Authors	Title	Year	Methods (study type, setting, participants)	Results	Conclusions	GRADE level of evidence
Chisti et al. [41]	Treatment failure and mortality amongst children with severe acute malnutrition presenting with cough or respiratory difficulty and radiological pneumonia	2015	•Cohort study: Prospective enrolment of SAM children aged 0–59 months admitted to the Intensive Care Unit or Acute Respiratory Infection ward of the Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh in April 2011 to June 2012 with cough or respiratory difficulty and radiological pneumonia •All the enrolled children were treated with ampicillin and gentamicin and micronutrients as recommended by the WHO •Comparison was made between pneumonic children with (n = 111) and without (n = 296) WHO-defined danger signs of severe pneumonia •Primary outcomes: Treatment failure (if a child required change of antibiotics) and deaths during hospitalisation •Further comparison was made of those who developed treatment failure and those who did not	•SAM children with danger signs of severe pneumonia more often experienced treatment failure (58% vs. 20%, p < 0.001) and fatal outcome (21% vs. 4%, p < 0.001) than those without danger signs •Only 6/111 (5.4%) SAM children with danger signs of severe pneumonia and 12/296 (4.0%) without danger signs had bacterial isolates in blood •In log-linear binomial regression analysis, after adjusting for potential confounders, danger signs of severe pneumonia, dehydration, hypocalcaemia and bacteraemia were independently associated with treatment failure and deaths in SAM children presenting with cough or respiratory difficulty and radiological pneumonia (p < 0.01) •Only 2 children with danger signs and 4 without danger signs of severe pneumonia had a blood culture isolate that was not susceptible to ampicillin and gentamicin •3 study children had a blood culture isolate which was not susceptible to ceftriaxone and only one child to ciprofloxacin •Overall, 18 (4.4%) children had bacteraemia, and the difference in bacteraemia between the groups was not significant •67 (16.5%) children had a history of prior use of antibiotics and only 2 (3%) of them had bacteraemia	•Ampicillin and gentamicin are insufficient for children with complicated SAM presenting with pneumonia •The result underscores the importance of further research, especially a randomised, controlled clinical trial to validate standard WHO therapy in SAM children with pneumonia, especially with danger signs of severe pneumonia, to reduce treatment failure and deaths •Biased by previous administration of antibiotics	C
Yebyo et al. [40]	Outpatient therapeutic feeding program outcomes and determinants in treatment of severe acute malnutrition in Tigray northern Ethiopia: a retrospective cohort study	2013	•Retrospective cohort study •628 children 6–59 months who had been managed for SAM as outpatients from April 2008 to Jan 2012 •The children were selected using systematic random sampling from 12 health posts and 4 health centres  •Tigray, Northern Ethiopia •Details of amoxicillin mg/kg not clarified •Children admitted to the outpatient treatment programme receive weekly rations of Plumpy Nut and supplements including vitamin A, folic acid tabs, antibiotics, deworming tabs and measles vaccine •Children did not have medication administration supervised	•Children who took amoxicillin had significantly faster recovery compared to children who did not take amoxicillin (χ 2 = 136.59, p < 0.0001) •Children who took amoxicillin had 95% (HR 1.95, 95% CI 1.17–3.23) a higher probability of recovery compared to those who didn't take amoxicillin	•The authors conclude that amoxicillin is a positive predictor of faster recovery in children with uncomplicated SAM, and postulate this is secondary to treating small bowel bacterial overgrowth which may be the source of systemic infection by translocation across the bowel wall, resulting in malabsorption of nutrients, failure to eliminate substances excreted in the bile, fatty liver and intestinal damage causing chronic diarrhoea •Biased by retrospective design and poor monitoring of medication administration	D
