London School of Hygiene & Tropical Medicine

Malnutrition contributes significantly to under 5 morbidity and mortality globally, with the World Health Organization (WHO) estimating 149 million children under age 5 as stunted and 45 million children as wasted.[1] Prevention and appropriate management of malnutrition could be a tool in the fight against antimicrobial resistance (AMR), particularly when considering the use of empiric antimicrobials prescribed during malnutrition-related illness.

What is the association between malnutrition and antimicrobial resistance?

Dietary deficiencies of crucial nutrients, vitamins in malnourished children affect proper immune cell function and pathogen response, thus increasing susceptibility to infections. [2] Consequently, there is higher consumption of antimicrobials in these children, resulting in removal of non-pathogenic bacteria colonisers from the gut and creating a favourable environment for resistant strains to grow.

In addition, protein energy malnutrition alters the gut microbiota with subsequent loss of beneficial bacteria (bifidobacteria and lactobacilli) in the gut and colonization by pathogenic bacteria that may be primed for AMR. [2]. This has been explored in a 2023 study of post-natal exposure to multiple micronutrient deficiencies in mice showing altered bacterial, fungal and viral/bacteriophage fecal populations after a 28-day low-micronutrient diet. [3] A retrospective metagenomic study published in 2023 on the effect of amoxicillin on the gut microbiome of children with severe acute malnutrition in Niger showed that use of amoxicillin caused an acute decrease in gut microbiome richness and increase in antimicrobial resistance genes due to selection of resistant bacteria.[4]

What are the current practices regarding antimicrobial use in malnourished children?

Generally, malnourished children only receive antimicrobials with clinical evidence of infection. [5] In the case of severe acute malnutrition (SAM), empiric routine broad-spectrum antimicrobials (most commonly amoxicillin) are recommended by the WHO as this improves their morbidity and mortality rates, as seen in a 2013 randomized control study comparing amoxicillin and cefdinir with placebo (relative risk of death with placebo vs amoxicillin 1.55 [95% confidence interval 1.07 to 2.24]; relative risk of death with placebo vs cefdinir 1.80 [95% confidence interval 1.22 to 2.64]).[5, 6]

There is debate about the routine use of anti-microbials in uncomplicated severe acute malnutrition. While a 2018 systematic review on guidelines for the treatment of SAM supports the continued use of broad-spectrum oral amoxicillin for treatment of uncomplicated SAM as outpatients, there are studies in which no long-term benefit was identified. This was seen in a randomized control trial from India in 2023, and requires further review.[7, 8]

Where to from here?

Improving nutrition is an important upstream strategy in tackling AMR. Malnutrition is preventable, and targeted programmes to improve childhood nutrition should be considered in the fight against AMR.

It is important to critically appraise the need for broad-spectrum antibiotic coverage, particularly in the key group of uncomplicated SAM. Guidelines need to find a balance between reducing mortality and over-prescribing of broad-spectrum antimicrobials that promote resistance. Recommendations should be context-specific to local disease epidemiology.

Finally, more research is required to understand the bidirectional link between malnutrition and AMR. The LSHTM AMR centre highlights a project looking at metagenomic screening for AMR in stool samples from children discharged from SAM outpatient treatment programmes in Senegal and South Sudan, which could have a huge impact in understanding AMR infections in the vulnerable populations and advising on current treatment recommendations.[9]

1.          World Health Organization. Malnutrition. Fact Sheets 2023 [cited 2024 22/02]; Available from: https://www.who.int/news-room/fact-sheets/detail/malnutrition#:~:text=Globally%20in%202022%2C%20149%20million,age%20are%20linked%20to%20undernutrition

2.          Holowka, T., D. van Duin, and L.A. Bartelt, Impact of childhood malnutrition and intestinal microbiota on MDR infections. JAC Antimicrob Resist, 2023. 5(2): p. dlad051.

3.          Littlejohn, P.T., et al., Multiple micronutrient deficiencies in early life cause multi-kingdom alterations in the gut microbiome and intrinsic antibiotic resistance genes in mice. Nat Microbiol, 2023. 8(12): p. 2392-2405.

4.          Schwartz, D.J., et al., Effect of amoxicillin on the gut microbiome of children with severe acute malnutrition in Madarounfa, Niger: a retrospective metagenomic analysis of a placebo-controlled trial. Lancet Microbe, 2023. 4(11): p. e931-e942.

5.          World Health Organization, Guideline: Updates on the management of severe acute malnutrition in infants and children. 2013: Geneva.

6.          Trehan, I., et al., Antibiotics as part of the management of severe acute malnutrition. N Engl J Med, 2013. 368(5): p. 425-35.

7.          Rao, Y.K., Baranwal, V., Midha, T. Javed, A., Kumari, P., A Randomized Controlled Trial on Comparison of Clinical Outcome in Uncomplicated SAM Managed with and without Antibiotics. Indian J Pediatr 2023. 90: p. 994–999.

8.          Williams, P.C.M. and J.A. Berkley, Guidelines for the treatment of severe acute malnutrition: a systematic review of the evidence for antimicrobial therapy. Paediatr Int Child Health, 2018. 38(sup1): p. S32-S49.

9.          Antimicrobial-Resistance-Centre. Highlighted Projects. 2024 [cited 2024 22/02]; Available from: https://www.lshtm.ac.uk/research/centres/amr/highlighted-projects.