RESUMEN
BACKGROUND: The management of complex orthopedic infections usually includes a prolonged course of intravenous antibiotic agents. We investigated whether oral antibiotic therapy is noninferior to intravenous antibiotic therapy for this indication. METHODS: We enrolled adults who were being treated for bone or joint infection at 26 U.K. centers. Within 7 days after surgery (or, if the infection was being managed without surgery, within 7 days after the start of antibiotic treatment), participants were randomly assigned to receive either intravenous or oral antibiotics to complete the first 6 weeks of therapy. Follow-on oral antibiotics were permitted in both groups. The primary end point was definitive treatment failure within 1 year after randomization. In the analysis of the risk of the primary end point, the noninferiority margin was 7.5 percentage points. RESULTS: Among the 1054 participants (527 in each group), end-point data were available for 1015 (96.3%). Treatment failure occurred in 74 of 506 participants (14.6%) in the intravenous group and 67 of 509 participants (13.2%) in the oral group. Missing end-point data (39 participants, 3.7%) were imputed. The intention-to-treat analysis showed a difference in the risk of definitive treatment failure (oral group vs. intravenous group) of -1.4 percentage points (90% confidence interval [CI], -4.9 to 2.2; 95% CI, -5.6 to 2.9), indicating noninferiority. Complete-case, per-protocol, and sensitivity analyses supported this result. The between-group difference in the incidence of serious adverse events was not significant (146 of 527 participants [27.7%] in the intravenous group and 138 of 527 [26.2%] in the oral group; P=0.58). Catheter complications, analyzed as a secondary end point, were more common in the intravenous group (9.4% vs. 1.0%). CONCLUSIONS: Oral antibiotic therapy was noninferior to intravenous antibiotic therapy when used during the first 6 weeks for complex orthopedic infection, as assessed by treatment failure at 1 year. (Funded by the National Institute for Health Research; OVIVA Current Controlled Trials number, ISRCTN91566927 .).
Asunto(s)
Administración Oral , Antibacterianos/administración & dosificación , Enfermedades Óseas Infecciosas/tratamiento farmacológico , Artropatías/tratamiento farmacológico , Administración Intravenosa , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/efectos adversos , Antibacterianos/farmacocinética , Femenino , Humanos , Análisis de Intención de Tratar , Masculino , Cumplimiento de la Medicación , Persona de Mediana Edad , Resultado del Tratamiento , Adulto JovenRESUMEN
OBJECTIVE: Recently we reported that human immunodeficiency virus (HIV)-infected Caucasian men treated with highly active antiretroviral therapy (HAART) have normal weight-adjusted bone mineral density (BMD), in contrast to most other cross-sectional analyses, which have reported low BMD in HIV-infected patients. We have now addressed the question of whether there is accelerated BMD loss over time in HIV-infected men. DESIGN: A 2-year, prospective, longitudinal study. SUBJECTS: Twenty-three HAART-treated, HIV-infected men and 26 healthy controls. MEASUREMENTS: All participants had measurements of BMD and bone-related laboratory parameters at baseline, and a repeat measurement of BMD at 2 years. RESULTS: In the HIV-infected men the mean age was 47 years, the mean duration of infection was 8.2 years, and the mean duration of HAART was 54 months. Over 2 years of follow-up, BMD increased from baseline in the HIV-infected men by 2.6% at the lumbar spine (P = 0.05 vs. baseline), and remained stable at the total hip (mean change 0.1%, P > 0.99) and total body (mean change 0.6%, P = 0.39). Mean changes in BMD in the control group were 1.4% at the lumbar spine, -0.1% at the total hip, and -0.8% at the total body. The HIV-infected men lost less total body BMD than the control group (P = 0.01). In the HIV-infected men, body weight remained stable over 2 years while fat mass decreased and lean mass tended to increase, whereas in the controls, body weight and fat mass increased while lean mass remained stable. CONCLUSIONS: Accelerated bone loss does not occur in HIV-infected men treated with HAART. Monitoring of BMD in HIV-infected men may not be necessary.
