Diagnosis of Clostridioides difficile infection by analysis of volatile organic compounds in breath, plasma, and stool: A cross-sectional proof-of-concept study

Abstract

Clostridioides difficile infection (CDI) is an important infectious cause of antibiotic-associated diarrhea, with significant morbidity and mortality. Current diagnostic algorithms are based on identifying toxin by enzyme immunoassay (EIA) and toxin gene by real-time polymerase chain reaction (PCR) in patients with diarrhea. EIA’s sensitivity is poor, and PCR, although highly sensitive and specific, cannot differentiate infection from colonization. An ideal test that incorporates microbial factors, host factors, and host-microbe interaction might characterize true infection, and assess prognosis and recurrence. The study of volatile organic compounds (VOCs) has the potential to be an ideal diagnostic test. The presence of VOCs accounts for the characteristic odor of stool in CDI but their presence in breath and plasma has not been studied yet. A cross-sectional proof-of-concept study analyzing VOCs using selected ion flow tube mass spectrometry (SIFT-MS) was done on breath, stool, and plasma of patients with clinical features and positive PCR for CDI (cases) and compared with patients with clinical features but a negative PCR (control). Our results showed that VOC patterns in breath, stool, and plasma, had good accuracy [area under the receiver operating characteristic curve (ROC) 93%, 86%, and 91%, respectively] for identifying patients with CDI.

A consensus conference to define the utility of advanced infectious disease diagnostics in solid organ transplant recipients

“…In observational studies, exhaled metabolites yielded comparable sensitivity and specificity to consensus criteria for the diagnosis of invasive pulmonary aspergillosis in transplant recipients 51 . Gas chromatography–mass spectrometry has also been applied to the diagnosis of bacterial, mycobacterial, and viral pneumonias as well as malaria and Clostridioides difficile colitis 52–55 . This method holds potential for early and non‐invasive diagnosis but requires further validation and standardization of breath collection and is currently limited to the research‐use only.…”

“…51 Gas chromatography-mass spectrometry has also been applied to the diagnosis of bacterial, mycobacterial, and viral pneumonias as well as malaria and Clostridioides colitis. [52][53][54][55] This method holds potential for early and non-invasive diagnosis but requires further…”

Detection of Clostridioides difficile infection by assessment of exhaled breath volatile organic compounds

“…As such, there is a compelling case for identifying a breath VOC profile that could be used to diagnose CDI. One small study that employed selected ion flow tube mass spectrometry has already demonstrated that a selected group of breath VOCs can be used to differentiate healthy and CDI patient breath samples [5].…”

“…In a previous study in which selected ion flow tube mass spectrometry was used to analyze VOCs in samples from 31 patients with CDI and 31 controls, John et al [5] found evidence that CDI patients have a characteristic VOC profile. A K-nearest neighbors classifier model (k = 7) showed excellent accuracy for identifying CDI, with an AUC of 93%.…”

Sensitivity and specificity of in vivo COVID-19 screening by detection dogs: Results of the C19-Screendog multicenter study

“…In the past few decades, volatile organic compounds (VOCs) have been attracting considerable interest as potential biomarkers of human disease [ 3 ]. Their production has been investigated in cancer [ [4] , [5] , [6] , [7] , [8] , [9] ] as well as metabolic [ [10] , [11] , [12] ] and infectious diseases [ 3 , [13] , [14] , [15] , [16] ].…”