RESUMEN
PURPOSE: Vancomycin treats methicillin-resistant Staphylococcus aureus infections in hospitalized patients, yet nephrotoxicity is a major risk. Dosing based on the ratio of vancomycin 24-hour area under the curve to minimum inhibitory concentration (AUC/MIC) is preferred over a trough-only vancomycin dosing approach to minimize the risk of acute kidney injury (AKI). This study compares the safety of AUC/MIC-guided and trough-only vancomycin dosing at a 255-bed hospital. METHODS: A retrospective cohort study of adult patients with stable renal function who received at least 3 days of intravenous vancomycin via either AUC/MIC or trough-only dosing was conducted. The primary outcome was AKI occurrence during treatment. Secondary outcomes included the frequencies of therapeutic, subtherapeutic, and supratherapeutic vancomycin troughs. Relative risk calculations were performed for all outcomes. RESULTS: 600 patients from the trough-only group and 561 patients from the AUC/MIC group were included. 121 patients from the trough-only group and 87 patients from the AUC/MIC group experienced AKI during treatment (relative risk [RR], 0.769; 95% CI, 0.599-0.988; P = 0.0397). Compared with the trough-only group, the AUC/MIC group was significantly less likely to have supratherapeutic troughs (RR, 0.703; 95% CI, 0.611-0.809; P < 0.0001) and significantly more likely to have therapeutic troughs (RR, 1.14; 95% CI, 1.069-1.211; P < 0.0001), with no significant between-group difference in subtherapeutic troughs (RR, 1.03; 95% CI, 0.854-1.25; P = 0.74). CONCLUSION: AUC/MIC dosing was associated with significantly lower risk of AKI, a lower risk of supratherapeutic trough levels, and a higher risk of therapeutic trough levels, with no significant difference in subtherapeutic troughs when compared to trough-only dosing. Limitations of this study included its retrospective nature and reliance on manual chart review.
Asunto(s)
Lesión Renal Aguda , Antibacterianos , Área Bajo la Curva , Staphylococcus aureus Resistente a Meticilina , Vancomicina , Humanos , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/prevención & control , Vancomicina/administración & dosificación , Vancomicina/efectos adversos , Vancomicina/farmacocinética , Estudios Retrospectivos , Masculino , Femenino , Persona de Mediana Edad , Antibacterianos/administración & dosificación , Antibacterianos/efectos adversos , Anciano , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Incidencia , Hospitales Comunitarios , Hospitales Rurales , Infecciones Estafilocócicas/tratamiento farmacológico , Estudios de Cohortes , Pruebas de Sensibilidad Microbiana , AdultoRESUMEN
We monitored the unfolding of human serum albumin (HSA) and glycated human serum albumin (gHSA) subjected to guanidine hydrochloride (GndHCl) by using fluorescence and circular dichroism (CD) spectroscopy. A two-state model with sloping baselines best described the Trp-214 fluorescence unfolding measurements, while a three-state model best described the far-UV CD unfolding data. Glycation of HSA increased the [D](50%) point by approximately 0.20M. This corresponded to an increase in the free energy of unfolding of gHSA relative to HSA of 2.6kJ/mol. The intrinsic fluorescence of Trp-214 in gHSA is 0.72 of that of HSA and the far-UV CD spectrum of gHSA is nearly identical to that of HSA. These results showed that glycation altered the local structure around Trp-214 while not significantly impacting the secondary structure, and this alteration translated into an overall change in the stability of gHSA compared to HSA.