Species-specific bacterial detector for fast pathogen diagnosis of severe pneumonia patients in the intensive care unit

Abstract

Rapid diagnosis of pathogens is the cornerstone of appropriate therapy and is also a great challenge to be overcome. Although NGS and some other PCR-based pathogen detection methods were applied to improve the speed and accuracy of clinical diagnosis, it was still a long way from the clinical needs of rapid and accurate diagnostic therapy in the intensive care unit (ICU). In this study, we aimed at developing a new rapid diagnostic tool, Species-Specific Bacterial Detector (SSBD), to evaluate the existence and quantification of 10 most usual pathogenic bacteria in ICU in 4 hours. Briefly, the species-specific genome fragments of each bacterium were identified by our algorithm using 1791 microbe genomes from 232 species and then used to combine with CRISPR/Cas12 to establish diagnosis tools. Based on the tests of 77 samples, SSBD demonstrated 100% sensitivity and 87% specificity compared with conventional culture test (CCT). Later on, an interventional random-grouped study was applied to evaluate the clinical benefits of SSBD. Briefly, SSBD demonstrated more accurate and faster diagnosis results and led to earlier antibiotics adjustment than CCT. Based on the results acquired by SSBD, cultivation results could deviate from the real pathogenic situation with polymicrobial infections. In addition, nosocomial infections were found widely in ICU, which should deserve more attention.