To address the problem of growing AMR in the country, the Government of India has launched the National Program on Containment of Antimicrobial Resistance, fueling R&D activities for rapid identification of microorganisms.
In light of the ever increasing problems related to the emergence of multidrug-resistant bacteria, rapid microbiological diagnostics are of growing importance. Timely pathogen detection and availability of susceptibility data are essential for optimal treatment, but are even more crucial for de-escalation of broad spectrum empiric therapies. Antibiotic resistance is a global public health threat, but nowhere is it as stark as in India. The crude infectious disease mortality rate in India in 2016 was 416.75 per 100,000 persons and is twice the rate prevailing in the United States when antibiotics were introduced.
Apart from resistant diseases, India is also confronting a sudden emergence of a range of infectious diseases such as dengue, chikungunya, swine flu, and malaria that pose a formidable public health challenge..
This rise in number of infectious diseases is fueling research and development activities in the field of clinical microbiology. Owing to current pressures and manual nature, microbiology instruments are experiencing unprecedented changes and evolving at a rapid pace. Constant improvement of available technologies (e.g., molecular methods) and introduction of new technologies (e.g., matrix-assisted laser desorption ionization time-of-flight [MALDI-ToF] mass spectrometry) have fundamentally changed diagnostic procedures. As a consequence, sensitivity and specificity as well as time-to-report have been dramatically improved. Contemporary diagnostics can rapidly provide powerful data that can impact patient lives and support infectious disease outbreak investigations.
Automation is also increasingly gaining a larger and more prominent role in the sector and is expected to help reduce the time required to undertake a number of processes and improve the efficiency of results. The need for accurate and rapid identification of infectious agents cannot be overstated. It enables actual reduction from conventional broad spectrum antimicrobial agents to specific targeted antimicrobial therapy. Total laboratory automation systems currently are available to handle specimens, streak plates, incubate, and digitally image cultures. That is one of the great things about microbiology at the moment. There has been more change and more advances in the last few years than there have been for decades.
The trend for advancement in instruments is expected to remain strong over the next few years as well, with an increasing number of companies already entering or willing to enter the field with the help of their clinical solutions for use across numerous sectors of clinical microbiology. For instance, Becton, Dickinson and Company has launched its next-generation diagnostic instrument, BD Phoenix M50 ID/AST system, for the rapid identification of bacteria and detection of antimicrobial resistance. Automation is also increasingly gaining a larger and more prominent role in the sector and is expected to help reduce the time required to undertake a number of processes and improve the efficiency of results. Technological advancements in monitoring equipment that have led to the development of multiplex microbiology testing products, such as Luminex’s xTAG gastrointestinal pathogen panel (GPP) multiplexed nucleic acid test, are allowing more exhaustive analysis of microbes and leading the field of clinical microbiology toward a healthy growth path.
Indian Market Dynamics
The Indian market for microbiology instruments and reagents in 2016 is estimated at Rs. 310 crore, maintaining an annual 5–6 percent growth. Reagents dominate with an 83 percent share. The instruments-based reagents are more popular, and commanded a share of 67 percent in 2016, while the non-instrument based reagents contributed the balance of 33 percent, having declined from 44 percent in 2015.
Biomerieux and BD India continue to lead the segment. Hi-Media has aggressive presence in the non-instruments based reagents segment. Beckman Coulter is gaining strength having acquired the microbiology business of Siemens Healthcare in January 2015.
2016–2017 saw microbiology automation as an important emerging trend in the industry with enrichment and transport media at the heart of it. It is being appreciated that flocked swabs facilitate greater specimen collection and complete elution, particularly for swine flu. The elution of a specimen from such swabs into liquid 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. Consequently, more and more labs are using flocked swabs in combination with a transport media to aid the recovery and detection of pathogens after collection.
The global clinical microbiology market was valued at USD 9.01 billion in 2016 and is projected to grow at a CAGR of 7.3 percent from 2017 to 2024, predicts Grand View Research. This high growth is 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.
Almost all analytical and therapeutic research projects demand reagents and chemicals, thus, the 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 share of the market.
