Abstract
Background and Aims
Gastrointestinal pathogen panels (GPPs) are increasingly being used for evaluation of diarrhea. The impact of these tests on patients with inflammatory bowel diseases (IBD) is unknown. We performed a time-interrupted cohort study comparing GPPs and conventional stool evaluation in patients with IBD with diarrhea.
Methods
We included 268 consecutive patients with IBD who underwent GPP (BioFire Diagnostics®) (n = 134) or conventional stool culture and Clostridium difficile polymerase chain reaction testing (n = 134) during suspected IBD flare between 2012 and 2016. Primary outcome was composite of 30-day IBD-related hospitalization, surgery, or emergency department visit; secondary outcome was IBD treatment modification.
Results
Overall, 41/134 (30.6%) patients tested positive on GPP (18 C. difficile, 17 other bacterial infections, and 6 viral pathogens) versus 14/134 patients (10.4%, all C. difficile) testing positive on conventional testing. Rate of IBD treatment modification in response to stool testing was lower in GPP group as compared conventional stool testing group (35.1 vs. 64.2%, p < 0.01). On multivariate analysis, diagnostic evaluation with GPP was associated with three times higher odds of IBD-related hospitalization/surgery/ED visit (95% CI, 1.27–7.14), as compared to conventional stool testing. This negative impact was partly mediated by differences in ordering provider specialty, with non-gastroenterologists more likely to order GPP as compared to gastroenterologists.
Conclusions
In patients with suspected flare of IBD, GPPs have higher pathogen detection rate and lead to lower rate of IBD treatment modification. A diagnostic testing strategy based on GPPs is associated with higher hospital-related healthcare utilization as compared to conventional stool testing, particularly when utilized by non-gastroenterologists.
Similar content being viewed by others
References
Landsman MJ, Sultan M, Stevens M, et al. Diagnosis and management of common gastrointestinal tract infectious diseases in ulcerative colitis and Crohn’s disease patients. Inflamm Bowel Dis. 2014;20:2503–2510.
Ananthakrishnan AN, Bernstein CN, Iliopoulos D, et al. Environmental triggers in IBD: a review of progress and evidence. Nat Rev Gastroenterol Hepatol. 2018;15:39–49.
Binnicker MJ. Multiplex molecular panels for diagnosis of gastrointestinal infection: performance, result interpretation, and cost-effectiveness. J Clin Microbiol. 2015;53:3723–3728.
Freeman K, Tsertsvadze A, Taylor-Phillips S, et al. Agreement between gastrointestinal panel testing and standard microbiology methods for detecting pathogens in suspected infectious gastroenteritis: Test evaluation and meta-analysis in the absence of a reference standard. PLoS ONE. 2017;12:e0173196.
Riddle MS, DuPont HL, Connor BA. ACG clinical guideline: diagnosis, treatment, and prevention of acute diarrheal infections in adults. Am J Gastroenterol. 2016;111:602–622.
Hanada Y, Khanna S, Loftus EV, Jr., et al. Non-clostridium difficile bacterial infections are rare in patients with flares of inflammatory bowel disease. Clin Gastroenterol Hepatol. 2017;16:528–533.
Axelrad JE, Joelson A, Nobel YR, et al. Enteric infection in relapse of inflammatory bowel disease: the utility of stool microbial PCR testing. Inflamm Bowel Dis. 2017;23:1034–1039.
Schunemann HJ, Oxman AD, Brozek J, et al. Grading quality of evidence and strength of recommendations for diagnostic tests and strategies. BMJ. 2008;336:1106–1110.
Palmela C, Chevarin C, Xu Z, et al. Adherent-invasive Escherichia coli in inflammatory bowel disease. Gut. 2018;67:574–587.
Limsrivilai J, Stidham RW, Waljee AK, et al. Gastrointestinal infectious agents detected by biofire filmarray GI PCR panel stool testing in active inflammatory bowel disease are common and are associated with a more benign course of IBD. Gastroenterology. 2017;152:S606.
Axelrad JE, Joelson A, Green PH, et al. Enteric infections are common in patients with flares of inflammatory bowel disease. Am J Gastroenterol. 2018. https://doi.org/10.1038/s41395-018-0211-8.
Gunnarsson RK, Lanke J. The predictive value of microbiologic diagnostic tests if asymptomatic carriers are present. Stat Med. 2002;21:1773–1785.
Author information
Authors and Affiliations
Contributions
Study concept and design were conceived by WA, WJS, and SS. Acquisition of data was made by WA. Analysis and interpretation of data were carried out by WA, NHN, and SS. The manuscript was drafted by WA and SS. Critical revision of the manuscript for important intellectual content was performed by NHN, BSB, PSD, DTP, DB, and WJS. The final manuscript was approved by WA, NHN, BSB, PSD, DTP, DB, WJS, and SS. Dr. Siddharth Singh who was the guarantor of the article had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
Corresponding author
Ethics declarations
Conflict of interest
None of the authors declare any potential conflicts of interested related to the contents of this manuscript. Dr. Boland has served as a consultant for Abbvie and has received research grants from Takeda and Janssen. Dr. Dulai has served as a consultant for Takeda and has received research grants from Takeda and Pfizer. Dr. Sandborn reports consulting fees from University of Western Ontario (owner of Robarts Clinical Trials, Inc), Abbvie, Akros Pharma, Allergan, Ambrx Inc., Amgen, Ardelyx, Arena Pharmaceuticals, Atlantic Pharmaceuticals, Avaxia, Biogen, Boehringer Ingelheim, Bristol Meyers Squibb, Celgene, Conatus, Cosmo Technologies, Escalier Biosciences, Ferring, Ferring Research Institute, Forward Pharma, Galapagos, Genentech, Gilead Sciences, Immune Pharmaceuticals, Index Pharmaceuticals, Janssen, Kyowa Hakko Kirin Pharma, Lilly, Medimmune, Mesoblast, Miraca Life Sciences, Nivalis Therapeutics, Novartis, Nutrition Science Partners, Oppilan Pharma, Otsuka, Palatin, Paul Hastings, Pfizer, Precision IBD, Progenity, Prometheus Laboratories, Qu Biologics, Regeneron, Ritter Pharmaceuticals, Robarts Clinical Trials, Salix, Seattle Genetics, Seres Therapeutics, Shire, Sigmoid Biotechnologies, Takeda, Theradiag, Theravance, Tigenix, Tillotts Pharma, UCB Pharma, Vascular Biogenics, Vivelix; research grants from Atlantic Healthcare Limited, Amgen, Genentech, Gilead Sciences, Abbvie, Janssen, Takeda, Lilly, Celgene/Receptos; payments for lectures/speakers bureau from Abbvie, Janssen, Takeda; and holds stock/stock options in Escalier Biosciences, Oppilan Pharma, Precision IBD, Progenity, Ritter Pharmaceuticals. Dr. Singh is supported by the American College of Gastroenterology and Crohn’s and Colitis Foundation, and has received research grants from Pfizer and AbbVie.
Ethics approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. For this type of study, formal consent is not required. This study was approved by the UCSD Institutional Review Board (IRB #161914).
Electronic Supplementary Material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Ahmad, W., Nguyen, N.H., Boland, B.S. et al. Comparison of Multiplex Gastrointestinal Pathogen Panel and Conventional Stool Testing for Evaluation of Diarrhea in Patients with Inflammatory Bowel Diseases. Dig Dis Sci 64, 382–390 (2019). https://doi.org/10.1007/s10620-018-5330-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s10620-018-5330-y