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Antibiotics Improve Survival in Severe Malnutrition

Oral antibiotics amoxicillin and cefdinir show efficacy in a randomized study of children with severe acute
malnutrition.
Linda MacArthur, PhD
February 14, 2013—In children with severe acute malnutrition, a one week course of amoxicillin or
cefdinir, combined with ready-to-use therapeutic food (RUTF), improved nutritional recovery and reduced
mortality compared with placebo, according to the findings of a double-blind, randomized trial conducted
in Malawi.
Mark Manary, MD, with Washington University in St. Louis, Missouri, and colleagues reported their
findings in the January 31, 2013 issue of The New England Journal of Medicine.
According to the researchers, the use of routine antibiotics for treatment of outpatient malnutrition is
based on observational data but this practice has not been tested in clinical trials. The current trial was
designed to determine the effect of antibiotic use on nutritional recovery and mortality rates, as compared
with placebo.
A total of 2767 children ages 6-59 months of age in rural Malawi with edema and a weight-for-height z
score of less than -3 were randomized to receive RUTF (175 kcal/kg body weight/day) and 1 week of
amoxicillin suspension (80-90 mg /kg/day divided into 2 doses, N=924), cefdinir suspension (14
mg/kg/day divided into 2 doses, N=923), or placebo (N=920). RUTF continued for the duration of the
study for 6 biweekly follow-up visits.
The primary outcome measures were nutritional recovery, as defined by the absence of edema and
weight-for-height z scores of -2 or higher, and mortality rates. Overall, the percent of children that did not
recover was significantly higher in the placebo group compared with the groups receiving amoxicillin or
cefdinir (14.9% vs. 11.3 and 9.1; P =0.02 for placebo vs. amoxicillin and P<0.001 for placebo vs. cefdinir).
Amoxicillin and cefdinir significantly reduced mortality rates compared with placebo (4.8% and 4.1% vs.
7.4%; P =0.02 for placebo vs. amoxicillin and P =0.003 for placebo vs. cefdinir).
Children with marasmic kwashiorkor had lower rates of nutritional recovery and higher mortality than
children with either kwashiorkor or marasmus. Fewer children failed to recover with antibiotics (30.8% for
amoxicillin and 30.1% for cefdinir compared with 40.9% for placebo) but the results did not reach
statistical significance.
Overall nutritional recovery rates were higher and death rates were lower among children that received
cefdinir than those that received amoxicillin, although these differences were not statistically significant
(P=0.22 for recovery and P=0.53 for death).
Treatment failure was significantly associated with younger age (P=0.02), marasmic kwashiorkor
(P=0.002), HIV exposure or infection, and greater growth stunting (P<0.001), and these factors were
significantly correlated with increased risk of death (P=0.01 for younger age and P<0.001 for others).
Good appetite upon enrollment correlated with reduced risk of death (P=0.001).
Adverse effects for amoxicillin included a generalized papular rash in one child. One child that received cefdinir developed thrush and another developed bloody diarrhea that resolved spontaneously. There was no reported severe allergy or anaphylaxis. According to the researchers, their results suggest that “children with uncomplicated severe acute malnutrition who qualify for outpatient therapy remain at risk for severe bacterial infection and that the routine inclusion of antibiotics as part of their nutritional therapy is warranted.” This study was funded by the Hickey Family Foundation, the Academy for Educational Development and grants for statistical consulting from NIH.

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