Clinical Significance of Nephrotoxicity in Patients Treated with Amphotericin B for Suspected or Proven Aspergillosis

Abstract

The records of 239 immunosuppressed patients receiving amphotericin B for suspected or proven aspergillosis were reviewed to determine rates of nephrotoxicity, dialysis, and fatality. The mean and median durations of treatment were 20.4 and 15.0 days, respectively. The creatinine level doubled in 53% of patients and exceeded 2.5 mg/dL in 29%; 14.5% underwent dialysis; and 60% died. A multivariate Cox proportional hazards analysis showed that patients whose creatinine level exceeded 2.5 mg/dL (hazard ratio [HR], 42.02; P<.001), allogeneic bone marrow transplantation (BMT) patients (HR, 6.34; P<. 001), and autologous BMT patients (HR, 5.06; P=.024) were at greatest risk for requiring hemodialysis. Use of hemodialysis (HR, 3. 089; P<.001), duration of amphotericin B use (HR, 1.03 per day; P=. 015), and use of nephrotoxic agents (HR, 1.96; P=.017) were associated with greater risk of death, whereas patients undergoing solid organ transplantation were at lowest risk (HR, 0.46; P=.002). These data indicate that elevated creatinine levels during amphotericin B treatment are associated with a substantial risk for hemodialysis and a higher mortality rate, but the risks vary in different patient groups.

A randomized comparison of empiric or pre-emptive antibiotic therapy after hematopoietic stem cell transplantation

“…This reduction in empiric antifungal therapy is less likely to be beneficial in autologous HSCT where the risk of nephrotoxicity and its associated morbidity is not as great as in allogeneic HSCT. 18,19 Two earlier studies of pre-emptive intravenous therapy in adults undergoing SCT undertaken in the early 1990s and late 1980s suggested a reduced incidence of BSI 1 and fever. 2 However, these trials were either not randomized 2 or included other interventions such as the use of laminar air-flow ventilation or the use of systemic non-absorbable antibiotics.…”

Optimizing antifungal drug dosing and monitoring to avoid toxicity and improve outcomes in patients with haematological disorders

“…26,76,[90][91][92][93][94][95] The risk of amphotericin-induced nephrotoxicity has been shown to double when two or more nephrotoxic agents (e.g. cyclosporin, aminoglycosides or foscarnet) are used concurrently.…”

Recomendaciones para el tratamiento de la infección por Aspergillus spp.

“…Recientemente se ha comunicado un metaanálisis que compara dichas formulaciones. De la revisión conjunta de toda la literatura, parece ser que la anfotericina B liposomal, además de disminuir la toxicidad, incrementa el porcentaje de éxitos terapéuticos y disminuye el riesgo de mortalidad relacionada con la infección [6][7][8] . Por otra parte, recientemente se han publicado los resultados de un estudio aleatorizado y abierto que compara la eficacia, la seguridad y la tolerancia de voriconazol frente a anfotericina B convencional en el tratamiento primario de la aspergilosis invasiva y se demuestra que los pacientes que recibieron voriconazol presentan una mejor respuesta (52,8% frente a 31,6%), una mayor supervivencia (70,8% frente a 57,9%) y menos efectos adversos que los tratados con anfotericina B desoxicolato 9 .…”