We present a 6-year-old female with B-cell acute lymphoblastic leukemia admitted for medullary relapse five years after initial diagnosis. Her re-induction chemotherapy included vincristine, dexamethasone, pegylated asparaginase, doxorubicin, and intrathecal methotrexate and cytarabine. While severely neutropenic on prophylactic micafungin, she developed headache, dizziness, fever, and seizures. Brain magnetic resonance imaging (MRI) revealed left superior parietal lobule leptomeningeal enhancement, concerning for infection or leukemic infiltration (Figure 1A). Within 48 hours, blood and CSF cultures demonstrated growth of a fungal pathogen, identified morphologically as Magnusiomyces clavatus . Her antifungal coverage was changed to voriconazole and liposomal amphotericin B. A whole body CT revealed disseminated fungal disease with innumerable small lesions in her liver, spleen, kidneys, pancreas, and lungs (Figure 1B). Blood cultures cleared after four days of combination antifungal treatment. A repeat CSF sample was sterile two weeks later. She had no history of foreign travel or high-risk environmental exposures.

Despite blood culture clearance, she continued to experience unrelenting spiking fevers (Figure 2A). After neutrophil count recovery, a repeat brain MRI showed development of a left parietal abscess and numerous punctate foci throughout the brain, representing disseminated central nervous system (CNS) fungal disease unveiled by immune reconstitution (Figure 1C). Flucytosine was added for additional antifungal action and CNS penetration. She underwent a left parietal craniotomy and drainage of the dominant abscess. Fungal culture of the contents of this abscess were sterile. Her fevers resolved after this procedure and shortly thereafter, she restarted cancer therapy with two cycles of blinatumomab.

She continued on combination antifungal therapy for seven months until CT imaging revealed gradual improvement in size and number of her disseminated lesions, allowing her to wean to only voriconazole (Figure 1D). With her fungal disease well-controlled and her malignancy in second complete remission (negative flow cytometry and high throughput sequencing), she successfully underwent a mismatched unrelated cord blood transplantation 10 months ago with no complications related to her fungal infection or antifungal toxicity. We intend to continue antifungal therapy through immune reconstitution and resolution of her imaging findings.

We report, to our knowledge, the first occurrence of aMagnusiomyces clavatus infection in North America and only the 11^th reported case in a pediatric patient. Further, our patient underwent a successful cord blood transplant without further fungal infection complications. M. clavatus , formerly phylogenetically classified as Geotrichum clavatum andSaprochaete clavata , is an arthroconidial, filamentous, yeast-like opportunistic fungus increasingly recognized as an emerging pathogen in immunocompromised patients^1,2. Closely related to, and potentially misidentified as, Magnusiomyces capitatus , its incidence has likely been underestimated prior to use of advanced identification techniques^3,4. Detailed ecological studies are scarce but other Magnusiomyces spp are ubiquitous in environmental sources like water, soil, and plants⁵. In one study of hospitalized adults, asymptomatic colonization with Magnusiomyces spp was relatively common, especially in the respiratory tract, and associated with invasive infection in immunocompromised individuals⁶. Hospital device and food contamination have been reported including nine cases of M. clavatus fungemia in France linked to a dishwasher and four cases of disseminated M. capitatus in Spain spread through milk flasks^7,8. Because isolates from multipleM. clavatus nosocomial outbreaks were from the same clade, human-to-human transmission is potentially possible in the setting of device contamination⁹. Invasive disease has been reported mostly in patients with hematologic malignancies and rarely with lymphoma, polycystic kidney disease, Crohn’s disease, hemophagocytic lymphohistiocytosis, aplastic anemia, and multiple myeloma. Most cases have occurred in France and Italy with occasional reports elsewhere in Eastern Europe, the Middle East, China, and South America (Figure 2B)^10-12. Case series have identified hematologic malignancy, chemotherapy, neutropenia, broad-spectrum antimicrobials, and central venous catheters as risk factors for infection^9,10. Chemotherapeutics that alter gut mucosa may lead to increased gut translocation associated with M. clavatus infection⁹. Reported cases frequently include significant dissemination². Isolates appear to be intrinsically resistant to echinocandins and fluconazole, but other azoles, amphotericin-B, and flucytosine have all demonstrated in vitro antifungal activity and low minimum inhibitory concentrations (MIC), though no clinical breakpoints have been defined for anyMagnusiomyces spp^2,13. The most commonly utilized antifungals have been combinations of voriconazole, posaconazole, amphotericin-B, and flucytosine¹⁰. Despite these therapies, M. clavatus mortality rates are 60-85% in some case series².

Pediatric cases of M. clavatus are much less common. Our literature search yielded 10 cases from 2007-2022 (Table 1)^{6, 14-23}. Acute leukemias were the most common underlying diagnoses and all patients were immunocompromised during infection. Disseminated spread occurred in all but two cases. Fungal isolates were identified almost exclusively from blood cultures with CSF and skin biopsy samples also documented^18,22. As with our case, the most commonly used antifungal regimen was voriconazole, amphotericin-B, and flucytosine. Mortality rates, when noted, are more favorable with survival in 80% of cases.

We present the first case of a M. clavatus infection in North America and the 11^th documented pediatric case.M. clavatus should be recognized as a rare, but emerging pathogen in pediatric oncology patients, particularly in the setting of hematologic malignancy and/or echinocandin-based antifungal prophylaxis²³. In this case, early identification, neurosurgical abscess drainage, and aggressive combination antifungal therapy led to successful management of disseminated disease, which allowed for an effective allogeneic hematopoietic stem cell transplant.