POINT
Automation as a benefit in clinical microbiology. Since inception, clinical microbiology has been dependent on a highly technical and skilled workforce to receive, process, and interpret results from a wide variety of clinical specimens with limited aid from automation. Clinical staff has complained of poor turnaround (TAT) while the laboratory inoculates appropriate media and awaits microbial growth. Ever-increasing specimen volumes and fewer available skilled workers have led laboratories to increasingly seek automated solutions for microbiology. Automation was introduced into the clinical microbiology laboratory in the 1960s as automated plating instruments but was initially met with limited success. Today, instruments are an integral part of many clinical laboratories and are used for specimen management, microbial detection, nucleic acid amplification, identification, and susceptibility testing.
In contrast to chemistry or hematology laboratories, which use standard collection tubes and a minimal diversity of specimens, microbiology laboratories must accept nearly any specimen type in any type of transport container. The absence of standardized collection devices and the lack of standardized transport media, complex specimen processing, and interpretation of cultures have left microbiology in the dark ages of automation. However, the advent of new technologies, such as mass spectrometry, liquid transport media, molecular techniques, and automated identification and susceptibility systems, has begun to simplify and allow for much greater standardization of the microbiology laboratory. This, combined with high-resolution digital imaging and robotics, has allowed microbiology to accomplish the impossible, i.e., to become automated.
Several factors have contributed to changing attitudes about automation in clinical microbiology, including declining reimbursement, an aging workforce, technological innovation, personnel shortages, demand for quality laboratory services, and demand for timely results.
Changing workforce.
Medical laboratory professionals play a critical role in health care, with the majority of medical diagnoses being based on laboratory tests (1). Unfortunately, the United States is facing a continuing shortage of qualified laboratory personnel, raising questions about the ability of laboratories to handle current and future testing demands. Much of the shortage in medical laboratory professionals is owed to an inability to train enough qualified practitioners to meet the demand for services, with 68.3% of vacancies requiring certification as a prerequisite (2). Moreover, there has been a steady decline in the number of medical laboratory training programs and in the number of students graduating from medical laboratory training programs (1). According to a 2003 study by the American Society for Clinical Pathology (ASCP), rural areas and areas served by smaller hospitals, in particular, are finding it increasingly difficult to recruit and retain qualified laboratory personnel (1). In its 2012 vacancy survey, the ASCP found the total vacancy rate for microbiology and specimen processing to be 5%, with 9% of microbiology department employees expected to retire in the next 2 years (2). As a result of the limited pool of qualified applicants, the survey also found that 50% of positions required 3 to 12 months to fill (2). In relation to new technology, the ASCP vacancy survey found nearly 75% of respondents indicating that new technologies did not cause changes in their staffing needs. However, those that were affected by new technologies found a decreased need for as large a staff (2).
The current and future shortage of trained medical laboratory professionals is also the result of a reduction in medical laboratory science training programs. Since 1992, the number of medical laboratory science training programs has decreased by more than 30% to fewer than 450 programs, nationwide. The lack of trained graduates and training programs is particularly problematic in rural areas, where recruiting certified technologists can be especially difficult.
With continued concern for vacancy and evaporating training programs, microbiology laboratories have been forced to address the acute labor shortage in a number of ways. Many laboratories have lowered prerequisites required to hire a medical laboratory professional, have begun to offer on-the-job training for nonlaboratory professionals, or have outsourced testing to reference laboratories as mechanisms of coping with labor shortage; others have turned to automation.
The benefit of automation in a labor shortage is to utilize the skills of medical laboratory professionals where they are most needed and to automate tasks that are repetitive and do not require the comprehensive skill set of a trained professional. As an example, a laboratory may elect to purchase an automated system for planting and streaking of urine samples and other liquid specimens while tasking a technologist to perform Gram stain review and processing of more-complex specimens, such as tissue. In this example, the laboratory utilizes automation to consistently plate urine samples, a mundane task for a laboratory professional, and utilizes the skilled professional for interpretation of critical specimens. By adopting a strategy of relegating a monotonous task to automation, while assigning interpretative or esoteric tasks to the technologist, the laboratory increases productivity per full time equivalent (FTE), increases reproducibility of the urine plating, and decreases monotonous responsibilities for laboratory professionals.
