Changes in the epidemiology of invasive fungal disease in a Pediatric Hematology and Oncology Unit: the relevance of breakthrough infections.

BACKGROUND: Invasive fungal disease (IFD) is a significant cause of morbimortality in children under chemotherapy or hematopoietic stem cell transplant (HSCT). The purpose of this study is to describe the changes in the IFD epidemiology that occurred in a Pediatric Hematology-Oncology Unit (PHOU) with an increasing activity over time. METHODS: Retrospective revision of the medical records of children (from 6 months to 18 years old) diagnosed with IFD in the PHOU of a tertiary hospital in Madrid (Spain), between 2006 and 2019. IFD definitions were performed according to the EORTC revised criteria. Prevalence, epidemiological, diagnostic and therapeutic parameters were described. Comparative analyses were conducted using Chi-square, Mann-Whitney and Kruskal-Wallis tests, according to three time periods, the type of infection (yeast vs mold infections) and the outcome. RESULTS: Twenty-eight episodes of IFD occurred in 27 out of 471 children at risk (50% males; median age of 9.8 years old, [IQR 4.9-15.1]), resulting in an overall global prevalence of 5.9%. Five episodes of candidemia and 23 bronchopulmonary mold diseases were registered. Six (21.4%), eight (28.6%) and 14 (50%) episodes met criteria for proven, probable and possible IFD, respectively. 71.4% of patients had a breakthrough infection, 28.6% required intensive care and 21.4% died during treatment. Over time, bronchopulmonary mold infections and breakthrough IFD increased (p=0.002 and p=0.012, respectively), occurring in children with more IFD host factors (p=0.028) and high-risk underlying disorders (p=0.012). A 64% increase in the number of admissions in the PHOU (p<0.001) and a 277% increase in the number of HSCT (p=0.008) were not followed by rising rates of mortality or IFD/1000 admissions (p=0.674). CONCLUSIONS: In this study, we found that yeast infections decreased, while mold infections increased over time, being most of them breakthrough infections. These changes are probably related to the rising activity in our PHOU and an increase in the complexity of the baseline pathologies of patients. Fortunately, these facts were not followed by an increase in IFD prevalence or mortality rates.

Disseminated lomentosporiosis in a heart transplant recipient: Case report and review of the literature.

BACKGROUND: Lomentospora prolificans (formerly S prolificans) is a saprophyte fungi that causes opportunistic infections in solid organ transplant (SOT) recipients. Resulting disseminated infections are difficult to treat and have a high mortality. Indications for antifungal prophylaxis after heart transplantation (HT) include CMV disease, reoperation, renal replacement therapy, extracorporeal membrane oxygenation (ECMO), and high environmental exposure to Aspergillus spores. However, the risk of breakthrough infections, such as Lomentosporiosis, remains a cause of concern. METHODS: We report the clinical findings, microbiology, treatment and outcome of a disseminated Lomentosporiosis in a heart transplant recipient with ECMO and antifungal prophylaxis. RESULTS: A 25-year-old male with complex grown-up congenital heart disease (GUCHD) was admitted for HT. He presented severe post-surgical complications including acute kidney injury and right heart and respiratory failure requiring venoarterial-ECMO, continuous renal replacement therapy (CCRT) and later on (+14) a ventricular assist device (VAD). Ganciclovir, cotrimoxazole, and antifungal prophylaxis with anidulafungin at standard doses had been started on day + 3 post HT. The patient presented seizures (+4), pancytopenia with mild neutropenia (days + 6 to + 11), influenza B (+7), and bacteremic Pseudomonas aeruginosa ventilator associated pneumonia (VAP) (+10). On days + 14 to + 16 Lomentospora prolificans was recovered from blood cultures, broncho aspirate, catheter tip, and skin biopsy. Despite treatment with L-AMB, voriconazole and terbinafine the patients died on day 17 after HT. Necropsy revealed disseminated infection with fungal invasion in central nervous system, heart, lung, cutaneous, and subcutaneous tissue. Broth microdilution tests demonstrated resistance to all antifungals. CONCLUSIONS: Lomentosporiosis is a rare complication that may emerge as a breakthrough invasive fungal infection in heart transplant recipients on ECMO despite antifungal prophylaxis.