Zinc Plus Antibiotic Reduces Treatment Failure in Infants

Posted by on Jun 1, 2012
in the category Paediatrics

By Joe Barber Jr, PhD

Source: Medscape News Today

Infants with probable serious bacterial infection who received zinc in addition to standard antibiotic therapy were less likely to suffer treatment failure, according to the findings of a randomized, double-blind, placebo-controlled trial.

Shinjini Bhatnagar, PhD, from the All India Institute of Medical Sciences in New Delhi and the Translational Health Science and Technology Institute in Gurgaon, Haryana, India, and colleagues published their findings online May 31 and in the June 2 print issue of the Lancet.

The authors state that the current treatments for infants with severe infections are less than optimal. "Despite advances in antimicrobial treatment, outcomes remain poor," the authors write. "Development of inexpensive and accessible interventions that could improve treatment outcomes and reduce case fatality is important."

To assess the effect of zinc supplementation on treatment success, Dr. Bhatnager and colleagues screened infants aged from 7 to 120 days at 3 hospitals in New Delhi between July 6, 2005, and December 3, 2008, for convulsions, fast breathing, severe chest indrawing, and other signs of serious bacterial infection. They then randomly assigned 700 patients to receive either zinc (352 patients, 332 assessed for treatment failure) or placebo (348 patients, 323 assessed for treatment failure) in addition to standard antibiotic care (ampicillin and an aminoglycoside, third-generation cephalosporin and an aminoglycoside, or intravenous cloxacillin). Overall, the investigators saw a 40% reduction in the risk for treatment failure in the zinc supplementation group compared with the placebo group.

The researchers included preterm infants (gestational age ≤ 32 weeks) who were older than 2 months at screening. They excluded infants weighing 1500 g or less; those requiring mechanical ventilation, inotropic drugs, or exchange transfusion; those with any serious underlying medical condition; those born to HIV-infected mothers; and those who received zinc during the present infective episode. The primary outcome of the trial was treatment failure (defined as a need to change antibiotics within 7 days of randomization, a need for intensive care, or death at any time within 21 days after randomization); the secondary outcomes included clinical time to recovery, time to achieve exclusive oral feeding, time to weight gain, and time to overall recovery.

No differences were observed in the baseline characteristics of the placebo and zinc supplementation groups. In a subgroup of patients aged from 7 to 60 days, zinc supplementation reduced the incidence of treatment failure by 54%.

Zinc had a greater effect in infants with diarrhea than in those without diarrhea, but no difference in treatment efficacy was observed between underweight and nonunderweight patients.

However, the researchers caution that additional research is necessary before zinc can be applied clinically to prevent treatment failure. "Future trials need to measure the efficacy of zinc treatment for probable serious bacterial infection in other settings — specifically, other studies should measure the effect of zinc supplementation on important outcomes in children who are diagnosed with serious bacterial infections without measurements of concentrations of C-reactive protein," the authors write. "If such trials show improvement in treatment outcomes, the use of zinc as an adjunct to antibiotic treatment might lead to substantial reductions in infant mortality, particularly in resource-constrained settings where second-line antibiotics and appropriate intensive care might be unavailable."

In a related commentary, Christa L. Fischer Walker, PhD, MHS, and Robert E. Black, MD, MPH, say they are encouraged by these findings but agree that additional research is necessary. "Bhatnagar and colleagues' promising results will need to be replicated before practical recommendations can be made," Dr. Fischer Walker and Dr. Black write. "The exact mechanism for the effect of supplemental zinc is unknown and needs further investigation, but the clinical benefits in diarrhoea and pneumonia in children younger than 5 years, and now in probable serious infections in young infants, suggest that therapeutic use of zinc could have wide application."

The authors and commentators have disclosed no relevant financial relationships.

Lancet. Published online May 31, 2012.