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New Research Suggests Outpatient C. difficile May be Underdiagnosed in US


Findings showed a high incidence of outpatient Clostridioides difficile infection despite a low rate of testing.

New Research Suggests Outpatient C. difficile May be Underdiagnosed in US / Image credit: ©gaetan/AdobeStock


New data from a retrospective cohort study on outpatient medically attended diarrhea (MAD) and incidence of outpatient Clostridioides difficile infection (CDI) showed a high incidence of CDI despite a low rate of testing, suggesting that outpatient CDI may be underdiagnosed.

CDI is one of the most common health care-associated infections in the US and can cause substantial burden to both health care systems and patients, according to study authors led by Sara Y. Tartof, PhD, MPH, epidemiologist, Department of Research and Evaluation, Kaiser Permanente Southern California, Pasadena. However, despite the Centers for Disease Control and Prevention observation that the majority of laboratory-confirmed CDI cases in older adults do not result in hospitalization, little is known regarding “the extent of undiagnosed medically attended CDI among persons in the community,” wrote Tartof and colleagues.

They continued: “Our objectives were to describe the population-based incidence of MAD and testing for C difficile in the outpatient setting, the population-based incidence of outpatient CDI, and healthcare utilization outcomes among patients with outpatient CDI.”

The study included adults aged ≥18 years treated for MAD at Kaiser Permanente Southern California and Kaiser Permanente Northwest between January 1, 2016, and December 31, 2021. Investigators identified MAD through International Classification of Diseases, Tenth Revision (ICD-10) and CDI via positive laboratory results. Incidence rates (IRs) of outpatient CDI were stratified by select demographic and clinical variables, according to the study.

Outpatient CDI was defined for the purpose of the study as no hospitalization ≤7 days after specimen collection. Outpatient CDI burden 12 months following index date was measured by CDI-associated health care visits, as well as CDI testing and treatment.


Investigators identified 777 533 MAD episodes, of which 12.1% (93 964/777 533) were tested for CDI. Among those tested, 10.8% (10 110/93 964) were positive for CDI.

Tartof and coauthors reported that outpatient CDI IR was 51 per 100 000 person-years (95% CI 49.8-52.2) but pointed to a decrease in incidence from 58.2 (95% CI 55.7–60.7) in 2016 to 45.7 (95% CI 43.7–47.8) in 2021.

When they evaluated associated health care utilization, they found that 44.1% of patients received an antibiotic 30 days before the index date of their first CDI episode. The most commonly used antibiotic classes among patients with outpatient CDI were cephalosporins (18.9%), fluoroquinolones (14.1%), and penicillin’s (13.2%), observed investigators.

Researchers found that 35.1% of patients with outpatient CDI had been hospitalized in the previous year, with the majority (84.1%) of first episodes of outpatient CDI being “community associated” (no hospitalizations 12 weeks prior to index date).

“Consistent with population-based studies of CDI incidence, the incidence of outpatient CDI was higher among females, non-Hispanic White members, and those with underlying comorbid conditions, and incidence increased with age,” added Tartof et al.

“Further studies on the quality-of-life impact of outpatient CDI on patients would be helpful to judge the disease burden of outpatient CDI,” investigators concluded. “Furthermore, the high incidence of outpatient CDI may contribute to transmission within households or other environments or may predispose high-risk patients with comorbidities to subsequent CDI infections in the event of an immunocompromising event or medication.”

Source: Tartof SY, Schmidt MA, Contreras R, et al. Burden of medically attended diarrhea and outpatient Clostridioides difficile infection among persons in 2 large integrated healthcare settings, 2016-2021. Open Forum Infect Dis. Published online January 11, 2024. doi:10.1093/ofid/ofad680

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