

The incidence rates were 47% and 53% in 2012 and 2019, respectively. Community-associated CDI includes cases wherein C. difficile-positive stool specimens are obtained in outpatient settings or three days following hospitalization from individuals with no night stay at healthcare facilities in the previous 12 weeks.

Recurrent C. difficile infections (rCDI) occur in 20.0% to 35.0% of CDI patients within one month. Among rCDI patients, less than 60% will subsequently develop reinfections.  

Recurrence risks are doubled after more than two recurrences. CDIs recur due to colonic microbiome dysbiosis with shifts in protective-type substances, such as short-chain-type fatty acid molecules and secondary bile acids, and spore germination by metabolites produced by Enterobacterales species.

Repetitive microbiota disruptions due to repeated courses of antibiotics such as amoxicillin, vancomycin, ampicillin, clindamycin, fluoroquinolones, and cephalosporins perpetuate recurrence risks. The vicious infection-reinfection cycle impedes recovery from CDI.

Risk factors, clinical presentations, complications, and impact on quality of life

Antibiotic therapy has been associated with increased risks of CDI. Antibiotic medications modify the intestinal microflora and permit C. difficile proliferation and the production of binary toxins, including A and B toxins.

CDI risks are more significant among females and older individuals with comorbidities such as kidney disease, hepatic disease, diabetes, multiple sclerosis, inflammatory bowel disease, and rheumatoid arthritis. In addition, immunocompromised individuals, individuals with recent hospitalizations, and prior use of proton pump inhibitors (PPIs), lipid-lowering agents, or corticosteroids have greater CDI risks.

CDIs have heterogeneous clinical presentations ranging from asymptomatic states to fatal colitis. C. difficile has been identified as the causative agent in 20% of antibiotic-related diarrhea cases among hospital-admitted individuals.

CDI clinical signs and symptoms include abdominal pain, vomiting, nausea, dehydration, mild-intensity to profuse-type diarrhea, peripheral edema, tenesmus, abdominal distension, and severe colitis. Most CDI patients recover within five days of antibiotic therapy initiation.

A few cases may result in circulatory-type shock. CDIs have enormous clinical impacts, with greater severity, functional loss, and death probabilities than hospitalizations associated with other diseases. The documented one-month CDI mortality rates range from 6% to 11% and have increased during the COVID-19 pandemic, especially among older individuals with a higher number of recurrences.

CDI complications include colectomy, sepsis, intestinal perforation, kidney failure, and megacolon. Bacterial translocations in CDI predispose to potentially-fatal bloodstream infections caused by Candida, Enterococcus, and Enterobacteriaceae.

CDIs can have long-term psychological, social, professional, economic, and emotional impacts on a patient’s quality of life and have been associated with adverse mental health outcomes, including anxiety and depression.

Daily activities, professional work, and sleep patterns are affected. In addition, rCDI patients have reported a loss of independence and traveling difficulties due to fear of uncontrolled diarrhea or fecal incontinence.

Inpatient annual hospital cost estimates associated with CDI and rCDI in the United States are $5 billion and USD 2.80 billion, respectively.

Conclusions

Based on the review findings, CDIs have detrimental health, psychological, social, and economic implications exceeding gastrointestinal symptoms. The CDI burden can be broadly divided into three categories, including clinical, economic, and humanistic burdens. Clinical CDI burdens include mortality, sepsis, colectomy, toxic megacolon, severe diarrhea, intestinal perforation, recurrent infections, intensive care unit admission, and kidney failure.

The economic CDI burden includes hospital readmission, inpatient costs, emergency department visits, increased hospital length of stay, pharmacy costs, out-of-pocket expenditure, reimbursement costs, and reimbursement penalties. The humanistic burden includes depression, anxiety, post-traumatic stress disorder, social isolation, absenteeism, loss of productivity, fear of repeated infections, and fear of infecting others.

CDI management requires multidisciplinary approaches, given the psychosocial impact of CDI. Efforts must be made to lower CDI costs and direct management toward preventing community-onset and recurrent C. difficile infections.