Do Children with Uncomplicated Severe Acute Malnutrition Need Antibiotics? A Systematic Review and Meta-Analysis

Abstract

BackgroundCurrent (1999) World Health Organization guidelines recommend giving routine antibiotics (AB) for all children with severe acute malnutrition (SAM), even if they have uncomplicated disease with no clinically obvious infections. We examined the evidence behind this recommendation.Methods and FindingsOVID-MEDLINE, EMBASE, COCHRANE, GLOBAL-HEALTH, CINAHL, POPLINE, AFRICA-WIDE-NiPAD, and LILACS were searched for AB efficacy, bacterial resistance, and infection rates in SAM. Following PRISMA guidelines, a systematic review and meta-analysis were performed. Three randomised controlled trials (RCT), five Cochrane reviews, and 37 observational studies were identified. One cohort-study showed no increase in nutritional-cure and mortality in uncomplicated SAM where no AB were used. (p>0.05). However, an unpublished RCT in this setting did show mortality benefits. Another RCT did not show superiority of ceftriaxone over amoxicilllin for these same outcomes, but adressed SAM children with and without complications (p = 0.27). Another RCT showed no difference between amoxicillin and cotrimoxazole efficacies for pneumonia in underweight, but not SAM. Our meta-analysis of 12 pooled susceptibility-studies for all types of bacterial isolates, including 2767 stricly SAM children, favoured amoxicillin over cotrimoxazole for susceptibility medians: 42% (IQR 27–55%) vs 22% (IQR 17–23%) and population-weighted-means 52.9% (range 23–57%) vs 35.4% (range 6.7–42%). Susceptibilities to second-line AB were better, above 80%. Prevalence of serious infections in SAM, pooled from 24 studies, ranged from 17% to 35.2%. No study infered any association of infection prevalence with AB regimens in SAM.ConclusionsThe evidence underlying current antibiotic recommendations for uncomplicated SAM is weak. Susceptibility-studies favour amoxicillin over cotrimoxazole. However, given that these antibiotics have side-effects, costs, and risks as well as benefits, their routine use needs urgent testing. With reliable monitoring, we believe that there is sufficient equipoise for placebo controlled RCTs, the only robust way to demonstrate true efficacy.

Antibiotic resistance patterns and beta-lactamase identification in Escherichia coli isolated from young children in rural Limpopo Province, South Africa: The MAL-ED cohort

“…Treatment for this condition often involves administration of antibiotics, as recommended by the W orld Health Organization (WHO); however, there is no strong evidence that this is the best course of action. [12] Considering our evidence that even without antibiotic exposure, children at risk of malnutrition often harbour resistance genes, it seems that the introduction of additional selective pressure could actually contribute to ill health rather than recovery. A 2014 study [13] found that the diversity of antibiotic resistance genes in the human gut microbiota appears to increase with age, although they did not look at individuals <3 years of age.…”

Broad spectrum β-lactam resistance in faecal Escherichia coli isolated from severely malnourished and nourished children attending Mbagathi district hospital, Nairobi: A case-control study

“…[3,4] This may warrant the empiric use of antimicrobials to boost their survival, but in the case of severe acute malnutrition complicated by diarrhea only, this predisposes a child to inappropriate antimicrobial use. [5,6] Antimicrobial resistance among Escherichia coli is of increasing global concern. [7] This has been associated with the emergence and spread of extended spectrum β-lactamase (ESBL)-producing E. coli, which are also frequently associated with resistance to quinolone and aminoglycosides.…”

Recovery, Relapse, and Episodes of Default in the Management of Acute Malnutrition in Children in Humanitarian Emergencies: A systematic review

“…Some have focused on comparing the inpatient model with the community model (Lenters et al, 2013;Schooness et al, 2013;Ashworth, 2006); some have assessed the appropriateness and efficacy of routine first-line antibiotics provided during outpatient care for children with uncomplicated SAM (Alcoba et al, 2013); and others have examined the effect of different ready-to-use foods (RUFs), including cost-effectiveness (Bhutta et al, 2008;Gera, 2010). Picot and colleagues (2012) reviewed various intervention studies that have been designed to treat infants and children aged under five years with SAM.…”