Breakthroughs in Rapid Diagnostic Technologies for Sepsis and Antimicrobial Resistance

Saransh Chaudhary, President, Global Critical Care, Venus Remedies and CEO, Venus Medicine Research Centre, in a recent conversation with India Pharma Outlook,discusses how innovations in sepsis and AMR diagnostics, therapies, and AI are enhancing early detection and improving patient outcomes. With a strong finance background from Cass Business School and Harvard University, Saransh joined Venus Remedies in 2016. He excels in drug discovery and development, driving key initiatives to augment the company’s intellectual property. He has published over 10 scientific papers and led innovative efforts in antimicrobial resistance.

What are the latest innovations in diagnostic technologies for sepsis and AMR, and how have they improved early detection and patient outcomes?

Recent innovations in diagnostic technologies for sepsis and antimicrobial resistance (AMR) have transformed the landscape of early detection and patient outcomes by offering faster and more precise diagnostic tools, enabling timely and targeted interventions. They include:

Rapid Molecular Diagnostics: PCR allows quick identification of pathogens and resistance genes, aiding treatment decisions. However, next-generation sequencing (NGS), while comprehensive, can take longer than clinically acceptable and is not widely accessible.

Automated Antibiotic Susceptibility Testing (AST): Systems like VITEK® 2 and Phoenix now deliver results in hours instead of days. However, even these may not be fast enough for critical sepsis cases. Microfluidic platforms further speed up the process by testing antibiotic susceptibility on a micro-scale, but these are not yet a standard practice.

Carbapenemase Detection: New tests like Carba 5 identify specific carbapenemase genes, enhancing precision over previous methods and enabling more targeted treatment for multi-drug-resistant infections.

Biomarker-based diagnostics: Tests for biomarkers like Procalcitonin (PCT) and C-reactive protein (CRP) facilitate early detection of bacterial infections and help guide antibiotic use, thus improving stewardship efforts.

Multiplex Syndromic Panels: Panels such as BioFire® and FilmArray® test multiple pathogens simultaneously, expediting diagnosis, but may not detect all possible pathogens and can be limited by cost and availability.

How are new antimicrobial agents and therapies addressing resistant strains, and what impact do these treatments have on managing AMR?

New antimicrobial agents and therapies are significantly advancing the fight against drug-resistant bacterial strains and countering antimicrobial resistance (AMR). Here is a lowdown:

New Antibiotics: New antibiotics like beta-lactam–β-lactamase inhibitor combinations (e.g., ceftazidime-avibactam) can neutralize drug-resistant bacteria, but most of the newly approved drugs have a narrow spectrum of activity and do not cover all resistance mechanisms. Zosurabalpin is a promising new drug from a completely new class of antibiotics that targets Acinetobacterbaumannii, a lethal gram-negative bacteria associated with hospital-acquired infections.

Mechanism-Guided Strategies: Efflux pump inhibitors are being explored to enhance existing antibiotics, but their clinical efficacy is yet to be established.

Alternative Therapies: Phage therapy shows promise against multidrug-resistant bacteria, but is not yet widely available due to regulatory and specificity challenges. CRISPR-Cas systems have the potential to disrupt resistance genes but are in early research stages.

These treatments impact AMR management by providing options against resistant strains, potentially reducing reliance on broad-spectrum antibiotics. However, their success depends on careful implementation to prevent further resistance development.

In what ways are AI and machine learning enhancing sepsis management and AMR research, and what emerging trends are notable?

AI and machine learning are enhancing sepsis management and AMR research by analyzing large datasets to predict risk factors and optimize treatments, though practical implementation faces challenges. Notable developments include:

Predictive Analytics: Machine learning models analyze electronic health records to identify patients at high risk for sepsis, enabling earlier intervention. However, the effectiveness depends on the availability of high-quality, structured data, which is limited in many settings.

AMR Pattern Prediction: AI algorithms predict antimicrobial resistance trends, aiding in antibiotic stewardship. Yet, these models require extensive data and validation before they can reliably inform clinical decisions.

Integration with Digital Health Records: Integration of AI with digital health records, like the Ayushman Bharat Health Account (ABHA) in India, holds potential but is in the early stages. Data privacy concerns and interoperability issues also pose challenges.

Emerging trends include the increased use of AI in diagnostics, the development of smart algorithms for treatment recommendations, and the potential for global data sharing to enhance predictive models.

What strategies are proving most effective in improving infection control to prevent sepsis and AMR, and how successful have they been?  

Effective infection control strategies are crucial for preventing sepsis and managing AMR. Here are some key strategies:

Antimicrobial Stewardship Programs (ASPs): ASPs optimize antibiotic use by ensuring appropriate drug selection, dosage, and duration. These programs have reduced antibiotic use by 15-30%, curbed the emergence of resistant strains like MRSA and CRE, and improved sepsis outcomes by ensuring timely and effective treatment.

Hand Hygiene:Emphasised by the WHO, proper hand washing before and after patient contact is a fundamental practice. Compliance with hand hygiene protocols has led to a 30-70% reduction in healthcare-associated infections, directly impacting sepsis prevention and AMR control.

