Satish S. Rao, MD, PhD, FACG1, Baharak Moshiree, MD, MSc2, Nikki Lee, PhD3, Mitchell L. Jones, MD, PhD3, Emil Chuang, MD3, Sharat Singh, PhD3; 1Medical College of Georgia at Augusta University, Augusta, GA; 2Atrium Health, University of North Carolina, Charlotte, NC; 3Progenity Inc., San Diego, CA
Introduction: Small Intestinal Bacterial Overgrowth (SIBO) is associated with abnormally high bacterial counts in the small intestine and symptoms of excess gas, bloating, distention, diarrhea and abdominal discomfort and diagnosis remains challenging. We aimed to compare the assay of a novel Smart Capsule Bacteria Detection System (SCBDS) with duodenal aspiration/culture in a multicenter clinical study in order to improve the diagnosis of SIBO. Methods: Duodenal aspiration was performed with a 3mm Liguory catheter under sterile condition in subjects suspected of SIBO (PM301 and PM305-001) or undergoing elective upper endoscopy (PM305-002) at three medical centers (Table 1). Aspirated fluid was sent to Local and Central microbiology labs for evaluation of total aerobic and anaerobic cultures [Total Bacteria Count (TBC)] and analysis by SCBDS Assay. Agreement was evaluated by comparing the kinetic slope to TBC Reference Standard using a ≥105 CFU/mL cutoff and performance using 2x2 Standard Test. Results: Total of 66 aspirate samples from patient suspected of SIBO (54) or undergoing elective endoscopy (12) (m/f= 18/48; mean age =54) were analyzed by TBC culture and SCDBS assay (Table 1). In PM301, the quantitative distribution of TBC in patients suspected of SIBO agreed with our previously reported review and there were no differences in proportion of subjects in TBC groupings, nor between Vacutainer® and ESwab™ containers (Figure 1). Overall agreement of SCDBS Assay with TBC Reference Standard was 94% (62/66) across clinical sites (Table 1). In PM301, it was determined that a kinetic slope of 10 could be used to make Positive and Negative SIBO calls and minimizing False Positive and Negatives with a ≥105 CFU/mL cutoff (Figure 2). Similar slope values were determined for SCBDS Assay performance using ≥104 and ≥103 CFU/mL cutoffs (Figure 2). Finally, performance of the SCDBS Assay, in PM301, showed a sensitivity of 100%, and specificity of 91%. Discussion: We found a high agreement between the SCBDS Assay and TBC Reference Standard in subjects suspected of SIBO and having endoscopic aspirate/culture, and across three centers. Due to the lack of access to endoscopic culture, its invasiveness, and complexity, the strong agreement and excellent performance characteristics of the SCBDS capsule represents a useful, novel, and non-invasive tool that aids diagnosis of SIBO. Although promising, we recognize that further clinical validation of model parameters and performance is needed.
TABLE 1: Overall agreement of the SCBDS Assay to Total Bacterial Count (TBC) Reference Standard in two clinical studies conducted at three clinical sites and positive SIBO call TBC cutoff of 10^5 CFU/mL.
FIGURE 1: Comparison of Local and Central laboratory bacterial counts (CFU/mL) where Central samples were collected and shipped in either Vacutainer® or Eswab™ tubes in subjects suspected of SIBO.
FIGURE 2: SCBDS Assay Slope (T0-Tmax) values of subjects (PM-301, top left and PM305, top right) categorized by 2x2 standard test using the TBC Assay Reference Standard with a ≥10^5 CFU/mL cutoff, as well as individual values of Positive and Negative Controls and a cutoff value (mean slope < 10^3 CFU/mL + 6SD) for making Positive and Negative calls. SCBDS Assay Slope (T0-Tmax) values of subjects (PM-301) categorized by 2x2 standard test using the TBC Assay Reference Standard with a ≥10^4 CFU/mL cutoff (Bottom left) and ≥10^3 CFU/mL cutoff (Bottom right) , as well as individual values of Positive and Negative Controls and a cutoff value (mean slope < 10^3 CFU/mL + 4SD) for making Positive and Negative calls.
Disclosures: Satish Rao: Progenity Inc. – Advisory Committee/Board Member, Consultant. Baharak Moshiree: Progenity Inc. – Advisory Committee/Board Member, Consultant. Nikki Lee: Progenity Inc. – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds). Mitchell Jones: Progenity Inc. – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds). Emil Chuang: Progenity Inc. – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds), Emil Chuang. Sharat Singh: Progenity – Employee. Progenity Inc. – Employee, Stockholder/Ownership Interest (excluding diversified mutual funds), Sharat Singh.