This retrospective analysis demonstrates that a cohort of children with SAM treated with amoxicillin as part of their home-based therapy regimen did not have a higher rate of recovery compared to those who did not receive routine antibiotics.
The primary limitation of this study is its retrospective design: baseline differences between the two cohorts may have contributed to the study’s primary finding. While habitual diet, socio-economic status, and overall living environments are very similar in the areas studied, those children treated with amoxicillin presented at an older age and with greater degrees of stunting and underweight, suggesting that the two populations may have been in different physiologic states at the time of enrollment. The greater degree of stunting and underweight among the children receiving amoxicillin may have been indicative of a higher prevalence of a chronic process such as HIV infection. However, the HIV rates in the Dowa district of Malawi, where children were treated by the standard protocol with amoxicillin, are reported to be 7.0% through inference from mortality rate, whereas HIV rates are reported to be 15.0% and 16.5%, in Malawi’s Chiradzulu and Machinga districts, respectively, where children were treated without antibiotics (Oster 2007
). Unfortunately, at the time these children were being treated, routine HIV testing was not readily available in this setting.
Although the two feeding programs studied are designed and operated very similarly (with the exception of the use of antibiotics in the standard protocol group), the different baseline characteristics of the two cohorts would suggest that there were some recruitment differences between the two groups. It is possible that the children treated without antibiotics presented earlier in the course of their illness or attended treatment sites in closer proximity to their villages, improving their chances of recovery. The local health aides serving these sites may have been more proactive in recruiting caretakers in the community to bring children to the clinic for screening and treatment, thereby including less severe cases in this group. Since the two feeding programs operated independently, other unquantifiable variances in the teaching and nutritional counseling provided by the programs’ staff may also have developed over time and contributed to the differences seen in the outcomes between the two groups.
Most of severely malnourished children in this study had kwashiorkor, and most were with mild edema, so the findings should not be generalized to populations where the predominant form of severe malnutrition is marasmus. In spite of this limitation, when children with kwashiorkor and marasmus were considered to have distinctly different forms of malnutrition, the recovery rates were significantly greater among children that did not receive amoxicillin for both kwashiorkor and marasmus.
Nevertheless, despite these baseline differences between the two groups of children, regression modeling showed home-based therapy without antibiotics to be associated with a higher rate of recovery at 4 weeks and a similar rate at 12 weeks, compared to the group of children who all received amoxicillin for 1 week. This finding that the recovery rate with amoxicillin therapy is delayed has biological plausibility when considering the clinical problem of antibiotic-associated diarrhea and the emerging knowledge of the way antibiotics disrupt the intestinal microbiome (Dethlefsen et al. 2008
; Preidis et al. 2009
). The marked difference in WHZ seen in the 4-week graduates also suggests that amoxicillin usage may be associated with delayed recovery. By 12 weeks, it is more likely that enough time had passed such that any adverse effect of the antibiotics would have resolved.
There are good reasons to limit unnecessary use of antibiotics in this setting. Foremost is that the routine inclusion of antibiotics as part of the therapy for SAM poses a burden on therapeutic feeding programs in terms of their cost and complexity, which adds to the already difficult task of identifying and providing these children RUTF. Any simplification or cost-reduction that can be made to the therapeutic feeding protocol (without leading to decreased rates of recovery) may lead to an expanded ability to provide home-based therapy to more children in more areas. Even if the final recovery rates are similar, our analysis would suggest that children who do not receive antibiotics may recover more quickly, saving further expenditures on clinical staff and the on the amount of RUTF needed to achieve recovery.
Additionally, antibiotic resistance is increasing worldwide, and can be particularly problematic in developing countries where treatment options against resistant organisms are more limited (Nys et al. 2004
; Okeke et al. 2005
; Okeke et al. 2007
). In the gut, resistant organisms rapidly develop when exposed to broad-spectrum antibiotics, often causing secondary infections that are difficult to treat; one of the primary routes of bacterial invasion in severe malnutrition is thought to be translocation of enteric flora across the compromised intestinal mucosa. Moreover, resistant bacteria may exhibit enhanced virulence (Dancer 2004
), further complicating a malnourished child’s chances for recovery.
Amoxicillin was used in the standard protocol group because of its relatively broad-spectrum of activity, low cost, and current usage by several national protocols in Africa, including Malawi. Evidence is mounting, however, that both amoxicillin and cotrimoxazole, the other commonly used antibiotic for this purpose, are becoming ineffective against the strains of bacteria that are found to be causing severe infections in this population of malnourished children (Manary et al. 2000
; Madanitsa et al. 2009
). Thus, while the constraints on the choice of antibiotics in resource-limited settings should not be underestimated, it is possible that a different routine antibiotic may have been of more benefit to these malnourished children.
Home-based therapy for acute malnutrition is robust partly because children who live far from health care facilities still have access to care. Routine antibiotic use for SAM, a hold-over from when treatment primarily took place in crowded hospital wards (WHO 1999
), may be complicating care in the home-based setting (WHO 2007
), even without any definitive evidence that this is a necessary component of treatment (Alcoba et al. 2009
; Bailey et al. 2009
The findings of this study must be considered preliminary; caution should be exercised in extrapolating these retrospective results to other settings. But these findings, together with growing evidence that the practice of administering routine antibiotics to vulnerable populations is ineffective and perhaps detrimental, highlight the need for randomized prospective trials to determine with certainty the necessity of routine antibiotics in the treatment of children with uncomplicated SAM. Prospective trails should include settings where kwashiorkor is the predominant form of SAM, as well as marasmus.