Infection Prevention Bundles: Evidence-based bundles, targeting infections like central line-associated bloodstream infection and ventilator-associated pneumonia, have achieved over 50% reductions in infection rates in critical care settings. These bundles are crucial for preventing infections that can lead to sepsis.

Vaccination Programs: Vaccines for diseases like pneumococcal and influenza have reduced infection rates by 60-90% in high-risk populations, thus indirectly bringing down the incidence of sepsis and reducing antibiotic use.

How are global public health initiatives and collaborations affecting the fight against sepsis and AMR, and what results have they achieved?

Global public health initiatives and collaborations, particularly Carb-X and BARDA, have been vital in combating AMR on the push side. Let’s examine how these initiatives and collaborative efforts have made a difference:

Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator (CARB-X): A global non-profit partnership funded by a consortium of governments and foundations, CARB-X has accelerated global antibacterial innovation by supporting the development of new antibiotics and other life-saving products to combat the most dangerous drug-resistant bacteria. Its portfolio represents the world’s most scientifically diverse, early-development pipeline of new antibiotics, vaccines, rapid diagnostics, and other products to prevent, diagnose, and treat life-threatening bacterial infections. In fact, CARB-X is the only global partnership that integrates solutions for the prevention, diagnosis, and treatment of life-threatening bacterial infections, translating innovation from basic research to first-in-human clinical trials.

Biomedical Advanced Research and Development Authority (BARDA): A US Department of Health and Human Services office established through the Pandemic and All-Hazards Preparedness Act which reports to the Office of the Assistant Secretary for Preparedness and Response (ASPR), BARDA is a leader in the development of antibacterial medical countermeasures through unique public-private partnerships with the industry. BARDA is also driving innovation to treat antibiotic-resistant infections.  It addresses the need for new and better antibiotics with novel mechanisms of action to combat antibiotic resistance by supporting the end-to-end development of products and providing capital and technical expertise to pharmaceutical companies with novel antimicrobial drug candidates. It is one of the only funders of late-stage clinical programs in this space at the moment.

UK’s Antimicrobial Products Subscription Model: This model stands out as a public health initiative on the pull side. Designed in response to the accelerating global crisis of antimicrobial resistance, the UK subscription pilot is based on the concept of delinking the volume of drugs sold from reimbursement. The idea behind this government initiative is that setting fixed payments for antibiotic access, rather than linking reimbursement to the volume of drugs sold, could eliminate incentives to oversell antimicrobials (for companies) and the disincentives for hospitals to use cheaper alternatives due to fixed reimbursement. The UK pilot is aimed at overcoming the long-standing innovation dearth in the antimicrobial space by increasing commercial profit margins and encouraging urgently needed innovation in pharmaceutical antimicrobial R&D.

WHO Global Action Plan on AMR: Since 2015, this plan has enhanced awareness, surveillance, and responsible antimicrobial use in line with the WHO’s One Health Approach. It has enabled over 130 countries to track resistance better, as a result of which they have managed to reduce unnecessary antibiotic use.

Global Antibiotic Research and Development Partnership (GARDP): Founded in 2016, GARDP develops new antibiotics and ensures access for vulnerable populations.

Global Antimicrobial Resistance Surveillance System (GLASS) and Vivli: These two organizations have done commendable work in AMR surveillance. While GLASS has standardized AMR data collection and improved global response to this public health threat, Vivli manages one of the largest AMR surveillance registries in the world.

What future breakthroughs or technologies could revolutionize sepsis and AMR management in the next decade, and how might they change current approaches?

Future breakthroughs and technologies are poised to revolutionize the management of sepsis and AMR, particularly in the field of rapid diagnostics encompassing metagenomics, Automated Antibiotic Susceptibility Testing (AST), and other evolving technologies, in the next decade. Rapid point of care assumes importance as it can provide us insights into what the bacteria is, what its underlying mechanism of resistance is, and how it responds to various drugs. This can go a long way in improving treatment outcomes.

The problem with sepsis is that by the time the right treatment starts, it is already too late as the infection has already spread, increasing the risk of mortality by as much as 50%. Therefore, it is only with the help of rapid diagnostics that you can personalize treatment.

Machine learning and AI are also important components of rapid diagnostics because what they are doing is giving a probability or risk profile which helps in diagnosis.

Here are the technologies and breakthroughs which can make a big difference in the foreseeable future:

Rapid Diagnostics: Advances in rapid diagnostic tools, such as metagenomic sequencing and point-of-care tests, can quickly identify pathogens and their resistance profiles, allowing for prompt and targeted treatment.

Immunotherapy and Host-Directed Therapies: Developing treatments that enhance the body’s immune response to infections may reduce the severity of sepsis and lessen reliance on antibiotics.

Personalized Medicine and Genomics: Tailoring treatments based on an individual’s genetic makeup and the genetic characteristics of the pathogen can improve treatment efficacy and reduce the development of resistance.

Alternative Therapies: Techniques like CRISPR-Cas systems and phage therapy offer novel ways to combat bacterial infections by directly targeting resistance mechanisms or using bacteriophages to eliminate harmful bacteria.

These technologies may change current approaches by enabling more precise, effective, and individualized treatments, improving patient outcomes, and reducing the spread of antimicrobial resistance.