Emerging Issues With Diagnosis and Management of Fungal Infections in Solid Organ Transplant Recipients

Abstract

Invasive fungal infections (IFIs) are being increasingly recognized in solid organ transplant (SOT) recipients, and delayed diagnosis can lead to graft loss and death. Therefore, there is a low threshold for prophylaxis and early initiation of empiric antifungal treatment, in this patient population. Meanwhile, the increasing consumption of antifungals is associated with high cost, medication toxicities and the emergence of resistance in Candida species, all of which call for rational use of antifungal agents. The implementation of fungal biomarkers, molecular diagnostic methods and direct detection of volatile fungal metabolites in breath samples could lead to faster diagnosis, early appropriate treatment and improved clinical outcomes, but also aid in the de‐escalation of antifungal treatment. Those novel diagnostic modalities need to be validated specifically in SOT recipients. Infectious diseases consultation can contribute to optimization of care through prompt initiation and appropriate modification of antifungal treatment, management of medication toxicities and drug‐drug interactions, as well as source control. In this review, we conceptually summarize recent advances in the diagnosis and management of IFI in SOT recipients, and highlight the importance of early diagnostic tools and good stewardship of antifungal drugs.

False positive bronchoalveolar lavage galactomannan: Effect of host and cut‐off value

“…Our findings support the conclusions of a previous study of immunocompromised patients, where those deemed unlikely to have IMI were not empirically treated, and no association was found between withholding antifungal therapy and all‐cause mortality . It should be noted that excessive use of antifungals is associated with significant collateral damage, specifically high‐costs, toxicities and significant drug‐drug interactions, and emergence of antifungal resistance …”

“…23 Our findings clearly support the implementation of higher cut-offs ( 34 It should be noted that excessive use of antifungals is associated with significant collateral damage, specifically high-costs, toxicities and significant drug-drug interactions, and emergence of antifungal resistance. [35][36][37] Other biomarkers have been incorporated into the microbiologic diagnosis of probable IA, specifically, βDG and serum GM. The serum Fungitel ® assay detects βDG, a fungal cell wall polysaccharide, and has reported sensitivity of 78% and specificity of 81% for IMI.…”

Biofilm: A Robust and Efficient Barrier to Antifungal Chemotherapy

“…The emergence and spread of systemic life-threatening fungal infections have increased in the last three decades, causing a major and alarming global concern [1][2][3][4][5][6][7]. The more widespread provision of new medical practices (e.g., immunosuppressive therapy, use of broad spectrum antibiotics and invasive surgical procedures such as solid organ and bone marrow transplantation) and the greater number of people suffering from predisposing conditions (e.g., immunocompromising status such as neutropenia, diabetes and human immunodeficiency virus infection, low-birth-weight newborns, burns, patients with cancer and critically ill patients requiring implanted medical devices or grafts) are the main factors that have been implicated in the augmented number of fungal infections [8][9][10][11][12] (Figure 1).…”

Invasive mould infections in solid organ transplant patients: modifiers and indicators of disease and treatment response

“…Decreasing immunosuppression is a cornerstone in the treatment of SOT recipients with suspected IMI [23]. IFD are mainly a consequence of immunosuppression [5], particularly after the strong inflammatory response elicited by corticosteroids [61]. Thus, the role of immunosuppression and immune tolerance mechanisms in the response to IMI treatment should not be underestimated.…”

“…Infection rates by Mucorales have been reported to be as high as 3% [2][3][4], whereas Cryptococcus incidence can reach 1.5% [2]. IFDs in SOT patients should be promptly diagnosed and treated, because they often lead to graft loss and death [5]. Mortality rates are high for all IFD, but in particular for mould infections, reaching 67-82% in patients with invasive pulmonary aspergillosis and 73% in cerebral forms of mucormycosis [2].…”