New microfluidic chip enables rapid antibiotic susceptibility testing for bloodstream infections

Failure to effectively control the presence of viable bacteria in the bloodstream, known as bacteremia, can lead to severe conditions such as bloodstream infections (BSI) and sepsis, characterized by a dangerous inflammatory response.

For BSI patients, timely and accurate antimicrobial prescriptions are crucial for significantly reducing mortality rates. However, the conventional method for testing antimicrobial susceptibility in BSI cases is time-consuming and burdensome, often forcing clinicians to rely on their experience for treatment decisions.

A team of researchers from Shandong University, Qingdao Institute of Bioenergy and Bioprocess Technology (QIBEBT) of the Chinese Academy of Sciences (CAS), and the Affiliated Hospital of Qingdao University has developed a groundbreaking solution—a microfluidic chip called the BSI-AST chip—for rapid AST from positive blood cultures (PBCs). Remarkably, the entire process, from extracting bacteria to obtaining AST results, now takes less than 3.5 hours. This innovative technology holds great promise for expediting the diagnosis and treatment of bloodstream infections.

The study, published in Analytical Chemistry on September 14, addresses a critical issue. Traditional AST methods typically require a minimum of two days to provide results after a positive blood culture is identified. This delay often leads to the use of empirical antibiotics, increasing the risk of worsening the patient’s condition and fueling antibiotic resistance—a pressing global concern.

The BSI-AST chip designed by the researchers can extract bacteria directly from PBCs within a mere 10 minutes and produce rapid AST results in just three hours. In a proof-of-concept study, the chip successfully performed direct AST on artificial PBCs containing E. coli, testing against 18 different antibiotics—all within the 3.5-hour timeframe. Furthermore, when applied to clinical PBCs, the chip demonstrated a substantial agreement rate of 93.3% with standard clinical methods, underscoring its reliability and potential for clinical diagnosis.

This innovation sets itself apart from previous microfluidic devices primarily used for purifying and concentrating microorganisms from subculture or urine samples with simpler compositions. The BSI-AST chip’s unique capability for direct AST from PBCs without the need for subculture represents a significant advancement. This achievement was made possible by introducing a separator gel to the microfluidic chip, enabling rapid extraction and enrichment of bacteria from PBCs. Coupled with centrifugal microfluidic enrichment technology, AST results can now be obtained in less than 3.5 hours directly from PBCs. Additionally, the chip’s ability to perform multiplexing analysis through antibiotic drying and array parallelization holds promise for quickly confirming or optimizing effective antibiotic therapy for BSI patients.

When combined with Clinical Antimicrobial Susceptibility Test Ramanometry (CAST-R), the BSI-AST chip provides a rapid and convenient solution for sample pretreatment, according to Prof. Xu Jian, the head of the Single-Cell Center at QIBEBT.

In summary, rapid AST in blood cultures is a game-changer for patients with clinical sepsis and has the potential to save lives. The ongoing exploration and research in this field are expected to enhance diagnostic capabilities and provide invaluable treatment guidance for infectious diseases in laboratory settings, effectively combatting the serious threat of microbial resistance to humanity.

Source: Chinese Academy of Sciences

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