Minding the antimicrobial testing gap: one way automated liquid handling is improving medicine
Automated liquid handlers are great for increasing assay efficiency and throughput while also improving accuracy, precision and trueness, so it can be surprising to find critical medical tests that are still being done manually. One area where the gold standard—the microdilution test—uses a manual method is evaluating bacterial sensitivity to antibiotics. Because of the time, effort, and complexity of the microdilution test, most hospital-based clinics need to send patient samples to a reference lab for analysis, which leads to a significant delay in the results. James Kirby, MD, Director of the Clinical Microbiology Laboratory at BIDMC and Associate Professor of Pathology at Harvard Medical School, is working to change the situation by automating the test so that it is faster and can be performed by personnel in a hospital clinic1.
Why the need for a faster microdilution test?
Typically, when a patient is diagnosed with a bacterial infection, the physician will determine which antibiotic to start with by evaluating the patient’s symptoms and making an educated guess about the identity of the bacteria. In the meantime, a patient sample is sent out to a reference lab to test for susceptibility to various antibiotics, which can add four- to six days to the process. This delay between initial diagnosis of a bacterial infection and determination of the most effective antibiotic to use is often referred to as the “antimicrobial testing gap.”
In the past, the microdilution test would often verify the physician’s original treatment choice, minimizing the impact of the delay in receiving the results. However, the increased spread of multi-drug-resistant bacteria has made the consequences of the antimicrobial testing gap more severe, as a physician’s initial antibiotic choice is increasingly the wrong one.
Overcoming the antimicrobial testing gap
In an effort to shorten the antimicrobial testing gap, Dr. Kirby and colleagues have automated and miniaturized the standard broth microdilution protocol (used to test the susceptibility of bacteria to antibiotics) using the same digital dispensing technology employed by ink jet printers—specifically, an HP D300 digital dispensing system. Their modified assay greatly simplifies the complexity of the process, reducing the labware need and setup time so that the microdilution test can now be performed in most hospital-based clinical labs. At the same time, the accuracy of the new method is the same as that for the standard assay, while the precision has been increased, improving overall assay quality. Lastly, because the test is now in a 384-well format, throughput is also much greater, adding to a reduction in the overall antimicrobial testing gap.
Moving into the clinic
The recent paper from Dr. Kirby’s lab1 provides a proof-of-concept validation for their streamlined microdilution test, and lays the groundwork for getting this technology that shortens the antimicrobial testing gap into clinical practice and hospital-based clinical labs. In addition, it highlights how automating an assay can significantly impact delivery of patient care.
Additional Resources
- Press Release: Beth Israel Deaconess Medical Center “Simple Method Quickly Tests Hard-to-Treat Bacteria’s Susceptibility to Different Antibiotics”
- Publication: JH Jorgensen and MJ Ferraro. Antimicrobial Susceptibility Testing: A Review of General Principles and Contemporary Practices. Clin Infect Dis. 49 (11): 1749-1755 (2009). doi: 10.1086/647952
- Website: The Kirby Laboratory’s description of their work.
References
1. Smith, K. P. & Kirby, J. E. Verification of an Automated, Digital Dispensing Platform for At-Will Broth Microdilution-Based Antimicrobial Susceptibility Testing. J. Clin. Microbiol. 54, 2288–2293 (2016). PubMed PMID: 27335151
About the Author
George Rodrigues, Ph.D.
George Rodrigues, Ph.D., is Senior Scientific Manager at Artel, the global leader in liquid delivery quality assurance. Rodrigues is responsible for developing and delivering communications and consulting programs designed to maximize laboratory quality and productivity through science-based management of liquid delivery. Rodrigues is Artel’s chief representative to key commercial clients, government regulatory bodies and industry organizations. His speaking and teaching engagements, along with his publications, build awareness of the challenges and solutions for laboratories in maintaining data integrity and confidence in their testing protocols. He plays a key role in developing the manufacturing and quality assurance processes for Artel products and organizes programs to assist pharmaceutical, biotechnology and clinical laboratories in improving their liquid delivery quality assurance and analytical process control. Rodrigues earned his BS in Chemical Engineering at the U.C. Berkeley, and a PhD in Chemical Engineering at the University of Wisconsin.
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