Health care-associated infections (HAIs) are linked to increased morbidity and mortality risk, as well as increases in health care-associated costs. Clostridioides difficile infection (CDI) is the most prevalent HAI in the United States, resulting in approximately 12,800 deaths each year.1-2 Although previous study results show that the estimated national burden of CDI declined by 36% between 2010 and 2020, HAI CDI continues to pose a risk in individuals receiving antibiotic therapy, especially those older than 65 years.3-4
There is a current lack of consensus regarding optimal diagnostics for CDI in the US. Although nucleic acid amplification testing (NAAT) has shown higher sensitivity than other assays, this approach may lead to the overdiagnosis of CDI, as NAAT detects the gene encoding the C difficile toxin rather than the toxin itself.3
Efforts are ongoing to improve CDI diagnosis, and some researchers have found promising results with machine-learning methods to predict the risk for CDI among hospitalized patients.5
Other study findings underscore the importance of a collaborative approach in reducing the burden of HAI CDI. As described in a 2022 study, a community hospital within an academic health care system achieved a 63% reduction in CDI diagnoses within the first year of implementing an interprofessional team approach with a focus on evidence-based interventions, including diagnostic and antibiotic stewardship, enhanced environmental cleaning, and increased education and accountability among team members. These results were sustained for 4 years, with a 77% reduction in CDI diagnoses reported.6
To gain further insight into current CDI trends and ongoing needs, we spoke with Lisa Winston, MD, professor of clinical medicine at the University of California, San Francisco (UCSF), and chief of staff and hospital epidemiologist at Zuckerberg San Francisco General Hospital and Trauma Center; Ryan Miller, DO, infectious disease specialist at Cleveland Clinic, Ohio; and Neha Nanda, MD, clinical associate professor of medicine at Keck School of Medicine at the University of Southern California (USC), and hospital epidemiologist at Keck Medicine of USC.
What is the current status of hospital-acquired CDI in the US, and do CDI diagnosis rates appear to be increasing, decreasing, or remaining the same?
Dr Winston: Hospital-onset CDI rates in the US have continued to decrease through 2020. While some HAIs such as central line-associated bloodstream infections, catheter-associated urinary tract infections, and ventilator-associated events increased in 2020 in association with the COVID-19 pandemic, hospital-onset CDI decreased by about 11% from 2019 to 2020, according to National Healthcare Safety Network data.7 Other surveillance data are generally consistent with this trend.
Dr Miller: Current data regarding CDI is difficult to obtain, as the Centers for Disease Control and Prevention’s (CDC) tracker is only updated through 2019. In my personal experience, different hospitals are experiencing different rates in 2022. Some hospitals have had higher CDI rates in 2022 than in previous years, whereas rates are the same in other hospitals. In 2019, the overall incidence of CDI was 121.2 cases per 100,000 persons, with 57.9 cases per 100,000 persons diagnosed with hospital-onset CDI.8
Dr Nanda: CDI rates have decreased over the past several years. For instance, based on data from the Emerging Infections Program CDI Working Group, which includes CDC and several state health department representatives, there was a decline in hospital-onset CDI cases and hospitalizations from 2011 to 2017. Interestingly, during this time period, the CDI burden in the community was unchanged.3
Looking at more recent data, there has not been much change between pre-COVID-19 pandemic rates in 2019 and those obtained during the pandemic in 2020.9
What are the best strategies to prevent and reduce the spread CDI?
Dr Winston: Traditional infection control strategies, including staff performing appropriate hand washing and wearing personal protective equipment (PPE), along with environmental cleaning that targets C difficile spores, are thought to be important in preventing CDI spread, though data are somewhat limited. The most important strategy for preventing infection is likely antibiotic stewardship.
Dr Miller: Judicious antibiotic use and faithful hand washing are the best strategies to help prevent spread. Diagnoses of CDI are thought to be due to the overgrowth and subsequent toxin production of the C difficile bacterium. If we alter the gut microbiota with antibiotics, then C difficile is more likely. Hospitals utilize sporicidal cleaning techniques to avoid environmental spread of C difficile spores, but individual practitioners can help by ensuring appropriate use of narrow-spectrum antibiotic with appropriate hand hygiene practices.
Dr Nanda: To reduce the burden of CDI, the best strategy is a multi-pronged approach based on 3 principles:
This can be achieved by having a high clinical suspicion and using appropriate diagnostics to accurately identify patients with CDI. Health care workers should be aware of signs and symptoms of infection, therefore ongoing education among caregivers is extremely important. Diagnostics are the mainstay of such a reduction program because it can be challenging to differentiate between individuals who are carriers and those with confirmed infection. This is because C difficile can be present in the body even without causing CDI.
Tools, both universal and targeted to C difficile, should be deployed effectively. This includes relying on hand hygiene, isolation of the case patient, and appropriate utilization of PPE. Health care settings should have easy access to water sinks and soap, and health care workers should be aware of the importance of hand hygiene. There should be processes in place — preferably electronic communication — to rapidly isolate the case patient. Lastly, while caring for patients with CDI, HCWs should have easy access to appropriate PPE.
Prevent new cases
This includes all levers outlined in rapid containment, in addition to proactive disinfection measures. Disinfection measures include optimal daily cleaning, which is the concrete and mortar of any disinfection program. Use of effective disinfection agents against CDI and ongoing education among environmental services staff are important for ensuring excellent adherence to containment measures. Other levers include ultraviolet (UV) disinfection to eradicate spores and bacteria. Furthermore, having a robust antibiotic stewardship program can prevent the emergence of new CDI diagnoses.
At Keck Medicine, we have relied on all 3 principles and have built a good operating model — by relying on automated processes — to reduce our CDI burden. We have created a unique diagnostic algorithm tailored to our patient population to help accurately diagnose and care for individuals with CDI.
