Technologies that include advanced genomics, proteomics, and rapid susceptibility tests are expected to cause dramatic changes by tackling some of the most important problems for microbial diagnostics.
Rapid identification of microorganisms in the clinical microbiology laboratory can be of great value for selection of optimal patient-management strategies for infections caused by bacteria, viruses, fungi, mycobacteria, and parasites. The switch to tailored therapy minimizes risks of antibiotics, namely, disruption of normal flora, toxic side effects, and selective pressure. There is a critical need for new technologies in clinical microbiology, particularly for bloodstream infections, in which associated mortality is among the highest of all infections.
The field of microbiology is moving exceptionally fast, in part because it can take full advantage of the new developments in microscopy, computational biology, synthetic biology, lab-on-chip approaches, and single-cell technologies. Advanced microbiology technologies are rapidly changing the ability to diagnose infections, improve patient care, and enhance clinical workflow. These tools are increasing the breadth, depth, and speed of diagnostic data generated per patient, and testing is being moved closer to the patient through rapid diagnostic technologies, including point-of-care (PoC) technologies.
While select stakeholders have an appreciation of the value/importance of improvements in the microbial diagnostic field, there remains a disconnect between clinicians and some payers and hospital administrators in terms of understanding the potential clinical utility of these novel technologies. Therefore, a key challenge for the clinical microbiology community is to clearly articulate the value proposition of these technologies to encourage payers to cover and hospitals to adopt advanced microbiology tests. Specific guidance on how to define and demonstrate clinical utility would be valuable. Addressing this challenge will require alignment on this topic, not just by microbiologists but also by primary care and emergency room physicians, infectious disease specialists, pharmacists, hospital administrators, and government entities with an interest in public health.
Both the pharmaceutical and diagnostic manufacturing industries will also be required to be involved in orchestrating the generation of clinical-utility evidence. Given that hospital administrators often prefer to undertake a trial period with new technologies to gain first-hand experience, diagnostic technology manufacturers may need to pursue collaborations for this to be actively achieved. Furthermore, they can work to guide not only microbiologists but also facilitate early partnership with those in clinical and financial roles about the design of studies, which could help illustrate the clinical utility of these deployed tools in a fair and balanced way. They can also play a role in helping community hospitals understand where to find clinical-utility information and how to share clinical-utility information so that advanced care approaches are not limited to academic medical centers alone.
Additionally, pharmaceutical leaders in the microbiology space may be required to actively participate in data gathering and publication, supporting the concept that next-generation antimicrobials may be more effective, particularly if paired with the most advanced diagnostic technologies. This will likely require active collaboration between pharmaceutical and diagnostic companies to ensure the clinical-utility benefit of appropriate prescribing of next-generation treatments is influenced by novel technologies entering the space.
Indian market dynamics
The Indian market for microbiology instruments and reagents in 2018 is estimated at ₹425 crore. bioMérieux and BD India continue to dominate the market, with BD dominating the reagents market and bioMérieux the instruments segment. Hi-Media is aggressive in non-instruments based reagents.
The instruments-based reagents were ₹235 crore in 2018, a 55.29 percent share of the total market, non-instruments reagents at ₹141 crore, at a 33.88 percent share and the instruments at ₹49 crore, at 11.53 percent.
The instruments are estimated at ₹49.2 crore, with 610 instruments sold in 2018. The market was dominated by identification and antibiotic susceptibility analyzers at 57.37 percent share. With an increased penetration of molecular platforms, the TB culture microbiology testing is on a gradual decline. In 2018 too, the market for both, TB culture analyzers and TB instrument-based reagents declined. IDST testing dominates with the instruments commanding a 57.37 percent share by volume and 30 percent market share by value, and the instruments-based reagents a 51 percent.
In India, the level of automation in the microbiology laboratory has been lagging behind that of other major clinical laboratory segments, such as chemistry and hematology. The slow acceptance of the technology is in part due to the complexity of developing automation suitable for microbiology tests.The introduction of automated microbiology instrumentation has been delayed by a number of intrinsic and technical problems. The diffusion of automated microbiology systems, once the technology was developed, has not matched that of other automated laboratory technologies. The acquisition of automation in microbiology has been slowed by forces less easily identifiable than the effects of various reimbursement plans. Automated microbiology is fast, but the costs per test, and initial capital investment are quite high. The research in microbiology should focus on fast, easy-to-use, rapid tests for bacterial, viral, and parasitic pathogens such as multidrug resistant organisms. Thus, a faster turnaround time (TAT) and immediate results are the major factors that will drive the microbiology market. Another important factor to be considered is to use biological reference materials that are authentic, traceable, and reliable to ensure the quality control of tests being performed. The need of the hour is to combine advanced IT solutions like artificial intelligence and nanotechnology with the existing diagnostic technologies to develop rapid, cost-effective tests which can be easily interpreted and made available across the entire country.
