C. difficile NAAT testing cannot distinguish between colonization and infection and can result in overdiagnosis and inappropriate treatment, especially when ordered in patients with low pretest probability.

Clinical assessment for CDI is critical to appropriate diagnosis and interpretation of laboratory findings.

Inappropriate treatment of patients colonized with C. difficile without actual clinical infection can increase the risk of multidrug-resistant pathogens such as VRE, recurrent C. difficile, hospital readmissions, and healthcare costs.

We recommend utilizing a multistep testing algorithm to maximize the sensitivity and specificity of available C. difficile tests and avoid the diagnosis of asymptomatic colonizers. Avoid retesting within 7 days of a negative test or as a test of cure after successful treatment.

We recommend involvement of the antimicrobial stewardship programs to provide oversight of antibacterial use and to guide C. difficile testing.