Current Blood Culture Diagnosis Workflow

Bloodstream infections (BSIs) affect millions of people each year, and diagnosing them is challenging, mainly because symptoms like fever and fatigue are non-specific and overlap with many other conditions. Fever, for instance, is a common response during inflammation or infection, which further complicates the diagnosis. This makes it difficult for doctors to quickly identify BSIs and begin appropriate treatment. 

Blood culture remains the gold standard for diagnosing these infections. A blood sample is drawn and placed in a culture bottle to incubate and detect microbial growth. If the culture is positive, broad-spectrum antibiotics are started while further testing is done to identify the pathogen. 

A gram stain is performed to differentiate between Gram-positive and Gram-negative bacteria. Further biochemical and molecular tests are used to identify the specific pathogen.

A key technology in this process is MALDI-TOF MS (Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry). This analyzes the protein profiles of bacterial samples to identify species in just minutes. However, the full identification process can still take from 24 hours to several days, depending on the microorganism's growth rate and the time needed for protein detection.

Determining the pathogen’s antibiotic resistance, usually using methods like broth microdilution or the ETEST gradient strip. These tests measure the minimum inhibitory concentration (MIC) of various antibiotics and help guide treatment decisions. Even this can take 24 hours or more.

Automated systems like VITEK 2 can speed up susceptibility testing, offering results in 9 to 18 hours. While these technologies speed up the process, it still takes several days—or even weeks—from blood culture collection to final identification and testing.

a flowchart of the current methods for diagnosing bloodstream infections (BSI)

This delay can have a significant impact on patient care. For instance, For every hour treatment is delayed in sepsis, survival rates drop by nearly 8%. This underscores the importance of quickly identifying the pathogen and starting the right treatment.

Challenges in BSI diagnosis

There are a lot of factors that underline this delay:

1. Low Pathogen Load: The number of microorganisms in the blood can often be very low, sometimes only 1 to 100 colony-forming units (CFU) per milliliter of blood. This low concentration means that it can be hard to detect the pathogen with traditional diagnostic methods, as the infection might not show up immediately in a blood culture.

2. Broad Range of Pathogens: Bloodstream infections can be caused by a wide variety of bacteria, viruses, and fungi. Some of these pathogens are more difficult to detect than others, and there is often a need to cover a broad spectrum of potential microorganisms in diagnostic tests. This breadth of pathogen coverage can make it challenging for conventional testing to quickly pinpoint the exact culprit.

3. Complex Blood Matrix: The blood itself presents a complex environment for detecting pathogens. Proteins, cells, and other components in the blood can interfere with diagnostic processes, making it harder to isolate and identify the microorganisms responsible for the infection.

Given these challenges, treatment becomes complicated. Most clinicians start with empirical therapy, meaning they use broad-spectrum antibiotics to cover a wide range of possible pathogens, but this approach is far from ideal. Without knowing the exact pathogen and its antibiotic resistance profile, doctors can’t ensure that the treatment is effective, which often leads to unnecessary or ineffective antibiotic use.

This is where the issue becomes even more concerning. According to a 2021 report by the CDC, 28% of antibiotic prescriptions in the United States were unnecessary. The overuse and misuse of antibiotics contribute not only to worse clinical outcomes for patients but also fuel the rise of antibiotic-resistant microorganisms. These resistant pathogens make future infections more difficult to treat and create a vicious cycle that exacerbates the problem on a global scale.

Advancements in the tech for BSI detection 

However, the management of bloodstream infections (BSIs) has been significantly evolving with the advent of advanced diagnostic techniques.

1. Rapid Molecular Diagnostics

Companies Involved:

• Sherlock Biosciences: Utilizes CRISPR technology for rapid diagnostics.

• Luminex: Offers multiplex molecular assays that can identify multiple pathogens simultaneously.

Working Principle:

Rapid molecular diagnostics leverage techniques like polymerase chain reaction (PCR) and CRISPR-based assays to detect pathogens in blood samples quickly. For instance, Sherlock Biosciences' INSPECTR platform employs synthetic biology to use freeze-dried synthetic gene networks that can identify specific nucleic acid sequences. When a target nucleic acid is detected, it activates a CRISPR-Cas enzyme, leading to a signal that can be read via simple methods like paper strips or mobile devices. This rapid identification allows for timely and appropriate antibiotic treatment, which is critical in managing BSIs effectively12.

2. Antimicrobial Stewardship Programs (ASPs)

Companies Involved:

• BD Diagnostics: Provides automated molecular systems that enhance laboratory efficiency.

• Roche Diagnostics: Offers a comprehensive range of molecular tests and stewardship solutions.

Working Principle:

Antimicrobial stewardship programs aim to optimize the use of antibiotics through guidelines and protocols that promote appropriate prescribing practices. By integrating rapid diagnostic tools, ASPs can help clinicians make informed decisions about antibiotic therapy based on the specific pathogens identified and their resistance profiles. For example, BD Diagnostics' systems streamline the process of pathogen detection and susceptibility testing, allowing healthcare providers to adjust treatment regimens promptly, thereby reducing unnecessary antibiotic use and combating resistance.

3. AI-Enhanced Pathogen Identification

Companies Involved:

• Luminex Corporation: Develops multiplex molecular assays for pathogen detection.

• BioMérieux: Offers rapid diagnostic solutions for infectious diseases.

Working Principle:

AI enhances pathogen identification through advanced molecular diagnostics that significantly reduce turnaround times for blood culture results. Techniques like multiplex PCR allow simultaneous detection of multiple pathogens and their resistance markers from blood samples. For instance, Luminex's VERIGENE system can identify bacterial pathogens and their genetic determinants of antibiotic resistance within hours. By integrating AI algorithms into these systems, the accuracy of pathogen identification is improved, facilitating quicker and more effective treatment decisions.

These innovations are reshaping the future of patient care. By enabling clinicians to quickly pinpoint the right pathogens and tailor treatments accordingly, these technologies are paving the way for more precise, targeted therapies. Reducing unnecessary antibiotic use tackles one of the biggest threats to global health—antimicrobial resistance—while also improving patient outcomes. As these technologies evolve, they will continue to refine the way infections are managed, fostering a healthcare system that is more agile, responsive, and sustainable. Rapid diagnostics aren’t just about faster results—they’re about building a smarter, more effective healthcare system that can keep up with the ever-changing landscape of infectious diseases.