The past few years have seen significant changes in clinical microbiology. On the regulatory front, as more assays receive FDA clearance, labs increasingly have the option to replace laboratory-developed tests (LDTs) with commercially available IVD tests. Respiratory panels are a good example. Technological advances continue to reduce turnaround time drastically, and, at the same time, a better understanding of how test results can be used to improve care is raising physician expectations. For example, while a turnaround time of 8 to 24 hours for a flu test was previously acceptable, a 20-minute to 2-hour time to result is now standard of care. Likewise, while a turnaround time of >24 hours for generating a C. difficile result was previously acceptable, a 1Â½- to 3-hour time to result is now becoming the standard of care.
Patient management, the decision to admit, and infection control measures often hinge on test results, with significant health outcome and cost ramifications. Microbiology results, once viewed as confirmatory and often delivered after patient management decisions were made, are now integral to clinical workflow. Patient-centric care, the mantra of today's healthcare, translates into patient-centric testing in the microbiology lab, with far-reaching implications for the lab workflow, how the lab is structured, and even how patient specimens are delivered to the lab.
Along with this trend toward patient-centric testing, has come a massive shift toward automation, driven by the need to better support clinical decisions with high-quality, timely results efficiently and cost-effectively. This trend is enabled by advances such as molecular diagnostics, digital microbiology, and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry (MS). These advances open the door to greater standardization of processes and results, automation, and a new level of operational excellence and performance.
Indian Market Dynamics
The microbiology instruments and reagents market for the clinical sector in 2015 was valued at Rs.290 crore. Contributing a major Rs.238 crore, reagents are the mainstay. The instruments-based reagents increased by 22 percent in value over 2014, and while the non-instruments-based reagents also increased by 22 percent in volume, they increased 15 percent in value terms. The balance Rs.52 crore is accounted for by instrumentation into clinical microbiology, which increased by a mere 3-4 percent over 2014.
biomerieux, is the leading player in this segment. BD India has aggressive presence too, closely followed by Beckman, with the Siemens product range.
The main challenge is that microbiology testing has yet to gain widespread acceptance. These practices need to be used more frequently. Perhaps it needs to be mandated that all antibiotic prescriptions need to be informed by a test so that use of inappropriate antibiotics is decreased, thereby reducing risk of antibiotic resistance, patient morbidity and mortality.
Also it is an ongoing challenge that while top level clinicians are aware of the intricacies of the procedures and its methodology, this does not travel to the mid-level and junior staff, hence compromising on patient care. Automation being expensive is yet to gain prominence.
Hospitals want hassle-free supply. Ready prepared media products, ready-to-use, prepared, and cultured media available in choice of plates, tubes, and bottles for the identification of microorganisms are being sought. These products have brought to the microbiological laboratory the highest levels of quality and performance. They are time- and cost-saving, easy and convenient to use, and provide constant high quality, ensuring that patients receive safe products.
There is an increase in awareness of aspects as drug resistance, antibiotic sensitivity and in what concentration the antibiotic must be used among healthcare professionals, policy-makers and patients. This is expected to drive this market.
The global clinical microbiology market was valued at USD 8.4 billion in 2015 and is projected to grow at a CAGR of 7.3 percent by 2024. The growth would be attributed to increasing demand for laboratory services in order to detect pathogen-based diseases coupled with escalating need for control measures for infectious disease spread. In addition, growing geriatric population and constantly widening targeted disease conditions are some of the major factors augmenting the use of clinical microbiology.
In 2016, the US FDA approved Cepheid, Inc.'s diagnostic assay, Xpert Carba-R. This assay is capable of identifying carbapenemase genes in bacterial culture. The increasing spread of class-A carbapenemase is creating growth opportunities for players operating in the market.
Leading players include biomerieux S.A. (France), Danaher Corporation (US), Becton, Dickinson and Company (US), Cepheid (US) Abbott Laboratories Inc. (US), Bio-Rad Laboratories Inc. (US), F. Hoffman-La Roche Ltd. (Switzerland), Alere Inc. (US), Bruker Corporation (US), and Hologic, Inc. (US).
The market is generally segmented by application [infectious disease (HIV, HPV, TB), oncology, genetics, microbiology, technology (PCR, microarray, DNA sequencing), end user (hospital, laboratories), and product (instruments, reagent, software)].
Reagents Have the Largest Revenue Share
Growth in the reagents segment is mainly driven by growing trend of reagent rental agreements (along with instrument sales) by prominent reagent manufacturers, increasing market availability of pathogen-specific kits across the globe, and growing demand for specific clinical microbiology reagents during epidemic outbreaks. The market is also witnessing rising private-public funding for research on specific infectious diseases. Almost all analytical and therapeutic research projects demand reagents and chemicals; as a result, penetration of reagents is growing. In addition, repeat purchase of reagents results in more revenue generation for the segment compared to instruments. Thus, the reagent segment accounted for the largest market share of around 35 percent in 2015.