|Indian Microbiology Automated Instruments Market||bioMérieux, BD India, Beckman Coulter (Siemens products), Thermo Fisher, and Trivitron|
|Indian Microbiology Instruments-based Reagents market||bioMérieux, BD India, Beckman Coulter (Siemens products),
and Thermo Fisher
|Indian Microbiology non Instruments-based Reagents market||Hi-Media, BD India, Thermo Fisher (oxoid), Bio-Rad, and Microxpress (Tulip Diagnostics), bioMérieux, Beckman Coulter (Siemens products), Merck Millipore, and Titan Biotech|
Some laboratorians still believe that current instrumentation is not the ultimate technology and expect better automation on the horizon.
The driving force behind the need for rapid reporting of microbiological test results is the clinical relevance in a time of financial austerity, a time when cost and healthcare effectiveness to the patient and diagnostician looms ever larger, and where after-the-fact results at high expense are coming under severe scrutiny worldwide.
Global market dynamics
The global clinical microbiology market is expected to reach USD 4.95 billion by 2023 from USD 3.63 billion in 2018, growing at a CAGR of 6.4 percent, predicts MarketsandMarkets. Technological advancements in the field of infectious disease diagnostics, rising incidence, and prevalence of infectious diseases and growing outbreak of epidemics, and increased funding and public-private investments for the development of novel products for infectious disease diagnosis are major factors driving growth of the clinical microbiology market.
Other factors leading to market growth include efficacy and availability of anti-viral treatments for diseases, such as periodontitis, gingivitis, chronic pulmonary obstructive disease, and rise in sex-related awareness amongst the population in developing countries. Various immunoassay techniques are implemented for rapid diagnosis of infection with accuracy that further leads to potential diagnostic platform and technologies, such as biochemical tests, microbial culture, and molecular diagnostics. Diseases, such as HIV, human papilloma virus (HPV), and Hepatitis B and C are forms of STDs that are severe and fatal, therefore, increasing the demand for the microbiology market. Increasing healthcare expenditure and presence of better medical infrastructures, such as hospitals and clinical labs, are some other drivers of the augmentation in the microbiology market. However, reimbursement concerns and an unfavorable regulatory scenario restrain market growth.
On the basis of applications, pharmaceutical segment is expected to dominate the overall microbial testing market in 2019 with the presence of well-established and globally accepted regulations that govern the evaluation of microbial contamination during pharmaceutical manufacturing and raw material-sourcing processes.
General Manager, Diagnostic Division
Technical advancements in microbiological sciences have considerably shortened the turnaround time of various microbial analyses. Advanced technologies have given birth to some of the most sophisticated integrated microbiological systems, capable of performing multiple tasks in one go. This has led to reduced labor by eliminating time-consuming tasks, including maintenance of permissive host cell lines, repeated microscopic examination, and immunostaining, associated with viral culture, thus saving costs.
Technological advancements in microbiological science have greatly increased the application of microbiology in clinical diagnosis. Not only limited to microbial diagnosis, microbiological advancements have led to the utilization of microbiology in development of a treatment plan. Prompt and sensitive detection of proteins related with human diseases plays an integral role in clinical diagnosis, treatment, and outcome evaluation.
Emerging technologies like high-throughput DNA sequencing have made possible the low-cost, comprehensive, culture-independent characterization of the microbiota of a broad range of media, providing a better picture of the microbial ecosystems. Great technical advances have led to the development of sensitive, quantitative, and multiplex assays. Technologies like rapid amplicon detection and low-cost polymerase chain reaction (PCR) devices have been developed in the form of a disposable paper, card or plastic, thus increasing the portability and to an extension, the availability of these technologies.
At present, ELISA (enzyme-linked immunosorbent assay) undoubtedly dominates the field of protein quantitation. The technology has greatly been improved and made more sensitive by integrating gold nanoparticles-based plasmonic sensors, yielding to more accurate and highly precise diagnosis of diseases like HIV, hepatitis, and many others.
Manufacturers are now developing single-use kits and rapid cards that are highly efficient and extremely prompt. From among a multitude of available rapid cards, those for dengue, malaria, and syphilis are being widely used. These kits are user friendly, accurate, cost effective, and are accepted throughout the world. With the use of latest technologies, instruments are being made more and more accurate that offer ease of operation and precise output. More and more sensitive detectors are being used that are efficient enough to record even the slightest of findings.
