Diagnosis of Bloodstream Infections: An Evolution of Technologies towards Accurate and Rapid Identification and Antibiotic Susceptibility Testing

Abstract

Bloodstream infections (BSI) are a leading cause of death worldwide. The lack of timely and reliable diagnostic practices is an ongoing issue for managing BSI. The current gold standard blood culture practice for pathogen identification and antibiotic susceptibility testing is time-consuming. Delayed diagnosis warrants the use of empirical antibiotics, which could lead to poor patient outcomes, and risks the development of antibiotic resistance. Hence, novel techniques that could offer accurate and timely diagnosis and susceptibility testing are urgently needed. This review focuses on BSI and highlights both the progress and shortcomings of its current diagnosis. We surveyed clinical workflows that employ recently approved technologies and showed that, while offering improved sensitivity and selectivity, these techniques are still unable to deliver a timely result. We then discuss a number of emerging technologies that have the potential to shorten the overall turnaround time of BSI diagnosis through direct testing from whole blood—while maintaining, if not improving—the current assay’s sensitivity and pathogen coverage. We concluded by providing our assessment of potential future directions for accelerating BSI pathogen identification and the antibiotic susceptibility test. While engineering solutions have enabled faster assay turnaround, further progress is still needed to supplant blood culture practice and guide appropriate antibiotic administration for BSI patients.

Evaluation of a Conformationally Constrained Indole Carboxamide as a Potential Efflux Pump Inhibitor in Pseudomonas aeruginosa

“…Additionally, about half of P. aeruginosa isolates from burn victims are carbapenem-resistant due to various mechanism [ 79 ], highlighting the potential beneficial outcome that TXA09155/levofloxacin treatment would have on these cases. Finally, time-consuming practices of pathogen identification and antibiotic susceptibility testing delay diagnosis and force clinicians to employ empirical antibiotic treatment, risking the development of antibiotic resistance [ 80 ].…”

Efficient filter-in-centrifuge separation of low-concentration bacteria from blood

“…10,11 Various rapid phenotypic and genotypic methods have been developed for this purpose. 12–16 However, the bottleneck in sepsis diagnosis lies in sample preparation, particularly in separating bacteria from whole blood, given that the concentration of bacteria is as low as 1–10 CFU mL −1 , whereas blood cells have concentrations in the range of 4–6 billion per mL for red blood cells (RBCs) and 5–10 million per mL for white blood cells (WBCs). Various methods have been investigated for bacterial separation, including sedimentation velocity-based differentiation, 17,18 inertial 19–21 and elastoinertial 22 microfluidics, acoustophoresis, 23,24 surface acoustic waves (SAW), 25 dielectrophoresis (DEP), 26 and magnetic beads based separation.…”

Diagnostic efficiency of the FilmArray blood culture identification (BCID) panel: a systematic review and meta-analysis

“…Traditionally, diagnosing BSI solely relies on blood culture, which has been considered the gold standard of pathogen detection [18]. However, there are some shortcomings with blood culture for the diagnosis of BSI, such as low sensitivity, prolonged turnaround time (>48 h), and being labour intensive or operator dependent [19][20][21][22]. Recent advances have emerged for the rapid and specific identification of pathogens from positive blood culture bottles, which include melting curve analysis, matrix-assisted laser desorption/ionization-time-of-flight (MALDI-TOF) and nucleic acid amplification technologies [23][24][25][26][27][28][29].…”