DNDi - João Roberto Ripper

Newborns are at significant risk from serious blood-stream infections, such as sepsis, as well as other serious bacterial infections such as pneumonia and meningitis. The situation is aggravated by AMR, as currently available treatments become less effective. Of great concern are the 214,000 neonatal sepsis deaths estimated to result from drug-resistant infections across the world in 2015.

At present, there is very little evidence to support the appropriate treatment of serious and drug-resistant infections in neonates. The lack of alternative treatment options means the WHO recommended regimen has not been updated in more than 50 years, despite increasing rates of resistance.

GARDP’s neonatal sepsis programme aims to develop new antibiotic treatments and provide an evidence-base for the use of antibiotics, both old and new, in neonates with confirmed or suspected sepsis.

 

Objectives, by 2023

  • Develop and deliver a new first-line antibiotic treatment for clinically-diagnosed neonatal sepsis (i.e. where the signs and symptoms indicate sepsis, but it is not possible to identify the bacteria) in areas experiencing high levels of drug-resistance to the current WHO recommended treatment regimen (ampicillin and gentamicin).
  • Develop evidence-based treatment(s) against confirmed or highly suspected neonatal sepsis as a result of multidrug-resistant Gram-negative infections.

 

The programme will incorporate a research network to design, implement, and interpret clinical trials for neonatal sepsis.

In July 2018, a global observational study began in Delhi, India. The study will collect clinical information on confirmed sepsis in up to 3,000 newborns in hospitals and/or neonatal units in Bangladesh, Brazil, China, Greece, India, Italy, Kenya, South Africa, Thailand, Vietnam, and Uganda.

GARDP has also developed two target product profiles (TPPs). The first is to re-purpose an existing (fosfomycin) for use – in a combination regimen – for the treatment of clinically diagnosed neonatal sepsis. A clinical trial to determine safety and appropriate dosing of fosfomycin is underway in Kenya.

The second TPP is for an antibiotic to treat confirmed or highly suspected neonatal sepsis resulting from multidrug-resistant Gram-negative infections.

 

More information

Neonatal Sepsis Programme Snapshot

A snapshot of the programme
English


Scientific articles

Tackling antimicrobial resistance in neonatal sepsis. The Lancet Global Health, November 2017
by Folgori L, Ellis SJ, Bielicki JA, Heath PT, Sharland M, Balasegaram M.


Target Product Profiles

Indication

Empiric treatment of neonatal sepsis, including meningitis (premature and term, early and late onset)

Patient population

Neonates with pSBI in settings of high prevalence of resistance to first line WHO empiric therapy

Route of administration

i.v. (intravenous), 30-120 min infusions

Dosing schedule

2-4 x daily

Efficacy

Comparable clinical activity to amoxicillin/gentamicin or ceftriaxone/gentamicin in claimed indication

Clinical activity in pathogens resistant to amoxicillin/gentamicin or ceftriaxone/gentamicin

Treatment duration

5-28 days

Safety/ Tolerability

Low propensity for resistance development, large therapeutic window concerning hepatotoxicity, nephro- and CNS-toxicity, no QT-prolongation

Drug interactions

Comparable to competitors

Key countries

Europe, the Americas, Asia, Africa

Price/ Day of therapy

Average ex-factory price at launch: low/DOT (directly observed therapy)

Pharmacoeconomics

Reduction of intensive care unit and hospitalization days (modelling). Reimbursable

Main competitors

Amoxicillin/gentamicin or ceftriaxone/gentamicin

Indication

Neonatal sepsis, where MDR Gram-negative pathogens have been demonstrated, including K. pneumoniae, P. aeruginosa or Acinetobacter spp. Including CROs

Neonatal meningitis

Patient population

Hospitalized neonates with severe infections, failure on optimal current  treatment and proven microbiology

Route of administration

i.v. (intravenous), 30-120 min infusions

Dosing schedule

2-4 x daily

Efficacy

Comparable clinical activity to existing options in claimed indication

Clinical activity in pathogens resistant to carbapenems

Treatment duration

5-28 days

Safety/ Tolerability

Low propensity for resistance development, large therapeutic window concerning hepatotoxicity, nephro- and CNS-toxicity, no QT-prolongation

Drug interactions

Comparable to competitors

Key countries

Europe, the Americas, Asia, Africa

Price/ Day of therapy

Average ex-factory price at launch: tbd/DOT (directly observed therapy)

Pharmacoeconomics

Reduction of intensive care unit and hospitalization days (modelling). Reimbursable

Main competitors

Colistin monotherapy


Updates

February 2018

Progress to date includes developing two target product profiles (TPPs) and building solid partnerships and multi-stakeholder collaborations. These include St George’s, University of London to conduct an observational study and input into the pharmacokinetic (PK) and pharmacodynamic (PD) assessment of potential drug candidates and the PENTA Foundation.

Discussions are ongoing to identify a partner to coordinate and monitor microbiological activities including determining the phenotypic and genotypic resistance profiles of invasive and colonizing Gram-negative isolates.

A scoping study of existing drugs and the drug pipeline is ongoing to identify treatments that meet the predefined criteria of the TPPs. The initial feasibility survey, conducted in 2017, confirms the critical need and high levels of drug resistance with significant variation in treatment protocols in place in countries. Protocols for an observational and clinical PK study are ready for implementation in early 2018. A stewardship and access plan is under development.