Zinc as adjunct treatment in infants aged between 7 and 120 days with probable serious bacterial infection: a randomised, double-blind, placebo-controlled trial.

BACKGROUND

Serious bacterial infections are a major cause of death in early infancy in developing countries. Inexpensive and accessible interventions that can add to the effect of standard antibiotic treatment could reduce infant mortality. We measured the effect of zinc as an adjunct to antibiotics in infants with probable serious bacterial infection.

METHODS

In this randomised, double-blind, placebo-controlled trial, we enrolled infants aged 7-120 days with probable serious bacterial infection at three hospitals in New Delhi, India, between July 6, 2005, and Dec 3, 2008. With computer-generated sequences, we randomly assigned infants in permuted blocks of six, stratified by whether patients were underweight or had diarrhoea at enrolment, to receive either 10 mg of zinc or placebo orally every day in addition to standard antibiotic treatment. The primary outcome was treatment failure, which was defined as a need to change antibiotics within 7 days of randomisation, or a need for intensive care, or death at any time within 21 days. Participants and investigators were masked to treatment allocation. All analyses were done by intention-to-treat. This trial is registered with ClinicalTrials.gov, number NCT00347386.

FINDINGS

352 infants were randomly assigned to receive zinc and 348 to placebo. 332 given zinc and 323 given placebo could be assessed for treatment failure. Significantly fewer treatment failures occurred in the zinc group (34 [10%]) than in the placebo group (55 [17%]; relative risk reduction 40%, 95% CI 10-60, p=0·0113; absolute risk reduction 6·8%, 1·5-12·0, p=0·0111). Treatment of 15 (95% CI eight to 67) infants with zinc would prevent one treatment failure. Ten infants receiving zinc died compared with 17 given placebo (relative risk 0·57, 0·27-1·23, p=0·15).

INTERPRETATION

Zinc could be given as adjunct treatment to reduce the risk of treatment failure in infants aged 7-120 days with probable serious bacterial infection.

FUNDING

Department of Biotechnology, Government of India; the European Commission; the Meltzer Foundation; and the Research Council of Norway.