TABLE 1.

Scenarios for clinically relevant (true positive) and clinically irrelevant (false positive/negative) organisms

Scenario
Clinically relevant (true positive)
Confirmed positive and primary etiology of illness: e.g., patient septic from Enterococcus bacteremia on blood culture, which was also identified on mNGS testing
Confirmed positive but not primary reason for hospitalization/severe acute illness: e.g., HSV gingivostomatitis in patient septic from Pseudomonas bacteremia, but HSV (and Pseudomonas) identified on mNGS testing and verified by standard workup (PCR swab and blood culture, respectively)
Not confirmed positive but consistent with infectious diagnosis: e.g., F. necrophilum identified in mNGS testing in patient diagnosed with aspiration pneumonia, although standard microbiological workup did not identify this organism
Clinically irrelevant (false positive or negative)
Pathogens that are likely contaminants: e.g., S. epidermidis identified on mNGS but no evidence of bloodstream infection and concurrent blood cultures negative with no treatment
Pathogens that may reflect gastrointestinal/skin colonization with no obvious manifestation in the patient: e.g., N. sicca coidentified in patient with respiratory failure/sepsis from adenovirus, and not confirmed on blood culture or treated
Pathogens with no known clinical significance: e.g., virus with no known associated infectious clinical manifestation
Pathogens identified on mNGS that were discordant with final clinical diagnosis made on the basis of standard microbiological workup: e.g., E. coli and H. influenzae on mNGS in setting of Streptococcus gordonii endocarditis identified from blood culture and universal PCR of valve tissue