OBJECTIVE: To systemically review the evidence in support of World Health Organization guidelines recommending broad-spectrum antibiotics for children with severe acute malnutrition (SAM). METHODS: CENTRAL, MEDLINE, EMBASE, LILACS, POPLINE, CAB Abstracts and ongoing trials registers were searched. Experts were contacted. Conference proceedings and reference lists were manually searched. All study types, except single case reports, were included. FINDINGS: Two randomized controlled trials (RCTs), one before-and-after study and two retrospective reports on clinical efficacy and safety were retrieved, together with 18 pharmacokinetic studies. Trial quality was generally poor and results could not be pooled due to heterogeneity. Oral amoxicillin for 5 days was as effective as intramuscular ceftriaxone for 2 days (1 RCT). For uncomplicated SAM, amoxicillin showed no benefit over placebo (1 retrospective study). The introduction of a standardized regimen using ampicillin and gentamicin significantly reduced mortality in hospitalized children (odds ratio, OR: 4.0; 95% confidence interval, CI: 1.7-9.8; 1 before-and-after study). Oral chloramphenicol was as effective as trimethoprim-sulfamethoxazole in children with pneumonia (1 RCT). Pharmacokinetic data suggest that normal doses of penicillins, cotrimoxazole and gentamicin are safe in malnourished children, while the dose or frequency of chloramphenicol requires adjustment. Existing evidence is not strong enough to further clarify recommendations for antibiotic treatment in children with SAM. CONCLUSION: Large RCTs are needed to define optimal antibiotic treatment in children with SAM with and without complications. Further research into gentamicin and chloramphenicol toxicity and into the pharmacokinetics of ceftriaxone and ciprofloxacin is also required.

OBJETIVO: Revisar sistemáticamente los datos que apoyan las directrices de la Organización Mundial de la Salud que recomiendan la administración de antibióticos de amplio espectro en niños con desnutrición grave (NDG). MÉTODOS: Se realizó una búsqueda en los resúmenes CENTRAL, MEDLINE, EMBASE, LILACS, POPLINE, CAB y en los registros de ensayos en marcha. Nos pusimos en contacto con expertos en la materia. Se realizaron búsquedas manuales en listas de referencia y en actas de congresos. Se incluyeron todo tipo de estudios, excepto los informes de casos clínicos individuales. RESULTADOS: Se recuperaron dos ensayos controlados aleatorizados (ECA), un estudio comparativo del antes y el después y dos informes retrospectivos sobre eficacia clínica y seguridad, junto con 18 estudios de farmacocinética. La calidad del ensayo fue generalmente baja y los resultados no se pudieron agrupar debido a su heterogeneidad. El tratamiento con amoxicilina por vía oral durante 5 días resultó ser tan efectivo como la ceftriaxona intramuscular durante 2 días (1 ECA). La amoxicilina no superó los beneficios de un placebo para el tratamiento de niños con desnutrición grave que no presentaban otras complicaciones (1 estudio retrospectivo). La introducción de un tratamiento estandarizado con ampicilina y gentamicina redujo de manera significativa la mortalidad entre los niños hospitalizados (oportunidad relativa, OR: 4,0; intervalo de confianza del 95%, IC: 1,7-9,8; 1 estudio comparativo del antes y el después). El tratamiento con cloranfenicol por vía oral resultó ser tan efectivo como la combinación de trimetoprima y sulfametoxazol en el tratamiento de niños con neumonía (1 ECA). Los datos de farmacocinética sugieren que las dosis normales de penicilinas, asociación de trimetroprim y sulfametoxazol y gentamicina resultan seguras en niños malnutridos, mientras que, en el caso del cloranfenicol, deberían ajustarse las dosis o la frecuencia de administración. Las evidencias existentes no son lo suficientemente sólidas para aclarar más las recomendaciones sobre tratamientos de antibióticos en niños con desnutrición grave. CONCLUSIÓN: Es necesario realizar amplios ECA para definir el tratamiento óptimo con antibióticos de los niños con desnutrición grave con y sin complicaciones. También es necesario investigar mejor la toxicidad de la gentamicina y el cloranfenicol y la farmacocinética de la deftriaxona y de la ciprofloxacina.

