Liver transplantation using sirolimus and minimal corticosteroids (3-day taper).

At our center, we have performed liver transplantation since 1995 with a rapid-taper steroid protocol (weaning steroids by day 14 posttransplantation). Beginning in 2000, we further reduced the use of corticosteroids to 3 days and added sirolimus to our immunosuppressive regimen. We report our experience with 39 patients who underwent liver transplantation with either tacrolimus or cyclosporin A (Neoral; Novartis Pharmaceuticals Corp., Summit, NJ) and sirolimus, with a 3-day tapered dose of corticosteroids. Thirty-two patients received a cadaveric graft and 7 patients received a right hepatic lobe from a living donor. All patients initially were administered either tacrolimus (0.1 mg/kg/d) or cyclosporin A (10 mg/kg/d) and sirolimus (6 mg/d for 1 day, followed by 2 mg/d), in addition to methylprednisolone on the first 3 days (1, 0.5, and 0.5 g/d) after transplantation. Patients were administered corticosteroids for presumptive or biopsy-proven evidence of acute cellular rejection (methylprednisolone, 1, 0.5, and 0.5 g on 3 successive days). Seventeen patients were administered tacrolimus and 22 patients were administered cyclosporin A. Six patients were excluded from analysis because they were administered sirolimus for less than 2 weeks. Mean duration of follow-up was 124 days. Patient survival was 36 of 39 patients (92%), and graft survival was 35 of 39 grafts (89%). Ten of 33 patients (30%) experienced 12 episodes of rejection (7 biopsy proven, 5 presumptive) compared with 70% in historical controls (P <.01). OKT3 was required in 1 of 33 patients (3%) compared with 37% in controls (P <.01). Twenty-six of 33 patients (79%) were not administered prednisone, and 7 of 33 patients (21%) were administered prednisone for reasons other than rejection. Posttransplantation, there was no significant change in values for creatinine, glucose, aspartate aminotransferase, bilirubin, cholesterol, and white blood cell counts. Platelet counts were significantly reduced, and hematocrits were significantly elevated (P <.05). Liver transplantation may be successfully performed with minimal use of corticosteroids by using sirolimus and either tacrolimus or cyclosporin A. Despite the absence of prednisone from our immunosuppressive protocol, the incidence of rejection and OKT3 use was lower than in historical controls. Patient and graft survival rates were identical to those of historical controls. The findings in this report will serve as the basis for a formal trial evaluating the efficacy of sirolimus in liver transplantation.

Outcomes from use of an evidence-based practice guideline.

The aim of evidence-based guidelines is primarily to improve patient outcomes without adding to the existing cost of care because both payers and policymakers want to identify health care costs that do not result in benefit to the patient. The purpose of the reported project was to generate a practice guideline for the treatment of uncomplicated acute cystitis in a female population, to determine the extent to which the guideline would be used by providers and to measure the cost and quality of outcomes from its use. A retrospective chart review was used to gather pre-guideline practice and cost data. Measurements included the type, frequency, and duration of antibiotic therapy and the use of urine cultures and both complications and routine followup visits. The implementation of an outpatient practice guideline resulted in a significant change in antibiotic prescribing and a trend toward a change in ordering cultures and clinic followup. There was also a significant decrease in treatment costs.

Once- versus twice-daily gentamicin dosing in neonates >/=34 Weeks' gestation: cost-effectiveness analyses.

OBJECTIVES: To compare performance and cost analysis of two gentamicin regimens in infants >/=34 weeks' gestation requiring antibiotics for a 72-hour rule-out sepsis evaluation. A once-daily dosing (ODD) regimen of 4 mg/kg was compared with a standard twice-daily dosing (TDD) regimen of 2.5 mg/kg every 12 hours. SETTING AND DESIGN: Infants at two university-affiliated Level III nurseries were prospectively temporally allocated to receive ODD (n = 27) or TDD (n = 28) as part of their 72-hour empirical antibiotic regimen. Performance of dosing regimens was based on target serum gentamicin concentrations (SGC) established prospectively as a peak of 5 to 10 microgram/mL and a trough of 2 microgram/mL, compared with none in the ODD group. Overall, 57% of the SGCs in the TDD group were outside the target concentration range versus 7% in the ODD group. Based on questionnaire results, a total 72-hour process cost of ODD versus TDD was compared for regimens with and without use of SGC analysis. If SGCs are obtained, more than 75% of the cost associated with gentamicin therapy is attributable to SGC analysis. Based on a cost-effectiveness analysis, ODD was the dominant dosing strategy in all categories analyzed. CONCLUSIONS: ODD of gentamicin at 4 mg/kg in neonates >/=34 weeks' gestation is the preferable treatment strategy based on: 1) significantly improved SGC performance compared with TDD; 2) elimination of the need for routine SGC collection in infants on short courses of therapy; and 3) significant antibiotic-associated hospital cost savings when compared with conventional therapy of TDD and SGC analysis.