Moreover, 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 the 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 2017 to 2024.
North America is the largest regional market for clinical microbiology and is followed by Europe. However, Asia-Pacific is expected to be the fastest growing region with a CAGR of 9.3 percent from 2017 to 2024. Booming medical tourism industry in the region is expected to spur the demand for microbial diagnostic and monitoring tests in Asian countries namely, 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, thus, boosting the growth in the region.
As a result of the rapid progress in research and development and introduction of automated laboratory systems, the giant players in the international clinical microbiology market have won the trump card of being the first movers. Very few international players are competing with each other. bioMrieux S.A., Cepheid Inc., Danaher Corporation, and Bruker Corporation are some of the major players that are leading the global market. These companies, due to high R&D expenditure and introducing automated laboratory systems, have gained the advantage of being the first movers. Moreover, with the entry of several new players such as Roche Diagnostics, Alere Inc., Becton Dickinson & Company, Hologic Inc., and others, the competition in the market is expected to intensify over the years.
Technology for modern clinical and public health microbiology laboratories has evolved at an impressive rate over the last two decades. alignical culture-based techniques are still the gold standard in many areas; however, they are already complemented by automated and molecular technologies to guarantee faster and better quality results. The most commonly used technologies include real-time polymerase chain reaction (RT-PCR) based systems and nucleic acid hybridization. They are used most powerfully to detect the presence of non-culturable or fastidious organisms.
When a state experiences an outbreak of an infectious disease, the time it takes to identify the disease can have a significant impact on the treatment and outbreak response. Now, that time period has been sharply reduced from what could take days, down to minutes thanks to the sophisticated type of mass spectrometry (MALDI-TOF). After organisms are cultured, the time for a bacterial identification is minutes when compared to the traditional methods, which can take days. From walk-away multiplex PCR assays to total laboratory automation, microbiologists are able to produce faster results of higher quality than ever before. Accurately and rapidly identifying infectious agents is critical in safeguarding public health.
WGS. In recent years, whole-genome sequencing (WGS) has been perceived as a technology with the potential to revolutionize clinical microbiology. It has shown advantages over conventional genotyping approaches for investigating epidemics. Since genomic sequencing information can be obtained in a few days, pathogen identification can be achieved in early states of a disease outbreak. Recent advances show that it can distinguish between different pathogen strains, detect co-infections, and even uncover new pathogens. This benefit also includes the discovery of emerging disease-causing viruses.
WGS data has uncovered new sequence information that has been used successfully to detect drug resistance determinants. In addition to detecting emerging drug-resistant microorganisms, the application of WGS helped to uncover mutations and other genetic factors associated with the spread of drug-resistant pathogens.
MALDI-TOF mass spectrometry. Mass spectrometric techniques for determination of single component have developed greatly over the past decade. Perhaps the most revolutionary advancement has been the application of MALDI-TOF mass spectrometry for organism identification. Not only is organism identification more accurate than growth-based systems, but identifications are produced more rapidly and at significantly lower cost. Taken together, these factors have led to widespread adoption and universal acceptance of the technology for routine clinical use globally. Its advantage includes high sensitivity, tolerance to buffers, fast data acquisition, and simple and robust instrumentation. MALDI-TOF has reduced the identification time, thus, leading to reductions in turnaround time and potentially beneficial patient impacts.
PCR. The discovery of PCR has revolutionized how clinicians diagnose infectious diseases and genetic disorders. Today, new advances in PCR technology, including more sensitive assays and high-throughput instruments, may further revolutionize healthcare. In the past three decades, PCR has evolved from end-point PCR, through real-time PCR, to its current version, which is the absolute quantitative digital PCR (dPCR).
dPCR has become an important new tool for use in the clinical microbiology laboratory. Its advantages over quantitative PCR (qPCR), including absolute quantification without a standard curve, improved precision, improved accuracy in the presence of inhibitors, and more accurate quantitation when amplification efficiency is low, make dPCR the assay of choice for several specimen testing applications.
