Clinical

Antibiotics boost effect of food in malnourished children

Last Updated: 2013-01-30 17:01:01 -0400 (Reuters Health)

By Gene Emery

NEW YORK (Reuters Health) - Seven days of liquid antibiotic therapy given to severely malnourished children as they consumed food supplements boosted their ability to gain weight and lowered their risk of death, according to a study in the sub-Saharan African nation of Malawi.

"There's something else going on with these kids physiologically, where food is not enough," said Dr. Indi Trehan of Washington University in St. Louis, who led the study.

"I think this study is going to return to the table the discussion of whether we know enough about the use of antibiotics, if carefully and thoughtfully done, as an adjunct to the treatment and reversal of malnutrition in children," said Dr. Irwin Rosenberg, former dean of the Friedman School of Nutrition and Policy at Tufts University. He was not involved in the research.

More than 20 million children have severe acute malnutrition and even with treatment with ready-to-use therapeutic food or RUTF -- a spread made of peanut paste, milk powder, sugar, oil and micronutrients - many die.

Many of the children have infections, but there has been controversy over whether antibiotics pose a greater harm than benefit in their treatment.

The study in the January 31 New England Journal of Medicine was designed to test whether antibiotic therapy, combined with food, helped.

"Malnutrition as a whole underlies about 30% to 50% percent of all childhood deaths worldwide and it's totally neglected," Dr. Rosenberg told Reuters Health in a telephone interview.

In Malawi, where 11% of adults are HIV-positive and 53% of children are stunted, the youngsters were treated at home with seven days of an antibiotic (or placebo) and RUTF for up to 12 weeks or until they showed improvement.

Among the 924 children, ages six to 59 months, who received amoxicillin, 88.7% recovered, compared to 85.1% of the 920 children who got placebo. Thus, the failure rate was 32% higher among placebo recipients.

For 923 children given the antibiotic cefdinir instead, the recovery rate was even higher -- 90.0% -- which translated to a 68% higher risk of failure with placebo over the drug.

More significantly, while the death rate was 7.4% among children who received placebo, it was 4.8% for amoxicillin and 4.1% for cefdinir. That translated to a death reduction of 35.6% for amoxicillin and 44.3% for 44.3% with cefdinir.

"Deaths accounted for the largest proportion of children who did not recover in each study group and for each type of severe acute malnutrition," the researchers said. "The overall mortality rate was 5.4%, but the rate was significantly higher among children who received placebo than among those who received either amoxicillin or cefdinir," the researchers said.

The dose of amoxicillin was 80-90 mg/kg and cost about $2.67 per child. The dose of cefdinir was 14 mg/kg and cost $7.85. The food cost about $50 per child.

"There is a bit of a difference in price, but it will get better," said Dr. Trehan. "We bought (the antibiotics) at cost, in America. If you're buying it on large scale from a generic manufacturer, the price should probably drop."

Other factors that seemed to be linked to a higher death rate included poor appetite, acute infectious symptoms, a younger age, being infected with HIV and not receiving treatment, and not having a father in the home.

Dr. Rosenberg told Reuters Health in a telephone interview that the idea of adding antibiotics to treat malnutrition has been around for a while, but "there's been resistance to that because of the talk of overuse of antibiotics."

"Even though we don't know exactly what the antibiotic introduction was actually doing, the study shows that if you address both the infectious arm with antibiotics and the nutritional arm with the nutritional supplement, you might very well get an improved outcome," Dr. Rosenberg said.

"This hidden crisis of malnutrition is an area where a lot of work is left to be done," Dr. Trehan said. "Unfortunately, we're not going to get a cure for a problem like malaria tomorrow. But if we can get these kids better nourished, they're much less likely to die from the mosquito that's going to bite them."

And in a related paper released online today in Science, Dr. Trehan and colleagues report that the severe acute form of malnutrition known as kwashiorkor is associated with certain gut bacteria, and not nutrition alone. This study too was done in Malawi. In a commentary, Dr. David Relman of Stanford University School of Medicine in Stanford, California says the findings "provide hope, in that by understanding the role of the gut microbiota in undernutrition, we can devise new ecologically inspired strategies for correcting this problem."

SOURCES:

http://bit.ly/Xk11Qc

N Engl J Med 2013; 368:425-435.

http://bit.ly/WBRxic

Science 2013.