The pace of diagnostic processes in clinical microbiology laboratories has largely been unchanged for almost 100 years, as availability of diagnostic results essentially depends on the growth of bacteria. It is well known that early availability of information on bacterial pathogens and their antimicrobial susceptibility is of key importance for the management of infectious diseases patients. Currently, using traditional approaches, it usually takes at least 48 hours for identification and susceptibility testing of bacterial pathogens. Therefore, the slowness of diagnostic procedures drives prolongation of empiric, potentially inappropriate, antibacterial therapies.

Over the last couple of years, the improvement of available techniques and introduction of novel technologies has fundamentally changed approaches toward pathogen identification and characterization. Importantly, these technologies offer increased diagnostic resolution while at the same time shorten the time-to-result, and are thus of obvious importance for antimicrobial stewardship.

The clinical microbiology market is rapidly growing due to the increasing adoption of automated and advanced technologies for laboratory instruments and analyzers. Growing geriatric population and thereby rising prevalence of infectious diseases is one of the major factors boosting the adoption of clinical microbiology in healthcare sector for disease diagnosis and monitoring. In addition, industry is gaining high momentum with launch of innovative products such as MALDI Biotyper, GeneXpert, and Myla IT performance management solutions. Moreover, with the US FDA approving the Xpert Carba-R, commercialization of clinical microbiology devices is expected to increase significantly over the next few years.

Technology Trends

New strategies are being employed to bring microbiological diagnostics into a new era. The newest technologies in the microbiology lab hold the potential to solve majority of problems. Molecular techniques can generate results and positive identifications remarkably quickly; so can matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS), which is having a significant impact on clinical microbiology.

MALDI-TOF. This technology is on a path to completely replace culture with biochemical methods for species identification. Current MALDI-TOF systems lead to more accurate and faster results, with less wasted materials and tech time. They generate high throughput of dozens of pathogens per run and reduces the identification time. Recently, MALDI-TOF has been applied directly to positive blood culture bottles for the rapid identification of pathogens, leading to reductions in turnaround time and potentially beneficial patient impacts.

Mass spectrometry. More recently, MS has played an increasing role in microorganism identification. MALDI-TOF MS is revolutionizing clinical microbiology, and is becoming widely used in the detection of bacterial, fungal, and viral diseases, as well as the determination of antibiotic resistance.Given that current methodologies require at least 48 to 72 hours for pathogen identification, there is certainly room for improvement. Future of clinical MS will hold more miniaturized systems and is likely to see growth in the use of automation. This is expected to help increase ease of use and lead to greater adoption by smaller laboratories.

Molecular diagnostics. During the last 10 years, molecular diagnosis has become increasingly important in clinical microbiology by overcoming the issue of accurate and timely diagnosis. Molecular diagnoses have markedly improved pathogen detection and identification and reduced the turnaround time from sample collection to definitive diagnosis. Compact and easy-to-use instruments allow rapid automation of the molecular tests and many ready-to-use kits arrived in the market making molecular diagnostics widely available. The sensitivity of the new molecular techniques is so high that direct examination or even cultures show their limits in terms of sensitivity, and their use as gold standards is now challenged.

PCR. Outside of academic research, much of the focus has been on molecular analysis approaches such as polymerase chain reaction (PCR) to enable the faster diagnosis of infection.The ability to successfully directly detect pathogens present within patient blood samples without the need for incubation in culture would be a very significant addition. To that end, several technologies in this area have been undergoing commercial development. Multiplexed probe PCR-based detection system has been shown to have higher specificity than sensitivity, when compared with conventional blood culture.

PCR can also be coupled with electrospray ionization mass spectrometry (PCR/ESI-MS) in order to address the issue of quickly diagnosing bloodstream infection. This platform can be used for the broad identification of fungal, candidal, and bacterial species.