Automation to Witness Fastest Growth
Commercialization of research projects is increasing the overall sample-processing volume in each project. As a result, demand for automated clinical systems is rapidly increasing to maintain uniformity and to reduce human errors associated with manual processing. Thus, the laboratory instrument segment is expected to grow with a CAGR of 8.5 percent from 2016 to 2024.
Respiratory Disease Segment to Dominate
Increasing levels of air pollution with industrialization is resulting in rapid escalation of respiratory disease prevalence. Also, amongst other infections, respiratory diseases spread rapidly owing to easy transfer of contagious pathogens. The respiratory disease segment is expected to show a significant growth of 8.51 percent over the next 8 years. Furthermore, prevalence of infectious diseases is high in developed as well as developing countries.
North America - Largest Regional Market
In 2015, North America accounted for the maximum revenue share of 41 percent and was closely followed by Europe. Highly developed industrial and healthcare sectors in the US are fueling the adoption of clinical microbial techniques in the country. In addition, stringent regulatory framework and presence of giant players in the country are augmenting the growth of the market.
Asia-Pacific is expected to be the fastest-growing region with a CAGR of 9.3 percent from 2016 to 2024. Japan is one of the leading countries with strong technological development and higher usage of microbial testing for various applications. In addition, China is another significant space contributing to the growth of the Asia-Pacific market.
Moreover, booming medical tourism industry in the region is expected to spur the demand for microbial diagnostic and monitoring tests in Asian countries particularly India, China, Thailand, and Malaysia. Furthermore, skilled labor at affordable cost and advanced manufacturing infrastructure is resulting in shifting of manufacturing facilities of major pharmaceutical players to Asia.
Microbiology has traditionally been associated with a diversity of patient specimens and transport media, lengthy culture, and visual results requiring human review. These factors, all of which hamper standardization, a prerequisite of automation, have left the microbiology lab in the dark ages. All this is changing with recent technological advances that are enabling automation at a time when microbiology most needs it to meet the multiple challenges of today's healthcare environment, declining reimbursement, and the shortage of trained personnel.
Enabling Technologies Continue to Evolve
Molecular diagnostics has truly been a transformational force in microbiology. The sensitivity it offers allows detection and identification of more organisms faster, without having to wait for culture results. Mycoplasma is a case in point. Another example is testing for sexually transmitted infections like Chlamydia trachomatis and Neisseria gonorrhoeae. In many ways, molecular diagnostics has made diagnostics more relevant. Previously, a patient suspected of chlamydia or gonorrhea would be treated empirically. Today, with faster time to result, treatment can begin after the pathogen is properly identified, reducing the unnecessary use of antibiotics. A study by Bauer KA et al., comparing clinical and economic outcomes before and after initiation of molecular testing of methicillin-resistant Staphylococcus aureus (MRSA) in positive blood cultures, demonstrated a mean reduction of 6.2 days in hospital stays and a USD 21,387 savings when molecular testing was combined with timely infectious disease consult and appropriate antibiotics use.
Molecular diagnostics offers other advantages - the availability of automated platforms, options in standalone specimen preparation and handling systems, and connectivity to the chemistry lab. All of these can help advance clinical microbiology through automation and better integration with the rest of the healthcare system.
Another transformational technology is MALDI-TOF, first commercially available for clinical microbiology in 2009. MALDI-TOF provides a cost-effective, standardized, and rapid method for identification of clinically significant bacteria, fungi, and mycobacteria. Importantly, MALDI-TOF procedures are relatively simple and do not vary based on organism. The integration of MALDI-TOF into the clinical microbiology workflow has decreased time to organism identification from days to hours. The impact on patient care is significant. One study on adult patients with bacteremia and candidemia demonstrated that the combination of MALDI-TOF diagnostic testing and an antimicrobial stewardship team decreased time to effective and optimal antibiotic therapy, which translated into lower mortality rate, shorter intensive care unit stays, and reduced recurrent bacteremia. For the first time, standardizing the identification process of bacterial isolates is now possible, enabling automation, improving workflow, and increasing efficiency.
The evolution of digital microbiology is changing the way culture plates are read, impacting not only turnaround time but also quality of results. Digital microbiology integrates automated imaging systems to capture images of culture plates at specified time intervals, robotics to move specimens across the lab, and software to process captured images and determine the presence of positive colonies for review and confirmation. For example, with digital imaging software, preset color thresholds, as defined by hue, saturation, and value, are employed to detect growth in chromogenic agar. In this way, negative plates can be identified for quick screening to confirm negative results, while only positive plates are reviewed one by one. This reduces substantially the number of plates reviewed and ensures better use of laboratorian time when trained personnel are scarce. The ability to rule out negative plates quickly not only saves personnel time but can expedite clinical decisions and reduce unnecessary intervention.
The advent of liquid transport media has been highly influential in improving specimen quality and enabling automation. Elution of specimens from newer flocked-style swabs into liquid phase has been shown to increase the release of viable organisms from the swab, improving sensitivity. And the liquid-based transport enables inoculation of the specimen with automated liquid-based specimen processors, an important step toward greater efficiency and standardization.
Microbiology Automation - Indications of Success
Automation enables workflow optimization, removing unnecessary delays and better utilizing the skills of trained lab professionals. One example is the use of an automated system for plating and streaking of urine and other liquid specimens, while trained personnel perform Gram stain review and the processing of more complex specimens. This saves time as well as improves consistency in urine plating while decreasing monotonous repetitive tasks for laboratorians. Another example is the ability to read cultures using an automated imager following specified incubation time rather than wait for the availability of personnel, a change that not only shortens time to result but also improves consistency of results and ensures that plates are not incubated beyond recommended duration, which can compromise specificity.
Quality improvement is an important benefit of automation, which allows standardization of techniques and reduction of human errors. A recent study demonstrated that automating specimen processing, specimen incubation, imaging of MRSA growth, and automated analysis reduced the number of false negatives. Compared with manual screening, sensitivity was 100 percent across three sites using three different commercially available culture media, and specificity ranged from 90.7 to 92.4 percent. Related to quality improvement are traceability and documentation. By automating the confirmation of multiple patient identifiers at multiple steps from specimen transport vessel to plates, the lab can prevent medical errors due to incorrect patient identification. In combination with inexpensive electronic data storage, digital microbiology facilitates documentation with image archiving for further review, for correlating Gram stain images with cultures, for use in teaching, and to share with inquiring physicians.
Perhaps the most important benefit of automation is its value in optimizing the lab workflow, which in turn positively impacts the clinical workflow. For example, changing from reading plates when personnel can get to them to reading them when they are ready to be read can make all the difference in optimizing turnaround time. In turn, this means availability of results when physicians need them. Knowing that the majority of specimens arrive at the lab between 8 p.m. and 2 a.m., for example, the lab can plan to read plates until 10 p.m., transition the staff to processing to get the plates to the incubator earlier, and start reading again at about 2 a.m., when the plates are ready to be read by the automated imager. In this way, results from specimens that arrive the night before will be in the physician's in-box the next morning. Another example is group-A strep, with most specimens coming from Outpatient and arriving between 8 p.m. and 2 a.m. With automated molecular diagnostics, results can be waiting for physicians the next morning. With the availability of technologies that offer group-A strep results in 20 minutes, physicians have the option to diagnose and begin treatment while the patient is still in the office. These changes have a very positive impact on physician satisfaction ratings.
Implementing Microbiology Automation
Microbiology automation is not without challenges. Cost is a significant barrier to automation, with the initial investment in capital acquisition, facility modifications, and, importantly, IT and connectivity to integrate the entire process from test requisition and specimen collection to final result. Overcoming the initial resistance of lab personnel is also sometimes a factor.
While many labs have implemented some automation solutions, especially in molecular diagnostics, the majority of labs are still in the planning process or looking to build on what they have started. As with any significant initiative, thorough need assessment, planning, and securing the buy-in of all stakeholders are the key. In this context, it is difficult to overemphasize the importance of two areas of focus in the planning stage - workflow and IT.
Automation cannot be done in a vacuum, and it is important to consider the overall workflow of the lab, not just specific processes being automated. Studies have shown that implementing automation without considering the overall workflow makes little impact on quality of care. To understand the overall lab workflow and the clinical workflow and how best to derive the maximum value from automation, labs need to review all facets of current lab operations. These include, for example, the mix of specimen types (i.e., whether processing can be automated), time they arrive at the lab, and expected time to result. The goal is to make sure there is clear understanding of how automation will be incorporated and how it will impact the overall workflow and, ultimately, patient care.
A second planning parameter that is sometimes left as an afterthought is IT. In the current imperfect world of connectivity, making sure that computer systems - from automation technology to MALDI-TOF to LIS to HIS - talk to each other is paramount. The need for integrated information flow cannot be overemphasized. Thus, getting the IT team involved from the beginning is a critical success factor. As higher-quality information is generated in a more timely manner, it is just as important to get it into the physician's hands without delay.
Of course, there are myriad of other factors to consider in planning automation - space planning is one example. Mapping out the post-automation workflow to reallocate staff time is another. A clear picture of the expected results and metrics for post-automation assessment will help track progress and guide adjustments once implementation begins.