RESUMEN
Candida infections represent a major threat in neonatal intensive care units. This is the first prospective study to obtain caspofungin plasma levels and safety data for neonates and very young infants. Patients of <3 months of age receiving intravenous amphotericin B for documented or highly suspected candidiasis were enrolled in a single-dose (n = 6) or subsequent multiple-dose (n = 12) panel; all received caspofungin at 25 mg/m(2) once daily as a 1-hour infusion. Caspofungin plasma levels were measured by high-performance liquid chromatography and compared to historical data from adults. Patient chronological ages ranged from 1 to 11 weeks, and weights ranged from 0.68 to 3.8 kg. Gestational ages ranged from 24 to 41 weeks. Geometric mean (GM) peak (C(1 h)) and trough (C(24 h)) caspofungin levels were 8.2 and 1.8 microg/ml, respectively, on day 1, and 11.1 and 2.4 microg/ml, respectively, on day 4. GM ratios for C(1 h) and C(24 h) for neonates/infants relative to adults receiving caspofungin at 50 mg/day were 1.07 and 1.36, respectively, on day 1, and 1.18 and 1.21, respectively, on day 4. Clinical and laboratory adverse events occurred in 17 (94%) and 8 (44%) patients, respectively. Five patients (28%) had serious adverse events, none of which were considered drug related. Caspofungin at 25 mg/m(2) once daily was well tolerated in this group of neonates/infants of <3 months of age and appears to provide relatively similar plasma exposure to that obtained in adults receiving 50 mg/day. However, the small number of patients studied precludes any definitive recommendations about caspofungin dosing for this group comprising a broad range of ages and weights.
Asunto(s)
Antifúngicos/farmacocinética , Equinocandinas/farmacocinética , Antifúngicos/administración & dosificación , Antifúngicos/efectos adversos , Antifúngicos/sangre , Superficie Corporal , Candidiasis/tratamiento farmacológico , Caspofungina , Ensayos Clínicos como Asunto , Esquema de Medicación , Equinocandinas/administración & dosificación , Equinocandinas/efectos adversos , Equinocandinas/sangre , Femenino , Fiebre/inducido químicamente , Humanos , Hipertensión/inducido químicamente , Hiperventilación/inducido químicamente , Lactante , Recién Nacido , Infusiones Intravenosas , Lipopéptidos , Masculino , Estudios Multicéntricos como Asunto , Estudios ProspectivosRESUMEN
BACKGROUND: This prospective, multicenter study examined the importance of hepatitis viruses as etiological agents of acute liver failure (ALF) and the outcome of ALF cases in Latin American children and adolescents. METHODS: The study was conducted for minimum 12 months in 9 centers in Argentina, Brazil, Chile, Colombia, Costa Rica, and Mexico during 2001-2002. Hospitalized patients aged 1-20 years with a suspected diagnosis of ALF were included in the study and tested for serologic markers for hepatitis A, B, and C viruses. RESULTS: Of the 106 patients enrolled, 88 were included in the analysis. Median age was 5 years, and 55% with ALF were aged 1-5 years. A total of 37 individuals (43%) tested positive for anti-hepatitis A virus (HAV) immunoglobulin M (IgM) as marker of acute HAV infection; one was positive for anti-hepatitis B core antigen IgM and negative for hepatitis B surface antigen. None had markers of hepatitis C virus infection. Mortality rates in the overall study cohort (45%) and for those who tested anti-HAV IgM positive (41%) were similar. Forty-one percent of all patients and 46% of those positive for anti-HAV IgM underwent transplantation. The mortality rate in those with liver transplantation was half of that in patients who were not transplanted (28% versus 57%). CONCLUSIONS: HAV was the main etiologic agent of ALF in the population studied.
Asunto(s)
Hepatitis A/complicaciones , Fallo Hepático Agudo/epidemiología , Adolescente , Adulto , Niño , Preescolar , Femenino , Hepatitis A/mortalidad , Anticuerpos de Hepatitis A/sangre , Anticuerpos contra la Hepatitis B/sangre , Anticuerpos contra la Hepatitis C/sangre , Humanos , Inmunoglobulina M/sangre , Lactante , América Latina , Fallo Hepático Agudo/mortalidad , Fallo Hepático Agudo/terapia , Trasplante de Hígado , Masculino , Prevalencia , Estudios ProspectivosAsunto(s)
Antiparkinsonianos/administración & dosificación , Ácido Fólico/sangre , Levodopa/administración & dosificación , Enfermedad de Parkinson/sangre , Enfermedad de Parkinson/tratamiento farmacológico , Tiamina/sangre , Anciano , Femenino , Humanos , Infusiones Parenterales/métodos , Masculino , Persona de Mediana EdadAsunto(s)
Antiparkinsonianos/efectos adversos , Antiparkinsonianos/farmacología , Duodeno/efectos de los fármacos , Levodopa/efectos adversos , Levodopa/farmacología , Enfermedad de Parkinson/psicología , Suicidio , Adulto , Antiparkinsonianos/uso terapéutico , Duodeno/fisiología , Humanos , Levodopa/uso terapéutico , Masculino , Enfermedad de Parkinson/tratamiento farmacológico , Suicidio/psicologíaRESUMEN
OBJECTIVE: This trial assessed the safety of a fully liquid investigational hexavalent DTaP-IPV-Hep B-PRP-T vaccine containing 10 µg Hansenula polymorpha-derived recombinant hepatitis B (hep B) antigen for primary vaccination of infants at 2, 4 and 6 months of age compared with licensed comparators. METHODS: Participants received the DTaP-IPV-Hep B-PRP-T vaccine (group 1, N = 1422) or licensed DTwP-Hep B//Hib (Tritanrix-Hep B/Hib) and oral poliovirus vaccines (group 2, N = 711). The incidence of severe fever (≥ 39.6°C rectal equivalent) in the 2 groups was compared statistically; reactogenicity was evaluated from parental reports. Anti-Hep B antibody titers were measured in a subset of participants (no hepatitis B vaccination at birth) 1 month after dose 3. RESULTS: The investigational vaccine was well tolerated. After any dose, fever (rectal equivalent temperature ≥ 38°C) was observed in 74.8% and 92.7% of participants in groups 1 and 2; severe fever was observed in 4.0% and 5.5% of participants. Solicited injection site and systemic reactions were numerically less frequent in group 1 than group 2, although this difference was not assessed statistically. In both groups, all participants included in the immunogenicity analysis achieved anti-Hep B ≥ 10 mIU/mL and ≥ 96.2% of participants achieved anti-Hep B ≥ 100 mIU/mL, although geometric mean titer was approximately 3-fold lower for the investigational vaccine. CONCLUSION: This new, fully liquid acellular pertussis hexavalent vaccine demonstrated less reactogenicity than the licensed comparator whole cell pertussis vaccine and was highly immunogenic for the new Hep B valence.
