Antibiotics Cuts Deaths Among Severely Malnourished Kids

Antibiotics added to nutritional therapy helped aid recovery and prevent deaths among severely malnourished children, findings that suggest routine use of the drugs should be considered in kids who suffer from acute hunger.

Children with severe malnutrition who were given amoxicillin had a 25 percent greater recovery rate and a 35 percent lower death rate than those who took a placebo, according to the study published in the New England Journal of Medicine. Those given the antibiotic cefdinir, sold as Omnicef by Abbott Laboratories, had a 40 percent better recovery rate and 45 percent reduced death rate.

More than 20 million children worldwide each year suffer from severe acute malnutrition, leading to 1 million deaths each year. While the recovery rate is between 85 percent and 90 percent, adding antibiotics may offer a cost effective approach to improve health and survival, said study author Indi Trehan.

“Childhood malnutrition remains the biggest, and unfortunately, most under-recognized, health problem in the world,” said Trehan, a clinical fellow in the Department of Pediatrics at Washington University in St. Louis and a visiting lecturer at the University of Malawi, in a Jan. 26 e-mail. “In the end no matter what advances we make in HIV or malaria or diarrhea, malnourished children will always be at the highest risk of death from these diseases. In terms of bang-for-buck, this is where we need to focus the most.”

Malnutrition Deaths

Malnutrition, defined by the World Health Organization as a very low weight for height and severe wasting, accounts for almost half of all child deaths under the age of 5 worldwide, Trehan said.

Amoxicillin cost about $2.67 per child in the study, while the cefdinir was $7.85. That expense can be lower if used on a large scale, the authors said. That compares with nutritional therapy that costs about $50 per child over the course of the treatment.

The study included 2,767 Malawi children ages 6 months to 4 years who had severe acute malnutrition. They were given amoxicillin, cefdinir or placebo for seven days in addition to nutritional therapy, which is a ready-to-use paste that doesn’t need to be mixed with water.

Trehan said it’s unclear how the antibiotics work to benefit these children. It could be that the children’s immune systems were so compromised by the malnutrition that they were unable to clear any simple infections on their own. By providing them the antibiotics early on, they may have been protected from typical childhood infections that came along during the study.

‘Worthwhile’ Investment

“We hope that international aid organizations and local health authorities will be able to incorporate the use of these simple antibiotics,” Trehan said. “We recognize that this will require additional financial and logistical resources, but the dramatic decrease in the mortality rates seen in this study has convinced us that this investment will be worthwhile for the benefit it provides to child survival worldwide.”

Another possibility, he said, was maybe the children already had an infection that “tipped them over the edge” into severe malnutrition and the antibiotics treated that condition.

Trehan said in other studies it’s been shown that the intestinal barriers of children who are malnourished are weak and porous so intestinal bacteria may be able move into the blood. It’s possible that the antibiotics might be helpful in limiting the amount of infection and inflammation in the gut, helping them to maximize absorption of the nutritional therapy.

Direct Link

There is also a particularly severe form of malnutrition, called kwashiorkor, which can’t be cured with nutrition alone, and that scientists recently tied to a type of bacteria in the gut. That finding, also by Trehan and researchers from Washington University in St. Louis, was published in the journal Science.

Researchers in the study looked at 317 pairs of Malawian twins in the first three years of their life. Over the study, half of the twin pairs were well nourished while in others, one or both twins developed kwashiorkor. They then found that the gut bacteria in those with the malnutrition who were given nutritional therapy became more similar to that of well-nourished children during treatment. When therapy was ended, the bacteria reverted back.

Children with kwashiorkor suffer swelling, liver damage, anorexia and skin ulcers.

New Evidence

To test the bacterial link to kwashiorkor, the researchers then put fecal bacteria from three twin pairs into mice that were germ free. The mice that had the bacteria from the twin with kwashiorkor and ate the Malawian diet developed symptoms of malnutrition. That provided the evidence of the link between the gut bacteria and kwashiorkor.

“The gut mucosa is the battleground not surprisingly between infection and malnutrition since it is the target of all sorts of infections from the environment and it is the site of the most immune activation,” Trehan said. But when it becomes so inflamed due to this immune activation, the enteropathy that develops puts the child at risk for malabsorption and further infections. It is this vicious cycle that we would like to continue to study.”