FISH. Early identification of microbial pathogens is essential for rational and conservative antibiotic use especially in the case of known regional resistance patterns. Fluorescence in situ hybridization (FISH) is one of the rapid methods for easy identification of microbial pathogens, and diagnosis of pathogens in human infections in the laboratory diagnostic routine. FISH analysis leads to immediate differentiation of infectious agents without delay due to the need for microbial culture. As a microscopic technique, FISH has the potential to provide information about spatial resolution, morphology, and identification of key pathogens in mixed species samples. Ongoing automation and commercialization of the FISH procedure have led to significant shortening of the time-to-result and increased test reliability.
Government of India is aware of the rising problem of multidrug resistance in the country which at times may lead to deaths due to invasive infectious complications. To address the problem, the government has launched the National Program on Containment of Antimicrobial Resistance under the 12th Five Year Plan with National Centre of Disease Control (NCDC) as the coordinating center. Under the program, Drugs and Cosmetics Rules of 1945 are amended to control the overuse of 24 antibiotics and other drugs through over-the-counter sale without prescription by pharmacies.
In alignment with global action plan, India’s action plan has objectives of enhancing awareness, strengthening surveillance, improving rational use of antibiotics, reducing infections, and promoting research and development activities in AMR. However, more efforts are required considering the large size of our country, magnitude of the problem, and the fact that AMR needs to be addressed comprehensively under One Health Approach.
The growing government investments in R&D along with increasing outbreak of various diseases, and rising incidence of infectious and resistant diseases will largely be responsible for the accelerated pace of growth of the overall market in the coming years. Researchers continue to push the limits of current technologies to broaden their utility in areas of antimicrobial susceptibility testing and accurate identification of pathogens. The combined efforts of progressive research and availability of increasingly sensitive technologies are sure to improve the quality of and add value to the services provided by clinical microbiology laboratories through advanced instrumentations in the near future.
Broth Dilution Method – The Preferred Choice for MIC
The growing burden of infectious diseases in India is amongst the highest worldwide. This scenario has led to irrational use of antibiotics. As per the State of World Antibiotics 2015 study conducted by the Centre for Disease Dynamics, Economics and Policy (CDDEP), New Delhi, India is the largest consumer of antibiotics ahead of China and the United States.
The indiscriminate use has in turn led to increased drug resistance. The crude infectious disease mortality rate in India is 416.75 per 100,000 persons – twice that of the United States (~200).
These statistics only bring forth the biggest challenge of antimicrobial resistance (AMR) and the need for judicious drug administration. A recent report estimates that by 2050, 10 million people will die every year due to AMR unless a global response to combat AMR is initiated.
In this regard, the role of microbiological diagnostic testing becomes crucial in identifying infections and advising appropriate antibiotic treatment.
The MIC (minimum inhibitory concentration) test is helpful to confirm resistance of microorganisms to an antimicrobial agent and to monitor the activity of new agents. Clinicians use MIC scores to select type and effective dose of antibiotics for special infections as well as to guide during use of drug of last resort.
Agar diffusion and broth dilution are available methods for diagnostic MIC testing. As per CLSI and EUCAST guidelines
though agar diffusion is the gold standard, MIC testing for certain antibiotics should be performed by broth dilution method only.
Standardized commercial kits available for MIC testing by this method can be adapted well by laboratories for routine or specific use. However, it is important to note that commercially available kits are coated with surfactants, which may hamper the efficacy since molecules tend to adsorb to testing surfaces. CLSI and EUCAST have evaluated colistin susceptibility testing methods and suggest use of broth dilution without surfactant, as the reference method.
Therefore, it is crucial to select kits which are not coated with surfactants. Transasia Bio-Medicals Ltd. has recently introduced single MIC testing strips for individual antibiotics by broth-dilution in a micro-well format. These kits do not use any surfactant but instead use pure water and special film coating material followed by vacuum drying. The entire procedure is quite robust when it comes to possible interferences and hence provides reliable results. These kits are in adherence to the CLSI and EUCAST guidelines.
Asst. Product Manager – Urinalysis & Microbiology,
Transasia Bio-Medicals Ltd.