RESUMEN
Raltegravir as initial HIV therapy was examined in a double-blind study; 160 patients were randomized to raltegravir (400 mg bid after dose-ranging), 38 to efavirenz, both with tenofovir/lamivudine. At week 240, HIV-RNA remained <50 copies per milliliter in 68.8% (raltegravir) versus 63.2% (efavirenz), and CD4 increases were 302 versus 276 cells per microliter, respectively. Early HIV-RNA decline predicted later CD4 increases in both groups. Raltegravir resistance was observed in 3 of 10 raltegravir recipients with virologic failure. Few drug-related adverse events were reported after week 48. Raltegravir had minimal effect on laboratory values, including lipids. Raltegravir with tenofovir/lamivudine showed durable efficacy and good tolerability over 5 years.
Asunto(s)
Antirretrovirales/administración & dosificación , Antirretrovirales/efectos adversos , Infecciones por VIH/tratamiento farmacológico , VIH-1/aislamiento & purificación , Pirrolidinonas/administración & dosificación , Pirrolidinonas/efectos adversos , Adulto , Anciano , Terapia Antirretroviral Altamente Activa/efectos adversos , Terapia Antirretroviral Altamente Activa/métodos , Recuento de Linfocito CD4 , Método Doble Ciego , Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos/epidemiología , Femenino , Infecciones por VIH/virología , Humanos , Masculino , Persona de Mediana Edad , ARN Viral/sangre , Raltegravir Potásico , Resultado del Tratamiento , Carga ViralRESUMEN
Increasing rates of invasive candidiasis caused by non-albicans Candida species have been reported worldwide. Particular concerns have been raised for C. parapsilosis because of reduced in vitro susceptibility to echinocandins. We identified 212 patients with invasive candidiasis due to non-albicans Candida species (>or=5 cases per species) in 5 clinical trials of caspofungin monotherapy from the pharmaceutical sponsor's (Merck and Co., Inc.) database: 71 cases were caused by C. parapsilosis, 65 by C. tropicalis, 54 by C. glabrata, 10 by C. krusei, 9 by C. guilliermondii, and 5 by C. lusitaniae. One hundred sixty-seven cases caused by C. albicans were also identified. Efficacy was assessed at the end of caspofungin therapy. Success (favorable overall response) required favorable clinical and microbiological responses. The mean APACHE II scores were 16.5 in the non-albicans group and 15.7 in the C. albicans group. Neutropenia at study entry was more common in the non-albicans group (12%) than in the C. albicans group (5%). The median duration of caspofungin therapy was 14 days in both groups. The success rates were 77% in both groups and at least 70% for each non-albicans species: 74% for C. parapsilosis, 71% for C. tropicalis, 85% for C. glabrata, 70% for C. krusei, 89% for C. guilliermondii, and 100% for C. lusitaniae. The times to negative blood culture were similar for the various species. The overall mortality rates were 26% in the non-albicans group and 29% in the C. albicans group. Drug-related serious adverse events and discontinuations due to caspofungin toxicity were uncommon. Although the sample sizes were limited, caspofungin demonstrated favorable efficacy and safety profiles in the treatment of invasive candidiasis caused by the following non-albicans Candida species: C. parapsilosis, C. tropicalis, C. glabrata, C. krusei, C. guilliermondii, and C. lusitaniae.
Asunto(s)
Antifúngicos/uso terapéutico , Candida glabrata , Candida tropicalis , Candidiasis , Bases de Datos Factuales/estadística & datos numéricos , Equinocandinas/uso terapéutico , APACHE , Adulto , Candidiasis/tratamiento farmacológico , Candidiasis/microbiología , Candidiasis/mortalidad , Caspofungina , Ensayos Clínicos Fase II como Asunto/estadística & datos numéricos , Ensayos Clínicos Fase III como Asunto/estadística & datos numéricos , Femenino , Humanos , Estimación de Kaplan-Meier , Lipopéptidos , Masculino , Persona de Mediana EdadRESUMEN
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.