Page et al. [14]	Infections in Children Admitted with Complicated Severe Acute Malnutrition in Niger	2013	•A clinical and biological characterisation of infections in hospitalised children with complicated SAM in Maradi, Niger •311 children 6–59 months •Study period October 2007 to July 2008 •SAM WfH<−3 Z-score of the median WHO growth standards and/or MUAC <110 mm and/or bipedal oedema •Complicated SAM defined as SAM accompanied by anorexia and/or kwashiorkor with bilateral pitting oedema and/or another severe condition (severe anaemia, severe respiratory tract infection, malaria with signs of severity, other severe infections such as meningitis or sepsis, diarrhoea with dehydration, lethargy or acute neurological disorders, sickle cell crisis) •Clinical examination, blood, urine and stool cultures and chest radiography were performed systematically on admission •Amoxicillin was given systematically or parenteral ceftriaxone in cases of suspected severe or complicated infectious syndrome. No mention of gentamicin in methodology •Treatment was modified based on indications such as non-improvement of clinical condition and/or results of bacterial culture and antibiotic sensitivity testing. Depending on the type of infection suspected, cloxacillin (skin infection, severe pneumonia, S. aureus bacteraemia) or ciprofloxacin (urinary tract infection, severe, explosive or persistent diarrhoea >72 hours, bloody diarrhoea, bacteraemia with suspected Gram-negative bacteria) was added in case of treatment failure, based on lack of improvement or worsening of symptoms within 72 hours of treatment •Children with uncomplicated malaria diagnosed either by rapid test and/or smear microscopy were given oral artesunate and amodiaquine for 3 days. Children with severe or complicated malaria received arthemether IM and then artesunate-amodiaquine if their condition improved, for 7 days in all	•Prevalence data: In the 311 children in the study, gastroenteritis was the most frequent clinical diagnosis on admission, followed by respiratory tract infections and malaria. •Blood or urine culture was positive in 17% and 16% of cases, respectively, and 36% had abnormal chest radiography. •Enterobacteria were sensitive to most antibiotics except amoxicillin and cotrimoxazole. •The median length of stay in the inpatient treatment facility was 8 days (IQR 6–13 days). •29 (9%) of children died; almost half of all deaths (48%, n  =  14/29) occurred within 48 h of admission. •The main causes of death recorded were sepsis (15), respiratory tract infection (4) and clinical suspicion of tuberculosis (2). •Overall, 20 (69%) children who died had one or several laboratory or X-ray-proven infections, including 8 bacteraemia (4 S. aureus, 2. H. influenzae, 1 Salmonella spp., 1 E. coli); 7 UTI (6 E. coli, 1 K. pneumoniae); 3 infectious diarrhoea (1 S. flexneri, 1 S. sonnei, 1 Salmonella spp.); 2 malaria and 2 RTI. •The CFR was 16% (n  =  8/51, p  =  0.1) in patients with a positive blood culture, 15% (n  =  7/41, p  =  0.2) in children with a UTI, 8.3% (n  =  4/62, p  =  0.5) in children with infectious diarrhoea and 4.5% (n  =  2/44, p  =  0.5) in those with malaria. •Clinical signs were poor indicators of infection and initial diagnoses correlated poorly with biologically or radiography-confirmed diagnoses	•The authors concluded that the data confirm the high level of infections and poor correlation with clinical signs in children with complicated SAM, and provide antibiotic resistance profiles from an area with limited microbiological data. These results contribute unique data to the ongoing debate on the use and choice of broad-spectrum antibiotics as first-line treatment in children with complicated SAM and reinforce the call for an update of international guidelines on management of complicated SAM based on more recent data’. •Limitations: Did not reach target sample size (n = 1000) owing to the premature closure of the MSF programme; resulted in missing data in particular the months of August to October, which correspond to the malnutrition and malaria peaks; secondly, diagnostic capacity is limited compared with developed country settings and it was difficult to ascertain diagnoses in some cases (e.g. TB diagnosed clinically). Third, glycaemia was not analysed here because it was measured after children were administered the appetite test, limiting its interpretation. Fourth, high prevalence of blood culture contamination may have resulted in underestimation of children who died from sepsis owing to inaccurate characterisation of culture results	D