RESUMEN
OBJECTIVES: The aim of the DiaFu study was to evaluate effectiveness and safety of negative pressure wound therapy (NPWT) in patients with diabetic foot wounds in clinical practice. DESIGN: In this controlled clinical superiority trial with blinded outcome assessment patients were randomised in a 1:1 ratio stratified by study site and ulcer severity grade using a web-based-tool. SETTING: This German national study was conducted in 40 surgical and internal medicine inpatient and outpatient facilities specialised in diabetes foot care. PARTICIPANTS: 368 patients were randomised and 345 participants were included in the modified intention-to-treat (ITT) population. Adult patients suffering from a diabetic foot ulcer at least for 4 weeks and without contraindication for NPWT were allowed to be included. INTERVENTIONS: NPWT was compared with standard moist wound care (SMWC) according to local standards and guidelines. PRIMARY AND SECONDARY OUTCOME MEASURES: Primary outcome was wound closure within 16 weeks. Secondary outcomes were wound-related and treatment-related adverse events (AEs), amputations, time until optimal wound bed preparation, wound size and wound tissue composition, pain and quality of life (QoL) within 16 weeks, and recurrences and wound closure within 6 months. RESULTS: In the ITT population, neither the wound closure rate (difference: n=4 (2.5% (95% CI-4.7% - 9.7%); p=0.53)) nor the time to wound closure (p=0.244) was significantly different between the treatment arms. 191 participants (NPWT 127; SMWC 64) had missing endpoint documentations, premature therapy ends or unauthorised treatment changes. 96 participants in the NPWT arm and 72 participants in the SMWC arm had at least one AE (p=0.007), but only 16 AEs were related to NPWT. CONCLUSIONS: NPWT was not superior to SMWC in diabetic foot wounds in German clinical practice. Overall, wound closure rate was low. Documentation deficits and deviations from treatment guidelines negatively impacted the outcome wound closure. TRIAL REGISTRATION NUMBERS: NCT01480362 and DRKS00003347.
Asunto(s)
Pie Diabético/terapia , Terapia de Presión Negativa para Heridas , Apósitos Oclusivos , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Alemania , Humanos , Análisis de Intención de Tratar , Masculino , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Método Simple Ciego , Resultado del Tratamiento , Cicatrización de HeridasRESUMEN
The objective of this study was to provide a pharmacokinetic/pharmacodynamic (PK/PD) analysis of moxifloxacin in patients with diabetic foot infections (DFI). The plasma concentration-time courses were determined in 50 DFI patients on day 1 and 3 after intravenous moxifloxacin 400 mg once-daily. A two-compartment population pharmacokinetic model was developed, identifying as covariates total body weight on central and peripheral volume of distribution (V1, V2) and ideal body weight on clearance (CL), respectively. For a 70 kg patient V1 was 68.1 L (interindividual variability, CV: 27.4%), V2 44.6 L, and CL 12.1 L/h (25.6%). Simulations were performed to calculate the probability of target attainment (PTA) for Gram-positive and Gram-negative pathogens with fAUC/MIC targets of ≥30 and ≥100, respectively. PTA was 0.68-1 for susceptible (MIC ≤0.5 mg/L according to EUCAST) Gram-positive, but <0.25 for Gram-negative pathogens with MIC ≥0.25 mg/L. With the exception of the first 24 hours of therapy, obesity affected PTA only marginally. Pharmacokinetic parameters in DFI patients were similar to those reported for healthy volunteers, indicating the appropriateness of the standard dose of moxifloxacin. Overall clinical efficacy has been shown previously, but PTA is limited in a subpopulation infected with formally susceptible Gram-negative pathogens close to the EUCAST breakpoint.
Asunto(s)
Antibacterianos/farmacocinética , Diabetes Mellitus/microbiología , Pie Diabético/tratamiento farmacológico , Pie Diabético/microbiología , Fluoroquinolonas/farmacocinética , Administración Intravenosa , Adulto , Anciano , Anciano de 80 o más Años , Antibacterianos/administración & dosificación , Antibacterianos/uso terapéutico , Área Bajo la Curva , Femenino , Fluoroquinolonas/administración & dosificación , Fluoroquinolonas/uso terapéutico , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Gramnegativas/patogenicidad , Bacterias Grampositivas/efectos de los fármacos , Bacterias Grampositivas/patogenicidad , Humanos , Masculino , Persona de Mediana Edad , Método de Montecarlo , MoxifloxacinoRESUMEN
AIMS: Charcot neuro-osteoarthropathy (CN) is a rare complication of diabetic foot syndrome associated with chronic inflammation of the foot and severe, limb-threatening musculoskeletal deformities. Aim of this study was to investigate patients with CN for comorbidities, amputations, ulcers, secondary diseases and mortality. METHODS: The study was conducted at a specialized German hospital for patients with diabetes. One-hundred and eleven patients were enrolled, and their course was followed over a period of 15 years. Association of CN with comorbidity, foot ulcers, amputations and mortality was assessed. Clinical course of patients was followed using two standardized questionnaires. RESULTS: Presence of CN was significantly associated with diabetic retinopathy (p = 0.047), plantar (p < 0.001), tarsal (p = 0.032) and middle-foot ulcers (p = 0.01). A significant correlation between the presence of CN and a history of amputations was seen (p = 0.022). Patients were at increased risk to suffer from subsequent amputations during follow-up when micro- and macrovascular comorbidities such as retinopathy (p = 0.01) and peripheral artery disease (p < 0.001) were present. Additionally, coronary artery disease (CHD) was identified as an independent predictor of mortality in the cohort of this study (OR 6.192, 95 % CI 1.155-33.208, p = 0.033). Median overall survival of patients with CN and CHD was significantly shorter than OS of patients without CHD (7.8 vs. 13.1 years, p = 0.0045, HR 2.8437, 95 % CI 0.9818-8.2364). CONCLUSIONS: In our study, CHD was the most important factor of survival in CN patients. For optimal management of CN, adequate diagnostics and treatment of CHD according to current guidelines should be considered.