Every year, more than half a million newborns die from sepsis in low- and middle-income countries because they cannot get a simple antibiotic injection in time. The problem is practical, not medical. Ceftriaxone, a long-acting antibiotic that can treat severe neonatal infections with just one daily dose, must be injected. In rural tropical areas, health centres are often hours away, so babies die at home before receiving treatment. A suppository—a medicine inserted rectally—could be given by a community health worker or even a family member, bypassing the need for a clinic visit. If this formulation works, it would transform neonatal sepsis from a death sentence into a treatable condition in the places where most deaths occur. The team has already developed prototype suppositories with an industrial partner and reduced the cost of the absorption enhancer. They will now test two formulations in healthy adults in Thailand, then select the best one for a small safety and absorption study in 60 hospitalised babies receiving treatment for infection. Adequate absorption and tolerability would lead to large mortality trials and, eventually, inclusion in global treatment guidelines—making widespread community-based treatment feasible in high-burden countries.
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Neonatal sepsis (life-threatening infection in infants aged below 28 days of age) is the single greatest cause of preventable death in children living in tropical countries, being responsible for more than half a million of the estimated 2.4 million deaths that occur each year. Most deaths occur at or near home. Prompt administration of effective antibiotics by injection is life saving, but is usually not possible in the rural tropics where health centres are frequently several hours' journey away from home. Alternative strategies are needed to deliver effective treatment at the community level. Since 2012 we have worked on the pharmaceutical development of a suppository formulation of ceftriaxone. Ceftriaxone is an antibiotic used to treat severe infections, including meningitis, which has the advantage of being dosed just once day because it is a long-acting medicine. Our goal is to make effective community-based neonatal sepsis treatment feasible at low cost, and therefore used early and widely enough to prevent a substantial proportion of neonatal deaths from sepsis in high-burden low- and middle-income countries. We have developed several prototype suppositories already and we are ready to move testing into humans. We have an industrial partner (Orofino Pharmaceuticals) who has evaluated our candidate formulations for feasibility for industrial production and has lowered the cost of producing the absorption enhancer that will be combined with the antibiotic in the formulation. In this research project we plan to manufacture two different suppositories and assess how well they are absorbed in healthy adults in Thailand first. Based on absorption and safety results from this study we will then select the leading formulation to be tested in babies. We plan to give 60 babies who are in hospital under treatment for an infection one dose of the suppository in addition to their usual treatment and evaluate the absorption of antibiotic in the suppository. If ceftriaxone is absorbed adequately by this route and is well-tolerated, we will assess this formulation in large trials to measure impact on mortality, with the longer term goal of including the treatment in global treatment guidelines. This would pave the way for widespread uptake in high burden low- and middle-income countries.
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