We studied this recently in a retrospective analysis, which seemed to suggest that antibiotics were not necessary: [url=http://www.ncbi.nlm.nih.gov/pubmed/20545919]Trop Med & Int'l Health 15(9):1022-1028[/url] Our group is now in the midst of a randomized controlled trial investigating this question: [url]http://clinicaltrials.gov/ct2/show/NCT01000298[/url] I am not aware of other research that directly addresses this question, but would love to hear from others who have more information.

This is a good question. Firstly, the child needs to be properly assessed to see if they already have a clinical syndrome requiring antibiotics (e.g. pneumonia) as outlined in WHO guidelines. Secondly, that the child is genuinely uncomplicated and can be managed at home. At that point, there is no good evidence to guide us. This has to be answered by a proper clinical trial and the well designed trial going on in Malawi mentioned by Indi Trehan should help to provide that answer. Factors such as likelihood of returning if the child becomes sick and quality of clinical assessment are likely to be important in subsequent implementation. In my setting, a common reason for inpatient mortality is late presentation with advanced infection and sepsis. Clearly, knowing when to give antibiotics and refer, and community mobilisation on care seeking when a malnourished child is actually sick are part of the broader picture.

this is an important question. The primary purpose of the antibiotic is to prevent recrudescence of an infection which is not evident because of diminution of the inflammatory response or aquisition of infection of an infection whilst the patient is immunodeficient. This intervention is meant to prevent death. The question then becomes "how many children is it worth treating with antibiotic to prevent one death?" Would you give antibiotics to 100 children to prevent one child from dying? or perhaps 500 or 1000? It is clear to me that teh size of such a study would need to be massive. Recovery in weight is not, in my opinion the appropriate end-point for such an investigation. The retrospective analysis showed recovery in 85 and 86% of children - ie 14-15% did not recover - how many deaths in each group, or transfer to hospital for serious deterioration with infection? how many defaulters? - were all the defaulters followed up to ensure that none of them were deaths? Then there is another important consideration - what is the rate of amoxycillin resistance in the study populaition? If it is as high as reported in Kenya (Bejon et al - Journal of Antimicrobial Chemotherapy (2005) 56, 232-235) 72% of gram negative isolates were resistant to amoxycillin before 2005, Cleary if amoxycillin resistance is as high as this one would not anticipate there to be any advantage in giving an ineffective drug.

I simply can not resist a line to the antibiotic discussion! Except for the costs of the the antibiotic and perhaps resistance. In the practical sense however, I perceive the presence of multiple infection sources in most management centers-as is the case in most developing countries still justifying need for antibiotics use. Is there any thing like prophylaxis with antibiotics?

