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Title: Antibiotics as Part of the Management of Severe Acute Malnutrition

Study Location: Malawi

Type of Paper: Original Article

Purpose: To determine whether routine administration of antibiotics as part of the management of severe acute malnutrition was associated with improved recovery and outcomes.

Measures: Mid-upper-arm circumference, weight, length/height, height-for-age

Participants: 2767 children between 6 and 59 months old with severe acute malnutrition symptoms of edema (kwashiorkor indicator), weight-for-height z-score of less than -3 (marasmus indicator) or both (marasmic kwashiorkor).

Methods: The study was a randomized, double-blind, placebo-controlled clinical trial comparing nutritional and mortality outcomes of children with severe acute malnutrition. Children were randomly assigned to one of three different conditions: standardized counseling and ready-to-use therapeutic food (RUTF) with a placebo (n=920), standardized counseling and RUTF with amoxicillin (n=924), and standardized counseling and RUTF with cefdinir (n=923). Children received 6 follow-up visits at 2-week intervals to repeat anthropometric measurements. Children whose condition did not change at follow-up visits remained in the study, receiving nutritional counseling and additional 2-week supply of RUTF. Children whose condition deteriorated were referred to inpatient care. Children were considered to have recovered from severe acute malnutrition if they were without edema and had a weight-for-height z-score of -2 or higher.

Results: Eight-eight percent of children enrolled in the study recovered from severe acute malnutrition. Children with marasmic kwashiorkor had higher mortality rates and recovered less frequently than children with either marasmus or kwashiorkor. Children who received placebo had a significantly lower proportion of recovery compared to those who received either amoxicillin or cefdinir. Mortality rates were lower and recovery rates were higher among children who received antibiotics compared to the placebo group. Recovery time was shortest among children receiving cefdinir when compared to amoxicillin and placebo, and shorter among children receiving amoxicillin compared to placebo. Weight gain from enrollment to the second follow-up visit was significantly greater among children receiving cefdinir compared to placebo. Additionally, children in both antibiotic groups had greater increases in mid-upper-arm circumference compared to the placebo group. Children with the lowest mid-upper-arm circumference and weight-for-height z-score were most likely to die or have treatment failure. Children with the lowest height-for-age z-score were least likely to recover. Children who were HIV seropositive had the highest risks of treatment failure and death.

Conclusions and Implications: Treatment failure rates were reduced by 24.4% when amoxicillin was added to routine therapy and 38.9% with the addition of cefdinir. Additionally, mortality rates were reduced by 35.6% and 44.3% with the addition of amoxicillin and cefdinir, respectively. Children with severe acute malnutrition remain at risk for severe bacterial disease, and the inclusion of antibiotics into routine nutritional therapy should be considered as evidenced by this study.

Limitations: Results are not generalizable to populations outside of rural Sub-Saharan Africa, due to the heavy burden of HIV infection and food insecurity.

Citation/Reference: Trehan, I., Goldbach, H.S., LaGrone, L.N., Meuli, G.J., Wang, R.J., Maleta, K.M., and Manary, M.J. Antibiotics as Part of the Management of Severe Acute Malnutrition. The New England Journal of Medicine. 2013; 368: 425-435. http://www.ncbi.nlm.nih.gov/pubmed/23363496

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