Assuntos
Docentes de Medicina/estatística & dados numéricos , Liderança , Pediatria/educação , Faculdades de Medicina/tendências , Inquéritos e Questionários , Adulto , Fatores Etários , Docentes de Medicina/tendências , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pediatria/tendências , Fatores Sexuais , Estados UnidosRESUMO
BACKGROUND: Daptomycin is approved for treatment of complicated skin/skin structure infections and Staphylococcus aureus bloodstream infections (bacteremia) in adults. This study was undertaken to determine the pharmacokinetics of daptomycin in pediatric patients 3-24 months of age with proven/suspected bacterial infection. METHODS: In this phase 1, multicenter, open-label, noncomparative pharmacokinetic and safety study, patients were enrolled in 3 age groups: 3-6, 7-12 and 13-24 months. Intravenous daptomycin (single dose) was infused over 30 minutes at 6 mg/kg in subjects 13-24 months of age and at 4 mg/kg in the younger groups. Blood was collected for analysis of daptomycin concentrations. RESULTS: Twenty-four subjects received daptomycin. Daptomycin exposures (area under the curve0-∞) in children 3-6 and 7-12 months of age receiving 4 mg/kg were similar (215 and 219 µg·h/mL, respectively). Children 13-24 months of age receiving a higher dose, 6 mg/kg, had higher exposures (282 µg·h/mL). Mean maximum plasma concentrations in the age groups were 38.7, 37.1 and 67.0 µg/mL, respectively. Daptomycin exposures based on mg/kg dosing were lower than previously reported for older children and adults, likely because of increased clearance and volume of distribution and decreased apparent elimination half-life. Single-dose daptomycin 4 and 6 mg/kg was well tolerated and was not associated with clinical or laboratory adverse events. CONCLUSIONS: To match known clinically and microbiologically effective exposures in adults, infants require higher mg/kg daptomycin doses. Daptomycin safety and efficacy have not been established in pediatric patients. Pediatric clinical trials are ongoing.
Assuntos
Antibacterianos/farmacocinética , Infecções Bacterianas/sangue , Daptomicina/farmacocinética , Administração Intravenosa , Antibacterianos/sangue , Área Sob a Curva , Infecções Bacterianas/tratamento farmacológico , Pré-Escolar , Daptomicina/sangue , Feminino , Meia-Vida , Humanos , Lactente , Masculino , Fatores de TempoRESUMO
OBJECTIVES: To describe the clinical characteristics and course of children with laboratory-diagnosed Rocky Mountain spotted fever (RMSF) and to identify clinical findings independently associated with adverse outcomes of death or discharge with neurologic deficits. STUDY DESIGN: Retrospective chart review of 92 patients at six institutions in the southeastern and southcentral United States from 1990 to 2002. Statistical analyses used descriptive statistics and multiple logistic regression. RESULTS: Children with RMSF presented to study institutions after a median of 6 days of symptoms, which most commonly included fever (98%), rash (97%), nausea and/or vomiting (73%), and headache (61%); no other symptom or sign was present in >50% of children. Only 49% reported antecedent tick bites. Platelet counts were <150,000/mm3 in 59% of children, and serum sodium concentrations were <135 mEq/dL in 52%. Although 86% sought medical care before admission, only 4 patients received anti-rickettsial therapy during this time. Three patients died, and 13 survivors had neurologic deficits at discharge. Coma and need for inotropic support and intravenous fluid boluses were independently associated with adverse outcomes. CONCLUSIONS: Children with RMSF generally present with fever and rash. Delays in diagnosis and initiation of appropriate therapy are unacceptably common. Prognosis is guarded in those with hemodynamic instability or neurologic compromise at initiation of therapy.
Assuntos
Rickettsia rickettsii/isolamento & purificação , Febre Maculosa das Montanhas Rochosas/diagnóstico , Febre Maculosa das Montanhas Rochosas/epidemiologia , Distribuição por Idade , Análise Química do Sangue , Criança , Pré-Escolar , Intervalos de Confiança , Feminino , Seguimentos , Hospitalização/estatística & dados numéricos , Humanos , Incidência , Masculino , Razão de Chances , Medição de Risco , Febre Maculosa das Montanhas Rochosas/fisiopatologia , Índice de Gravidade de Doença , Distribuição por Sexo , Taxa de Sobrevida , Estados Unidos/epidemiologiaRESUMO
OBJECTIVE: To evaluate the efficacy and safety of ganciclovir therapy in neonates with congenital cytomegalovirus (CMV) disease. STUDY DESIGN: Neonates with symptomatic CMV disease involving the central nervous system were randomly assigned to receive 6 weeks of intravenous ganciclovir versus no treatment. The primary end point was improved brainstem-evoked response (BSER) between baseline and 6-month follow-up (or, for patients with normal baseline hearing, normal BSER at both time points). RESULTS: From 1991 to 1999, 100 patients were enrolled. Of these, 42 patients had both a baseline and 6-month follow-up BSER audiometric examination and thus were evaluable for the primary end point. Twenty-one (84%) of 25 ganciclovir recipients had improved hearing or maintained normal hearing between baseline and 6 months versus 10 (59%) of 17 control patients (P=.06). None (0%) of 25 ganciclovir recipients had worsening in hearing between baseline and 6 months versus 7 (41%) of 17 control patients (P<.01). A total of 43 patients had a BSER at both baseline and at 1 year or beyond. Five (21%) of 24 ganciclovir recipients had worsening of hearing between baseline and > or =1 year versus 13 (68%) of 19 control patients (P<.01). A total of 89 patients had absolute neutrophil counts determined during the course of the study; 29 (63%) of 46 ganciclovir-treated patients had grade 3 or 4 neutropenia during treatment versus 9 (21%) of 43 control patients (P<.01). CONCLUSIONS: Ganciclovir therapy begun in the neonatal period in symptomatically infected infants with CMV infection involving the central nervous system prevents hearing deterioration at 6 months and may prevent hearing deterioration at > or =1 year. Almost two thirds of treated infants have significant neutropenia during therapy.