Microarrays. Microarray analysis has the capability to offer robust multiplex detection and characterization for a variety of infectious disease pathogens but has just started to enter the diagnostic microbiology laboratory. Today multiple microarray platforms exist, including printed double-stranded DNA and oligonucleotide arrays, in situ-synthesized arrays, high-density bead arrays, electronic microarrays, and suspension bead arrays. Although the use of microarrays to generate gene expression data has become routine, applications pertinent to clinical microbiology continue to rapidly expand. Microarray technology has impacted diagnostic microbiology, including the detection and identification of pathogens, determination of antimicrobial resistance, epidemiological strain typing, and analysis of microbial infections using host genomic expression and polymorphism profiles.

WGS. The hottest issue in the field of clinical microbiology in latest years is the application of whole genome sequencing (WGS) to clinical diagnostics and therapeutics through the methodology of Next generation sequencing. The single nucleotide polymorphism (SNP) based analysis increases the accuracy and sensitivity of species identification by marked discriminatory power, and the ability of tracking of transmission process enables infection control. A great number of species and subspecies are now represented in the WGS database, which is updated continuously.

Bioinformatics methods are being used in microbiome research to discover host-pathogen interactions, relationships between microbiome dynamics and diseases, and correlations between bacterial sequence variation and clinical outcomes. Using the bioinformatics algorithms and tools to integrate the microbiological data and clinical data is expected to be very helpful to better understand the mechanisms of diseases.

Digital imaging and analysis systems. These instruments can integrate with a lab's automated blood culturing and antibiotic susceptibility testing and can reduce the time needed to identify bacterial growth. Their algorithms and artificial intelligence automatically read, interpret, and segregate plates. Such systems hold the potential to move current laboratories to the digital microbiology era through high-resolution culture plate imaging, improving speed, interpretation, reliability, and accessibility of results. The larger-than-life image or high resolution images can help techs detect growth invisible to the naked eye on the actual plate. This high-resolution image approach for differential image analysis is a reliable warranty for accurate pathogen growth detection.

Road Ahead

Technologies providing rapid information on bacterial pathogens and their antimicrobial susceptibility are of key importance for the management of infectious diseases patients. The introduction of MALDI-ToF into routine diagnostics led to a significant acceleration of highly specific species identification and is regarded as a major advance in the field of clinical microbiology. In addition, rapid molecular tests offer significant opportunities to further reduce the time-to-result for pathogen identification and information on key resistance determinants.

Moreover, novel approaches in phenotypic susceptibility testing herald an era in which medical microbiology can also substantially support the early stages of clinical decision-making. Information will be especially useful to limit usage of last resort antimicrobials to those cases in which narrow-spectrum antimicrobials are not appropriate. With next-generation sequencing (NGS) becoming implemented into routine diagnostic procedures, additional improvements are on the horizon. Most importantly, it has already become evident that technical improvements resulting in a shorter time-to-result only translate into benefit for the patient if rapid, structured communication, and interpretation of clinical microbiology results are available for the responsible clinician.

Microbiology is never black and white, but when one can provide positive pathogen identifications after only 18 to 24 hourseven if the culture is mixedthe benefits to the lab, clinicians, and patients are significant.

Dr Aruna Poojary
Second Opinion
Improved Turnaround Time for Infection Diagnostics

Clinical microbiology testing has taken centre stage for the diagnosis of infections, be it bacteria, viruses, fungi, or parasites which cause infections and epidemics.Clinical Microbiology as a science evolves on a daily basis with new technology being developed rapidly.The thrust and the focus of all new technology are rapid diagnostics and automation. Automation has helped enhance key laboratory performance attributes like consistency, quality, and a slower total turnaround time (TAT). Rapid diagnostics assays, be it chromatography based assays or the molecular assays are in great demand because they greatly help in better management. Molecular methods based on nucleic acid detection or the use of proteomics is preferred rapid methods because they have better sensitivity and specificity over chromatography assays.While both these methods have their shortcomings, they have markedly improved the TAT, which is essential for clinical microbiology tests to be clinically relevant.

