Antibiotics improve outcomes in treatment of severe acute malnutrition

Jan 30th – NEJM – In a study published today, inclusion of antibiotics in therapeutic regimens for children with severe acute malnutrition improved recovery and mortality rates.

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1. Inclusion of antibiotics in therapeutic regimens for children with severe acute malnutrition improved recovery and mortality rates.

2. Of the children who recovered, those who received antibiotics had greater improvements in weight gain and upper arm circumference.

Greater than 1 million children die annually from severe acute malnutrition worldwide.  Prior studies suggest that severe infections are highly prevalent in malnourished children, which have led to guidelines recommending routine administration of antibiotics in the treatment of this disease though there was no prior evidence to support their use.  This is the first clinical trial to test this hypothesis.  The results of this study suggest that routine antibiotics along with standard RUTF and counseling do in fact improve nutritional and mortality outcomes in children with severe acute malnutrition.

While baseline characteristics of all groups were similar, only about 30% of enrollees were tested for HIV (a prevalent infection in Malawi).  20% tested HIV positive and of these, only about 30% were receiving anti-retroviral therapy.  This statistic suggests a high prevalence of untreated HIV infection. As patients with untreated HIV are very likely to have other infections responsive to antibiotics, this is a possible explanation for the results. Given the high prevalence of HIV infection in this study population, these results may not apply to regions at lower risk for HIV.  Further studies examining the long-term outcomes of routine antibiotic use are likely to be the next step in implementing this therapy.

Click to read the study in NEJM

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Image: PD

1. Inclusion of antibiotics in therapeutic regimens for children with severe acute malnutrition improved recovery and mortality rates.

2. Of the children who recovered, those who received antibiotics had greater improvements in weight gain and upper arm circumference.

This [randomized controlled trial] study: sought to determine if the routine administration of antibiotics for children with severe acute malnutrition would improve outcomes.  The study enrolled children between 2009 and 2011 at multiple clinics in rural Malawi.  Only children well enough to be treated as outpatients were included in the study.  A total of 2767 children aged ~ 6 months to 5 years all received standard treatment involving ready-to-use therapeutic food (RUTF), but were then randomized to one of three additional treatments: amoxicillin, cefdinir, or placebo.  The rate of recovery in children who received placebo was significantly lower than those who received antibiotics; additionally mortality was significantly higher in children who received placebo than those who received amoxicillin (RR 1.55; 95% CI, 1.07-2.24) or cefdinir (RR 1.8; 95% CI 1.22-2.64).  Weight gain was significantly higher in children who received cefdinir than in those who received placebo, while upper arm circumference improved in children who received either antibiotic.

Further reading:

  1. Management of severe malnutrition: a manual for physicians and other senior health workers
  2. Comparison of home-based therapy with ready-to-use therapeutic food with standard therapy in the treatment of malnourished Malawian children: a controlled, clinical effectiveness trial

In sum: Greater than 1 million children die annually from severe acute malnutrition worldwide.  Prior studies suggest that severe infections are highly prevalent in malnourished children, which have led to guidelines recommending routine administration of antibiotics in the treatment of this disease though there was no prior evidence to support their use.  This is the first clinical trial to test this hypothesis.  The results of this study suggest that routine antibiotics along with standard RUTF and counseling do in fact improve nutritional and mortality outcomes in children with severe acute malnutrition.

While baseline characteristics of all groups were similar, only about 30% of enrollees were tested for HIV (a prevalent infection in Malawi).  20% tested HIV positive and of these, only about 30% were receiving anti-retroviral therapy.  This statistic suggests a high prevalence of untreated HIV infection. As patients with untreated HIV are very likely to have other infections responsive to antibiotics, this is a possible explanation for the results. Given the high prevalence of HIV infection in this study population, these results may not apply to regions at lower risk for HIV.  Further studies examining the long-term outcomes of routine antibiotic use are likely to be the next step in implementing this therapy.

Click to read the study in NEJM

By Akira Shishido and Mitalee Patil

More from this author: Pneumocystis linked to sudden infant deathsContinuous infusion of beta-lactams may be superior to bolus therapyNovel antiviral drug reduces influenza viral loadThree months of antibiotics appear to effectively treat early-onset spinal implant infections[Physician Comment] Recurrent early Lyme disease is caused by reinfection, not relapseHospital Acquired MRSA pays no attention to vancomycin effectivenessOseltamivir treats avian flu earlyLinezolid treats Chronic Extensively Drug-Resistant TB but has a high incidence of adverse effectsIntermittent and continuous antiretroviral therapies are equivalent in the treatment of acute HIV-1 infection, Peginesatide is noninferior to epoetin for anemia in hemodialysis patients [EMERALD Trials]

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