Clinical Outcomes of Treated and Untreated C. difficile PCR-Positive/Toxin-Negative Adult Hospitalized Patients: a Quasi-Experimental Noninferiority Study.

Clostridioides difficile infection (CDI) is routinely diagnosed by PCR, with or without toxin enzyme immunoassay testing. The role of therapy for positive PCR and negative toxin remains unclear. The objective of this study was to determine whether clinical outcomes of PCR+/cycle threshold-based toxin (CT-toxin)- individuals vary by result reporting and treatment strategy. We performed a quasiexperimental noninferiority study comparing clinical outcomes of PCR+/CT-toxin- individuals by reporting PCR result only (most patients treated) with reporting CT-toxin result only (most patients untreated) in a single-center, tertiary academic hospital. The primary outcome was symptomatic PCR+/CT-toxin+ conversion at 8 weeks. Secondary outcomes included 7-day diarrhea resolution, hospital length of stay, and 30-day all-cause mortality. A total of 663 PCR+/CT-toxin- test results were analyzed from 632 individuals with a median age of 61 years (interquartile range [IQR], 44 to 72) and 50.4% immunocompromised. Individuals in the preintervention group were more likely to have received CDI therapy than those in the intervention group (91.5 versus 15.1%; P < 0.001). Symptomatic toxin conversion at 8 weeks and hospital length of stay failed to establish the predefined thresholds for noninferiority. Lack of diarrhea resolution at 7 days and 30-day all-cause mortality was similar and established noninferiority (20.0 versus 13.7%; adjusted odds ratio [aOR], 0.57; 90% confidence interval [CI], 0.32 to 1.01; P = 0.1; and 8.6 versus 6.5%; aOR, 0.46; 90% CI, 0.20 to 1.04; P = 0.12). These data support the safety of withholding antibiotics for selected hospitalized individuals with suspected CDI but negative toxin.