Clinical Utility of Broad-Range Universal PCR for Pathogen Identification

Data regarding an assessment of universal broad-range PCR sequencing (uPCR) for pathogen detection published in Clinical Infectious Diseases demonstrated the utility of the technique and how to maximize its use.

Investigators identified 1062 clinical samples with uPCR results from medical records of patients admitted to University of California, San Francisco (UCSF) Medical Center or UCSF Benioff Children’s Hospital between November 2011 and July 2019. For each case with a positive uPCR result, investigators determined the results of microbiologic and pathology studies, final diagnosis, clinical significance of a positive result, and whether a positive result changed clinical management. Results were considered clinically significant when the isolated pathogen was compatible with the patient’s clinical syndrome without a better alternative explanation.

The 1062 clinical specimens were obtained from 864 unique patients. The median age was 50 years, 15.5% were aged <18 years, and 53.9% were male. From these specimens, there were 2280 uPCR results: 734 were bacterial, 824 fungal, and 722 mycobacterial.

Overall, uPCR was positive in 16.5% of the samples (95% CI, 14.3-18.8). In terms of clinical significance, 10.1% of all samples and 61.1% of all positive uPCR results were deemed significant. There was substantial variation by specimen type.

Clinical management was changed by a positive uPCR result in 4.1% of the 1062 specimens tested. Among the 107 samples deemed clinically significant, management was changed 41.1% of the time. The 2 most common reasons that a clinically significant uPCR result did not change management were when appropriate antimicrobial therapy was guided by other positive investigations, and appropriate antimicrobial therapy had already been started empirically and no changes were indicated. There were no cases found in which the response to a positive uPCR resulted in inappropriate management.

Investigators were unable to assess the true sensitivity and specificity of uPCR compared with culture-based reference. They also could not evaluate how a negative result changed management, because this data is rarely documented. While unlikely, due to clear documentation of how uPCR influenced clinical decisions, the effect of uPCR results on clinical decision-making may have been misclassified by the retrospective nature of the study.

Despite these limitations, this study included the analysis of a large, real-world cohort at a representative tertiary hospital with inclusion of a broad array of clinical specimens. According to investigators, this work showed that uPCR “has important clinical utility for pathogen detection in challenging cases in which infection is suspected.” There have been no clear recommendations to date as to when to employ uPCR testing. The results do suggest that the yield of the test will be maximized on tissue-based specimens, especially those with inflammation and/or direct visualization of organisms on corresponding pathology.

Reference

Kerkhoff AD, Rutishauser RL, Miller S, Babik JM. Clinical utility of universal broad-range PCR amplicon sequencing for pathogen identification: a retrospective cohort study [published online January 7, 2020]. Clin Infect Dis. doi:10.1093/cid/ciz1245