Teamwork and partnership between various departments such as infection control, environmental services, materials and management, information technology, and those with direct patient interaction, including physicians, nurses, trainees, and all caregivers, has allowed us to sustain our successes and incorporate new tools and levers as the science evolves.
Are there any recent developments or emerging findings that have or may help to further reduce the burden of CDI?
Dr Winston: Multiple studies have suggested that strategies to decrease inappropriate antibiotic prescribing and to specifically decrease prescribing of antibiotics associated with CDI, such as fluoroquinolones, are effective in decreasing the rate of infection.3
Dr Miller: New treatments, including fidaxomicin and bezlotoxumab, are available for high-risk patients. The Infectious Disease Society of America released updated guidelines regarding CDI treatment in June 2021.10 Information about environmental cleaning is in development, including the use of UV light for terminal cleaning of hospital rooms.
Dr Nanda: There is growing literature focused on models to predict which individuals will develop CDI. These models incorporate demographic and clinical variables and can inform us about “modifiable” factors to prevent CDI. The implementation of these models, if scaled, could have a huge impact on the burden of CDI. Today, there are few models, and they rely on facility-level data that cannot be universally applied.5
What are some of the key remaining needs in this area in terms of research or otherwise?
Dr Winston: A number of novel approaches to prevent CDI are being studied. Unfortunately, the administration of probiotics does not appear to be an effective strategy. Areas of interest include the administration of oral agents to bind or inactivate antibiotics in the gastrointestinal tract and the use of fecal microbiota transplantation to treat and prevent CDI relapses.4 Development of an effective vaccine to prevent CDI would be a major advance, but so far this has proved difficult.
Dr Miller: CDI can be difficult to diagnose as the testing algorithms are complicated and nonspecific. Currently, hospital systems employ different testing techniques, including polymerase chain reaction, toxin enzyme immunoassay, and glutamate dehydrogenase testing.4 In an ideal world, CDI would have a more universal and reliable testing method, but it has been difficult to develop for a bacterium that can colonize the colon without causing disease.
CDI remains difficult to treat, especially when it comes to disease recurrence. Once someone has had CDI, recurrence is more likely and may be difficult to manage. Research on the prevention of CDI recurrence is ongoing, so hopefully there will soon be treatment breakthroughs. The best thing we can do for our patients, though, is to use antibiotic stewardship to help prevent the initial infection. Over-prescribing antibiotics can have deadly consequences in patients with CDI, including antibiotic resistance.
Dr Nanda: There are 2 areas in which, with appropriate investment, we can reduce the burden of CDI: research and expanded surveillance. In terms of research, increasing resources toward CDI diagnostics and individualized risk stratification to predict CDI can have a huge impact on CDI burden. For diagnostics, currently we do not have an easily accessible “gold standard” test with a rapid turnaround time, so we rely on diagnostic algorithms which entail stepwise testing. In addition, commonly used algorithms require clinical judgment and are not 100% accurate. Individualized risk stratification, based on predictive models as mentioned above, is another area for growth.
By expanding C difficile surveillance outside hospital settings and into clinics, urgent care centers, and other settings, we can prevent community transmission and therefore reduce the overall burden of CDI.
- Luo Y, Grinspan LT, Fu Y, et al. Hospital-onset Clostridioides difficile infections during the COVID-19 pandemic. Infect Control Hosp Epidemiol. 2021;42(9):1165-1166. doi:10.1017/ice.2020.1223
- Centers for Disease Control and Prevention. Clostridioides difficile infection. Accessed October 21, 2022.
- Guh AY, Mu Y, Winston LG, et al; On behalf of the Emerging Infections Program Clostridioides difficile Infection Working Group. Trends in U.S. burden of Clostridioides difficile infection and outcomes. N Engl J Med. 2020;382(14):1320-1330. doi:10.1056/NEJMoa1910215
- Czepiel J, Dróżdż M, Pituch H, et al. Clostridium difficile infection: review. Eur J Clin Microbiol Infect Dis. 2019;38(7):1211-1221. doi:10.1007/s10096-019-03539-6
- Panchavati S, Zelin NS, Garikipati A, et al. A comparative analysis of machine learning approaches to predict C. difficile infection in hospitalized patients. Am J Infect Control. 2022;50(3):250-257. doi:10.1016/j.ajic.2021.11.012
- Walter C, Soni T, Gavin MA, Kubes J, Paciullo K. An interprofessional approach to reducing hospital-onset Clostridioides difficile infections. Am J Infect Control. 2022;S0196-6553(22)00096-7. doi:10.1016/j.ajic.2022.02.017
- Weiner-Lastinger LM, Pattabiraman V, Konnor RY, et al. The impact of coronavirus disease 2019 (COVID-19) on healthcare-associated infections in 2020: a summary of data reported to the National Healthcare Safety Network. Infect Control Hosp Epidemiol. 2022;43(1):12-25. doi:10.1017/ice.2021.362
- Centers for Disease Control and Prevention. 2019 annual report for the Emerging Infections Program for Clostridioides difficile Infection. Accessed October 21, 2022.
- Rose AN, Baggs J, Kazakova SV, et al. Trends in facility-level rates of Clostridioides difficile infections in US hospitals, 2019-2020. Infect Control Hosp Epidemiol. 2022;19:1-8. doi:10.1017/ice.2022.69
- Johnson S, Lavergne V, Skinner AM, et al. Clinical practice guideline by the Infectious Diseases Society of America (IDSA) and Society for Healthcare Epidemiology of America (SHEA): 2021 focused update guidelines on management of Clostridioides difficile infection in adults. Clin Infect Dis. 2021;73(5):e1029-e1044. doi:10.1093/cid/ciab549