Search Results (121)

Background: Posaconazole is an antifungal medication used to treat invasive fungal infections (IFI) in pediatric onco-hematological patients. Its approval for pediatric use was recent, and limitations still apply. Despite limited data, the safety and efficacy profile appear generally favorable in children. This study describes how posaconazole is used across centers affiliated with the Associazione Italiana Ematologia e Oncologia Pediatrica (AIEOP). Methods: A national survey was conducted among physicians within the AIEOP network to evaluate current use of posaconazole in pediatric cancer patients, including those undergoing hematopoietic stem cell transplantation (HSCT). A 25-item web questionnaire was developed and distributed in June 2024. Data analysis involved descriptive statistics. Results: Twenty-one of thirty-one centers (68%) responded, reporting availability of various posaconazole formulations: oral suspension (76%), delayed-release tablets (95%), and intravenous solution (14%). Posaconazole was primarily used for prophylaxis in patients with acute lymphoblastic leukemia (ALL, 38%), acute myeloid leukemia (AML, 38%), and aplastic anemia (19%). It was also used as secondary prophylaxis against previous possible or probable IFI or as salvage therapy for probable or confirmed aspergillosis or mucormycosis, often combined with other treatments. Drug plasma level monitoring was common but varied in scheduling across centers. Most centers (74%) discontinued posaconazole if adverse events suspected drug–drug interactions, such as with vincristine. Conclusions: Posaconazole is widely used in AIEOP centers, though application varies significantly. This variability emphasizes the need for prospective studies to better define indications, dosing, and monitoring protocols for pediatric use of this antifungal. Full article

Background: Invasive aspergillosis (IA) is a life-threatening infection in immunocompromised patients, including those with hematologic malignancies and hematopoietic stem cell transplants. While adult IA has been well characterized, data on pediatric populations remain limited, and potential age-related differences are often overlooked in current management guidelines. Methods: We conducted a retrospective matched cohort study at a tertiary cancer center, evaluating IA cases diagnosed over a 31-year period. Pediatric patients (≤18 years) with proven or probable IA were matched 1:3 with adult IA cases based on year of diagnosis, underlying disease, and history of hematopoietic cell transplantation. We compared demographics, clinical presentation, diagnostic modalities, microbiology, antifungal prophylaxis, and treatment approaches between the two groups. Results: The study included 34 pediatric and 102 matched adult IA cases. Pediatric patients were significantly more likely to present with neutropenia (p = 0.04) and sinus involvement (p = 0.048). Serum galactomannan testing was more often positive in pediatric patients (p = 0.027), whereas bronchoalveolar lavage galactomannan was more frequently positive in adults (p = 0.003). Differences in antifungal prophylactic regimens were also observed. Conclusions: Our findings underscore significant age-related variations in IA epidemiology, diagnostics, and management. These results support the development of age-specific diagnostic algorithms and antifungal strategies. Full article

Background: Adult acute lymphoblastic leukemia (ALL) patients are at increased risk of invasive fungal infections (IFIs) due to intensive therapy and prolonged neutropenia. While pediatric guidelines support administering fluconazole or mold-active agents, the evidence in adults is limited. This study presents the first multicenter retrospective comparison of fluconazole and micafungin use in this setting. Methods: We retrospectively analyzed 336 adult ALL patients from 11 centers in Türkiye (2010–2024) who received fluconazole (n = 230) or micafungin (n = 106) during induction chemotherapy. IFIs were classified according to the EORTC/MSG criteria. Results: The median age was 38.5 years, and 38.7% were female. Proven/probable IFIs occurred in 8.9% of patients, with similar rates between the fluconazole and micafungin groups (8.7% vs. 9.4%; p = 0.82). Multivariate analysis confirmed no significant association between the prophylactic antifungal type and IFI incidence, indicating comparable outcomes across groups. The median prophylaxis duration was longer with fluconazole, while the discontinuation rates, switch patterns, and subsequent antifungal use were comparable. The overall infection rates (~60%) and distribution of bacterial, viral, and polymicrobial infections were similar between the two groups. Prior bacterial infection increased the risk of IFI by 2.7-fold, and IFI-positive patients had longer neutropenia. At the end of induction, the remission, refractory, and mortality rates were similar between groups. The median overall survival was 24 months. Conclusions: Fluconazole and micafungin showed similar efficacy as the primary antifungal prophylaxis treatment in adult ALL patients. Given the limited evidence in adults and the ongoing need to optimize antifungal strategies, prospective randomized trials directly comparing these agents in this population are needed to confirm and expand upon our findings. Full article

