Combination Antifungal Therapy in Organ Transplant Recipients

Abstract

We thank Dr. Bal for his interest in our report and for his comments. Somewhat lower overall mortality rates in lung transplant recipients with invasive aspergillosis in the literature are attributable largely to cases with tracheobronchitis or bronchial anastomotic infections, a locally invasive form of aspergillosis (1). Mortality in the lung transplant recipients with invasive pulmonary aspergillosis is similar to that in other types of organ transplant recipients (1). In our study, 11/13 lung transplant recipients in the combination therapy group had invasive pulmonary aspergillosis, and only two had anastomotic infections (biopsy proven). A beneficial effect of combination therapy in the overall study population could not be attributed to a marginally higher number (P=0.21) of lung transplant recipients in this group (2). Indeed, most of the benefit of combination therapy appeared to be in non-lung transplant recipients. As shown in Table 3 (2), combination therapy was less beneficial in lung transplant recipients and was most beneficial in renal transplant recipients. Lung transplantation when added to the multivariate model in Table 2 (2) showed no correlation with mortality (hazard ratio 1.25; 95% CI: 0.53–2.97, P=0.60). The control group in the study by Herbrecht and colleagues received amphotericin B deoxycholate, and not a lipid formulation of amphotericin B (3). Indeed, there has been much speculation if the results of this study would have been different had a lipid formulation of amphotericin B been used instead of amphotericin B deoxycholate (4). At the time that our study was conceived and planned, lipid formulations of amphotericin B were the standard antifungal therapy for invasive aspergillosis in organ transplant recipients. With regards to mechanical ventilation, combination therapy appeared to be of greater benefit than lipid amphotericin B in ventilated patients. Mortality rate at 90 days was 46% (6/13) in mechanically ventilated patients in the combination therapy group and 74% (17/23) in those in the lipid amphotericin B group (hazard ratio 0.48; 95% CI: 0.20–1.15, P=0.10). Multivariate analysis showed that combination therapy was associated with improved survival in mechanically ventilated patients, but not in nonventilated patients (Table 1). Finally, we concur with the author and have explicitly noted in our paper the need for further studies in this important area.TABLE 1: Effect of combination therapy on 90-day mortality stratified by mechanical ventilationNina Singh Marilyn M. Wagener VA Medical Center and University of Pittsburgh Pittsburgh, PA