Long-term Risk of Atypical Fungal Infection After Near-Drowning Episodes: In Reply

Abstract

We thank Drs Garzoni and Garbino for their letter regarding our article.1 We appreciate their comments and believe that the observations they have made in 2 adult tsunami survivors on the long-term risk of severe infections with Scedosporium apiospermum (the asexual form of Pseudallescheria boydii) after submersion are very relevant for the management of the infectious complications in patients after submersion.2 It is important to share this information, because most data on invasive fungal infections are based on studies in neutropenic patients. Victims of submersion are supposed to be healthy and immunocompetent, leading to a particular course of their infections, which mandates a specific and especially aggressive diagnostic and therapeutic approach. This is demonstrated nicely by both a Garzoni et al article2 and our article.1Nevertheless, 2 comments can be made. First, although similar very late and silently progressive complications after submersion can be expected for Aspergillus species as well, they have not been described, thus far, to the same extent. In the 3 published cases of central nervous system (CNS) aspergillosis after near-drowning, the time interval between the submersion incident and first radiologic signs of nonpulmonary invasive aspergillosis was 13, 14, and 15 days, respectively.1,3,4Second, we do not agree with the antifungal treatment (voriconazole + amphotericin B) proposed by Garzoni and Garbino as the empirical treatment of choice in suspected fungal infections after submersion. Although the optimal therapy for invasive aspergillosis is actually not yet known, we believe that there are 2 reasons why amphotericin B has no place in the empirical treatment of suspected invasive fungal infections after submersion. In the first place, the vast majority of published cases were correlated with P boydii, which responds poorly to amphotericin B. Moreover, the histologic and microbiologic resemblance of this fungus to Aspergillus may interfere with a correct diagnosis, which may give rise to an Aspergillus-directed but incorrect antifungal treatment.5 In the second place, amphotericin B penetrates poorly into the cerebral tissue, which makes it useless in case of CNS invasion irrespective of the antifungal spectrum of the involved fungus.Although systematically designed prospective research is currently lacking, we believe, on the basis of the available evidence, that voriconazole should be considered as the treatment of choice for a suspected pulmonary or invasive fungal infection after submersion. Voriconazole is effective against Aspergillus species and P boydii and is the only antifungal drug that penetrates sufficiently into the CNS tissue.Currently, no data are available to support the combination of antifungal drugs for the treatment of P boydii. Recently published research suggests the potential superiority of combination therapy for invasive aspergillosis. On the basis of theoretical considerations and 1 retrospective evaluation, the combination of voriconazole and caspofungin may be superior compared with voriconazole alone.6,7 Caspofungin exerts in vitro activity against both Aspergillus species and P boydii. If combination therapy is considered for a patient after submersion for the treatment of a suspected invasive fungal infection, the combination of voriconazole and caspofungin is currently the most reasonable one.