Comparison of the clinical course of Clostridium difficile infection in glutamate dehydrogenase-positive toxin-negative patients diagnosed by PCR to those with a positive toxin test

Abstract

Objectives: To evaluate the potential role of PCR-based assays in the over-diagnosis of Clostridium difficile infection (CDI) by using a validated diagnostic algorithm in daily clinical practice. Methods: We performed a retrospective cohort study evaluating all C. difficile-positive stool samples identified at our institution during a 12-month period, to compare outcomes and recurrence rates between patients with a positive enzyme immunoassay (EIA) for both glutamate dehydrogenase (GDH) and toxin A/B ('toxin-positive group'), with those with GDH-positive, toxin-negative samples in whom the diagnosis was made by a positive PCR-based assay ('toxin e /PCR þ group'). Medical records were reviewed by two independent investigators blinded to the mode of diagnosis. Results: We analysed 231 first CDI episodes (106 (45.8 %) in the 'toxin-positive group' and 125 (54.1%) in the 'toxin e /PCR þ group'). Both groups had similar baseline characteristics. Patients in the 'toxin-positive group' presented more frequently with a severe/severe complicated form than those in the 'toxin e /PCR þ group' (36 (33.9%) versus 24 (19.2%); p 0.011) and had more recurrences (27 (25.5%) versus 9 (7.2%); p 0.001). Diagnosis of CDI based on a GDH/toxin-positive EIA independently predicted severe/severecomplicated course (adjusted OR 2.11; 95% CI 1.06e4.22; p 0.033) and recurrence (adjusted OR 3.79; 95% CI 1.65e8.69; p 0.002). There were no differences in all-cause mortality (12.3% versus 12.0%; p 0.95) or CDI-attributable mortality (4.7% versus 4.8%; p 0.93). Conclusions: Toxin-positive patients were more likely to have severe-complicated forms of CDI and recurrences. Nevertheless, CDI-related complications may still occasionally occur among toxin-negative patients diagnosed by PCR, which stresses the need for individualized clinical evaluation.

Clinical Characteristics and Outcomes of Hematologic Malignancy Patients With Positive Clostridium difficile Toxin Immunoassay Versus Polymerase Chain Reaction Test Results

“…Our results differ from studies of general medical patients that have found those with toxin EIA(+) C. difficile results to have both a greater prevalence of CDI clinical characteristics and worse outcomes compared to PCR (+)/EIA (−) results 7,8 . A prospective study without GDH screening found those with PCR (+)/EIA (−) results to have a lower prevalence of leukocytosis, fewer number of stools, and lower rates of adverse outcomes, including mortality and recurrent CDI 7 .…”

“…However, the 30-day mortality of 0.6% in the PCR (+)/EIA (−) group in this study compared to 15% in our study highlights the significant difference in study populations. Another recent study also demonstrated higher rates of leukocytosis, fever, and severe CDI as well as recurrent C.difficile infection with an EIA(+) result versus PCR (+)/EIA (−) result after GDH screening, but did not find a difference in mortality between the groups 8 . Notably, our study included only samples collected through routine clinical care and were tested via a multistage process which included a C.difficile GDH screening test.…”

Toxin B PCR Amplification Cycle Threshold Adds Little to Clinical Variables for Predicting Outcomes in Clostridium difficile Infection: a Retrospective Cohort Study

“…In a recently published retrospective cohort study (8), we found that both the occurrence of severe or complicated forms of CDI and recurrence were significantly more common among patients with a positive EIA for both GDH and toxin A/B than among those with GDH-positive, toxin-negative samples for whom the diagnosis of CDI was made by a positive PCR-based assay. In the present study, our aim was to evaluate if toxin B PCR C T adds something to the combination of clinical variables and free toxin detection by EIA in predicting recurrence or a poor CDI outcome.…”

“…Episodes of CDI without adequate information were excluded, as well as those without a traceable 8-week follow-up after the end of treatment and those for which the C T result for the tcdB PCR was not available. More details about the cohort on which the present study is based are described elsewhere (8). The local clinical ethics committee approved the study protocol.…”

“…"Poor outcome" was defined as the occurrence of a severe or severe-complicated first CDI episode and/or all-cause death within the first 8 weeks after the end of treatment. Other study definitions are detailed elsewhere (8).…”