The Role of a Sequencing-based Clinical Intestinal Screening Test in Patients at High-risk for Clostridium Difficile and Other Pathogens

A Case Report

Maureen Hitschfeld; Elena Tovar; Sarah Gupta; Elisabeth M. Bik; Christina Palmer; Michael C. Hoaglin; Daniel E. Almonacid; Jessica Richman; Zachary S. Apte


J Med Case Reports. 2019;13(9) 

In This Article

Case Presentation

This patient is a 29-year-old white woman from the USA with a medical history significant for severe IBS-D (diagnosed at age 12) and anxiety disorder. In July 2015, she presented with severe bleeding hemorrhoids secondary to IBS, which required hemorrhoidectomy and anal sphincterotomy in August 2015. The week before the surgery she developed pharyngitis and was treated with azithromycin, which resulted in mucousy diarrhea and abdominal discomfort. She tested negative for C. difficile antigen and toxins at that time.

A week after surgery, she developed a perirectal abscess that had formed at the site of the sphincterotomy and was prescribed orally administered ciprofloxacin. Despite moderate symptom improvement, in September 2015 she required an abscess incision and drainage procedure and Penrose drain insertion. Prior to the surgery she was given a single dose of clindamycin. An additional 2-week course of ciprofloxacin and metronidazole was then prescribed. In late September 2015 she was admitted to the hospital for two nights due to further complications related to the abscess and was then diagnosed as having a perianal fistula.

In November 2015, she was prescribed clindamycin for an episode of group C streptococcal-positive pharyngitis. In late November 2015, she was also diagnosed as having Ehlers–Danlos syndrome, which according to her medical record may partially explain the poor wound healing from the perirectal abscess. In December 2015, her fistula required an anus seton placement. She was treated with multiple courses of ciprofloxacin and metronidazole off and on from December 2015 to January 2016.

In January 2016, following up on her recurrent pharyngitis, she was diagnosed as having chronic tonsillitis which led to tonsillectomy. In February 2016, 2 weeks after the surgery she was prescribed clindamycin. At the beginning of March 2016, she was diagnosed as having bacterial vaginosis and was prescribed orally administered metronidazole. A week later she was diagnosed as having vaginal candidiasis and was prescribed orally administered fluconazole. In April 2016, she complained of dysuria and was prescribed ciprofloxacin. After 2 days, when urine analysis results came back negative, she was asked by her physician to stop the treatment.

In June 2016, she presented for follow-up with ongoing diarrhea and abdominal pain. She was diagnosed as having C. difficile diarrhea, her antigen and toxins laboratory results were indeterminate, and a toxigenic strain was confirmed by polymerase chain reaction (PCR). She was prescribed a 6-week course of orally administered vancomycin. After a week of treatment her symptoms worsened, and following discussion with her gastroenterologist her treatment was switched to a 2-week course of metronidazole. Hours later, she was admitted to the hospital for a 4-day period for colitis. Her C. difficile antigen and toxin test returned negative during her admission. She received intravenously administered metronidazole treatment during her hospitalization. Her symptoms improved during her hospital stay, with 1–2 soft bowel movements a day. At discharge her metronidazole course was stopped and she was again prescribed vancomycin, which she took for over a month. She continued to experience GI irregularity (3–5 bowel movements a day) beyond what she had experienced secondary to her IBS prior to her surgeries. In March 2017, she was prescribed rifaximin for 2 weeks to treat chronic diarrhea.

In November 2017, she was prescribed a series of clinical intestinal tests (SmartGut™, uBiome Inc., San Francisco, USA) with the instructions to administer the test at home whenever she was experiencing a noticeable change of GI symptoms, then follow-up with her health care provider to discuss the results. This sequencing-based test requires that patients use a sterile swab to transfer a small amount of fecal material from toilet paper into a vial containing a lysis and stabilization buffer that preserves the microbial DNA for transport by mail back to the laboratory for processing, which involves DNA extraction, 16S ribosomal RNA (rRNA) gene amplification, and sequencing.[45] She first used this test in November 2017, about a month after completing a 2-week course of rifaximin. The results revealed a number of microbial organisms that were outside the healthy reference ranges, but she was negative for all pathogenic organisms included in the test, including C. difficile (Figure 1).

Figure 1.

Selected results from the first SmartGut™ test report taken by the patient in November 2017 (Clostridium difficile negative). Three relevant parts of the clinical intestinal test SmartGut™ report generated after sample analysis are shown here: pathogens section, diarrhea from the infections section, and irritable bowel syndrome from the gut conditions section. The actual report is much more comprehensive and includes: other gut conditions such as inflammatory bowel disease, including ulcerative colitis and Crohn's disease, and gastrointestinal symptoms; diet and lifestyle conditions, such as obesity, kidney stones, type 2 diabetes, non-alcoholic fatty liver disease, and prediabetes; and cardiovascular health conditions, such as atherosclerosis and cardiovascular disease, among others

Between November and December 2017, her GI symptoms worsened considerably; her daily bowel movements increased from 3–4 to 6–10, stool consistency became more mucous-like and gelatinous, and she was experiencing more pain with defecation. She re-tested with SmartGut™ test again in January 2018. Her results continued to reveal a number of microbial organisms outside the healthy range and, this time, her sample also indicated the presence of C. difficile (Figure 2). She immediately contacted her primary care provider, who re-tested her for C. difficile and confirmed indeterminate CDI by antigen and toxins A and B. Additional PCR testing at a regional laboratory confirmed the sample was positive for a toxigenic C. difficile strain. As a result of testing, her clinician started her on fidaxomicin; her symptoms improved rapidly. By April 2018, she had returned to her baseline in regard to her IBS-related GI symptoms with no blood in her stools.

Figure 2.

Selected results from the second SmartGut™ test report taken by the patient in January 2018 (Clostridium difficile positive)

In addition, the second SmartGut™ sample was tested for toxins A and B by sequencing at uBiome Inc. laboratory in San Francisco, USA, which resulted positive for both and confirmed the toxigenic nature of the C. difficile strain.