Asunto(s)
Fármacos Anti-VIH/uso terapéutico , Densidad Ósea/fisiología , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/fisiopatología , VIH-1 , Adulto , Terapia Antirretroviral Altamente Activa , Composición Corporal , Estudios de Casos y Controles , Distribución de Chi-Cuadrado , Humanos , Masculino , Persona de Mediana Edad , Estudios ProspectivosRESUMEN
CONTEXT: Recent studies have reported low bone mineral density (BMD) in HIV-infected patients. Annual iv administration of 4 mg zoledronate has been shown to increase BMD and suppress bone turnover in postmenopausal women. OBJECTIVE: The objective of the study was to determine whether annual administration of 4 mg zoledronate will increase BMD in HIV-infected men receiving highly active antiretroviral therapy. DESIGN AND SETTING: A 2-yr randomized placebo-controlled trial was conducted in a clinical research center. PARTICIPANTS: A total of 43 HIV-infected men were treated with highly active antiretroviral therapy for at least 3 months, with BMD T score less than -0.5. INTERVENTION: Participants received annual iv administration of 4 mg zoledronate or placebo. All participants took 400 mg/d calcium and 1.25 mg/month vitamin D. MEASUREMENTS: BMD at the lumbar spine, total hip and total body, and bone turnover markers were measured. RESULTS: At the lumbar spine, BMD increased by 8.9% over 2 yr in the zoledronate group compared with an increase of 2.6% in the control group (P<0.001). At the total hip, BMD increased by 3.8% over 2 yr in the zoledronate group compared with a decrease of 0.8% in the control group (P<0.001). At the total body, BMD increased by 2.3% over 2 yr compared with a decrease of 0.5% in the control group (P<0.001). Urine N-telopeptide decreased by 60% at 3 months in the zoledronate group and thereafter remained stable. CONCLUSIONS: Annual administration of zoledronate is a potent and effective therapy for the prevention or treatment of bone loss in HIV-infected men. The current data provide the first trial evidence of the BMD effects of annual zoledronate beyond 1 yr in any population, as well as being the first reported trial in men.
Asunto(s)
Terapia Antirretroviral Altamente Activa , Conservadores de la Densidad Ósea/uso terapéutico , Densidad Ósea/efectos de los fármacos , Difosfonatos/uso terapéutico , Infecciones por VIH/tratamiento farmacológico , Imidazoles/uso terapéutico , Adulto , Índice de Masa Corporal , Tamaño Corporal , Conservadores de la Densidad Ósea/administración & dosificación , Difosfonatos/administración & dosificación , Esquema de Medicación , Humanos , Imidazoles/administración & dosificación , Masculino , Persona de Mediana Edad , Placebos , Ácido ZoledrónicoRESUMEN
OBJECTIVE: Recent studies have reported low bone mineral density (BMD) in patients infected with human immunodeficiency virus (HIV). Frequently these findings have been attributed to treatment with highly active antiretroviral therapy (HAART). We sought to determine whether BMD in HIV-infected men treated with HAART for at least 3 months is different from that in healthy controls, and, if so, what HIV-related factors might explain this finding. DESIGN: Cross-sectional analysis. PATIENTS: Fifty-nine HIV-infected Caucasian men treated with HAART, and 118 healthy community-dwelling controls. Each HIV-infected man was age-matched (within 5 years) to two controls. MEASUREMENTS: All participants had measurements of BMD and bone-related laboratory parameters. RESULTS: The mean duration of known HIV infection was 8.5 years, and of treatment with HAART was 52 months. There was no significant difference in mean BMD between groups at the lumbar spine (HIV group: 1.23 g/cm2, controls: 1.25 g/cm2; P = 0.53) or total body (HIV group: 1.18 g/cm2, controls: 1.20 g/cm2; P = 0.09). At the total hip the HIV-infected group had significantly lower BMD than the control group (HIV group: 1.03 g/cm2, controls: 1.09 g/cm2; P = 0.01). The HIV-infected group were, on average, 6.3 kg lighter than the controls. After adjusting for this weight difference, HIV infection was not an independent predictor of BMD at any site (lumbar spine P = 0.79; total hip P = 0.18; total body P = 0.76). CONCLUSIONS: HIV-infected men treated with HAART are lighter than healthy controls. This weight difference is responsible for a small decrement in hip BMD. Overall, BMD is not significantly reduced in HIV-infected Caucasian men treated with HAART.