Risk Factors of Invasive Aspergillosis after Heart Transplantation: Protective Role of Oral Itraconazole Prophylaxis

Abstract

The study was designed to identify a subset of heart transplant (HT) recipients who could benefit from the administration of targeted antifungal prophylaxis and to evaluate the efficacy of oral itraconazole as the preventive drug. We have analyzed the risk factors for invasive aspergillosis (IA) in our entire population of HT recipients (1988)(1989)(1990)(1991)(1992)(1993)(1994)(1995)(1996)(1997)(1998)(1999)(2000)(2001)(2002) and also the role of oral itraconazole prophylaxis that was provided to all patients since 1995 [400 mg q.d. of itraconazole oral (PO) for 3-6 months]. There were 24 cases of IA. Our main results indicate that the independent risk factors for IA after heart transplantation are: re-operation (RR 5.8; 95% CI 1.8-18, p = = 0.002), cytomegalovirus (CMV) disease (RR 5.2; 95% CI 2-13.9, p = = 0.001), post-transplant hemodialysis (RR 4.9; 95% CI 1.2-18, p = = 0.02), and the existence of an episode of IA in the HT program 2 months before or after the transplantation date (RR 4.6; 95% CI 1.5-14.4, p = = 0.007). Itraconazole prophylaxis showed an independent protective value against developing IA (RR 0.2; 95% CI 0.07-0.9, p = = 0.03) and also determined a significantly prolonged 1-year survival (RR 0.5; 95% CI 0.3-0.8, p = = 0.01). We believe that antifungal prophylaxis in heart transplant patients should be offered at least to patients with one or more of these predisposing conditions.

AspergillusInfections in Transplant Recipients

“…Recovery of Aspergillus species from respiratory tract cultures, particularly of A. fumigatus, is highly predictive of invasive aspergillosis in these patients (212). Reoperation, CMV disease, posttransplant hemodialysis, and the existence of an episode of invasive aspergillosis in the institution's heart transplant program 2 months before or after the transplantation date have been shown to be independent risk factors for invasive aspergillosis in heart transplant recipients (213).…”

“…Invasive aspergillosis occurs in 3.3 to 14% (average, 6%) of heart transplant recipients (100,101,120,124,205,206,212,213,280,331). Aspergillus infections are the most commonly occurring mycoses in heart transplant recipients, accounting for 69.8% of all invasive fungal infections after heart transplantation (101).…”

Profilaxis antifúngica en niños y adultos sometidos a trasplante de órganos sólidos y de precursores hematopoyéticos

“…Entre los factores de riesgo identificados se encuentran la re-intervención quirúrgica, enfermedad por CMV, insuficiencia renal y la existencia de casos de aspergilosis en los dos meses previos en la unidad de hospitalización del paciente 38 . En trasplante pulmonar se han descrito como factores de riesgo para aspergilosis la colonización de la vía aérea por Aspergillus spp., la infección por CMV, la hipogamaglobulinemia 18 y se han comunicado brotes de aspergilosis en este grupo de pacientes expuestos a construcciones en el hospital 39 .…”

“…95% 0,3 -0,8 p = 0,01). Los autores recomiendan uso de profilaxis al menos en pacientes con condiciones predisponentes, tales como re-intervención quirúrgica, infección por CMV, necesidad de diálisis post-trasplante y presencia de aspergilosis en otros pacientes de la misma unidad clínica en los últimos dos meses 38 .…”

Fungal Infections in Transplant and Oncology Patients

“…In immunocompromised hosts, Aspergillus most commonly presents as invasive pulmonary aspergillosis, often with subsequent dissemination [16][17][18]. In lung transplant recipients, Aspergillus may also cause tracheobronchitis and bronchial anastomotic infection.…”