Malnutrition continues to be a major public health problem in the developing world, with severe acute malnutrition affecting approximately 19 million children younger than the age of 5 years worldwide. The classification of malnutrition may be mild, moderate, or severe based on clinical assessment, anthropometry, and biochemistry. Severe acute malnutrition is defined by weight-for-height more than three z-scores below the mean (i.e., more than three standard deviations below the mean), and/or malnutrition with edema of both feet.1 Uncomplicated severe acute malnutrition is defined as severe acute malnutrition without edema and without anorexia, fever, hypothermia, vomiting, severe dehydration, severe anemia, altered consciousness, altered respiration, or moderate to severe skin infection. Severe acute malnutrition is a life-threatening condition that substantially increases mortality and disease burden among children, therefore requiring specialized medical attention.

In 1999, the World Health Organization (WHO) introduced guidelines in the Management of Severe Malnutrition: A Manual for Physicians and Other Senior Health Workers.2 The manual includes a 10-step ordered approach of three treatment phases to improve the identification and treatment of severe acute malnutrition. The first phase includes the initial treatment to stabilize the child’s condition. The second phase includes rehabilitation involving increasing energy content and volume of feeds to recover the lost weight. The third phase includes follow-up after discharge to ensure proper development.

Children with severe acute malnutrition are especially susceptible to infections. Unlike well-nourished children who respond to infection with an inflammatory or febrile response, malnourished children with serious infections may just seem apathetic or drowsy.2 The infection therefore can be hidden from clinical presentation. The WHO 10-step approach recommends the routine use of broad-spectrum antibiotics because data indicated that early treatment of bacterial infections with effective antibiotics improved the nutritional response to feeding, preventing septic shock and reducing mortality. More recently, the WHO and the United Nations in 2007 supported a community-based model in which children with uncomplicated severe acute malnutrition were treated at home.3 There is limited evidence to support that the same medical protocol of routine antibiotics within the inpatient care setting be used in community-based treatment.

The double-blind, placebo-controlled trial, organized by Dr. Sheila Isanaka and her colleagues, was conducted at four health centers in the rural health district of Madarounfa, Niger. Children between 6 and 59 months of age with uncomplicated severe acute malnutrition were randomly assigned to receive amoxicillin or placebo for 7 days. Each child also received the standard care of ready-to-use therapeutic food (RUTF) (170 kcal per kilogram per day; Plumpy’Nut Nutriset) for outpatient treatment of uncomplicated severe acute malnutrition. A total of 2412 children underwent randomization, and 2399 children included in the analysis. Nutritional recovery at or before 8 weeks, identified as the primary outcome, occurred in 65.9% (790 of 1199) of children in the amoxicillin group vs 62.7% (752 of 1200) in the placebo group.

The study determined that there was no significant difference in the likelihood of nutritional recovery (risk ratio for amoxicillin vs placebo, 1.05; 95% confidence interval [CI], 0.99-1.12; P = 0.10). Secondary evaluation showed that amoxicillin decreased the risk of hospitalization by 24% and the risk of transfer to inpatient care by 14%. There were no between-group differences in the mean length of stay among hospitalized patients or rate of recovery, as children in both groups recovered quickly given adequate inpatient care, mitigating any risk associated with the absence of amoxicillin treatment inclusion. Overall, this study found no significant benefit of routine amoxicillin use with respect to nutritional recovery among children with uncomplicated severe acute malnutrition in Niger.

COMMENTARY

The notion that routine antibiotic therapy in the treatment of uncomplicated severe acute malnutrition is always necessary or beneficial is called into question by this study. Eliminating routine antibiotic use in community-based treatments would simplify treatment and result in cost savings with regard to medications, staff, and infrastructure for delivery. Furthermore, a decreased risk of antibiotic use might minimize the risk of resistant microbial strain emergence, fostering responsible antibiotic stewardship. Research providing evidence that antibiotics should be used routinely in community-based treatments for uncomplicated severe acute malnutrition is limited. This valuable study brings into consideration the elimination of routine use of antibiotics in the protocol for uncomplicated severe acute malnutrition community-based treatment, specifically for children in regions where access to appropriate healthcare facilities and services is available. Notably, access to adequate healthcare services is not universal to all children with malnutrition, especially in rural regions of the developing world where malnutrition rates are the highest. Additionally, not all children with uncomplicated malnutrition have a similar clinical presentation, as some children will have comorbid illnesses that require special attention.

A study done in Malawi in 2013 evaluating the use of routine antibiotic therapy for “uncomplicated” severe acute malnutrition demonstrated that amoxicillin significantly reduced the risk of treatment failure and death as compared to placebo.4 It is important to note that this study included a high-risk study population, characterized by a high burden of kwashiorkor and human immunodeficiency virus (HIV) infection, in contrast to the study done in Niger, which predominately included malnutrition due to marasmus and a population with low prevalence of HIV infection.

Continued surveillance of regions that have access to adequate healthcare facilities and resources would be required before we could eliminate the routine antibiotic regimen in community-based treatment for uncomplicated severe acute malnutrition. Isanaka’s study nicely showed that routine antibiotic use may not always be necessary, but essentially the application of this study should be limited only to settings with excellent outpatient follow-up and access to inpatient care (since more children in the placebo group required subsequent transfer to inpatient care). In regions with limited follow-up and access to adequate healthcare facilities, children with uncomplicated severe acute malnutrition should be admitted and given antibiotics to avoid deterioration or illness from hidden infections. This well-designed study illustrates that there is a need for further investigation to support the continued practice of widespread use of antibiotics in uncomplicated severe acute malnutrition. 

REFERENCES

  1. Lazzerini M, Tickell D. Antibiotics in severely malnourished children: Systematic review of efficacy, safety and pharmacokinetics. Bull WHO 2011;89:594-607.
  2. World Health Organization. Management of Severe Malnutrition: A Manual for Physicians and Other Senior Health Workers. World Health Organization, Geneva, 1999.
  3. World Health Organization. Community based management of severe acute malnutrition: A joint statement. World Health Organization & World Food Programme & United Nations System Standing Committee on Nutrition & United Nations Children’s Fund, Geneva, 2007.
  4. Trehan I, et al. Antibiotics as part of the management of severe acute malnutrition. N Engl J Med 2013;368:425-435.