Abstract

BackgroundCDI is a frequent cause of morbidity and mortality in hospitalized patients. Despite advances in rapid CDI testing, there are often delays between the onset of symptoms and receipt of test results. We sought to test the hypothesis that the altered CDI intestinal microbiome has a unique volatile metabolite profile, distinct from the profile of patients with other causes of antibiotic-associated diarrhea, which potentially can be used to identify patients with CDI.MethodsWe prospectively collected fresh stool samples from inpatients with suspected CDI at an academic tertiary care hospital from July 2015 to November 2017, adsorbed volatile metabolites from each sample onto sorbent tubes within an hour of sample collection, and used thermal desorption-gas chromatography/tandem mass spectrometry to identify each metabolite. All patients were exposed to at least one antibiotic agent in the prior 90 days, and only patients receiving empiric CDI treatment or with formed stool samples were excluded. We used logistic regression models, adjusting for prior anti-anaerobic antibiotic therapy and CDI severity (serum albumin <3 g/dL and WBC ≥ 15,000/mm3 or abdominal tenderness) and adjusting for multiple testing using Storey’s q-value procedure (with a threshold of q ≤ 0.05), to examine the relationship between CDI, as determined by the reference standard of the cell culture cytotoxicity neutralization assay, and each metabolite.ResultsIn our 565-patient cohort, median age was 61 years (IQR 50, 70) and 277 (49%) were male; 173 (31%) had abdominal pain in the 24 hours before testing, 59 (10%) had fevers in the prior 24 hours, 22 (4%) had an ileus, 74 (13%) had mental status changes in the prior 24 hours, 89 (16%) were hospitalized in the ICU at the time of testing, 45 (7%) were receiving pressors, 82 (15%) had a WBC ≥ 15,000/mm3, and 137 (24%) had a serum lactate > 1.5 mmol/L. Ultimately, 155 patients were diagnosed with CDI. Ten metabolites (Table 1, Figure 1) were differentially distributed in patients with and without CDI.ConclusionWe identified a suite of volatile metabolites that differentiates stool from patients with and without CDI; this profile may ultimately be used to identify patients with CDI. Disclosures All authors: No reported disclosures.

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