Molecular diagnostics imperative to combat AMRSeptember 14, 2018
Dr Aparna Kotekar
THE DISCOVERY of antibiotics was a significant milestone in healthcare that resulted in a reduction in morbidity and mortality caused by bacterial infections. Ironically, better access to antibiotics has resulted in its overuse and misuse, leading to development of resistance to these antibiotics. Considering that infectious diseases account for 20-25% of all deaths in India, it is really a matter of concern that our armamentarium of antibiotics against infections is soon going to become obsolete.
As per a recent report in the Proceedings of the National Academy of Sciences (2018), antibiotic usage more than doubled in India in 15 years (2000 – 2015). Not only are antibiotics freely available without prescriptions in India but even when prescribed, an estimated 50-60% of these prescriptions are unnecessary. The problem is not limited to India. A large study in the US published in 2013 showed that out of 40 million people given antibiotics for respiratory conditions, 27 million did not really need it. In our country, low healthcare spending, prevalence of counterfeit antibiotics with sub-optimal dosing, and a high frequency of incomplete antibiotic course (especially among the lower income group where antibiotics are used for symptomatic relief instead of microbial eradication) make the situation worse. In a majority of cases, infections are empirically treated in the absence of information about the identity of the infectious agent and antibiotic resistance in the pathogen. This is a chronic problem especially in critical care settings where multiple high level antibiotics are used. In a study conducted by iGenetic Diagnostics in MUmbai, it was found that while only 28% of patients admitted in ICUs with CNS infections had bacterial infections, almost all were being empirically treated with high level antibiotics. Long-term indiscriminate use of antibiotics can also result in increased invasive fungal infections as well as increased morbidity due to drug THE DISCOVERY of antibiotics was a significant milestone in healthcare that resulted in a reduction in morbidity and mortality caused by bacterial infections. Ironically, better access to antibiotics has resulted in its overuse and misuse, leading to development of resistance to these antibiotics. Considering that infectious diseases account for 20-25% of all deaths in India, it is really a matter of concern that our armamentarium of antibiotics against infections is soon going to become obsolete.
Exposure of microorganisms to antibiotics results in drug-resistance. These drugs kill susceptible pathogens, and allow antibiotic-resistant ones to proliferate. Broadspectrum antimicrobials increase the selective pressure on bacteria and result in the emergence of multi-drug resistant pathogens. Drug resistance develops either by acquisition of genes that are responsible for inactivating antibiotic molecules or by target gene mutation. The former is especially dangerous as it can spread quickly by horizontal gene transfer. Thus, antimicrobials become ineffective leading to persistent infections, and ultimately result in the spread of these resistant microbes in the community. As per the World Health Organization’s (WHO’s) “Antimicrobial Resistance- Global Report on Surveillance” of 2014, the incidence of resistance in common pathogens like E. coli, K. pneumoniae and S. aureus was about 50%. This is quite alarming considering that no new antibiotics have been developed in the last 4 decades. Thus, AMR has become a global health crisis which could render even common infections untreatable with existing antibiotics.
Evidence-based use of antibiotics and de-escalation can go a long way in curtailing the spread of AMR. For this, detection of the pathogen and antibiotic resistance patterns are absolutely critical. Traditionally, this is done by microbial culture and sensitivity which can easily take around 72 hours for bacteria and longer for fungi. Besides, microbiological methods show false negativity in patients pre-treated with antimicrobials, and have low sensitivity for slow growing, intracellular and fastidious microbes. Additionally, most routine labs cannot culture viruses and hence rely only on serological tests for diagnosing viral infections. These tests suffer from low sensitivity and specificity.
Molecular methods overcome the limitations of microbiological and serological methods reducing the time to results in identifying pathogens and antibiotic resistance. In India, most labs that do molecular diagnostics rely on point-of-care (POC) devices that currently suffer from low detection limits, low specificity and detect a limited range of organisms and antibiotic resistance markers. This often results in false negatives, erroneous polymicrobial reports and low rates of detection of both pathogens and antimicrobial resistance. iGenetic Diagnostics, which conducted the AMR India study, have of late developed highly sensitive molecular diagnostic assays that quickly and accurately pin-point the cause of infections and antibiotic resistance. Using multiplexed PCR assays, it can diagnose over a 100 pathogens including a variety of bacteria, fungi, viruses and parasites as well as antibiotic resistance within 8 hours. The assays are extensively validated, highly specific, cover a wider range of syndromes, detect many more pathogens and according to clinicians, it has detection limits that are far superior to other molecular diagnostic tests available in the market. In addition to multiplexing the PCR assays to reduce costs, this test also allow customization of these diagnostic panels making them affordable.
iGenetic’s internal data shows that the detection rates with comprehensive syndromic evaluation panel is between 50-60% while cases where only single or a limited number of pathogens were ordered have abysmal detection rates of about 12-15%. This shows that we need a drastic change in our approach to combating infections. In today’s age where we are not geographically limited, we need to consider a wider array of pathogens. By incorporating molecular diagnostics into decision-making when treating infections, we may be able to stem the tide of chronic antibiotic overuse leading to antibiotic resistance. This starts with educating all stakeholders of the importance of spending time and resources on rapid diagnostics in the short-term to get long-term benefits of conservation of life-saving antibiotics.
A study conducted at the Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER), Puducherry, India, showed that molecular diagnostics reduced deaths due to neonatal sepsis from 18% to 3% along with decreasing the number of antibiotics used per patient. This shows that molecular diagnostics enables evidence-based antibiotic use rather than empirical antibiotic treatment with broad-spectrum, high-level antibiotics. These tests can be used effectively for antibiotic stewardship programmes aimed at reducing the spread of antibiotic resistance. They also serve to decrease healthcare costs by lowering consumption of expensive 3rd-line drugs, cut ICU/hospital stay and result in better patient outcomes including reduced morbidity and mortality.
The author is Director, Molecular Genetics, iGenetic Diagnostics Pvt Ltd, Mumbai.