Antibiotics Help in Malnutrition Treatment in Children

Joe Barber Jr, PhD

January 30, 2013

The use of antibiotics in combination with ready-to-use therapeutic food appears to be associated with significant improvements in recovery and mortality rates among children with uncomplicated severe acute malnutrition, according to the findings of a randomized, double-blind, placebo-controlled trial.

Indi Trehan, MD, MPH, DTM&H, from Washington University in St. Louis, Missouri, and the University of Malawi in Blantyre, Malawi, and colleagues published their findings online January 31 in the New England Journal of Medicine.

The authors mention that several studies identified high rates of clinically significant infections among severely malnourished children. "This observation has led to treatment guidelines recommending the use of routine antibiotic agents even for children treated as outpatients, although outpatients are presumably much less likely to have a systemic infection than are patients with complicated cases that require inpatient care," the authors write. "This recommendation for the use of routine antibiotics is based on expert opinion and has not been directly tested in a clinical trial," they continue, "and observational data suggest that antibiotics are unnecessary and perhaps even harmful in children with uncomplicated severe acute malnutrition (i.e., children with good appetite and no clinical signs of sepsis)."

In the study, the authors enrolled children aged 6 to 59 months in rural Malawi with evidence of kwashiorkor and/or marasmus and randomly assigned them to receive amoxicillin, cefdinir, or placebo for the initial 7 days of therapy, in addition to ready-to-eat therapeutic food. Among the 2767 eligible children, both amoxicillin (relative risk [RR], 1.32; 95% confidence interval [CI], 1.04 - 1.68; P = .02) and cefdinir (RR, 1.64; 95% CI, 1.27 - 2.11; P < .001) were associated with higher rates of recovery than placebo.

In addition, compared with placebo, children in the amoxicillin (RR, 1.55; 95% CI, 1.07 - 2.24; P = .02) and cefdinir (RR, 1.80; 95% CI, 1.22 - 2.64; P = .003) groups were less likely to die.

In the multiple logistic regression model adjusted for baseline characteristics such as age, type of malnutrition, and height-for-age z score, a number of variables, including older age (odds ratio [OR], 1.007; 95% CI, 1.001 - 1.017; P = .02, for each additional month), the presence of kwashiorkor alone (OR, 5.88; 95% CI, 4.15 - 8.33; P < .001) or marasmus alone (OR, 1.74; 95% CI, 1.22 - 2.47; P = .002) compared with marasmic kwashiorkor, and an increase in the height-for-age z score (OR, 1.19; 95% CI, 1.09 - 1.31; P < .001) were associated with higher odds of recovery, whereas HIV seropositivity in the mother or child was associated with lower odds of recovery (OR, 0.36; 95% CI, 0.27 - 0.47; P < .001).

"Overall, 88.3% of the children enrolled in the study recovered from severe acute malnutrition," the authors write. There was no statistical advantage to amoxicillin over cefdinir for either recovery (P = .22) or death (P = .53).

"Our 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," the authors add. "Further studies are needed to evaluate long-term outcomes of routine antibiotic use in children with uncomplicated severe acute malnutrition and to determine whether a specific high-risk target population can be better defined," they conclude.

Dr. Trehan received grants from the Nationals Institutes of Health, the Hickey Family Foundation, and the Academy for Educational Development. Other authors reported receiving research funds from the Hickey Family Foundation and the Academy for Educational Development.

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