Peer-reviewed article
Defining a target product profile for antimicrobials to treat severe paediatric bacterial enteric infections in low- and medium-income countries, caused by <i>E. coli</i>, <i>Shigella</i>, <i>Salmonella</i> and <i>Campylobacter</i> species.
Attwood M, Choola T, Duffy E, Gigante V, Harwell J et al. ·
Summary
Written by AI, not yet AICS's view · claude-haiku-4-5-20251001Paediatric diarrhoea caused by bacterial pathogens kills around 500,000 children yearly in low- and middle-income countries, yet antimicrobial resistance rates are not well understood and no new antibiotics are being developed specifically for children. This paper defines the desired characteristics of a new antimicrobial drug to treat severe bacterial diarrhoea in children in these settings. The new drug should work as well as current treatments, be available in oral and intravenous forms, be safe for children, and remain stable in hot climates.
Key points
- Paediatric diarrhoea is associated with 500,000 childhood deaths annually in low- and middle-income countries
- E. coli, Shigella, Salmonella and Campylobacter are among the most common bacterial causes
- Antimicrobial resistance rates for these pathogens are poorly quantified
- No new antibacterials are currently in development specifically for paediatric diarrhoea
- Target product profile specifies need for oral and intravenous formulations that are stable at elevated temperatures
Limitations
This is a descriptive paper defining desired drug characteristics rather than evaluating an intervention or providing epidemiological data. It does not present original research on burden of disease, resistance patterns, or efficacy of treatments.
Abstract
Paediatric diarrhoea is associated with 500 000 childhood deaths each year in low- and middle-income countries (LMICs). Enteropathogenic Escherichia coli, Shigella spp., Salmonella spp. and Campylobacter spp. are among the most common causative bacterial pathogens, however, their burden and rates of antimicrobial resistance (AMR) are poorly quantified. Current treatment typically involves oral and intravenous rehydration fluids, nutritional support for malnourished children, antibiotics for severe bacterial infections, antiemetic and anti-diarrheal medications, and analgesics. The World Health Organization recommends first-line empirical treatment of ciprofloxacin, with alternatives of third-generation cephalosporins or azithromycin. At present, no new antibacterials are in development specifically to treat paediatric diarrhoea. Target product profiles (TPPs) are used typically in drug development and describe the desired characteristics of a new therapeutic. In this paper, we aim to define a TPP for the development of novel antimicrobials for the treatment of severe paediatric diarrhoea in LMICs. Oral and intravenous formulations are preferable. Safety, tolerability, resolution of clinical signs and symptoms must be equivalent or better than standard of care (SoC) therapy. Interactions with commonly used therapies such as zinc, milk and traditional cures should be minimal. In addition, formulations should be stable at elevated temperatures and for extended periods of time to facilitate access and distribution across LMICs.