By - January 06, 2022
Editor's note: This essay is part of an ongoing series about the evolution of the laboratory over the past century, and part of ASCP's 100th Anniversary celebration.
At the dawn of 1922, the U.S. and the world continued to recover from the Great Pandemic. As a result of that pandemic, from 1918-1919 an estimated 500 million people were infected worldwide with approximately 50 million deaths (675,000 in the U.S.). It was not until the 1930s that the causative agent of this pandemic was identified as a virus, influenza A, and not a bacterium, and not until the 1940s that a vaccine was developed to combat the virus.
Fast forward to 2022 and the world is once again grappling with the effects of a pandemic – COVID-19. This pandemic has resulted in more than 250 million cases worldwide with more than 5 million deaths. Cases were reported in Wuhan, China in late December 2019. By early February, 2020 the cause of the infection was known, named SARS-CoV-2, and a vaccine was made available in December 2020.How times have changed...
The 1929 publication of Alexander Fleming’s discovery of the effect of penicillin on gram positive organisms ushered in the antibiotic era. The subsequent explosion of antibiotic development in the mid-20th century led many to speculate that the field of infectious diseases would be “phased out” and consequently the need for the clinical microbiology laboratory would wane since most infectious diseases would be dramatically reduced or eliminated. Most would agree that this prediction was misguided. The past 50 years have seen a significant increase emerging and reemerging infectious diseases and has reinforced the importance and criticality of the clinical microbiology laboratory in patient care.
The clinical microbiology laboratory of the past used conventional culture techniques, agar plates and single-tubed biochemicals to identify bacteria and conventional cell culture to grow viruses. Antibiotic susceptibility testing based on disc diffusion or broth dilution to distinguish susceptible strains of bacteria from their resistant variants was performed but was labor intensive. Due to the time required to perform testing, results were often not available in a timeframe that was helpful to clinical decision making.
Through creativity and innovation, today’s clinical microbiology laboratory is radically different than those of the 20s and 30s. While conventional culture techniques and antimicrobial susceptibility tests are still mainstays, automation and molecular diagnostic techniques have revolutionized the field. The advent of “total laboratory automation” affords clinical microbiologists the opportunity to reduce specimen processing time, improve standardization of cultures, and decrease turnaround time. Automated specimen processing standardizes plating and streaking. “Smart incubators” equipped with digital imaging systems can be used to capture images of plates at designated times to minimize interruptions in culture incubation. These images can then be used for subsequent culture work up. Automated colony recognition software (“artificial intelligence”) can also be used to triage cultures with growth and no growth to increase the efficiency of culture interpretation.
Organism identification and susceptibility testing has also evolved. The use of single tube biochemicals gave way to the use of “rapid” enzymatic tests. A significant advancement in organism identification occurred with development of miniaturized multitest media and kits. This miniaturization was further refined into automated instrumentation organism identification and phenotypic antimicrobial susceptibility testing which perform tasks previously performed manually by technical staff and reduce the time required to obtain results. The introduction of the use of matrix-assisted laser desorption ionization time of flight (MALDI-TOF) mass spectrometry has revolutionized the ability of the clinical microbiology laboratory to identify organisms. It produces more accurate, cost-effective organism identification significantly more rapidly than other commercial manual and automated phenotypic identification systems. This in turn provides more rapid patient diagnosis and ultimately better patient care.
While automation has had a significant impact on the ability of clinical microbiologists to contribute to patient care, the evolution of molecular techniques has changed the clinical microbiology paradigm from conventional laboratory methods that rely on phenotypic expression of antigens or biochemical products, to molecular methods for the rapid identification of infectious agents. It all started with the discovery of DNA by Watson, Crick, and colleagues and only gained momentum with the introduction of polymerase chain reaction (PCR), the technique that can produce multiple copies of a segment of a DNA in just a short period of time, by Kary Mullis.
Molecular techniques have truly revolutionized the diagnosis of infectious diseases and have also evolved since the discovery of PCR. Initial PCR tests could detect and identify specific organisms, but were very labor intensive and could only be performed by those well versed in molecular techniques. New fully automated, sample to answer, testing systems and nucleic acid amplification technologies now have the capability to produce rapid results for a variety of organisms causing infection via syndromic panels with minimal test set up, systems that are easy to use and at decreasing cost. Tests can easily be performed by well-trained clinical microbiologists and some even at the point of care. This has resulted in the ability to detect infection of previously undetectable and fastidious organisms in real time to affect patient care decisions. The use of this technology was key to the ability of the clinical microbiology laboratory to respond to testing needs for SARS-CoV-2. Molecular techniques also provide for the detection of many antimicrobial resistance genes, providing vital information for therapy decisions more rapidly than conventional antimicrobial susceptibility testing.
The clinical microbiology laboratory will continue to evolve and is ready to tackle the challenges that the 21st century will bring. For instance, the use of next generation sequencing and whole genome sequencing will likely become more prevalent in the clinical microbiology laboratory as a reliable and useful tool for organism identification, detection of resistance genes and detection of organisms in clinical specimens.
Over the past 100 years clinical microbiologists as well as other laboratory professionals have been an important, behind the scenes member of the healthcare team. The recent pandemic has focused a spotlight on the importance of the clinical microbiology laboratory and laboratory professionals as a whole to patient care. Clinical microbiologists must continue to expand their skills to adopt new practices and technologies to remain in the forefront of innovation as well as maintain an open line of communication with clinical colleagues to emphasize our importance to the patient care team.
Director, Clinical Microbiology Laboratory UF Health Jacksonville