Technical innovation.
Among the innovations leading to automation in clinical microbiology, the transition to liquid-based microbiology is among the most influential. Advantages of liquid-based microbiology include homogenization of specimens into a liquid phase (as opposed to receipt of specimens of various viscosities, such as stool and sputum, and receipt of specimens submitted on collection devices, including swabs), which enables more-consistent inoculation of medium. Elution of specimen from newer flocked-style swabs into liquid phase has demonstrated a significant increase in the release of viable organisms from the swab, which translates into increased sensitivity for detection of microorganisms in the specimen (3). While improvement in the sensitivity of culture is paramount, it is also important to note that the specimen is associated not with the swab but with the liquid phase of the transport device. The presence of the specimen in a liquid-based transport enables inoculation of the specimen and smear preparation with automated liquid-based specimen processors.
A second technical innovation that has driven laboratories to automation is matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) mass spectrometry. MALDI-TOF mass spectrometry has revolutionized microbial identification by providing a cost-effective method that is standardized. The technology offers accurate, rapid, and inexpensive identification of microorganisms isolated from clinical specimens. MALDI-TOF procedures are highly amenable to automation because they are relatively simple, do not change based on organism, and are reproducible. Additionally, spotting of target plates and extraction of proteins can be standardized for most organisms, and when combined with automation, automated crude extraction using the on-plate formic acid extraction method can be performed with minimal staffing.
Industry changes.
Changes in the industry are multiple. Demand for laboratory testing is increasing. Overall testing volumes are expected to increase 10 to 15% per year for the next 20 years, due in part to an aging population that will require more health care (4, 5). Additional testing is also being driven by innovations in medicine that continue to expand life expectancy and manage ever-more-complex patients. For example, more patients are receiving indwelling devices which can become infected, increasing the demand for laboratory services. Infection control also continues to drive utilization of laboratory services through patient screening initiatives and increased vigilance to isolate patients colonized with multidrug-resistant pathogens and to prevent their spread within the health care environment. Each of these factors, while increasing the quality of health care, contributes to increased demand on the laboratory, despite continued labor shortages. Consolidation of laboratories, particularly for microbiology testing, also continues to increase due to cost reductions associated with economies of scale. Larger laboratories have a greater potential to benefit from lab automation than smaller laboratories. The 24-h, 7-day/week (24/7) microbiology laboratory is becoming much more common, and automation that can shorten TAT is being viewed more favorably. The 24/7 microbiology laboratory also allows cultures to be read following a specified incubation rather than waiting for the day shift, a scientifically unnecessary delay which can result in delays in turnaround times.
Several studies have evaluated the clinical impact of rapid microbiology and its impact on antimicrobial stewardship. For example, Kerremans et al. (6) evaluated the effect of accelerated diagnostics on antibiotic use and patient outcomes using 1,498 patients with positive cultures from sterile body fluids. In the control arm (n = 752), routine microbiology was performed using broth subcultures and the Vitek Legacy system (bioMérieux, Marcy l'Etoile, France) to identify bacteria. In the study arm (n = 746), identification and susceptibility testing were performed directly on positive blood culture bottles using the Vitek 2 system (bioMérieux). The study found a mean reduction in TAT of 13 h for identification and 20 h for susceptibility results in the rapid arm compared to TATs in the control arm. The decreased TATs led to earlier modification of antibiotic therapy in the rapid arm and a reduction in defined daily doses of antibiotics used (6). In a recent review by Livermore and Wain (7), the authors determined that in the United Kingdom, management of only 3% of community-acquired respiratory infections and approximately 50% of cystitis cases is guided by laboratory results (7), in part due to the slowness of bacteriology. Further, it is critical in patients with pneumonia to receive appropriate antibiotics within the first hour for diagnosis. When empirical antibiotic therapy is not appropriate, mortality can increase each hour of delay (7–9).
Microbiological delays lead to empirical overtreatment of many patients who are not infected with resistant pathogens, which leads to increased antibiotic resistance. The increase in resistance can lead to increased acuity of patient presentation, which increases the length of stay and costs of health care (10). Many of these issues can in part be traced back to practices in the microbiology laboratory. Today, in most laboratories, plate reading is primarily a day shift activity. Total laboratory automation will facilitate reading plates as they are ready to be read without increases in staffing, resulting in decreased turnaround times and more efficient decisions by the medical community.