We report a rare case of Rhodotorula mucilaginosa fungemia with a suspected abdominal origin in a 73-year-old man with advanced haematological disease on fluconazole prophylaxis. The patient presented with febrile neutropenia caused by a jejunal microperforation. Despite broad-spectrum antibiotics, the fever persisted, and Rhodotorula mucilaginosa was isolated from blood cultures. High-dose liposomal amphotericin B achieved microbiological clearance and clinical improvement. The case was further complicated by coinfection with Aspergillus fumigatus and Klebsiella oxytoca. To our knowledge, this is one of the few reported cases of abdominal Rhodotorula fungemia, and the first described in the context of fluconazole prophylaxis. This report emphasises the importance of recognising Rhodotorula as a true pathogen and highlights the challenges of managing rare fungal infections in immunocompromised hosts. Full article

There are no data available on the effectiveness and safety of isavuconazole (ISA) for treating breakthrough invasive fungal infections (bIFIs). A retrospective and prospective cohort study was conducted between January 2020 and March 2025 in 13 centers in Argentina. Hematologic diseases (HD) and hematopoietic cell transplantation (HCT) patients who received ISA for IFI were included and followed for 12 weeks. Patients with proven and probable bIFIs and non-bIFIs were compared. One hundred and sixty-three patients were included. IFIs were classified as proven (13.5%), probable (26.9%) and possible (59.5%). Among 66 proven and probable IFIs, 53% were bIFIs, with aspergillosis and mucormycosis being the most common. Twenty-three (34.8%) patients had acute myelogenous leukemia, and 40.9% had received HCT. Forty-eight (72.7%) patients experienced neutropenia, with a median duration of 26 days (interquartile range [IQR] 16–44). Fluconazole and posaconazole were the most frequently received antifungal prophylaxis. ISA was prescribed as first-line therapy in 31 (46.9%) patients. The other 35 received ISA as a continuation therapy, mainly as a step-down therapy after liposomal amphotericin B. Four (6.1%) patients developed adverse effects, and one discontinued ISA. The 90-day overall clinical response between patients with bIFI vs. non-bIFI was 91.4% vs. 70.9% (p = 0.052). The 90-day overall and IFI-related mortality rates were, respectively, 11.4% vs. 32.3% (p = 0.068) and 5.7% vs. 9.7% (p = 0.659). The study data evidence ISA effectiveness and safety for the treatment of HD and HCT patients with and without bIFIs. Full article

Evolving antifungal prophylaxis approaches have reshaped candidemia patterns and outcomes in hematological malignancy (HM) patients. This study aimed to evaluate temporal changes in candidemia incidence, species distribution, and factors associated with mortality in relation to prophylaxis practices. Adult HM patients with candidemia between 2009 and 2023 were included. Clinical and microbiological data were analyzed, and candidemia rates were compared across different prophylaxis periods. Sixty-six patients were identified, with acute myeloid leukemia (AML) being the most common underlying malignancy (40.9%). Non-albicans Candida species predominated, especially C. krusei and C. tropicalis. In AML patients, candidemia incidence significantly decreased over time (β = −0.694, p = 0.004), with the lowest rates observed during the extended-release posaconazole tablet era (2016–2023). However, 30-day mortality remained high (53%) and unchanged across periods. Multivariate analysis identified C. tropicalis and total parenteral nutrition as independent risk factors for 30-day mortality (OR: 4.3 and 4.6, p < 0.05), while antifungal prophylaxis was protective (OR: 0.07, p = 0.017). In patients with AML, posaconazole prophylaxis, particularly in the extended-release tablet formulation, significantly reduced the incidence of candidemia. However, overall 30-day mortality rates remained high, with C. tropicalis being a major contributor. Thus, individualized prophylaxis and treatment strategies are crucial for improving outcomes. Full article

Mold-active prophylaxis has reduced the incidence of invasive pulmonary aspergillosis (IPA) in patients with hematological malignancies (HMs), but breakthrough IPA (Bt-IPA) is increasingly encountered. Therefore, we studied determinants of Bt-IPA risk and its prognostic significance. We retrospectively reviewed culture-positive proven/probable IPA cases in HM patients at MD Anderson Cancer Center (2016–2021). Bt-IPA and non-Bt-IPA cases were compared to characterize risk factors, clinical presentation, and outcomes. Independent predictors of 42-day all-cause mortality were assessed using propensity score-adjusted Cox regression. Among 118 IPA cases, 50 (42.4%) were Bt-IPA. Bt-IPA was associated with acute leukemia/myelodysplastic syndrome, active HM, severe neutropenia (<100/mm³), and graft-versus-host diseases. Uncommon Aspergillus species (non-fumigatus, flavus, terreus, or niger) were more frequent in Bt-IPA than non-Bt-IPA (20.4% vs. 4.8%, p = 0.010). Forty-two-day mortality was higher in Bt-IPA (65.3% vs. 37.3%, p = 0.003), but Bt-IPA itself was not an independent predictor or mortality (p = 0.064), which was instead driven by neutropenia (p = 0.020) and hypoalbuminemia (p = 0.002). In conclusion, Bt-IPA accounted for nearly half of contemporary IPA cases and was linked to host-related risk factors and the recovery of uncommon Aspergillus species. Although not an independent prognostic predictor, Bt-IPA reflected poor host status. Thus, early diagnosis, immune enhancement strategies, and effective first-in-class antifungals may improve outcomes. Full article

Aspergillosis in immunocompromised individuals is a serious and potentially life-threatening infection, as the weakened immune system cannot effectively fight the Aspergillus fungus. This review provides an in-depth examination of aspergillosis in patients with various conditions that compromise immunity, including hematological disorders, HIV, SARS-CoV-2 pneumonia, influenza, and those who have undergone solid organ transplants. The clinical manifestations of aspergillosis are influenced by factors such as the host’s underlying comorbidities, immune response, and immune suppression due to medications or treatments. The review delves into the epidemiology of aspergillosis, exploring various risk factors that predispose individuals to infection. It also discusses the wide range of clinical symptoms, highlighting the challenges in diagnosis and the importance of early detection. The review contrasts traditional diagnostic approaches with emerging molecular techniques, emphasizing the role of advanced diagnostics in improving outcomes. A proposed clinical decision-making flowchart is provided to assist healthcare professionals in managing suspected cases of aspergillosis. In addition to diagnostic challenges, the review addresses antifungal prophylaxis, pre-emptive therapy, and the growing concern of pharmacological resistance to antifungal agents. It concludes with a discussion of future research directions, underscoring the need for improved therapeutic strategies and preventative measures in immunocompromised patients to reduce the burden of this severe fungal infection. Full article

Onychomycosis is a prevalent and clinically relevant complication among individuals with diabetes. It is associated with an elevated risk of secondary fungal and bacterial infections, foot ulceration, and, in advanced cases, amputation. Factors contributing to the increased prevalence of onychomycosis in this population include age, peripheral vascular disease, poor glycemic control, neuropathy, suboptimal foot hygiene, and nail trauma. While dermatophytes are the most common pathogens, diabetic patients are more prone to mixed infections involving Candida species with varying antifungal susceptibility profiles, necessitating accurate identification to guide therapy. Prompt diagnosis and early intervention are important to prevent complications. Systemic antifungals such as terbinafine and itraconazole are considered first-line therapies, particularly for moderate to severe onychomycosis. However, drug interactions, renal, hepatic, and metabolic comorbidities may necessitate individualized treatment plans. For patients with mild to moderate disease, or contraindications to oral therapy, topical agents such as efinaconazole or tavaborole offer viable alternatives. Adjunctive measures, including education on foot hygiene, prompt treatment of tinea pedis, and environmental sanitization, are important in preventing recurrence and reinfection. This review summarizes the epidemiology, diagnosis, and treatment considerations for onychomycosis in diabetic patients, emphasizing the need for individualized care to improve outcomes in this high-risk population. Full article

