Optimising Antibiotic Treatment for Sick Malnourished Children

Summary

Children with severe malnutrition who are admitted sick to hospitals have a high mortality, usually because of infection. All children with severe malnutrition admitted to hospitals are treated with antibiotics. However, policymakers are not sure that the current antibiotics are the most effective. It is possible that the antibiotics that are currently used as second-line should be used first. Finding this out will need a large trial comparing different antibiotics. To prepare for such a trial the investigators first want to make sure that the doses given are correct for malnourished children. The investigators also want to check whether malnourished children more commonly carry resistant bacteria in their feces than well-nourished children. The study is important because the types of antibiotics and the doses needed to fight infection may be different in malnourished children because of the changes in their body due to malnutrition and the types of bacteria present.

Conditions

• Malnutrition

Interventions

DRUG

Ceftriaxone

Ceftriaxone is active against a broad spectrum of gram positive and gram negative bacteria, including intracellular bacteria (e.g. Salmonellae, Staphylococci). Its antibacterial effect is dependent on time above the minimum inhibitory concentration(MIC). Ceftriaxone is highly protein-bound and elimination depends on glomerular filtration rate. In severely ill adults, elimination is highly variable. Alteration in plasma proteins, volume of distribution and renal function in sick severely malnourished children could significantly alter pharmacokinetics (PK). Despite several published studies on the PK of ceftriaxone in children, none have included severe malnutrition.

DRUG

Metronidazole

Metronidazole is effective against Giardia, which is common amongst children with SAM; and against other anaerobic infections, including small bowel bacterial overgrowth and Clostridium difficile colitis. Small cohort studies suggest there may be benefits for nutritional recovery. However, metronidazole can cause nausea and anorexia, potentially impairing recovery from malnutrition and may also cause liver and neurological toxicity. Changes in body composition as well as metabolic and drug elimination mechanisms may alter the potential toxicity or effective dose.

Sponsors & Collaborators

• KEMRI-Wellcome Trust Collaborative Research Program

  collaborator OTHER

• Centre for Research in Therapeutic Sciences, Strathmore University, Nairobi Kenya

  collaborator UNKNOWN

• University College, London

  collaborator OTHER

• Centre for Microbiology Research, Kenya Medical Research Institute

  collaborator UNKNOWN

• Centre for Clinical Research, Kenya Medical Research Institute

  collaborator UNKNOWN

• University of Oxford

  lead OTHER

Principal Investigators

• James A Berkley, Paediatrics · KEMRI Wellcome Trust Research Programme and University of Oxford

Study Design

Allocation

NA

Purpose

TREATMENT

Masking

NONE

Model

SINGLE_GROUP

Eligibility

Min Age

2 Months

Max Age

59 Months

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2016-04-01

Primary Completion

2016-09-30

Completion

2017-09-30

Countries

• Kenya

Study Locations