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Repeat PCR Testing ‘Should Not be Used’ to Predict Recurrent CDI
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SAN ANTONIO — The median time to a first negative stool polymerase chain reaction test after the treatment of Clostridioides difficile infection was 9 days, which helped to indicate when physicians can expect to see a negative test, according to data presented at the American College of Gastroenterology Annual Meeting
“The results from our study provide a time frame within which physicians can expect stool PCR for C. difficile to become negative,” Srishti Saha, MBBS, MD, a postdoctoral research fellow at Mayo Clinic in Rochester, Minnesota, told Healio Gastroenterology and Liver Disease. “This is valuable in interpreting results of a repeat test in patients who have persistent or recurrent diarrhea post-CDI treatment.”
Saha and colleagues conducted a prospective study of 50 patients (median age, 51 years; 66% female) with CDI at the Mayo Clinic from October 2009 to May 2017.
Twenty-four percent had prior CDI.
Time to first negative PCR test from the start of treatment served as the primary endpoint.
An additional endpoint included time to first negative PCR by treatment received – metronidazole vs. vancomycin.
Half of the patients received metronidazole, while 44% received vancomycin. The remaining patients received combination of metronidazole and vancomycin (n = 2) and fidaxomicin (n = 1).
“Clostridioides difficile infection is the most common health care associated infection in the United States, with several tests available for its diagnosis,” Saha said in an interview. “PCR, one of the most commonly used tests, is highly sensitive but can remain positive after appropriate treatment of CDI. Often, patients continue to have diarrhea after their CDI episode. Repeat testing with PCR in such a scenario presents a clinical conundrum, as it can represent recurrence of CDI, or persistent colonization with the bacteria.”
As a result, Saha noted that it raises many questions as to how long a PCR remains positive after CDI treatment, as well as does the type of antibiotic treatment impact the time to a negative PCR.
“We found that PCR became negative a median 9 days after treatment initiation,” she said. “This was not affected by antibiotic treatment received. Patients who had a positive PCR during treatment tended to have a higher risk of recurrence within 56 days of treatment, though this was not statistically significant. Patients with a positive PCR after treatment completion did not have higher risk of recurrence.”
Saha noted that this study is one of few looking at repeat PCR testing in CDI and its implications.
“The results are promising and indicate that PCR positivity may have a role in recurrence prediction, though this would need to be confirmed in a larger study,” she said. “Our results also suggest that at present, repeat PCR testing should not be used to predict recurrence.” – by Ryan McDonald
Reference:
Saha S, et al. Abstract 5. Presented at: American College of Gastroenterology Annual Scientific Meeting; Oct. 25-30; San Antonio.
Disclosures: The researchers report no relevant financial disclosures.
Perspective
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Gautam Mankaney, MD
Diarrheal illness due to Clostridioides difficile is the most common cause of hospital-acquired diarrheal illness and has surpassed MRSA as the most common cause of hospital-acquired infection as well, which is a big deal. With its changing epidemiology, the recurrence rates are increasing as well, with rates as high as 30% following the first episode. Once you have a recurrence, the rates for a second recurrence are even higher, reaching as high as 60% for a third recurrence. To further compound the issue, many hospital patients are colonized with C. diff – up to 13% of patients after a week of hospitalization – but colonization does not necessarily translate into a clinical infection. A frequently used test for C. diff identification is the stool based nucleic acid amplification test that tests positive in both asymptomatic and symptomatic cases.
Thus, challenges we face in the field include: Why are we having so many recurrences? Why are recurrence rates increasing? Can we predict who will either fail treatment or have a recurrence? And with a significant number of patients colonized, how can we separate asymptomatic colonization from true infection?
This abstract tackles some of these. The authors studied the kinetics of PCR positivity in C. diff and whether test positivity during or after treatment was a marker for recurrence. The average time from a positive to negative test was 9 days, and there was a trend toward predicting recurrence in those with a persistently positive test.
Right now, the IDSA guidelines recommend that we do not recheck asymptomatic individuals for clearance of C. diff for the reasons I outlined above, in particular the high colonization rates as well as the high sensitivity but poor specificity of the PCR test
This presentation gives us a timetable on when we could potentially recheck stool for clearance, but it is a small study. For now, my recommendation to other providers is that symptoms matter a lot when determining whether an individual has resolved or recurrent infection. Once you’ve treated someone for C. diff, I would not check a C. diff PCR to document clearance. If symptoms are suggestive of recurrent C. diff infection, then get the test. It all comes down to a strong clinical suspicion, the most important tool we have today.
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