Neonatal Sepsis: India Joins a Critical Global Trial

A major international effort to find better antibiotic treatments for newborn sepsis has now reached India. The NeoSep1 trial recruited its first Indian patient at the Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER) in Puducherry, marking the start of the country’s involvement in a study built around tackling antimicrobial resistance head-on. Neonatal sepsis, a life-threatening bloodstream infection affecting babies under 90 days old, hits premature and low-birth-weight infants especially hard, and remains India’s leading cause of newborn deaths.

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From Puducherry to Rohtak and Beyond Understanding the Threat Why India Needs Its Own Data What the Trial Hopes to Achieve

From Puducherry to Rohtak and Beyond

A second baby has since been enrolled at Pt. B.D. Sharma PGIMS in Rohtak, and Lokmanya Tilak Municipal College and General Hospital in Mumbai is next in line to join. India isn’t alone in this: the trial is already running in Vietnam and Pakistan, with Malaysia, Bangladesh and Uganda set to come on board soon. Behind the effort is the GARDP Foundation, working alongside the UCL Innovative Clinical Trials Unit, City St George’s, University of London, and the Penta Foundation.

Per a GARDP statement, the plan is to enrol 3,000 newborns across Asia and Africa by the end of 2028. The trial has already recruited newborns in Ghana, Kenya and South Africa as part of that push.

Understanding the Threat

Neonatal sepsis is a dangerous bloodstream infection striking babies under 90 days old, and it hits premature and low-birth-weight infants disproportionately hard. Doctors split it into two types: early-onset, which shows up within the first 72 hours of life, and late-onset, which can appear anywhere from 28 to 90 days in, according to a book on the subject by Meenakshi Singh.

Worldwide, sepsis ranks as the second-leading cause of newborn deaths, killing more than a million infants every year. India’s situation is particularly stark: a paper in the Journal of Clinical Neonatology, titled “Neonatal Sepsis in India: Epidemiology, Risk Factors and Preventive Strategies from a Public Health Perspective,” argues that sepsis still drives roughly 30-40% of all neonatal deaths in the country, despite real progress in neonatal care overall.

The paper’s author, Ahmed Abdulaziz Almohammadi, put the human cost in concrete terms: “In India, neonatal sepsis accounts for an estimated 30%–40% of all neonatal deaths, translating to approximately 2,00,000–2,50,000 preventable deaths annually. Despite substantial reductions in under-five mortality over the past two decades, progress in reducing neonatal mortality has lagged, with sepsis representing a persistent and largely preventable cause of death.”

Why India Needs Its Own Data

India’s sepsis problem doesn’t quite mirror what’s seen elsewhere in the world. Dr. Almohammadi points out that the bacteria behind neonatal sepsis in India look quite different from those found in high-income countries. Gram-negative organisms dominate in most Indian studies, with Klebsiella pneumoniae, Escherichia coli, Acinetobacter species and Pseudomonas aeruginosa accounting for the bulk of bacterial isolates, many of them already showing multidrug resistance. Group B Streptococcus, the top cause of neonatal sepsis in wealthier nations, makes up just 2-5% of India’s cases.

That gap is exactly why NeoSep1 matters for India: it’s designed to build an India-specific profile of the disease, accounting for local factors that make it worse or better. The trial is using something called a Personalised Randomised Controlled Trial (PRACTical) design, a first for this kind of research, which evaluates and ranks multiple antibiotic regimens for newborn sepsis. GARDP spokespersons say this approach should help clinicians pick the treatment that actually fits their local situation, rather than relying on one-size-fits-all guidance.

What the Trial Hopes to Achieve

Ultimately, the goal is to find one or more treatments, safe, effective and affordable, that can cut down the number of newborns dying from drug-resistant sepsis, particularly in low- and middle-income countries. The trial’s first phase, run in South Africa and Kenya in 2023, worked out and confirmed the right doses of fosfomycin and flomoxef for use in newborns alongside other antibiotics.

Nishad Plakkal, the trial’s Principal Investigator in India and Head of the Department of Neonatology at JIPMER, described how the study works in practice: “The study is a pragmatic trial and allows clinicians to make the diagnosis of sepsis as they normally would. However, to ensure the inclusion of infants with a high probability of infection, we use a sepsis severity score that we derived from an earlier global observational study (NeoOBS). Our microbiology team cultures the baby’s blood (and sometimes spinal fluid) to help identify the organism causing sepsis, typically within a day or two. They also identify antibiotic-resistant infections.”

Dr. Plakkal added that the trial’s primary outcome, the central question it’s built to answer, is whether the infant survives the first 28 days. Secondary outcomes being tracked include survival to 90 days, whether additional antibiotics are needed, how long the baby stays in hospital, and whether they’re readmitted afterward.

Key Takeaway: India’s participation in the NeoSep1 global clinical trial marks an important step in addressing neonatal sepsis and the growing challenge of antimicrobial resistance through evidence-based, locally relevant treatment strategies. By evaluating multiple antibiotic regimens using an innovative trial design and generating India-specific data on disease patterns and drug resistance, the study aims to improve survival among newborns, particularly premature and low-birth-weight infants who are most vulnerable.

Conducted in collaboration with international research institutions across Asia and Africa, the trial strengthens India’s contribution to global public health research while supporting efforts to reduce neonatal mortality, improve antimicrobial stewardship, and develop effective, affordable treatments for drug-resistant infections.

M.C.Q.

Question 1: The NeoSep1 trial, in which India has recently begun participation, is primarily aimed at: