Invasive mold infections (IMIs) remain a leading cause of morbidity and mortality in susceptible pediatric populations. Numerous challenges exist in diagnosis and management, with limited pediatric clinical trial data.

Primary amebic meningoencephalitis (PAM) is a rare but rapidly fatal infection of the central nervous system caused by the thermophilic free-living amoeba Naegleria fowleri. The disease often presents with clinical and cerebrospinal fluid (CSF) findings that closely mimic acute bacterial meningitis, making early diagnosis particularly challenging. We report the case of a 29-year-old woman with poorly controlled type 1 diabetes who presented with acute fever, severe headache, vomiting, and meningeal signs. Within 24 hours, her condition progressed to visual and auditory hallucinations, generalized tonic-clonic seizures, and decreased consciousness. CSF analysis revealed neutrophilic pleocytosis, elevated protein levels, and low glucose concentration, initially suggesting bacterial meningitis. Brain MRI demonstrated bilateral cortical-subcortical hyperintense lesions involving the frontal, insular, and temporal regions, with associated microhemorrhages, consistent with necrotizing meningoencephalitis. Further history revealed a recent nasal ablution using warm lake water. Microscopic examination of CSF showed findings suggestive of an amoeboid trophozoite, raising suspicion for N. fowleri infection, although definitive parasitological confirmation could not be obtained. Empirical therapy with liposomal amphotericin B, fluconazole, and rifampicin was initiated promptly. The patient showed progressive clinical improvement, with complete recovery of consciousness and marked radiological resolution of lesions on follow-up imaging. This case highlights the diagnostic challenges posed by PAM and underscores the importance of early clinical suspicion and prompt empirical therapy in suspected cases, even in the absence of definitive laboratory confirmation.

Blastomycosis is a rare fungal infection, and disseminated disease in pregnancy is exceedingly uncommon. We report a 26-year-old primigravida at 28 weeks' gestation who presented with progressive knee arthritis and erythematous nodular skin lesions. Skin biopsy and synovial fluid culture confirmed blastomyces dermatitidis. She was treated initially with liposomal amphotericin B but transitioned to itraconazole due to electrolyte abnormalities. Despite complications of severe knee pain and hypokalemia, she improved clinically. At 39 weeks, she underwent induction of labor and cesarean delivery for obstetric indications. The infant was healthy, and placental pathology showed mild villitis without fungal elements. The mother completed 12 months of itraconazole therapy with full remission. This case highlights the importance of considering disseminated fungal infections in pregnancy and adds to the limited literature on maternal and neonatal outcomes of blastomycosis.

Breakthrough invasive fungal infections (bIFIs) are a challenging serious complication in high-risk hematologic patients and allogeneic hematopoietic stem cell transplantation recipients that may negatively impact their outcome. Despite advances in antifungal prophylaxis, diagnostics, and supportive care, bIFI occurrence reflects a complex interaction between host immunosuppression, emergence of resistant pathogens and pharmacological variables, including subtherapeutic drug exposure. Candida spp. have shifted towards non-albicans yeasts, whereas breakthrough mold infections more frequently involve non-fumigatus Aspergillus, Mucorales, Fusarium spp., and Scedosporium/Lomentospora spp. Early clinical recognition, rapid therapy escalation, aggressive diagnostic investigation, a switch to liposomal amphotericin B-based regimens in patients on azole prophylaxis, and therapeutic drug monitoring are essential to improve outcomes. Reducing the growing global burden of bIFIs will also require improved access to high-quality diagnostics and strengthened educational and stewardship efforts that prioritize antifungal resistance as an urgent health concern.

Background: Infantile hepatic hemangiomas (IHH) are common benign vascular tumors in infancy with diverse presentations. Methods: We report a 7-week-old infant presenting with hepatosplenomegaly, multiple skin and hepatic hemangiomas, anemia, and recurrent lung infections. Results: Treatment included propranolol, corticosteroids, and sirolimus, along with antifungal prophylaxis with fluconazole. The patient developed pneumothorax and pulmonary aspergillosis. Despite antifungal therapy with voriconazole and liposomal amphotericin B, along with surgical intervention, her condition deteriorated, resulting in multi-organ failure and death at 8.5 months of age. Conclusions: This case illustrates the complexity of IHH management and highlights the risk of severe infections during immunosuppressive therapy even when standard prophylaxis protocols are applied.

The visceral leishmaniasis (VL) caused by Leishmania infantum and Leishmania donovani is regarded as one of the deadliest forms of parasitic diseases, claiming thousands of victims a year, and is particularly prevalent in tropical and subtropical climates. Even though a healthy immune system can often combat or control the infection, in immunocompromised individuals, the disease emerges chronically, aggressively, and often fatally. In recent years, VL has become a significant public health threat in vulnerable populations due to the increased prevalence of conditions such as HIV/AIDS, hematological malignancies such as lymphoma and leukemia, and the increased use of immunosuppressive drugs among organ transplant recipients. This review aimed to provide an overview of the challenges and limitations related to diagnosing, preventing, and treating VL in immunocompromised patients, as well as their clinical and epidemiological consequences. An analysis of recent clinical and epidemiological data has indicated that common diagnostic tests, especially serological tests such as rK39 and DAT, are insufficiently sensitive and specific for immunocompromised patients, and that molecular methods such as PCR and qPCR are necessary to accurately diagnose and treat early. In the context of treatment, liposomal amphotericin B is still regarded as a first-line drug in many regions of the world, but its effectiveness has been significantly limited due to toxicity, drug resistance, and frequent relapses in immunocompromised individuals. Moreover, prevention programmes for this group of patients remain ineffective due to the lack of definitive preventive drugs and effective vaccines, as well as weak population screening. According to recent immunological studies, deficiencies in cellular immune responses, particularly impaired T helper cell (CD4+) function, defective IFN-γ production, and compromised macrophage function in parasite clearance, play a significant role in the complex pathogenesis of VL in immunosuppressed patients. In patients infected with HIV, Leishmania infection synergistically increases viral loads, reduces antiretroviral therapy response, and increases mortality. In conclusion, the results of this study indicate that VL among immunocompromised patients is not only clinically and therapeutically more challenging but may also, epidemiologically, play a hidden role in the survival of the human reservoir and the spread of the disease.

Management of pulmonary mucormycosis includes intravenous liposomal amphotericin-B (L-AmB), followed by posaconazole or isavuconazole. We aimed to determine the optimal L-AmB duration before switching to triazole therapy. Using data from a retrospective study in France, we performed an emulated trial evaluating stopping L-AmB after 14 days (short treatment) versus continuing L-AmB (long treatment). The benefit of combination L-AmB therapy was also investigated. A cloning, censoring, and weighting approach was used to account for immortal time and indication biases. Ninety-four cases of pulmonary mucormycosis were included, of which 35% had dissemination. Eighty-nine patients received L-AmB first-line therapy for a median of 25 (IQR: 12-54) days, including 18 patients as combination therapy. L-AmB was discontinued for adverse events in 16/89 patients (18%). Treatment was switched to posaconazole (n = 38) or isavuconazole (n = 9) in 47 cases and was switched back to L-AmB due to disease progression in 11/47 (23%) cases. Overall, the 180-day mortality was 54%. Diagnosis in the ICU, dyspnea at diagnosis, disseminated disease, and ground-glass opacities on chest CT scan were associated with increased mortality. No difference in 180-day survival was found between patients receiving short or long L-AmB treatment (HR=0.80, 95% CI [0.29-1.99]) and between patients receiving L-AmB alone or in combination (HR=1.14, 95% CI [0.56-2.32]) in emulated trials, although confidence intervals were wide. Switching to triazole therapy after 14 days of L-AmB treatment was as effective as longer durations while reducing L-AmB side effects. Combination therapy did not improve prognosis. These results could inform randomized clinical trials assessing different first-line therapeutic strategies for pulmonary mucormycosis.

Mucormycosis ranks third among invasive mycoses after Candidiasis and Aspergillosis and is associated with high mortality. Its incidence has increased with the rising number of immunosuppressed patients. In developing countries, the most common predisposing factor is uncontrolled diabetes mellitus (DM), whereas in developed countries it is immunosuppressive conditions. To examine local epidemiological data, predisposing factors, diagnostic and therapeutic options and survival in our center eighty-six adult mucormycosis patients between 2000 and 2020 were retrospectively analyzed. Thirty-nine (45.35%) were male, 47 (54.65%) were female, and the median age was 52 years (IQR, 42.5-62). The most frequent clinical presentation was sinus involvement, observed in 77 cases (89.53%). Of these, 38 (44.18%) were sinonasal, 5 (5.81%) sinoorbital, 9 (10.47%) rhinocerebral, and 25 (29.07%) rhino-orbito-cerebral mucormycosis. The remaining 9 cases (10.47%) had pulmonary mucormycosis. Predisposing factors included hematologic diseases in 51 patients (59.30%), DM in 33 (38.37%), solid organ transplantation (SOT) in 7 (8.14%), and solid organ malignancy in 7 (8.14%). The most common symptoms were fever (70.93%), swelling around the eyes and face (51.16%), pain (40.7%), erythema (34.88%), nasal discharge (30.23%), and headache (25.58%). Most frequent physical examination findings were necrotic lesions in the oral cavity and sinuses (87.21%), ophthalmoplegia (29.07%), ptosis (26.74%), vision loss (25.58%), and proptosis (22.09%). In all cases, amphotericin B formulations were preferred as initial therapy. Patients who received combination therapy (n = 14), 13 used posaconazole (POS) + liposomal amphotericin B (L-AmB) and one patient used itraconazole (ITC) + L-AmB. POS was administered to 14 patients receiving sequential oral therapy. The median duration of amphotericin B therapy was 46.5 days (IQR, 14.7-84.5), and the median total duration of antifungal therapy was 46.5 days (IQR, 14.7-90.3). The most common adverse effect of amphotericin B formulations was hypokalemia [L-AmB 68.75%, amphotericin B deoxycholate (AmB-D) 54.84%, amphotericin B lipid complex (ABLC) 50%]. At least one surgical intervention was performed in 74.42% of cases. The 12-week mortality rate was 48.84%, overall mortality rate was 61.63%. In analysis advanced age [12-week: OR: 1.04 (95% CI: 1.01-1.07), p = 0.011; overall: OR: 1.04 (95% CI: 1.01-1.07), p = 0.026 respectively], coexistence of both hematologic disease and DM [12-week OR: 5.73 (95% CI: 1.16-28.33), p = 0.032] associated with mortality. No significant difference was observed in 12-week mortality between surgical and non-surgical patients (p = 0.107). In contrast, overall mortality was significantly higher in the non-surgical group (81.8% vs. 54.7%, p = 0.024). In univariable logistic regression analysis, surgical intervention was associated with a 73.2% reduction in the odds of overall mortality (OR: 0.268, 95% CI: 0.082-0.882, p = 0.030). In the multivariable logistic regression analysis, age was the only variable significantly associated with 12-week and overall mortality (respectively, p = 0.004 and p = 0.026). Each one-year increase in age was associated with an OR of 1.05 (95% CI: 1.02-1.09) for 12-week mortality and 1.04 (95% CI: 1.01-1.07) for overall mortality. In conclusion; our study showed that despite advanced diagnostic methods and antifungals, mortality remained high, sinus involvement was the most frequent involvement, surgical debridement increased survival, but increasing age was associated with poor prognosis.

Rasamsonia species are thermophilic fungi that primarily cause infection in immunocompromised patients. R.argillacea species complex is frequently misidentified as a pathogen due to its morphological similarity to the genera Penicillium and Paecilomyces and its incidence remains undetermined. This situation further complicates the process of timely diagnosis and treatment. Rasamsonia species can be identified using internal transcribed spacer (ITS) sequence analysis, which is considered the primary fungal barcode. Accurate species identification is imperative for the administration of appropriate antifungal treatment. In this report, a case of acute myeloid leukaemia (AML) with R.argillacea growth was presented. A 69-year-old female patient diagnosed with AML who was undergoing chemotherapy was admitted to the hospital due to febrile neutropenia. Despite the administration of appropriate antibiotic therapy, the patient's fever did not respond and her respiratory distress worsened. A subsequent chest computerized tomography scan revealed the presence of bilateral nodular lesions and halo findings in some nodules. The empirical liposomal amphotericin B was initiated at a dosage of 3 mg/kg/day. Following a 17-day course of empirical amphotericin B therapy, the patient exhibited an escalation in respiratory distress and an increase in her blood galactomannan (GM) level (Platelia™ Aspergillus Ag; Bio-Rad, France). Consequently, intravenous (IV) voriconazole was administered at a loading dose of 2x6 mg/kg followed by a maintenance dose of 2x4 mg/kg. Notwithstanding the administration of voriconazole therapy, the patient's blood GM levels persisted at elevated levels on three separate occasions. Consequently, a bronchoalveolar lavage (BAL) sample was obtained for further analysis. However, no growth was detected in the bronchoalveolar lavage (BAL) culture. The BAL GM level was found to be elevated (optic indices: 4.38). The patient developed increasing respiratory distress and confusion and was intubated. A deep tracheal aspirate (DTA) sample was collected. The patient died shortly thereafter. Velvety, beige-colored colonies were observed in the culture media to which the DTA sample inoculated. Microscopic examination of the culture using a lactophenol cotton blue stain revealed cylindrical conidia, rough-walled conidiophores and long, pointed phialides. The isolate was identified as R.argillacea using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (Bruker, Bremen, Germany). This isolate could not be identified based on colony morphology and microscopic appearance; however, it was identified as R. argillacea using the ribosomal DNA ITS region. Its antifungal susceptibility was then assessed using the microdilution method according to the Clinical and Laboratory Standards Institute M38-A2 guidelines. The minimum inhibitory concentrations (MICs) for the antifungal drugs were as follows: fluconazole >64 μg/mL, itraconazole 0.5 μg/mL, voriconazole >16 μg/mL, posaconazole 0.5 μg/ mL, anidulafungin ≤0.015 μg/mL, micafungin 0.03 μg/mL and amphotericin B 1 μg/mL. In this case, the patient died without the causative agent being identified. Although it cannot be definitively stated that R. argillacea was the cause of the patient's mortality due to the lack of an autopsy, this case was presented because it is the first suspected case of R. argillacea isolated and confirmed by molecular methods in Türkiye and to highlight the importance of not neglecting Rasamsonia species which are rare mold fungi.

Cryptococcus neoformans is an encapsulated opportunistic yeast widely distributed in the environment and classified as critical-priority fungal pathogen by the World Health Organisation due to its high mortality and limited access to timely diagnosis and effective treatment. Infection is typically acquired via inhalation, with the primary pulmonary focus often remaining asymptomatic. Particularly in individuals with impaired cell-mediated immunity, it may disseminate hematogenously to central nervous system (CNS), skin and other organs. Cutaneous cryptococcosis is a rare clinical manifestation and in most cases, represents secondary involvement of disseminated disease. Its clinical presentation is highly variable and may mimic cellulitis, abscesses, ulcers or necrotizing soft-tissue infections, posing significant diagnostic challenges. Ruxolitinib is a Janus-kinase inhibitor used to treat myelofibrosis and polycythemia vera. By suppressing interferon-γ and interleukin-12-mediated immune responses, it impairs macrophage activation, reduces T-helper-1 cell responses, suppresses natural-killer cell function, and regulates hematopoietic activity. However, these immunomodulatory effects predispose patients to invasive opportunistic infections, particularly fungal infections. In the literature, cryptococcal infections associated with ruxolitinib have been reported in a limited number of case reports, most commonly involving the pulmonary and/or central nervous system. Cutaneous involvement is exceedingly rare, and to date, no cases from Türkiye have been reported. In this case report, a 67-year-old woman with myelofibrosis who had been receiving ruxolitinib therapy for three-years and developed cutaneous cryptococcosis infection mimicking necrotizing fasciitis, accompanied by asymptomatic pulmonary involvement was presented. Despite broad-spectrum antibacterials, a small papule on the medial thigh rapidly progressed over 25 days, with severe disproportionate pain raising suspicion of necrotizing fasciitis. On admission, physical examination revealed an 8×8 cm ulcerative tissue defect on the left thigh, with surrounding erythema, ecchymosis, desquamation and hemopurulent discharge. Magnetic resonance imaging demonstrated findings suggestive of necrotising soft-tissue infection, prompting urgent surgical intervention. Intraoperatively, diffuse inflammation and patchy necrotic areas were observed and surgical debridement followed by vacuum-assisted wound closure was performed. Microbiological cultures of deep-tissue specimens yielded C.neoformans and the pathogen was confirmed by matrix-assisted laser desorption/ ionisation-time-of-flight-mass spectrometry (MALDI-TOF-MS). Antifungal susceptibility testing showed minimum inhibitory concentrations of 0.5 µg/mL for amphotericin B and 4 µg/mL for fluconazole. Histopathological examination demonstrated yeast cells within a background of suppurative inflammation and focal necrosis. Although the patient had no respiratory symptoms, chest computed tomography revealed a cavitary pulmonary nodule consistent with fungal infection. Bronchoalveolar lavage cultures showed no microbial growth. Evaluation for central nervous system involvement resulted negative for India-ink staining and cerebrospinal fluid multiplex polymerase chain reaction (PCR) test. These findings were considered consistent with systemic cryptococcosis involving the skin and lungs. Antibacterials were discontinued and intravenous liposomal amphotericin-B plus fluconazole was initiated. After central netvous system involvement was excluded, sequential therapy with fluconazole was planned. Ruxolitinib dose was adjusted by haematology. Significant clinical improvement was observed in the early phase of treatment and pain however, the patient died due to acute pulmonary embolism. This case highlights a rare cutaneous presentation of ruxolitinib-associated cryptococcosis and emphasizes the importance of clinical awareness for opportunistic fungal infections in immunosuppressed patients.

Candida dubliniensis is an opportunistic yeast closely related to Candida albicans and an uncommon cause of central nervous system (CNS) infection. While isolates are often susceptible to azoles, reduced susceptibility or acquired resistance may occur, making species identification and antifungal susceptibility testing clinically relevant. We report a 3-year-old boy with Philadelphia chromosome-positive B-cell precursor acute lymphoblastic leukemia (ALL) in hematologic remission who developed chronic meningitis during maintenance chemotherapy. The initial presentation was non-specific (marked somnolence without fever or meningeal signs) and lumbar puncture performed to exclude CNS relapse revealed neutrophil-predominant pleocytosis and elevated protein; the cerebrospinal fluid (CSF) culture grew C. dubliniensis. Treatment with intravenous liposomal amphotericin B followed by prolonged fluconazole led to clinical improvement and sterile CSF. Six months later, progressive gait disturbance, limb pain, and episodic severe headaches recurred; repeat CSF cultures again yielded C. dubliniensis, with a changed susceptibility profile. Spine MRI demonstrated leptomeningeal enhancement involving the cauda equina nerve roots. Intravenous voriconazole with therapeutic drug monitoring was initiated and combined with intrathecal liposomal amphotericin B (seven doses, dose-escalated up to 3 mg), which was well tolerated and associated with rapid neurologic improvement, CSF sterilization, and radiologic resolution. At 12 months of follow-up, the patient remained infection-free and in leukemia remission. This case highlights that C. dubliniensis chronic meningitis may present subtly yet progress, requiring repeated CSF cultures with susceptibility testing; intrathecal liposomal amphotericin B can be a safe and effective adjunct to systemic therapy in refractory or recurrent disease.