Invasive Fungal Infections in Lung Transplant Recipients

(See Reply by Baker and Alexander on Volume 72, Issue 2, 15 January 2021, Pages 366–7.) To the Editor—We would like to thank Baker and colleagues for their prospective single-center study of invasive fungal infections (IFIs) in lung transplant recipients during the first 180 days posttransplant [1]. This study clearly demonstrated the incidence and timing of IFIs with a standard prophylaxis regimen of aerosolized amphotericin B lipid complex (ABLC); however, clinical applicability and generalizability of these results remain limited. We noted with interest that invasive candidiasis (IC) was the most common IFI in this study cohort. This finding diverges from the results of previous retrospective single and multicenter studies of lung transplant recipients, where Aspergillus species have consistently been identified as the most frequent causative pathogens [2–5]. In addition, surprisingly, Baker and colleagues demonstrated that most cases of IC (n = 58 [62%]) involved the pleural space or deep surgical incision site with a median time to diagnosis of just 31 days. These findings may suggest that seeding of Candida occurred at the time of operation. Further details about whether there were any identifiable risk factors, surgical or otherwise, such as Candida colonization of the donor or recipient lungs prior to transplant or use of extracorporeal membrane oxygenation (ECMO), that increased the risk of IC may certainly contribute to understanding of the pathogenesis of these findings. Identification of specific risk factors mayalso allow for a targeted systemic antifungal strategy to prevent such infections. We were struck by the fact that 58 of the 93 (62%) episodes of IC were due to pleural (n = 43) and deep surgical (n = 15) infections. One may opine that aerosolized ABLC was ineffective in preventing infections arising at these anatomical sites. We also noted that in addition to aerosolized ABLC, micafungin prophylaxis was given to patients who had delayed chest closure after lung transplantation and those on ECMO. The authors document that 18 cases of breakthrough IC occurred on prophylactic systemic antifungal therapy, including 16 of 18 (88%) cases that broke through micafungin therapy. The authors cite micafungin extraction by the ECMO circuit as a potential explanation for breakthrough IFIs but do not report on the number of lung transplant recipients requiring ECMO and what proportion of IFIs occurred in in the context of ECMO use. In vitro studies have demonstrated that micafunginas well as voriconazole, but not caspofungin orfluconazole, are extracted by the EMCO circuit [6, 7]. In critically ill patients, the use of ECMO results in a 23% reduction in the area under the curve concentration of micafungin [8]. As therapeutic drug monitoring is not routinely available for micafungin, its use in patients on ECMO should be avoided; if this is not possible, it would be prudent to consider an increased dose. Antifungal prophylaxis is advantageous in preventing IFIs in lung transplant recipients. However, universal aerosolized ABLC prophylaxis with the addition of micafungin for specific indications may not offer optimum coverage. Perhaps an alternative strategy, preemptive targeted therapy, may prove to be more effective, as demonstrated by others [9]. Potential conflicts of interest. C. R. reports grants from Astellas Pharma Canada, Chimerix Inc, Cidara, Merck Canada Inc, and Pfizer Canada Inc; personal fees from Merck Canada Inc, Pfizer Canada Inc, Avir Pharma, Pendopharm, Roche Pharma Canada, Sunovion Pharmaceuticals Canada Inc, and Teva Pharmaceutical Industries Ltd, outside the submitted work. T. M. reports no potential conflicts of interest. Both authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

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