OBJECTIF: Évaluer de façon systématique la preuve de l'application des directives de l'Organisation mondiale de la Santé recommandant les antibiotiques à large spectre chez les enfants présentant une malnutrition aiguë sévère (MAS). MÉTHODES: Les recherches ont été réalisées dans les registres des essais CENTRAL, MEDLINE, EMBASE, LILACS, POPLINE, CAB Abstracts, ainsi que dans d'autres registres d'essais en cours. Des experts ont été contactés. Des recherches ont également été effectuées manuellement sur des listes de référence et des comptes rendus de conférence. Tous les types d'étude, à l'exception des rapports de cas uniques, ont été inclus. RÉSULTATS: Deux essais contrôlés randomisés (ECR), une étude avant/après et deux rapports rétrospectifs sur l'efficacité et la sécurité cliniques ont été récupérés, avec 18 études pharmacocinétiques. La qualité des essais était généralement médiocre et les résultats n'ont pas pu être mis en commun à cause de leur hétérogénéité. L'amoxicilline orale pendant 5 jours était aussi efficace que la ceftriaxone intramusculaire pendant 2 jours (1 ECR). Pour la MAS sans complication, l'amoxicilline n'a montré aucun avantage par rapport à un placebo (1 étude rétrospective). L'introduction d'un régime normalisé utilisant l'ampicilline et la gentamicine a considérablement réduit la mortalité chez les enfants hospitalisés (rapport des cotes, RC: 4.0; intervalle de confiance de 95%, IC: 1,7-9,8; 1 étude avant/après). Le chloramphénicol oral était aussi efficace que le triméthoprime-sulfaméthoxazole chez les enfants souffrant de pneumonie (1 ECR). Les données pharmacocinétiques suggèrent que des doses normales de pénicilline, de cotrimoxazole et de gentamicine sont sans danger chez les enfants souffrant de malnutrition, alors que la dose ou la fréquence du chloramphénicol nécessite un ajustement. Les preuves existantes ne sont pas assez solides pour clarifier davantage les recommandations en matière de traitement antibiotique chez les enfants souffrant de MAS. CONCLUSION: De grands ECR sont nécessaires afin de définir le traitement antibiotique optimal chez les enfants souffrant de MAS avec ou sans complications. Des recherches supplémentaires dans la toxicité de la gentamicine et du chloramphénicol et dans la pharmacocinétique de la ceftriaxone et de la ciprofloxacine sont également requises.

BACKGROUND: Diarrhoea causes around two million child deaths annually. Zinc supplementation could help reduce the duration and severity of diarrhoea, and is recommended by the World Health Organization and UNICEF. OBJECTIVE: To evaluate oral zinc supplementation for treating children with acute or persistent diarrhoea. CRITERIA FOR CONSIDERING STUDIES FOR THIS REVIEW: In November 2007, we searched the Cochrane Infectious Diseases Group Specialized Register, CENTRAL (The Cochrane Library 2007, Issue 4), MEDLINE, EMBASE, LILACS, CINAHL, mRCT, and reference lists. We also contacted researchers. SELECTION CRITERIA: Randomized controlled trials comparing oral zinc supplementation (≥ 5 mg/day for any duration) with placebo in children aged one month to five years with acute or persistent diarrhoea, including dysentery. DATA COLLECTION AND ANALYSIS: Both authors assessed trial eligibility and methodological quality, extracted and analysed data, and drafted the review. Diarrhoea duration and severity were the primary outcomes. We summarized dichotomous outcomes using risk ratios (RR) and continuous outcomes using mean differences (MD) with 95% confidence intervals (CI). Where appropriate, we combined data in meta-analyses (using the fixed- or random-effects model) and assessed heterogeneity. MAIN RESULTS: Eighteen trials enrolling 6165 participants met our inclusion criteria. In acute diarrhoea, zinc resulted in a shorter diarrhoea duration (MD -12.27 h, 95% CI -23.02 to -1.52 h; 2741 children, 9 trials), and less diarrhoea at day three (RR 0.69, 95% CI 0.59 to 0.81; 1073 children, 2 trials), day five (RR 0.55, 95% CI 0.32 to 0.95; 346 children, 2 trials), and day seven (RR 0.71, 95% CI 0.52 to 0.98; 4087 children, 7 trials). The four trials (1458 children) that reported on diarrhoea severity used different units and time points, and the effect of zinc was less clear. Subgroup analyses by age (trials with only children aged less than six months) showed no benefit with zinc. Subgroup analyses by nutritional status, geographical region, background zinc deficiency, zinc type, and study setting did not affect the results' significance. Zinc also reduced the duration of persistent diarrhoea (MD -15.84 h, 95% CI -25.43 to -6.24 h; 529 children, 5 trials). Few trials reported on severity, and results were inconsistent. No trial reported serious adverse events, but vomiting was more common in zinc-treated children with acute diarrhoea (RR 1.71, 95% 1.27 to 2.30; 4727 children, 8 trials). AUTHORS' CONCLUSIONS: In areas where diarrhoea is an important cause of child mortality, research evidence shows zinc is clearly of benefit in children aged six months or more. PLAIN LANGUAGE SUMMARY: In developing countries, millions of children suffer from severe diarrhoea every year. This is due to infection and malnutrition, and many die from dehydration due to the diarrhoea. Giving fluids by mouth (using an oral rehydration solution) has been shown to save children's lives, but it seems to have no effect on the length of time the children suffer with diarrhoea. Children in developing countries are often zinc deficient. Zinc supplementation is a possible treatment for diarrhoea though it can have adverse effects if given in high doses. The review of trials identified 18 trials involving 6165 children of all ages. Zinc reduced the time that children over the age of six months suffered from symptoms of acute or persistent diarrhoea. However, there were insufficient data to see any impact on the number of children who died. More children vomited when given zinc, but it was considered that the benefits outweighed these adverse effects. Zinc seemed to have no impact on children aged less than six months. In areas where diarrhoea is an important cause of child mortality, research evidence shows zinc is clearly of benefit in children aged six months or more with diarrhoeal diseases.