The growth clinical microbiology segment is reflected in market projections indicating that the instruments and reagents of this segment are likely to increase from USD 3.35 billion in 2016 to USD 5.77 billion in 2021 with a CAGR of 11.5 percent during this period.The key drivers for the growth are increase in the emerging and re-emerging pathogens, antimicrobial resistance among pathogens especially bacteria, and the need for rapid TAT. Improved public awareness with more dispensable income to spend on healthcare is the social drivers of growth for the microbiology market. Another important reason for rapid and sustained growth is the opening of corporate hospital chains and their emphasis on accreditation and hospital infection control where identification of organisms causing hospital outbreaks and their prevention is a key element.

Prospective buyers opt for automated rapid diagnostic instruments which have a small foot print as space always remains a constraint to a laboratory. Availability of bidirectional interfacing and a user-friendly interface are other essential aspects of such instruments for a buyer. The most important challenge for the clinical microbiology segment has been the cost of reagents and instruments. Presence of local players who can provide quality products helps over the cost limitations. Another challenge is to bring research based techniques to a routine clinical microbiology laboratory for better diagnosis. Improved funding through public private partnerships would help deal with the above challenge. The future of clinical microbiology will be improved detection of all pathogens including new ones with rapidity with reduced cost making them reach the smallest market for improved infectious disease diagnostics.

Dr Aruna Poojary
HOD,
Department of Pathology & Microbiology
Breach Candy Hospital Trust
Mumbai

Dr Aparna Jairam
Second Opinion
Trending Toward Market Growth

Whole world is focused on India as the fastest growing hub for healthcare. The increasing population, increased life expectancy, better paying capacity, increased awareness, and more income to middle class population is making the healthcare sustainable. There are many corporate labs, group practice labs, and single labs or diagnostics setups across our country trying to provide the diagnostic backup for our patients and clinicians. We cannot ignore that Hospital based laboratories will be taking largest share of this sector due to large inpatient and emergency services.

Microbiology with molecular platform in the next five years, followed by genetic menu as the top grosser will revolutionize the healthcare sector. Microbiology is often misunderstood as blood, urine, stool samples with plating, reports within 4-5 days.

However, with advent of technology in IVD, the field is evolving everyday with the test methods and the techniques to that extent that the test results are available as early as two hours with minimal interference and best report outcome like automated cultures, minimum inhibitory concentration (MIC) for drug sensitivity, TB identification and sensitivity, serological tests, and on.

The growth for microbiology is emphasizing on faster turnaround time (TAT), minimal human interference-

  • Accuracy and uniformity in reporting, for ex: Pseudomonas will be reported by all labs for the same sample with MIC of similar values to the antibiotics. This will assist in great way to achieve antibiotic stewardship and thus reducing antibiotic exposure and resistance to patients. Automated microbiology setups include complete solution i.e. from sample loading to result output with MIC.
  • Faster TAT for patients, thus reducing hospital stay of the patients and availability of beds for the critical patients.
  • Better management of infectious diseases like Tuberculosis - TB results within two hours of sample collection with sensitivity and thus assisting to differentiate the TB patients from MDR patients.
  • Microbiology also includes serology and infectious diseases. Latest introduction of methods like fourth generations assays for HIV, HCV. These assays will reduce the window period of detection of infection and these tests are cheaper than PCR assays. Thus screening of patients will help in detecting the cases in the early stage.
  • Diagnostic technology platforms where CSF, body fluids, blood can be used for diagnosing the viral, bacterial infections within two hours. Methodology is automated real time PCR. This will be tremendous value to clinicians as they can decide the course of treatment and admission.

Hospital acquired infections leading to septicemia is the leading cause of death in patients with long stay in the hospital. Finally, when the stay of the patient reduced with right dose of the antibiotics, will result in reduction of nosocomial infections.

IVD-microbiology is on the fast track of growth, the only challenge is the high CapEx required initially and lack of skilled personnel to interpret these reports.

Dr Aparna Jairam
Founder,
Dr. Aparna's Pathology Laboratory
Mumbai


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