Conversion to tacrolimus alone compared to full immunosuppression following cardiac transplantation (TACTFUL).

BACKGROUND: Cardiac transplantation requires lifelong immunosuppressant medications to prevent rejection. However, some patients may not tolerate multiple immunosuppressants due to adverse effects. At our institution, patients may be converted to monotherapy with tacrolimus if unable to tolerate a combination regimen. This study evaluated the outcomes among patients converted to tacrolimus monotherapy compared with those maintained on combination immunosuppression. METHODS: This single-center, retrospective cohort study included patients who received heart transplants at Sentara Norfolk General Hospital between January 2015 and July 2021. Patients were classified as receiving tacrolimus monotherapy (Mono) or combination immunosuppression (Combo). The primary outcome was all-cause mortality with key secondary outcomes including incidence of 2R/3R rejection, necessity for renal replacement therapy, and infection. RESULTS: 112 patients were included (Mono = 25, Combo = 87). Median age at transplant was 53.8 years (Mono) and 52.1 years (Combo). The most common reasons for conversion to monotherapy were leukopenia, infection, and gastrointestinal (GI) distress. There was no difference in mortality (0 in Mono, 11 in Combo; p = .09) or percentage of patients with 2R/3R rejection (24% in Mono, 32.2% in Combo; p = .43). No Mono group patients experienced rejection after converting from combination therapy. 24% of Mono group patients resumed at least one additional immunosuppressive medication during the study period. Median time to monotherapy was 9.0 months, with a total median duration on monotherapy of 16.0 months. A median of 3.3 years of follow-up was observed for patients in Mono and 3.4 years in Combo (p = .29). CONCLUSION: Selected patients who do not tolerate combination immunosuppression can be safely transitioned to tacrolimus monotherapy as a means of controlling adverse events without an increased risk of mortality or rejection.

Retrospective Cohort Study of the Incidence of Acute Kidney Injury with Vancomycin Area under the Curve-Based Dosing with Concomitant Piperacillin-Tazobactam Compared to Meropenem or Cefepime.

Acute kidney injury (AKI) is a complication associated with vancomycin. Previous studies demonstrated that the combination of vancomycin and piperacillin-tazobactam increases the risk of AKI compared to vancomycin with meropenem or cefepime. These studies did not utilize area under the curve (AUC)-based dosing, which reduces vancomycin exposure and may decrease nephrotoxicity compared with trough-based dosing. This study evaluated the incidence of AKI in patients receiving AUC-dosed vancomycin with either concomitant piperacillin-tazobactam (VPT) or meropenem or cefepime (VMC). This retrospective cohort study included patients admitted to Sentara Norfolk General Hospital between October 2019 and September 2020 who received AUC-dosed vancomycin and concomitant piperacillin-tazobactam, meropenem, or cefepime for at least 48 h. The primary outcome was the incidence of AKI during treatment or within 24 h of discontinuation. A total of 435 patients (VPT, n = 331; VMC, n = 104) who received a median duration of 4 days of treatment were included. The incidence of AKI was significantly higher with VPT than with VMC (13.6% versus 4.8% [P = 0.014]). Multivariable analysis showed VPT to be an independent risk factor for the development of AKI (odds ratio [OR], 3.00 [95% confidence interval {CI}, 1.15 to 7.76]). VPT was associated with more frequent AKI than VMC, even with the relatively short courses of antimicrobial therapy administered in this population. In comparison with the precedent in the literature for trough-based vancomycin dosing, our results suggest that the use of AUC-based vancomycin dosing in combination with piperacillin-tazobactam, meropenem, or cefepime may result in a lower overall incidence of AKI.