I think there are several important issues here: i) the 'one size fits all' approach may not be appropriate: There are likely to be differences in risks and benefits of antibiotic treatent between the 'well-looking but thin' child who is either MAM or SAM, and complicated, sick children in terms of the degree of immune dysfunction, subclinical infection and reductive adaptation. I agree with Prof Golden that the true answer about uncomplicated 'walk-in' SAM is about rates of readmission and death. However, we do not yet have these data. Antibiotics are not recommended for uncomplicated moderate acute malnutrition (MAM), but it seems unlikely that a child with MUAC 11.6cm is much different to one with MUAC 11.4cm if they do not have a clinical complaint. There is an addiional question regarding HIV infected children who are already taking cotrimoxazole prophylaxis... do they need something more during uncomplicated SAM? There is good evidence from other fields that short course antibiotics are effective in preventing serious infection in vulnerable children. Cotrimmoxazole prevented more than 90% of pneumonias in children with measles in Guinea Bissau: see [url] http://www.ncbi.nlm.nih.gov/sites/ppmc/articles/PMC1702442/ [/url] Malnutrition is the commonest cause of secondary immune deficiency worldwide. Epidemiological evidence of increased susceptibility to death from infectious disease (even in mild or moderate malnutrition) is overwhelming. The mechanisms are less clear. A key aspect is likely to be impaired barriers to infection at the skin and gut/respiratory mucosa. In terms of systemic immune deficiency, there are relatively few consistent findings. T cells responses such as delay type hypersensitivity (eg tuberculin test) do appear consistently impaired, but other mechanisms either have not been studied or have been studied at a time of active infection, making interpretation difficult. In Kilifi, Kenya, we have used a demographhic surveillance system (DSS) to track survival following inpatient rehabiliation and treatment of complicated SAM. We have found a very high mortality from common infectious diseases for 6 months after treatment, which remains above that of the avergae population even at one year. Although this my reflect social disadvantage, we believe it is good evidence that these children have taken a severe 'hit' to immunity, which takes time to recover, probably longer than anthropometric recovery. These children were genrally admitted with very complicated SAM: septicaemia, shock and severe infections at presentation. However, subsequent mortality, even for MAM who were admitted becuase they were sick are well above baseline. ii) These treatments must be tested in well designed clinical trials: The questions are of enormous public health importance, but there are real risks of cost, logistics and antimicrobial resistance. For this reason, I support the trial that is going on in Malawi. If this eventually points to the need a large international trial, then that should be done. This is normal for major public health questions such as malaria treatment (eg recent Aquamat trial), malaria vaccine (current RTSS trial) or pneumococcal vaccines to need large, international and well funded trials. The same is true of nutritional interventions, especially in relation to cost-effectiveness. Evidence from such trials is the key to knowing what to do in practice, but also the key to harnessing donor and govenment support for implementation. After seeing our post-discharge mortality data, we are currently conducting a randomised trial along the Kenyan coast of daily cotrimoxazole (septrin) prophylaxis among HIV-negative children with complicated SAM. They will receive the study drug (cotrimoxazole or placebo) at stabilisation and continue for 6 months, with follow up to 12 months. All other usual treatment and nutritional rehabilitation is given. The primary endpoint is mortality, secondary endpoints are readmission (including full microbiological work up), toxicity and antimicrobial resistance of carriage (nose and rectal) and disease-causing bacteria. [url] http://clinicaltrials.gov/ct2/show/NCT00934492 [/url] iii) There are two sides to the question of antimicrobial resistance: a) To what extent does resistance reduce the efficacy of the antibiotic treatment? Again, there are likely to be differences between antibiotics. One key piece of data is that in the HIV trials, cotrimoxazole prophylaxis was highly effective, even in areas of high levels of cotrimoxazole resistance (see: [url] http://www.ncbi.nlm.nih.gov/pubmed/15555666 [/url]). Thus, the inhibitory concentration of drug to prevent overt infection may be cosiderably lower than that needed to treat an established infection. Similarly, low doses of penicillins are effective in preventing infections in other type of immune deficiency (eg splenectomy) b) To what extent does the widespread (necessary or unecessary) use of an antibiotic cause it? This differs between antibiotics and usage patterns. Ceftrixone, for example, is extremely good at rapidly causing resistance, both becuase of it's mode of action on bacteria and because it is recirculated through the bile system and reabsorbed in the gut exposing resident gut bacteria over it's long half life. Resistance genes can easily jump from resident to pathogenic bacteria in the gut. In summary, these are questions of great public health importance that need to be tackled with adequately powered (large) multi centre trials with proper follow up, detection of death and readmission and the presence and important of antimicrobial resistance. As a community, we shoudl first be willing to acknowledge the areas where there are not good data from clinical trials to guide our practice, and secondly not shy away from doing the trials that are needed, as they are the only way these questions can be answered.

Dear Jay Berkley Could you kindly share preliminary results on the study of prophylaxis for malnutrition children as described in your excellent and insightful reply to the above question. I'm looking forward to your findings which i believe are pertinent in reducing mortality in malnourished children during the treatment and post treatment period.

Hi Kiross Look at the review on the same : http://www.who.int/bulletin/online_first/10-084715.pdf http://clinicaltrials.gov/ct2/show/NCT01000298 ( Already listed in the previous post ) Regards

Dear Mordecai These questions will hopefully be greatly informed by the two trials mentioned in this thread. However, they are both randomized and the arm each child is allocated to is blinded to the investigators, as per gold standard trials procedures. Therefore, it is not possible, or proper, to examine results as the trial progresses. Either they run to the full planned sample size, or an independent data and safety monitoring board stops the trial early because of clear benefit or harm. Results can only be published after this. jay

Results of the Malawi study was presented at a CAPGAN conference last month. Antibiotics (amoxicillin and Cefdinir) were shown to reduce risk of death compared to placebo. However, I worry that the study is not powered enough to detect a difference in mortality. I am sure Indi can correct me if I am wrong, but the need for large trial still exists.

Since the CAPGAN 2009 appeal, Action contre la Faim (ACF-France) and scientific partners have been planning a randomized trial testing antibiotics in “uncomplicated-SAM”, and the planning stage is almost completed. Since preliminary Indi Trehan et al.'s results at CAPGAN 2011 seem highly important for future trials, we would kindly accept any suggestions to optimize our methods, power, measured outcomes (mortality, complications coded as IMCI diagnostics, medical transfers, non-responders, cured rate, weight-gain, length of stay, etc). You can also contact us directly: Gabriel Alcoba at the Geneva Children’s Hospital: gabriel.alcoba@hcuge.ch, or Benjamin Guesdon at ACF bguesdon@actioncontrelafaim.org.

Hi Kiross See the findings from the Malawi study on antibiotics use in SAM management http://www.fantaproject.org/downloads/pdfs/FANTA-CMAM-Antibiotic-Study-Mar2012.pdf Regards