RESUMO
BACKGROUND: A lung transplant patient with invasive aspergillosis (IA) manifested symptoms of voriconazole-induced transaminitis with systemic voriconazole and progression of IA after switching to oral posaconazole. With limited options for standard triazole therapy, aerosolized delivery with one of the second-generation triazoles was considered. METHODS: Feasibility for aerosolized delivery was evaluated using cascade impactor and analysis of physicochemical characteristics of voriconazole (10 mg/mL) and posaconazole (6, 12 mg/mL) solutions. RESULTS: Both triazoles showed favorable characteristics for aerosol delivery with mass median aerodynamic diameter, geometric standard deviation, respirable fraction (<5.4 µm) of 2.8 µm, 2.0, 86%; 3.4 µm, 2.4, 78%; and 3.0 µm, 2.3, 79% for voriconazole and 6, 12 mg/mL of posaconazole, respectively. Aspergillus fumigatus isolate from the patient was more susceptible to voriconazole, and hence aerosolized voriconazole was introduced around the third month posttransplant at 40 mg TID for 1 week, 40 mg BID for 1 week, followed by 40 mg daily thereafter, along with IV caspofungin (50 mg/d) and liposomal amphotericin B (300 mg/d). The aerosol regimen was well tolerated by the patient with undetectable trough plasma levels of voriconazole. Bronchoscopy at the fourth month revealed improvement in anastomotic plaques with reduction in bronchoalveolar lavage galactomannan values (7.48-2.15 ng/mL). This consolidated aerosolized and intravenous regimen was maintained until 2.97 years posttransplant. CONCLUSIONS: The intravenous solutions of both second-generation triazoles showed characteristics that were suitable for aerosol delivery. Our report further adds to the therapeutic experience with the use of aerosolized voriconazole for IA in a lung transplant patient.
Assuntos
Aspergilose/tratamento farmacológico , Infecções Fúngicas Invasivas/tratamento farmacológico , Infecções Respiratórias/tratamento farmacológico , Triazóis/administração & dosagem , Voriconazol/administração & dosagem , Administração por Inalação , Adulto , Aerossóis/administração & dosagem , Antifúngicos/administração & dosagem , Aspergilose/diagnóstico , Broncoscopia , Estudos de Viabilidade , Feminino , Humanos , Infecções Fúngicas Invasivas/diagnóstico , Transplante de Pulmão/efeitos adversos , Infecções Respiratórias/diagnósticoRESUMO
BACKGROUND: Acute cellular rejection (ACR) is a major risk factor for chronic lung allograft dysfunction after lung transplantation. Acute cellular rejection can persist or recur despite augmentation of immunosuppression by conventional methods. There are limited therapeutic options in treating these recurrent and refractory ACRs. We describe our experience with cyclophosphamide therapy for recurrent and refractory ACR in lung transplant recipients. METHODS: Six consecutive patients who were treated with cyclophosphamide for recurrent or refractory ACR were included in the series. The primary outcome measures were improvement in ACR score and forced expiratory volume at 1 second. Secondary outcome measures included adverse drug events including bone marrow suppression, gastrointestinal side effects, and infections. RESULTS: Five of the 6 patients treated demonstrated complete resolution of ACR on follow-up biopsies. Acute cellular rejection score improved after cyclophosphamide treatment (P = 0.03). None of the patients had high grade (≥A3) ACR in the 3 months after cyclophosphamide administration. Cyclophosphamide had no effect on forced expiratory volume at 1 second trend or bronchiolitis obliterans score. All patients tolerated cyclophosphamide with minor gastrointestinal side effects, mild bone marrow suppression, and nonfatal infections that were amenable to treatment. CONCLUSIONS: Cyclophosphamide therapy is an option in treating recurrent and refractory ACR in patients who have failed conventional treatments. Cyclophosphamide is tolerated well without serious adverse drug events (ADE).
RESUMO
BACKGROUND: Traditional immunosuppressive regimens (ISR) used in lung transplantation rely on calcineurin inhibitors (CNI) that occasionally cause severe adverse reactions necessitating discontinuation. Belatacept is a novel costimulation antagonist approved for use in renal transplantation which lacks data in lung transplantation. This series aims to describe the response to belatacept ISR in 11 lung transplantation recipients after CNI failure. METHODS: Single-center, retrospective medical record review of adult lung transplant recipients (LTR) before and after conversion to belatacept-based ISR. Patients were evaluated at fixed time points before and after belatacept initiation. Primary outcome was incidence of acute cellular rejection (ACR). Secondary outcomes included incidence of infection, chronic lung allograft dysfunction (CLAD) progression, death, change in mean arterial pressure, and estimated glomerular filtration rate. RESULTS: Eleven LTRs received belatacept with a mean of 246 (91-1064) days of follow-up after conversion. Four were changed to belatacept for thrombotic thrombocytopenic purpura, 3 for posterior reversible encephalopathy syndrome, 2 for recurrent ACR, 1 for CLAD, and 1 for renal-sparing. ACR was not different before and after belatacept (P = 0.17). Mean estimated glomerular filtration rate was significantly higher postbelatacept (32.53 vs 45.26, P = 0.04). Mean incidence of infections (24.4% vs 16.0%, P = 0.55) and mean arterial pressure (97.5 vs 92.1 P = 0.38) were not different. Progression of CLAD occurred in 2 patients. At the end of follow-up, 7 of 11 patients were alive. CONCLUSIONS: Belatacept-based ISR appear to produce reasonable results in LTRs who fail CNI-based ISR. Larger prospective trials appear warranted in lung transplantation.