Exposure-Response Relationships for Isavuconazole in Patients with Invasive Aspergillosis and Other Filamentous Fungi

Isavuconazole, the active moiety of the water-soluble prodrug isavuconazonium sulfate, is a triazole antifungal agent for the treatment of invasive fungal infections. The purpose of this analysis was to characterize the isavuconazole exposure-response relationship for measures of efficacy and safety in patients with invasive aspergillosis and infections by other filamentous fungi from the SECURE clinical trial. Two hundred thirty-one patients who received the clinical dosing regimen and had exposure parameters were included in the analysis. The primary drug exposure parameters included were predicted trough steady-state plasma concentrations, predicted trough concentrations after 7 and 14 days of drug administration, and area under the curve estimated at steady state (AUCss). The exposure parameters were analyzed against efficacy endpoints that included all-cause mortality through day 42 in the intent-to-treat (ITT) and modified ITT populations, data review committee (DRC)-adjudicated overall response at end of treatment (EOT)

Acid-base profile in patients on PD

Acid-base profile in patients on PD. Secular trends in dialysis dose in peritoneal dialysis (PD) and modes of dialysis delivery [automated PD (APD) versus continuous ambulatory PD (CAPD)] require a reexamination of acid-base status in patients treated with these renal replacement modalities. We explored steady-state acid-base profile and its determinants in 175 patients on CAPD and 77 patients on APD. The majority (62% to 70%) of patients had serum bicarbonate levels in the normal range, and a minority (17% to 27%) had values just above 28mEq/L. Only a small percentage (10% to 12%) of patients in either the CAPD or the APD groups had a serum HCO3 less than 22mEq/L, an indication of the successful correction of acidosis in most patients. The anion gap was elevated (>16mEq/L) in the majority of patients on CAPD and APD and bore an inverse relationship to serum HCO3 and a direct relationship to serum albumin and serum phosphate. In CAPD patients, but not APD patients, a significant inverse relationship was observed between the anion gap and peritoneal permeability as assessed by four-hour D/Pcreatinine. The correction of acidosis in PD appears to be predominantly achieved by the continuous supplementation of alkali via dialysis, with residual renal function not differentiating the degree of correction. Steady-state serum bicarbonate in patients on CAPD appeared to be responsive to the underlying peritoneal membrane permeability characteristics of the patient that govern alkali loss and gain, but the higher dialysate volumes in APD appear to override this effect. Higher albumin, blood urea nitrogen (BUN), and phosphate in patients with lower HCO3 suggest a discrepancy between daily acid load and dialysis dose

Predictive Value of Brain Natriuretic Peptides in Patients on Peritoneal Dialysis: Results from the ADEMEX Trial

Background and objectives: Natriuretic peptides have been suggested to be of value in risk stratification in dialysis patients. Data in patients on peritoneal dialysis remain limited