Trials assessing the effectiveness of the use of antibiotic treatment in treating severe malnutrition in children


Research Description:

Background Children with severe malnutrition who are admitted sick to hospitals have a high mortality in hospital and after discharge, usually because of infection. According to WHO guidelines all children with severe malnutrition admitted to hospitals are treated with antibiotics (currently recommended penicillin or gentamicin plus gentamicin) because many have infections that may not be clearly seen. However, we are not sure that the current antibiotics are the most effective since no studies have been carried out to determine which antibiotics used for treating malnourished children are the most effective. It is possible that the antibiotic that is currently used as second-line (ceftriaxone) should be used first, however as well as a lack of evidence of effectiveness, it carries a greater risk of causing antimicrobial resistance affecting the patients themselves and the community. A second area of uncertainty is the use of metronidazole, an antibiotic given to reduce bacterial growth in the small bowel that causes malabsorption, and to treat parasitic infections. World Health Organisation Guidelines acknowledge opinions and practice vary on it’s use and lack of evidence from trialss.  Phase 1 (completed)
  • Pharmacokinetics of Ceftriaxone and Metronidazole in sick, severely malnourished children
  • Pre-trial rectal swab surveillance of carriage of antimicrobial at admission and discharge. 
Phase 2 (ongoing)
  • Multicentre 2×2 factorial randomised trial of first line empiric treatment:
    • Ceftriaxone vs. Penicillin plus Gentamicin (open label)
    • Metronidazole vs. placebo (double-blind)
  • The primary endpoint is mortality
  • Secondary endpoints include safety, readmission to hospital and growth
  • Sub-studies are examining the carriage of antimicrobial resistance and serious bacterial infections at initial admission to hospital, during admission and after discharge.
  • The study is also examining costs of care incurred by facilities and families, cost effectiveness of the antibiotics, and costs associated with antimicrobial resistance Children aged ³2 months admitted to hospital with severe malnutrition eligible for IV antibiotics under WHO guidelines are being included at hospitals in Kenya and Uganda in Kilifi, Nairobi, Mombasa and Mbale. Children are followed up at days 14, 45 & 90 days after admission to hospital. 
The study is coordinated by The KEMRI/Wellcome Trust Research Programme in Kenyan where it forms part of a set of studies focussing on children who are vulnerable to life-threatening infections. FLACSAM is funded by the UK MRC/DfID/Wellcome Trust Joint Global Health Trials Scheme as a grant to the University of Oxford. The principal investigator is Professor James A Berkley.