Who is at risk of Clostridioides (C.) difficile infection, particularly in terms of demographics, medical history, and current medications such as antibiotics and proton pump inhibitors (PPIs)?

Who is at Risk of Clostridioides difficile Infection?

Multiple patient populations face elevated CDI risk, with antibiotic exposure being the single most critical modifiable risk factor, followed by advanced age, healthcare exposure, immunosuppression, and specific comorbidities like inflammatory bowel disease. 1

Primary Risk Factors

Antibiotic Exposure (Most Important Modifiable Risk)

• High-risk antibiotics include third-/fourth-generation cephalosporins, fluoroquinolones, carbapenems, and clindamycin 1
• Risk increases 7- to 10-fold during antibiotic therapy and in the first month after exposure, remaining elevated for up to 3 months post-cessation 1, 2
• Even single-dose antibiotic prophylaxis with gut-penetrating antibiotics increases CDI risk 3
• Exposure to multiple antibiotics significantly compounds the risk 2, 3
• Continued use of antibiotics for infections other than CDI significantly increases recurrence risk 1

Proton Pump Inhibitor (PPI) Use

• PPI use is associated with a 2.34-fold increased risk of initial CDI and 1.73-fold increased risk of recurrent CDI 4
• Among community-acquired CDI cases without antibiotic exposure, 31% received PPIs 1
• The risk is particularly pronounced when PPIs are combined with antibiotics, especially in patients receiving fewer antibiotics (adjusted hazard ratio 15.7 with one antibiotic vs. 2.7 with five or more) 5
• PPI use during incident CDI treatment increases recurrence risk by 42% 6

Demographic and Healthcare-Related Factors

• Advanced age is one of the most important risk factors, potentially as a surrogate for severity of illness and comorbidities 1, 2
• Duration of hospitalization increases risk proportionally, serving as a proxy for exposure duration to the organism and antibiotics 1, 2
• Recent healthcare exposure: 82% of community-acquired CDI cases had some healthcare exposure in the preceding 12 weeks 1
• Previous hospitalization is the main risk factor for colonization upon hospital admission 1

Special High-Risk Populations

Inflammatory Bowel Disease (IBD)

• Patients with IBD, especially ulcerative colitis, face >3% risk of CDI within 5 years of diagnosis 1
• IBD patients are 33% more likely to suffer recurrent CDI 1
• CDI in IBD patients increases colectomy risk, postoperative complications, and mortality 1

Immunocompromised Patients

• Solid organ transplant recipients: 7.4% overall prevalence (5-fold greater than general medicine patients), with highest risks in multiple organ transplants, followed by lung, liver, intestine, kidney, and pancreas 1
• Cancer patients have higher risk due to chemotherapy-induced immunosuppression 1
• HIV/AIDS patients: Risk is stronger in those with low CD4 counts or meeting clinical AIDS criteria 1
• Hematopoietic stem cell transplant patients: Rate approximately 9 times greater than hospitalized patients overall, with twice the rate in allogeneic versus autologous transplants 1

Chronic Kidney Disease

• Patients with chronic kidney disease and end-stage renal disease have approximately 2- to 2.5-fold increased risk of CDI and recurrence 1
• 1.5-fold increased risk of severe disease with similarly increased mortality 1

Community-Acquired CDI Risk Factors

In a multivariate analysis of community-acquired cases, the following were independently associated with CDI 1:

• Specific antibiotic classes: Cephalosporins (adjusted OR 19.02), clindamycin (adjusted OR 35.31), fluoroquinolones (adjusted OR 30.71), and beta-lactam/beta-lactamase inhibitor combinations (adjusted OR 9.87)
• Healthcare utilization: Emergency department visit (adjusted OR 17.37)
• Demographics: White race (adjusted OR 7.67)
• Comorbidities: Cardiac disease (adjusted OR 4.87), chronic kidney disease (adjusted OR 12.12), and IBD (adjusted OR 5.13)
• Medications: Corticosteroid exposure (OR 1.81) 1

Critical Clinical Pitfalls

• Asymptomatic carriers: 8.1% colonization rate upon hospital admission, with 29% of CDI cases associated with asymptomatic carriers rather than symptomatic CDI patients 1
• Environmental contamination: Spores can survive for months in the environment despite regular cleaning 1
• Post-treatment shedding: Patients recently treated for CDI continue high-level shedding even after diarrhea resolution, with skin contamination and environmental shedding remaining elevated 1-4 weeks after treatment 1
• Peripartum women: Emerging evidence shows increasing CDI incidence in previously low-risk populations including healthy peripartum women 1