RESUMEN
Infants and young children with severe acute malnutrition (SAM) are treated with empiric broad-spectrum antimicrobials. Parenteral ceftriaxone is currently a second-line agent for invasive infection. Oral metronidazole principally targets small intestinal bacterial overgrowth. Children with SAM may have altered drug absorption, distribution, metabolism, and elimination. Population pharmacokinetics of ceftriaxone and metronidazole were studied, with the aim of recommending optimal dosing. Eighty-one patients with SAM (aged 2-45 months) provided 234 postdose pharmacokinetic samples for total ceftriaxone, metronidazole, and hydroxymetronidazole. Ceftriaxone protein binding was also measured in 190 of these samples. A three-compartment model adequately described free ceftriaxone, with a Michaelis-Menten model for concentration and albumin-dependent protein binding. A one-compartment model was used for both metronidazole and hydroxymetronidazole, with only 1% of hydroxymetronidazole predicted to be formed during first-pass. Simulations showed 80 mg/kg once daily of ceftriaxone and 12.5 mg/kg twice daily of metronidazole were sufficient to reach therapeutic targets.
Asunto(s)
Antiinfecciosos/administración & dosificación , Ceftriaxona/administración & dosificación , Trastornos de la Nutrición del Niño/fisiopatología , Fenómenos Fisiológicos Nutricionales Infantiles , Desnutrición/fisiopatología , Metronidazol/administración & dosificación , Estado Nutricional , Enfermedad Aguda , Factores de Edad , Antiinfecciosos/efectos adversos , Antiinfecciosos/farmacocinética , Ceftriaxona/efectos adversos , Ceftriaxona/farmacocinética , Trastornos de la Nutrición del Niño/diagnóstico , Preescolar , Simulación por Computador , Cálculo de Dosificación de Drogas , Femenino , Humanos , Lactante , Fenómenos Fisiológicos Nutricionales del Lactante , Kenia , Masculino , Desnutrición/diagnóstico , Metronidazol/efectos adversos , Metronidazol/farmacocinética , Modelos Biológicos , Índice de Severidad de la EnfermedadRESUMEN
BACKGROUND: Large for gestational age (LGA) accounts for about 6.3% of admissions in kenyatta national hospital, newborn unit. As a policy all IGA's, defined by birth weight of 4000 g and above are admitted for 24 hours to monitor blood glucose levels. The rational for this policy is questionable and contributes to unnecessary burden on resources needed for new born care. OBJECTIVE: To study birth weight related incidence of hypoglycemia and hypocalcaemia in stable low risk lgas in knh and use it to establish a new admission weight based criteria. PATIENTS AND METHODS: prospective cohort study done in new born-unit, post natal and labour wards of knh. Term lga neonates (birth weight = 4000 g) were recruited as subjects and controlled against term appropriate weight (aga) neonates. RESULTS: the incidence of hypoglycemia and hypocalcaemia in lgas was 21% and 9% respectively. Hypoglycemia was rarely encountered after 12 hours of life in lgas. Hypoglycemia and hypocalcaemia showed a direct upward relationship with weight beyond 4250 g. No significant difference in incidence of hypoglycemia and hypocalcaemia between controls and 4000-4249 g category to justify their routine admission to newborn unit. CONCLUSION: the study identified 4275 g as new admission birth weight criteria for stable term low risk IGA's admission.
