PCR and EIA Tests Not Reliable for Distinguishing Clostridium difficile from Colonization

Matthew Ziegler, MD

Clinical characteristics and outcomes of patients with hematologic malignancy and a positive Clostridium difficile (C. diff) test, whether diagnosed by the polymerase chain reaction (PCR) or enzyme immunoassay (EIA) method, do not significantly differ, according to a retrospective study.

These findings suggest that PCR and EIA testing methods may not be entirely reliable among patients with hematologic malignancy for distinguishing C. diff infection from colonization.

Researchers, led by Matthew Ziegler, MD, a fellow in the Division of Infectious Diseases at the University of Pennsylvania, retrospectively evaluated patients with an active hematologic malignancy and a positive C. diff test during hospitalization at the Hospital of the University of Pennsylvania between 2015 and 2017. Patients’ stool samples were evaluated for toxin A, toxin B, and glutamate dehydrogenase (GDH), and those that were negative for toxins A and B and positive for GDH were tested again for toxin genes using PCR.

The investigators evaluated clinical characteristics such as comorbidities, antibiotic use in the previous month, clinical signs and symptoms, etc., and outcomes—toxic megacolon, recurrent C. diff disease in 90 days after index testing, in-hospital mortality, and hospital readmission—of patients with PCR- and EIA-positive C. diff test results.

During the 27-month study period, approximately 11.6% of tests for C. diff were positive. A total of 101 patients with C. diff admitted to the hospital with a hematologic malignancy tested for a PCR-positive/EIA-negative result, whereas 81 patients tested for EIA-positive. Leukocytosis, defined as a white blood cell count of >15,000 cells/mm³, was more common among non-neutropenia patients with EIA-positive results than those with PCR-positive/EIA-negative results (P = .02).

The investigators noted no significant differences between patients in regard to diarrhea, fever, severe C. diff, in-hospital mortality, intensive care unit (ICU) transfer rate, or colitis. The overall in-hospital mortality and ICU transfer rates were rather high (18% and 25%, respectively), but no differences in these rates were observed between groups. Medications associated with an increased risk for C. difficile in both groups included acid suppressants and systemic antibiotics.

“While studies in general medical patients have found patients with C. diff with PCR-positive results to fare better than those with EIA-positive results, we were surprised by the high rates adverse outcomes in patients with hematologic malignancy and a PCR-positive test, with rates of ICU transfer of 22% and in-hospital mortality of 15%,” Ziegler told MD Magazine. “Although the high mortality may be attributable to the underlying malignancy, more patients in the PCR-positive group were diagnosed with toxic megacolon and required colectomy than in the EIA-positive group.”

The relatively small sample size, as well as the retrospective nature of the study, precluded the researchers’ ability to evaluate for an association between C. diff testing modalities and patient outcomes. Also, the findings from this study may not generalize to populations other than those with a hematologic malignancy.

“PCR-positive results for C. diff should be treated seriously in patients with hematologic malignancy,” Ziegler added, “and future studies are urgently needed to determine optimal methods to differentiate colonization from active infection with C. diff.”

The study, “Clinical Characteristics and Outcomes of Hematologic Malignancy Patients With Positive Clostridium difficile Toxin Immunoassay Versus Polymerase Chain Reaction Test Results,” was published in Infection Control & Hospital Epidemiology.