Jorgenson Margaret R, Descourouez Jillian L, Marka Nicholas A, Leverson Glen E, Smith Jeannina A, Andes David R, Fernandez Luis A, Foley David P
Department of Pharmacy, University of Wisconsin Hospital and Clinics, Madison, WI, USA.
Division of Transplantation, Department of Surgery, University of Wisconsin-Madison School of Medicine and Public Health, Madison, WI, USA.
Transpl Infect Dis. 2019 Oct;21(5):e13156. doi: 10.1111/tid.13156. Epub 2019 Aug 23.
Invasive fungal infection (IFI) after liver transplant (LTx) is associated with extensive morbidity and mortality. Targeted prophylaxis reduces risk, but qualifying criteria, drug of choice and regimen are unclear and compliance is inconsistent.
Assess the impact of a risk factor-based fungal prophylaxis protocol (FPP) after LTx on fungal infection rates, fungal epidemiology, and transplant outcomes.
Observational cohort study of adult LTx recipients between July 1, 2009, and June 30, 2017. Patients in the FPP group were given a set dose of 400 mg fluconazole without renal adjustment on POD 1-14 via pharmacist delegation protocol.
One hundred and eighty-nine patients met inclusion criteria; 50 in the FPP and 139 in the pre-implementation comparator group. Of those who would be considered high-risk, 22.3% received antifungal prophylaxis prior to FPP implementation vs 92% after implementation (P < .0001). There were significantly fewer fungal infections in the FPP group at 1 year (12.5% vs 26.6%, P = .03). IFI in the pre-implementation control group was due to Candida species in 95% of cases; 30% were species with reduced fluconazole susceptibility. IFI in the FPP group was due to Candida species in all cases, and no isolates had reduced fluconazole susceptibility. Aspergillus did not account for any IFI between the groups. One-year patient and graft survival were similar between groups. In a multivariable model accounting for patient and donor age, donor type, MELD, and cold ischemic time, FPP was protective against fungal infection (HR 0.3, P = .015). FPP did not significantly impact graft survival (HR 0.4, P = .14), but trended toward improved patient survival. (HR 0.18, P = .06).
Implementation of a targeted FPP utilizing static dosing of fluconazole 400 mg × 14 days to those that meet high-risk criteria significantly reduces invasive fungal infection after liver transplant. Use of this protocol did not adversely affect fungal epidemiology and may have a positive impact on allograft and patient survival. Future large prospective studies are needed to better evaluate survival impact.
肝移植（LTx）后侵袭性真菌感染（IFI）与广泛的发病率和死亡率相关。靶向预防可降低风险，但合格标准、首选药物和方案尚不清楚，且依从性不一致。
评估基于风险因素的肝移植后真菌预防方案（FPP）对真菌感染率、真菌流行病学和移植结局的影响。
对2009年7月1日至2017年6月30日期间的成年肝移植受者进行观察性队列研究。FPP组患者在术后第1 - 14天通过药剂师授权方案给予固定剂量400mg氟康唑，无需根据肾功能调整剂量。
189例患者符合纳入标准；FPP组50例，实施前比较组139例。在那些被认为是高风险的患者中，22.3%在FPP实施前接受了抗真菌预防，而实施后这一比例为92%（P <.0001）。FPP组1年时的真菌感染明显较少（12.5%对26.6%，P =.03）。实施前对照组的IFI在95%的病例中由念珠菌属引起；30%为对氟康唑敏感性降低的菌种。FPP组的IFI在所有病例中均由念珠菌属引起，且没有分离株对氟康唑敏感性降低。曲霉菌在两组间均未导致任何IFI。两组间1年的患者和移植物存活率相似。在一个考虑患者和供体年龄、供体类型、终末期肝病模型（MELD）和冷缺血时间的多变量模型中，FPP可预防真菌感染（风险比[HR] 0.3，P =.015）。FPP对移植物存活没有显著影响（HR 0.4，P =.14），但在患者存活方面有改善趋势（HR 0.18，P =.06）。
对符合高风险标准的患者实施使用400mg氟康唑固定剂量×14天的靶向FPP可显著降低肝移植后的侵袭性真菌感染。使用该方案对真菌流行病学没有不利影响，可能对同种异体移植物和患者存活有积极影响。未来需要进行大型前瞻性研究以更好地评估对存活的影响。