The future continues to look bright for microbiology technologies and reagents. Further growth in microbiological technology would pave way for advanced tests for more accurate diagnosis of disease, more efficient methods for designing and making drugs that act at the molecular level of the body and, therefore, be less or virtually non-toxic but highly effective.
Reagents account for the largest revenue share in the global clinical microbiology market. The segment includes products such as solutions, primers, master mixes, and kits used in various diagnostic assays. Reagents currently capture the largest revenue share, with more than 60 percent attributed to repeat purchase, driven by need for new set of reagents for new tests. The segment is expected to remain dominant over the next 6 years. Factors, such as higher cost of specialized kits and constant repeat purchase, are expected to drive the segment in coming years. The market is witnessing rising investments in research and development (R&D). Almost all analytical and therapeutic research projects demand reagents and chemicals, thereby driving penetration of reagents. It is estimated that automated microbiology instruments will experience a rapid growth over the next 5 years.
Geographically, North America is expected to account for the largest share of the global clinical microbiology market in 2019, with easy accessibility and high adoption of advanced diagnostic techniques, technological advancements in microbial testing techniques, rising geriatric population, and growing public-private funding to support microbiology-based research in the region.
Microbiology market in Asia-Pacific, specifically in India, is rapidly transforming with renewed interests in recent years on health and disease awareness. Liquid-based microbiology specimen collection devices, automated specimen processing, and digital imaging with AI-reading algorithms are adding value to microbiology laboratories now and will do so in the future as well as clinicians and manufacturers will work together to conquer the challenges. Manufacturers are also focusing on reducing the time to results, developing new reagents to expand the range of bacteria that can be detected by new systems, and identify resistant bacteria, creating tests to analyze the susceptibility of bacteria to new antibiotics launched by the pharmaceutical industry, automating the microbiology lab, and strengthening connectivity within laboratories. The next decade, and particularly the next few years, should prove intriguing as manufactures strive to further impact clinical decision making for infectious diseases by technological advances in clinical microbiology instruments.
The advances and innovations in microbial diagnostic technologies over the last decade are beginning to have a significant impact on the way one diagnoses and manages infectious diseases. In the coming years, an additional cohort of new microbial diagnostics is expected to enter the space. Technologies that include advanced genomics, proteomics, and rapid susceptibility tests are expected to cause dramatic changes by tackling some of the most important problems for microbial diagnostics. Additionally, advanced analytic tools, such as artificial intelligence and machine learning, can enhance the information extracted from the data these technologies collect. For example, the menu of culture-independent nucleic acid amplification tests and syndromic panels is expanding. These advances will likely favor the deployment of culture-independent reporting of antimicrobial-resistance (AMR) determinants, including the creation of a clear correlation of AMR genotype to antimicrobial susceptibility phenotype/MICs. Also, automated microscopy is being leveraged for early detection of sepsis by detection of morphological changes in monocytes indicative of dysregulated immune response or morphological changes in bacteria, indicative of drug susceptibility.
Antimicrobial stewardship in hospitals and role of diagnostics in it
Antimicrobial resistance has been identified as a major threat by the World Health Organization (WHO, 2012) owing to the lack of new antibiotics in the development pipeline and infections caused by multi-drug-resistant pathogens becoming untreatable. In 2015, the WHO set out the global action plan for AMR (WHO, 2015) and a subsequent broader stewardship framework. To achieve this approach, an integrated stewardship approach has been advocated, encompassing antimicrobial stewardship, diagnostic stewardship, and infection control. There are numerous drivers for AMR. Human antimicrobial misuse and overuse is a key driver factor, as are suboptimal dosing, lack of availability, and/or under-use of rapid diagnostics or point-of-care tests and insufficient infection prevention and control.
Diagnostic stewardship refers to the appropriate use of laboratory testing to guide patient management, including treatment, in order to optimize clinical outcomes and limit the spread of antimicrobial resistance. This requires a seamless partnership between clinical laboratories, pharmacists, and infectious diseases clinicians, so that appropriate tests are ordered and diagnostic information is translated into appropriate management in real time. Laboratories play a key role in antimicrobial stewardship. However, they are often not used optimally or, in many parts of the world, they do not exist or have poor capacity and capability to deal with the problem. Integration of diagnostics with other AS interventions to provide fast accurate identification and susceptibility testing, will achieve better clinical outcomes and timely streamlining/de-escalating of empiric broad-spectrum antibiotics in seriously ill patients. Many studies have assessed algorithms based on procalcitonin (PCT) as a rapid-reacting biomarker of bacterial infection for antibiotic stewardship. Recent systematic reviews showed benefits of PCT among patients with respiratory tract infection and sepsis by significantly reducing antibiotic exposure as well as a trend toward reduced costs and reduced length of ICU stay.
bioMérieux has always been driven by a pioneering spirit and unrelenting commitment to improve public health worldwide. Our diagnostic solutions bring high medical value to healthcare professionals, providing them with the most relevant and reliable information, as quickly as possible, to support treatment decisions and better patient care.
