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Background Invasive fungal infections (IFIs) are common following lung transplantation. Isavuconazole is unstudied as prophylaxis in organ transplant recipients. We compared effectiveness and tolerability of isavuconazole and voriconazole prophylaxis in lung transplant recipients. Methods A single-center, retrospective study of patients who received isavuconazole (September 2015–February 2018) or voriconazole (September 2013–September 2015) for antifungal prophylaxis. IFIs were defined by EORTC/MSG criteria. Results Patients received isavuconazole (n = 144) or voriconazole (n = 156) for median 3.4 and 3.1 months, respectively. Adjunctive inhaled amphotericin B (iAmB) was administered to 100% and 41% of patients in the respective groups. At 1 year, 8% of patients receiving isavuconazole or voriconazole developed IFIs. For both groups, 70% and 30% of IFIs were caused by molds and yeasts, respectively, and breakthrough IFI (bIFI) rate was 3%. Outcomes did not significantly differ for patients receiving or not receiving iAmB. Independent risk factors for bIFI and breakthrough invasive mold infection (bIMI) were mold-positive respiratory culture and red blood cell transfusion >7 units at transplant. Bronchial necrosis >2 cm from anastomosis and basiliximab induction were also independent risk factors for bIMI. Isavuconazole and voriconazole were discontinued prematurely due to adverse events in 11% and 36% of patients, respectively (P  = .0001). Most common causes of voriconazole and isavuconazole discontinuation were hepatotoxicity and lack of oral intake, respectively. Patients receiving ≥90 days prophylaxis had fewer IFIs at 1 year (3% vs 9%, P  = .02). IFIs were associated with increased mortality (P  = .0001) and longer hospitalizations (P  = .0005). Conclusions Isavuconazole was effective and well tolerated as antifungal prophylaxis following lung transplantation. [ABSTRACT FROM AUTHOR]

Studies describing invasive fungal infections (IFIs) after chimeric antigen receptor-modified T-cell (CAR-T-cell) therapy are limited. Although post-CAR-T-cell IFIs appear to be uncommon, they are associated with significant morbidity and mortality. Specific risk factors for IFIs in CAR-T-cell recipients have not been fully characterized and are often extrapolated from variables contributing to IFIs in patients with other hematologic malignancies or those undergoing hematopoietic cell transplant. Optimal prophylaxis strategies, including the use of yeast versus mold-active azoles, also remain ill-defined. Further research should investigate key risk factors for IFIs and establish an evidence-based approach to antifungal prophylaxis in these patients in order to improve clinical outcomes. [ABSTRACT FROM AUTHOR]

Data on invasive mold infections (IMIs) after chimeric antigen receptor-modified T-cell (CAR-T-cell) therapy are limited. We describe 2 patients with post–CAR-T-cell IMI (Fusarium, Mucorales) and review the published literature. We propose strategies to prevent IMIs in patients, based on the IMI rate and presence of neutropenia or steroid use. [ABSTRACT FROM AUTHOR]

Background IFI is a significant complication following lung transplant (LT). VOR was universal antifungal px in our LT program from 2004 to October 2015, at which time px was changed to ISA. We compared the efficacy and tolerability of VOR vs. ISA px in LTR. Methods We reviewed all LTR from September 2013 to February 2018 who received VOR or ISA Px. The standard duration of px was 3 or 4 months following basiliximab and alemtuzumab induction, respectively. All patients were followed for ≥1 years post-Tx. IFI was defined by revised EORTC/MSG criteria. Results In total, 310 LTR were included, 149 and 161 of whom received ISA and VOR px, respectively. There was no difference in demographics, underlying diseases, single vs. double LT, or induction therapy (alemtuzumab vs. basiliximab) between the 2 groups. At 1-year after LT, 9% (14) and 8% (13) of patients in ISA and VOR groups developed IFI, respectively (P = 0.5). 5% (7) and 3% (5) of patients developed breakthrough (BT) IFI during ISA and VOR px, respectively (P = 0.6; Figure 1, P = 0.4, Kaplan-–Meier). ISA BT included pneumonia (PNA, 2), endobronchial IFI (2), mediastinitis (1), chest wall IFI (1), and candidemia (1). ISA BT patients were infected with Aspergillus fumigatus (3; 2 with ISA MIC = 0.5 µg/mL, 1 MIC = 1 µg/mL), black mould (1), and yeasts (3; 2 C. glabrata , 1 C. albicans). VOR BT IFI included PNA (2), endobronchial IFI (1), empyema (1), and chest wall IFI (1). VOR BT IFIs were due to A. ustus , A. niger , A. lentulus , black mould, and Rhizopus spp (1 each). All Aspergillus VOR BT isolates exhibited VOR MIC ≥2 µg/mL. Patients with IFI were more likely to have positive pre-LT respiratory fungal culture (P = 0.01) and grade ≥3 ischemic reperfusion injury (IRI) post-LT (P = 0.01). VOR and ISA were prematurely discontinued in 53% (85) and 14% (21) of patients due to adverse events, respectively (P < 0.0001). Hepatotoxicity was more common with VOR (22%, 35) than ISA (5%, 7) (P < 0.0001). IFI was an independent risk factor for death at 1 year (Figure 2, P < 0.0001, Kaplan–Meier). Conclusion ISA was as effective as VOR in preventing IFI in LTR, and significantly better tolerated. Pre-LT fungal culture positivity and grade ≥3 IRI post-LT were risk factors for the development of IFI. IFI within 1-year post-LT had a significant impact on mortality Disclosures Fernanda P. Silveira, MD, MS, FIDSA, Ansun: Grant/Research Support; Qiagen: Grant/Research Support; Shire: Grant/Research Support; Whiscon: Grant/Research Support. [ABSTRACT FROM AUTHOR]

B Introduction/Hypothesis: b COVID-19 patients (pts) in the ICU are vulnerable to invasive fungal infections (IFIs), especially invasive aspergillosis (IA) and candidiasis (IC). Rectal candida colonization and serum BDG were positive during screening in 66% and 62% of pts, respectively. A weekly IFI screening algorithm was implemented in December '20, which utilized yeast colonization score, serum -d-Glucan (BDG), serum and respiratory galactomannan (GM) and T2 Candida® (T2C). [Extracted from the article]