Lynn-Green, E.

Abstract Rationale Extracorporeal membrane oxygenation (ECMO) is an increasingly utilized form of life support for patients with cardiac and/or respiratory failure. Fungal infections remain a serious challenge in patients supported by ECMO, with an estimated prevalence of up to 10% and high morbidity and mortality. While routine antifungal prophylaxis is uncommon in ECMO centers and widely debated, its impact on incidence, pathogenic organisms, resistance patterns, and outcomes has not been described. Methods This was a ten-year experience study of fungemia in patients receiving ECMO where most patients received antifungal prophylaxis. Institutional protocol was to prescribe prophylactic fluconazole based on risk stratification, substituted with echinocandins if indicated. Adults (18 years and older) with ECMO runs between 2014-2024 were screened for fungal organism growth on culture, then narrowed to those with positive blood cultures drawn in the window from 24 hours after cannulation through 72 hours after decannulation. Clinical, microbiological, and outcomes data were descriptively summarized. Institutional review board approved with a waiver of informed consent. Results Among 1,039 adult ECMO runs (979 patients), thirteen patients with fungemia were identified for a calculated incidence rate of 1.29 per 1000 ECMO days (95% CI 0.75 to 2.23). Twelve patients (92%) received antifungal prophylaxis; 85% had echinocandin and 38% azole exposure, with some overlap. Median duration of antifungal exposure was 14 days prior to positive culture. Seven patients (54%) had an open sternum at the time of ECMO cannulation, while 11 (85%) had femoral ECMO access. Four patients (31%) had Candida species isolated from other sources prior to fungemia (mediastinum and respiratory system). Candida parapsilosis (31%), C. albicans (23%), and C. guilliermondii (15%) were the most common isolates. The most likely sources were vascular access catheters (38%) and mediastinum (31%). Seven patients (54%) had suspected or confirmed seeding of ECMO hardware after positive blood cultures, though only two circuit exchanges were performed. Four patients (31%) showed evidence of non-susceptibility to their prophylactic antifungal class (Table 1), with a median 35-day exposure prior to positivity among those patients. Only 62% of patients demonstrated blood culture clearance (median 3 [IQR 2.5-7.75] days). Nearly all patients (92%) died within the hospital stay, including all patients with resistant organisms. Conclusions In an ECMO center with routine antifungal prophylaxis practices, the rate of fungemia identified during ECMO support was low. When fungemia developed, there was a high proportion of drug resistance and mortality. This abstract is funded by: None

Abstract Non-tubercular mycobacteria (NTM) present a serious challenge in managing lung transplant candidates and recipients. Pretransplant NTM isolation has been associated with post-transplant NTM infection and significantly increased mortality risk. Strategies for managing pre-transplant NTM isolation vary widely in clinical practice. We present a 35-year-old lung transplant candidate from a tuberculosis-endemic country with severe pulmonary hypertension and Eisenmenger Syndrome due to unrepaired atrial septal defect, who underwent bilateral lung transplantation. Two years prior to transplant, she was successfully treated for pulmonary tuberculosis with six months of an unknown regimen in her home country. After moving to the U.S., she received M. tuberculosis (MTB) clearance from her state tuberculosis board, with three negative sputum samples six months prior to transplant. During her transplant evaluation, multi-drug-resistant M. fortuitum complex was isolated from one mycobacterial sputum culture. There was no clinical or radiographic evidence of active lung infection, and no targeted therapies were added. Standard peri-transplant antibiotics (vancomycin, cefepime, and caspofungin) were given. The patient received basilixamab for induction immunosuppression, and tacrolimus, mycophenolate mofetil, and prednisone for maintenance immunosuppression. Explant pathology showed necrotizing granuloma in the right upper lobe with acid-fast bacilli (AFB). The differential diagnosis included non-viable MTB, viable MTB despite prior clearance, or M. fortuitum. Three bronchoscopy washings were obtained in the first week post-transplant and returned negative for MTB by PCR, AFB stain, and culture. In collaboration with the Mycobacteriology laboratory, broad-range PCR testing was performed on the formalin-fixed paraffin-embedded samples from the explanted right lung, which was positive for MTB complex DNA. In total, the patient completed six sputum samples within the year pre-transplant and six respiratory samples within a month post-transplant, all of which returned negative for MTB by PCR, AFB stain, and culture. Blood flow cytometric (FC) immunoprofiling with mycobacterial antigens and controls was conducted (Escalante et al. 2015). The patient's FC antigen-specific activated T-cell profiling was consistent with a reduced risk of latent TB infection (FC CD4+ CD25+CD134+ T-cells (RD1-peptides-nil) = 0.19%). T-cell reactivity to MTB300 and PPD antigens suggested prior MTB, NTM, and/or BCG vaccination exposures. She progressed well without any preventive therapy for LTBI. FC immunoprofiling one year after transplantation showed similar results. She continues to have good pulmonary function and quality of life in her second-year post-transplant without evidence of NTM or MTB infection. Escalante P, et al. Combinatorial Immunoprofiling in Latent Tuberculosis Infection. Am J Respir Crit Care Med. 2015;192(5):605-17. PMCID: PMC4595688.