Asunto(s)
Vacuna contra Difteria, Tétanos y Tos Ferina/administración & dosificación , Vacunas contra Haemophilus/administración & dosificación , Vacunas contra Hepatitis B/administración & dosificación , Vacuna Antipolio de Virus Inactivados/administración & dosificación , Toxoide Tetánico/administración & dosificación , Vacuna contra Difteria, Tétanos y Tos Ferina/efectos adversos , Vacuna contra Difteria, Tétanos y Tos Ferina/inmunología , Femenino , Vacunas contra Haemophilus/efectos adversos , Vacunas contra Haemophilus/inmunología , Vacunas contra Hepatitis B/efectos adversos , Vacunas contra Hepatitis B/inmunología , Humanos , Esquemas de Inmunización , Inmunización Secundaria , Lactante , Masculino , México , Perú , Vacuna Antipolio de Virus Inactivados/efectos adversos , Vacuna Antipolio de Virus Inactivados/inmunología , Toxoide Tetánico/efectos adversos , Toxoide Tetánico/inmunología , Vacunas Combinadas/administración & dosificación , Vacunas Combinadas/efectos adversos , Vacunas Combinadas/inmunologíaRESUMEN
OBJECTIVES: To evaluate an investigational, fully liquid hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus-hepatitis B-Haemophilus influenzae type b (DTaP-IPV-Hep B-PRP-T: Hexaxim™) vaccine for primary and booster vaccination of healthy children in Mexico. METHODS: Infants (N=1189) were randomized to receive one of three lots of the DTaP-IPV-Hep B-PRP-T vaccine or a licensed hexavalent control vaccine (Infanrix™ hexa) for primary vaccination at 2, 4 and 6 months. All participants who completed the primary series and agreed to participate in the booster part of the study received a dose of the investigational vaccine at 15-18 months of age. Validated serological assays and parental reports were used to assess immunogenicity and safety, respectively. RESULTS: Post-primary vaccination, ≥95.8% of participants in both the DTaP-IPV-Hep B-PRP-T and control groups were seroprotected (SP) against diphtheria, tetanus, poliovirus, hepatitis B and PRP, or had seroconverted (SC) to the pertussis toxin (PT) and filamentous hemagglutinin (FHA) pertussis antigens. The SP/SC rates induced by the three DTaP-IPV-Hep B-PRP-T lots were equivalent. No differences in SP/SC rates were observed between the pooled lots of investigational vaccine and the control vaccine. Antibody persistence at 15-18 months was comparable between groups, with strong increases in all antibody concentrations post-DTaP-IPV-Hep B-PRP-T booster. Both vaccines were well tolerated for primary vaccination, as was the booster dose of DTaP-IPV-Hep B-PRP-T. CONCLUSION: These study findings confirm the suitability of the combined, fully liquid DTaP-IPV-Hep B-PRP-T vaccine for inclusion in routine childhood vaccination schedules.
Asunto(s)
Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/administración & dosificación , Vacunas contra Haemophilus/administración & dosificación , Vacunas contra Hepatitis B/administración & dosificación , Inmunización Secundaria , Vacuna Antipolio de Virus Inactivados/administración & dosificación , Anticuerpos Antibacterianos/sangre , Anticuerpos Antivirales/sangre , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/efectos adversos , Vacunas contra Difteria, Tétanos y Tos Ferina Acelular/inmunología , Vacunas contra Haemophilus/efectos adversos , Vacunas contra Haemophilus/inmunología , Vacunas contra Hepatitis B/efectos adversos , Vacunas contra Hepatitis B/inmunología , Humanos , Lactante , México , Vacuna Antipolio de Virus Inactivados/efectos adversos , Vacuna Antipolio de Virus Inactivados/inmunología , Vacunas Combinadas/administración & dosificación , Vacunas Combinadas/efectos adversos , Vacunas Combinadas/inmunologíaRESUMEN
La resistencia de M. tuberculosis a los fármacos es un problema de salud a nivel mundial. Se han implementado programas de control cuyos objetivo incluyen la detección de casos y un tratamiento acortado y estandarizado. Se revisan los factores de riesgo de presentar fármaco-resistencia al tratamiento contra la tuberculosis y los mecanismos de resistencia, así como la vigilancia epidemiológica, que junto con recomendaciones específicas es fundamental para el éxito de los programas