Academic journal article Bulletin of the World Health Organization

Antibiotics in Severely Malnourished Children: Systematic Review of Efficacy, Safety and Pharmacokinetics

Academic journal article Bulletin of the World Health Organization

Antibiotics in Severely Malnourished Children: Systematic Review of Efficacy, Safety and Pharmacokinetics

Article excerpt

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 peniciliins, 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.

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Resume

Antibiotiques chez les enfants gravement denutris: evaluation systematique de l'efficacite, de la securite et de la pharmacocinetique

Objectif Evaluer de facon systematique la preuve de l'application des directives de l'Organisation mondiale de la Sante recommandant les antibiotiques a large spectre chez les enfants presentant une malnutrition aigue severe (MAS).

Methodes Les recherches ont ete realisees dans les registres des essais CENTRAL, MEDLINE, EMBASE, LILACS, POPLINE, CABAbstracts, ainsi que dans d'autres registres d'essais en cours. Des experts ont ete contactes. Des recherches ont egalement ete effectuees manuellement sur des listes de reference et des comptes rendus de conference. Tous les types d'etude, a l'exception des rapports de cas uniques, ont ete inclus.

Resultats Deux essais controles randomises (ECR), une etude avant/apres et deux rapports retrospectifs sur l'efficacite et la securite cliniques ont ete recuperes, avec 18 etudes pharmacocinetiques. La qualite des essais etait generalement mediocre et les resultats n'ont pas ou etre mis en commun a cause de leur heterogeneite. L'amoxicilline orale pendant 5 jours etait aussi efficace que la ceftriaxone intramusculaire pendant 2 jours (1 ECR). Pour la MAS sans complication, l'amoxiciiline n'a montre aucun avantage par rapport a un placebo (1 etude retrospective). L'introduction d'un regime normalise utilisant l'ampiciiline et la gentamicine a considerablement reduit la mortalite chez les enfants hospitalises (rapport des cotes, RC:4.0; intervalle de confiance de 95%, IC: 1,7-9,8; 1 etude avant/ apres). Le chloramphenicol oral etait aussi efficace que le trimethoprimesulfamethoxazole chez les enfants souffrant de pneumonie (1 ECR). Les donnees pharmacocinetiques suggerent que des doses normales de penicilline, de cotrimoxazole et de gentamicine sont sans danger chez les enfants souffrant de malnutrition, alors que la dose ou la frequence du chloramphenicol necessite un ajustement. Les preuves existantes ne sont pas assez solides pour clarifier davantage les recommandations en matiere de traitement antibiotique chez les enfants souffrant de MAS. …

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