Predictors of Clostridioides difficile Infection-Related Complications and Treatment Patterns among Nucleic Acid Amplification Test-Positive/Toxin Enzyme Immunoassay-Negative Patients

Abstract

The addition of toxin enzyme immunoassay (EIA) to nucleic acid amplification tests, including PCR, creates challenges in the diagnosis and management of Clostridioides difficile infection (CDI). There are limited data in large cohorts, with discordant results, that is, PCR-positive/EIA-negative (PCR⁺/EIA⁻) results. We conducted a retrospective cohort study on all PCR⁺/EIA⁻ adult inpatients and assessed CDI-related complications and clinical failure. We identified 240 individuals. Twenty-three (9.6%) patients experienced a CDI-related complication, including 2 cases of megacolon, 1 colectomy, and 22 intensive care unit (ICU) admissions. In multivariable logistic regression analyses, baseline severe disease by Infectious Diseases Society of America (IDSA) criteria (odds ratio [OR], 5.84; 95% confidence interval [CI], 1.88 to 18.1; P = 0.002), baseline fulminant colitis (OR, 84.7; 95% CI, 14.3 to 500; P < 0.001), fever of >38.5°C (OR, 4.61; 95% CI, 1.42 to 15.0; P = 0.011), and proton pump inhibitor (PPI) use (OR, 3.50; 95% CI, 1.19 to 10.3; P = 0.023) were associated with increased odds of CDI-related complications. For 67 PCR⁺/EIA⁻ patients who did not receive complete treatment, clinical failure was observed in 10 (15%) patients. A comparison of PCR⁺/EIA⁻ patients who received complete treatment to all 112 PCR⁺/EIA⁺ patients showed no differences in CDI-related complications (11% and 13% for PCR⁺/EIA⁻ and PCR⁺/EIA⁺ patients, respectively), 60-day all-cause mortality (17% and 18% for PCR⁺/EIA⁻ and PCR⁺/EIA⁺ patients, respectively), or recurrent CDI (7% and 9% for PCR⁺/EIA⁻ and PCR⁺/EIA⁺ patients, respectively). Predictors of CDI-attributable complications among PCR⁺/EIA⁻ patients include baseline severe disease by IDSA criteria, baseline fulminant colitis, and fever of >38.5°C. Identifying the subgroup of PCR⁺/EIA⁻ patients who could have true disease, and therefore allowing them to be targeted for treatment, is critical.