Next-generation sequencing (NGS) methods and proteomics (e.g., MALDI-TOF) are expected to impact key diagnostic segments in the future. In contrast to PCR panels, these methods have the potential for hypothesis-free detection of pathogens and host-response markers. NGS-based analysis of pathogens further allows phenotypic prediction, such as detection of AMR determinants, virulence factors, and mobile genetic elements. Also, whole-genome sequencing of isolates by next-generation sequencing allows strain typing at nucleotide-level resolution for epidemiological studies and infection control. These methods have tremendous potential in the clinical microbiology lab, opening a novel paradigm for diagnostics.
However, to be deployed clinically and realize this potential, these technologies will need to build on efforts associated with more established technology that has demonstrated clinical utility. Adoption of these technologies may also require hospitals and payers to place a higher priority on infection control than they do currently and to support their infection-control centers.
The need for improvements in microbial diagnostics, and thereby in management of infectious disease, is clear and urgent. This need has the potential to be filled by a combination of new technologies that have entered the diagnostic space or will enter it shortly. However, there is a clear gap in the field that is preventing these technologies from being widely deployed to fill the current unmet clinical need for rapid and improved testing. While the necessity of deploying better microbial diagnostics is not lost on microbiologists and infectious-disease specialists, other key stakeholders have lower awareness. Therefore, a collective effort is needed from microbiologists and clinicians handling infectious diseases to communicate to other stakeholders the costs and downsides of the current standard of care. Demonstrating and communicating how the low cost of phenotypic methods is often offset by the high cost of preventable morbidity and mortality that comes from a slow diagnostic standard of care, and how new tests can directly impact and improve clinical decision making, is needed. Clearly defining and describing these issues to commercial payers, hospital administrators, and government regulators will smooth the deployment of these technologies and benefit individual and communal health.
Bacterial suspensions – An ordinary mix with an extraordinary science
Dr Rahul Warke
Director Research and Development (Microbiology)
HiMedia Laboratories Pvt. Ltd.
Preparation of microbial suspensions is usually one of the simple, routine, and repetitive tasks generally performed in a microbiological laboratory. Commonly used bacterial suspension fluids include bacteriological saline, phosphate buffered saline (PBS), and Ringer’s solution. An ideal suspension fluid should ensure preservation of health of bacterial cells without allowing them to multiply further. However, saline, PBS, and Ringer’s solution do not support bacterial viability beyond 6 hours of suspension. Aquino Rehydrol – rehydration fluid for GPT (growth promotion testing), an isotonic solution, helps to resolve the issues faced with these common bacterial suspension fluids.
Bacterial cells are surrounded by a highly sensitive, semi-permeable membrane which maintains a continuous dialogue with external environment. This dialogue is facilitated via various facets of cellular machinery.
Porins/aqua-porins located in the cell membrane are amongst the first to respond to changes in the osmotic pressure. Accumulation of osmolytes (inorganic ions, commonly K+, and organic molecules like trehalose, glutamate, glycine-betaine) is another significant response to the osmotic changes in the environment. Coordinated control of accumulation and release of these solutes is mediated through various enzymes, transporters, and channels. Studies have shown direct correlation of solute concentrations within the cells with the growth rate of the bacterial cells. Growth is found to be directly proportional to cytoplasmic hydration, which in turn is governed through solute concentration within the cells. Organic osmolytes are known to rehydrate cytoplasmic environment, stimulating the growth of cells. Careful formulation of suspension fluid in coherence to cellular dynamics can impart stability to suspended cells, thereby effectively serving the purpose of the formulation.
Aquino Rehydrol keeps bacterial cells healthy, viable, and stable (without multiplication) in suspension for up to 21 days at −20°C. This cost-effective solution ensures hassle-free growth-promotion testing by reducing tedious and time-consuming dilution preparations. Besides GPT, this fluid deems fit for multiple tasks involving sampling and transport of bacterial specimen over longer durations.
A multipurpose suspension fluid can ease several microbiological activities in a laboratory while simultaneously ensuring healthy recovery of tested bacterial cultures. Clinicians and microbiologists can maintain and study their isolates from any samples/specimens using this multipurpose suspension solution. The convenience of Aquino Rehydrol additionally makes detailed antibiotic sensitivity studies and identification stress-free.