Kinetics of polymerase chain reaction positivity in patients with Clostridioides difficile infection

Abstract

Background: Polymerase chain reaction (PCR) is a sensitive test for diagnosing Clostridioides difficile infection (CDI) and could remain positive following resolution of CDI. The kinetics of PCR positivity following antibiotics for CDI is unknown. We studied this and whether it predicted CDI recurrence. Methods: Adults with CDI from October 2009 to May 2017 were included. Serial stool samples within 60 days of treatment were collected. Recurrent CDI was defined as diarrhea after interim symptom resolution with positive stool PCR within 56 or 90 days of treatment completion. Contingency table analysis was used to assess the risk of recurrence. Results: Fifty patients were included [median age: 51 (range = 20–86) years, 66% women]. Treatment given was metronidazole, 50% (25); vancomycin, 44% (22); both, 4% (2); and fidaxomicin, 2% (1). Median duration of treatment for all 50 patients was 14 (range = 8–60) days. The median duration of treatment in patients who got prolonged therapy (>14 days) ( n = 10) was 47 (range = 18–60) days. Median time to negative PCR was 9 (95% CI, 7–14) days from treatment initiation, which did not differ by antibiotics given ( p = 0.5). A positive PCR during or after treatment was associated with a higher risk of recurrence at 56 days ( p = 0.02) and at 90 days ( p = 0.009). Conclusion: The median time to negative PCR in CDI was 9 days from treatment initiation. The PCR positivity during or after treatment may be useful for recurrence prediction; larger studies are needed to validate these results.

Clostridioides difficile PCR Positivity on Successive Days after Treatment Initiation

“…One prior study from Mayo Clinic found that the median time to negative PCR in C. difficile infection was 9 days from treatment initiation [8]. This is not consistent with our study's findings, but caution is warranted in generalization of the findings of that study to the general population, as only 50 patients were included in the study despite being an 8-year-long prospective study at a large tertiary referral care center.…”

“…In light of our study’s findings, entirely dismissing repeat PCR testing in C. difficile infection appears inopportune, and it would be prudent to re-examine the clinical utility of testing for cure in C. difficile infection. The study on C. difficile PCR positivity on follow-up testing from Mayo Clinic did find that a positive PCR test during or after treatment completion was associated with a higher risk of recurrence [8]. We hypothesize that the correct interpretation of a positive PCR test for a microorganism in a living human is that it represents living microorganisms or microorganisms that were alive until very recently.…”

Validation of clinical risk tools for recurrent Clostridioides difficile infection

“…While our rCDI may have over captured some cases, we believe a symptom-based definition is a pragmatic approach to identify clinically relevant rCDI retrospectively, especially considering that PCR testing often remains positive regardless of rCDI. 35 Our resulting rate of recurrence (22.7%) approximates rates from prospective trials (∼25%). 25 40% of retrospective rCDI events occurred without retesting at the same health system laboratory, Figure 2.…”