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.

Evaluation of Two Rapid Diagnostic Clostridioides difficile Infection Tests in a Chinese Hospital: A Real-world Analysis

“…We compared the outcomes of patients with toxin EIA-negative, TC-positive, and toxin EIA-positive/TC-positive results to assess their clinical characteristics. The results showed no difference in clinical characteristics and outcomes, consistent with previous reports (28,29). However, research in the US reported that patients with positive NAAT-toxins had more complications and a higher blood leucocyte count than patients who were only positive for NAAT (30).…”

Multistep Testing Algorithms for Clostridioides difficile Infection

“…Many patients with discordant results on multistep screening testing have risk factors for C difficile and a clinical presentation consistent with CDI, and approximately 70% are treated with antibiotics for CDI . Compared with patients who have positive results on both C difficile multistep screening tests, patients with discordant results have less severe illness, reduced recurrence rates, and a lower mortality rate, although fulminant CDI can occur . Therefore, treatment should not be withheld if there is high clinical suspicion of CDI …”

“…Individuals with test results positive for GDH antigen and negative for toxin EIA can undergo NAAT to determine whether they have a toxigenic strain of C difficile . Many patients with discordant results on multistep screening testing have risk factors for C difficile and a clinical presentation consistent with CDI, and approximately 70% are treated with antibiotics for CDI . Compared with patients who have positive results on both C difficile multistep screening tests, patients with discordant results have less severe illness, reduced recurrence rates, and a lower mortality rate, although fulminant CDI can occur .…”

Novel immunoassay for diagnosis of ongoing Clostridioides difficile infections using serum and medium enriched for newly synthesized antibodies (MENSA)

“…However, the sole reliance on molecular diagnostics without querying the host response will likely result in false positive diagnoses and unwarranted overtreatment. Recent literature underscores the potential for overtreatment despite this multi-step approach (17).…”