Quality.
The final driver of automation is our continually changing health care system. Laboratories of the future will no longer be paid based on the services that they perform but instead will be incentivized based on their contribution to delivery of quality care. In other words, health care in the future will be paid based upon keeping patients out of the hospital. This shift in reimbursement will mean that laboratories can no longer operate in a vacuum, concerned only about in-laboratory time and cost per test; instead, they will need to add value to patient care. Value from the laboratory will mean reducing the number of tests ordered for each patient, focusing on those tests that will actually aide in the diagnosis. Additionally, providing results at the time of care, rather than 2 to 5 days after care has been delivered, will be crucial. For microbiology, this will mean identifying novel technologies that will provide results in less time, determining when culture is appropriate and beneficial to the patient, and reducing turnaround times. While most microbiology laboratories do not have control over emerging technologies, they can control turnaround times through a variety of measures. Automation can help transform microbiology laboratories from a primarily day shift operation to a 24/7 laboratory. Reading cultures when they are ready to be read, instead of when the day shift arrives, can result in improved turnaround time, thus adding value to patient care.
Beyond changes in the delivery of health care, demand by clinicians for new tests continues to grow, not just in total numbers but also for the types of testing performed. The balance between molecular tests and culture-based assays will likely continue to shift toward molecular. Both the trend toward molecular testing and decreasingly shorter lengths of stay for hospital inpatients has led to increased demand for more-rapid turnaround times for infectious disease assays. This will mean that the current and future automation systems will need to incorporate both culture and molecular testing into a single specimen stream and manage both laboratory techniques. This will certainly add a level of complexity to automation systems, as the automation will need to (i) recognize the specimen type based on barcode, (ii) pipette the correct volume of liquid into various molecular systems, and (iii) manage data before transmitting them to the laboratory information system.
Traceability is another aspect of quality laboratory testing. Automated specimen processors and total laboratory automation solutions provide far greater traceability than when the same testing is performed manually. For example, during initial specimen management, labeling of plates, and transfer of a specimen from the transport vessel to plates, we rely on medical laboratory professionals to confirm multiple patient identifiers at multiple steps in the preanalytical process. If the professional omits confirmation of patient identification, wrong results can be inadvertently reported, potentially leading to inappropriate care. In the case of automation, the instrument is programmed to confirm the identification of each specimen by barcode each time the specimen is handled, a significant step in preventing medical errors.
Evidence-based medicine is the application of peer-reviewed literature to the art of patient care. One method of employing evidence-based medicine is through the use of clinical practice guidelines and standard techniques. The goal of these guidelines is the standardization of selected aspects of medical care to ensure both high quality and cost-effectiveness (11, 12). Standardization of microbiology practices such as syndromic algorithms and standardized techniques in the laboratory can easily be achieved using laboratory automation and can increase safety within the laboratory. Laboratory staff frequently suffer ergonomic injuries as a result of repetitive tasks, such a urine inoculation and pipetting, which are avoided with automation. Repeat tasks also can be standardized using automation, minimizing variation between laboratory staff and minimizing costs associated with human error. Quality control (QC) may also be improved, owing to avoidance of human error. Standardization of nucleic acid extraction may even contribute to reduction in contamination or mislabeling errors (13).
Through standardization, laboratory errors, such as selecting the wrong plates for inoculation, mislabeling, and cross-contaminating specimens, can be greatly reduced by eliminating human errors. Further, significant delays occur in microbiology when colonies must be subcultured for isolation due to poor technique or insufficient isolation of colonies. When subculture is required, delays in results of up to 24 h is not uncommon. Through automation, variation in mixing and in selection of the specimen is minimized and transfer of a standardized volume is achieved. This has repeatedly been demonstrated to reduce the need for subculture, reducing laboratory turnaround times.
In quality, digital microbiology combined with inexpensive electronic data storage also offers the laboratory a nearly endless capacity to archive images. Images of Gram stains can be easily correlated with cultures and stored for future review. Additionally, images can be used for instruction of medical laboratory professionals and pathologists or sent electronically to an inquiring physician at the click of a mouse.
Nathan A. Ledeboer
