Anti-Infectives: How New Research is Shaping Infection Control

In an exclusive interaction with India Pharma Outlook, Dr. Pankaj Gupta, Senior Medical Director at Pfizer India, sheds light on the escalating threat of antimicrobial resistance in India’s ICUs. He discusses evolving treatment strategies such as targeted therapies, real-time surveillance, innovative antibiotics, regulatory reforms, and precision-based infection control to combat multidrug-resistant Gram-negative pathogens like NDM-producing Enterobacterales. A seasoned pharmaceutical strategy leader, Dr. Gupta brings deep expertise across Medical Affairs, Clinical Research, and Public Health, backed by credentials from top institutions and recognition in rare diseases and oncology leadership.

With antimicrobial resistance escalating in India’s ICU settings, particularly from Gram-negative pathogens, how are treatment strategies evolving to address this clinical crisis effectively?

In India's ICU settings, antimicrobial resistance from Gram-negative pathogens such as Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii is a significant concern. The carbapenem resistance rates among these pathogens are extremely high, making infections difficult to treat. Targeted antibiotic therapy is crucial in combating antimicrobial resistance, particularly in ICU environments. By focusing on the specific pathogens causing an infection, targeted therapy ensures that the most effective antibiotics are utilized, reducing the risk of resistance development. This approach minimizes the use of broad-spectrum antibiotics, which can disrupt the gut microbiome and lead to undesirable side effects. Rapid diagnostics play a vital role in quickly identifying resistance mechanisms, enabling early and appropriate targeted therapy. Furthermore, targeted therapy enhances patient outcomes by ensuring timely and precise treatment, which is essential for critically ill patients.

The second most important strategy is the development of new antibiotics and innovative treatments to combat resistant pathogens, where pharmaceutical companies play a key role. Innovative antibiotics can help prolong the effectiveness of existing treatments by providing new options to which bacteria have not yet developed resistance.

Thirdly, surveillance is a fundamental component in the fight against antimicrobial resistance (AMR). It helps track changes in microbial populations, detect resistant strains early, and support the investigation of outbreaks. By monitoring resistance patterns, healthcare providers can make informed decisions about treatment protocols and antibiotic use, ensuring that the most effective therapies are employed. Additionally, surveillance systems like Pfizer's ATLAS (Antimicrobial Testing Leadership and Surveillance) provide comprehensive bacterial susceptibility data, aiding clinicians and public health officials in understanding local epidemiology and making informed treatment decisions. Healthcare professionals can access the database free of cost by logging onto the Atlas website, which provides 15 years of cumulative antibiotic susceptibility data across the globe.

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β-lactam/β-lactamase inhibitor combinations are gaining traction in tertiary hospitals across India, but how effective are they proving against multidrug-resistant infections in practice?

β-Lactam/β-lactamase inhibitor (BL-BLI) combinations are a class of antibiotics that pair a β-lactam antibiotic with a β-lactamase inhibitor. The β-lactam component targets the bacterial cell wall synthesis, while the β-lactamase inhibitor protects the β-lactam from degradation by β-lactamase enzymes produced by resistant bacteria. These combinations are gaining traction in tertiary hospitals across India due to their effectiveness in combating carbapenem-resistant infections, particularly those caused by multidrug-resistant (MDR) Gram-negative bacteria.

Carbapenem resistance is a significant challenge in treating bacterial infections, especially in India. Carbapenem-resistant Enterobacterales (CRE) produce enzymes such as carbapenemases, which degrade carbapenem antibiotics, rendering them ineffective. Among these, metallo-β-lactamases (MBLs) like New Delhi metallo-β-lactamase (NDM) are particularly problematic. NDM-producing Enterobacterales are widespread in India and pose a severe threat due to their high resistance to multiple antibiotic classes. These bacteria are often resistant to multiple antibiotics, making infections difficult to treat and control.

There is an unmet need for newer options to treat these resistant infections that have limited treatment options.

Aztreonam-avibactam is a newer BL-BLI combination that offers a promising solution for treating infections caused by MBL-producing bacteria. Aztreonam is a monobactam antibiotic that is stable against MBLs, while avibactam inhibits other β-lactamases, including class A, class C, and some class D enzymes. This combination restores the activity of aztreonam against bacteria that co-produce MBLs and other β-lactamases, providing a much-needed treatment option for MDR Gram-negative infections.

Clinical trials have demonstrated that ATM-AVI is effective and well-tolerated in treating complicated intra-abdominal infections and hospital-acquired or ventilator-associated pneumonia. The combination has shown efficacy in both in vitro and in vivo studies, and its regulatory approvals underscore its potential public health impact.

Recent regulatory reforms are accelerating infectious disease trials in India. How conducive are these frameworks for validating narrow-spectrum anti-infectives aimed at targeted use?

India's recent regulatory reforms have paved the way for a more streamlined development of targeted narrow-spectrum anti-infectives. Despite the current lack of specific guidelines, the country's diverse healthcare landscape and high burden of infectious diseases present opportunities for innovative solutions. The growing threat of antimicrobial resistance highlights the need for tailored approaches. Narrow-spectrum agents can play a crucial role in addressing this challenge. To move forward, focusing on enhanced diagnostic capabilities will help identify pathogens and track resistance patterns. Streamlined regulatory processes will facilitate the development and approval of targeted therapies and robust clinical trials tailored to the Indian population will ensure effective treatments. The National Action Plan for Antimicrobial Resistance provides a solid foundation for surveillance and trend analysis. By leveraging this framework, India can develop targeted narrow-spectrum anti-infectives that improve patient outcomes and combat antimicrobial resistance.

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As precision-based infection control gains momentum in India, what cutting-edge anti-infective innovations are likely to shape the next decade of care delivery?

Precision-based infection control in India is set to be shaped by several cutting-edge anti-infective innovations, including the development of novel β-lactam/β-lactamase inhibitor combinations. This combination is designed to target metallo-β-lactamases and other resistant pathogens, offering a promising solution for multidrug-resistant infections. Additionally, advancements in rapid diagnostics and molecular characterization techniques are enhancing the ability to identify and treat infections more effectively. The integration of artificial intelligence and machine learning in antimicrobial stewardship programs is also expected to optimize prescription practices and improve patient outcomes. Furthermore, the adoption of innovative IPC practices and comprehensive training programs will continue to play a crucial role in reducing healthcare-associated infections and improving patient safety.