New Molecular Diagnostic Approaches to Bacterial Infections and Antibacterial Resistance

Abstract

Recent advances in the field of infectious disease diagnostics have given rise to a number of host- and pathogen-centered diagnostic approaches. Most diagnostic approaches in contemporary infectious disease focus on pathogen detection and characterization. Host-focused diagnostics have recently emerged and are based on detecting the activation of biological pathways that are highly specific to the type of infecting pathogen (e.g., viral, bacterial, protozoan, fungal). Although this progress is encouraging, it is unlikely that any single diagnostic platform will fully address the clinician's need for actionable data with short turnaround times in all settings.

Keywords: gene expression profiling; host response diagnostics; host-pathogen interactions; infectious diseases diagnostics; nucleic acid biomarkers; point-of-care testing.

Figure 1.

Overview of the development process for a host diagnostic biomarker. Begin with a population that is dichotomized by susceptibility, diagnosis, or prognosis. Omic measurements are run on acquired samples, which generates large quantities of data. Dimension reduction and statistical analyses generate a classifier or signature that distinguishes the desired characteristic from the original population. The classifier is then validated against a different population to test generalizability. (Used with permission from Yang WE, et al. Host-based diagnostics for detection and prognosis of infectious diseases. In: Sails A, Tang YW, eds. Methods in Microbiology. Elsevier Ltd, 2015;42[13]:465–500.)

Figure 2.

Comparison of time to organism identification, availability of phenotypic antimicrobial susceptibility results, and first appropriate modification of antimicrobial therapy for the subset of study subjects with organisms represented on the rapid multiplex polymerase chain reaction (rmPCR) panel (n = 481). Time 0 is when the positive Gram stain result was reported. Median time in hours (interquartile range [IQR]) to organism identification: control 22.3 (17–28), both rmPCR and rmPCR + stewardship 1.3 (0.9–1.6); de-escalation: control 39 (19–56), rmPCR 36 (22–61), rmPCR + stewardship 20 (6–36); escalation: control 18 (2–63), rmPCR 4 (1.5–24), rmPCR + stewardship 4 (1.8–9). *P < .05 vs control; †P < .05 vs control and rmPCR groups. (Used with permission from Banerjee R, et al. Randomized Trial of Rapid Multiplex Polymerase Chain Reaction-Based Blood Culture Identification and Susceptibility Testing. Clin Infect Dis. 2015 Oct 1;61(7):1071–80.)