Background/Objective: Candidemia is a serious complication following intensive chemotherapy and is associated with high mortality in pediatric patients. This study aimed to identify the factors associated with 28-day mortality in pediatric patients with candidemia. Methods: We retrospectively analyzed 63 pediatric patients diagnosed with acute leukemia and candidemia following intensive chemotherapy. Clinical characteristics, laboratory findings, and epidemiological data were collected. Antifungal susceptibility data were available for 60 patients. Kaplan–Meier survival analysis was used to estimate the 28-day mortality rate, and Cox regression was performed to identify prognostic factors. Results: The 28-day mortality rate among the 63 patients (57.1% male, median age 9.74 years) was 36.5%. Candida tropicalis was the predominant species (96.8%). Antifungal susceptibility rates were 100% for amphotericin B and caspofungin and 22.2% for fluconazole. The factors independently associated with reduced 28-day mortality were an absolute lymphocyte count (ALC) ≥ 0.2 G/L at the time of candidemia diagnosis (5.3% vs. 50% mortality; hazard ratio [HR] = 0.08; 95% confidence interval [CI], 0.01–0.61), the use of antifungal prophylaxis (AFP) (26.3% vs. 52%; HR 0.31; 95% CI, 0.13–0.74), and granulocyte transfusion (GTX) combined with granulocyte colony-stimulating factor (G-CSF) (20% vs. 47.4%; HR = 0.31; 95% CI, 0.11–0.85). Conclusions: Our findings suggest that an ALC ≥ 0.2 G/L, AFP, and the administration of a GTX combined with G-CSF may be considered favorable prognostic factors. Full article

Pneumocystis pneumonia (PCP) is a serious fungal infection affecting immunocompromised hosts. Decompensated cirrhosis leads to cirrhosis-associated immune dysfunction (CAID), a form of impaired cellular immunity that may predispose patients to opportunistic infections such as PCP. We conducted a retrospective review of 727 patients with proven or probable PCP from 2017 to 2025. Of these, 33 had decompensated cirrhosis. These patients were stratified into two groups: Cirrhosis Only (n = 16) and Cirrhosis with Additional Immunocompromising Conditions (n = 17). Among the patients with cirrhosis, the overall mortality was 48%, with the 90-day mortality reaching 57.6% (95% CI: 39.2–74.5%). Compared with those without cirrhosis, the patients with cirrhosis had a higher risk of mortality (OR: 4.08, 95% CI: 2.01–8.30, p < 0.001), increased intensive care unit (ICU) admission (87% vs. 42%, p < 0.001), and greater need for renal replacement therapy (54.6% vs. 7.5%, p < 0.001). These findings suggest that decompensated cirrhosis alone may represent a sufficient and underrecognized risk factor for PCP, with a high associated mortality. Given the preventable nature of this infection, future studies are needed to assess the incidence, define the risk, and investigate the role of prophylaxis in this vulnerable population. Full article

Background: Invasive fungal infections (IFIs) after liver transplantation (LT) remain a concern. No universal protocol for antifungal prophylaxis in LT exists. Antifungal prophylaxis varies across European centers. Studies suggest risk stratification for prophylaxis. This study assessed IFI frequency and outcomes in adult LT recipients without antifungal prophylaxis and evaluated risk stratification for predicting IFIs. Method: A retrospective analysis of clinical and microbiological data from 244 liver transplant patients focused on IFI within 100 days post-transplantation. Of these, 225 (92%) had right liver transplants from living donors. We assessed two risk stratification models for predicting IFI: one categorizes patients into low- and high-risk groups, and the other divides patients into three categories, with two eligible for prophylaxis and one not. Results: Of 244 patients, 3% (seven individuals) developed invasive fungal infections (IFI), including two aspergillosis and five candidiasis. IFI occurred in 8% of high-risk and 2% of low-risk patients in the first stratification, with no significant difference between groups (p = 0.144). In the second stratification, IFI was found in 4% of the target and 2% of non-target groups, without a significant difference (p = 0.455). Patients with IFI showed higher mean MELD scores of 21.71 ± 2.35 versus 17.04 ± 6.48 in those without IFI (p < 0.05). Conclusions: This study evaluated IFI outcomes without systemic antifungal prophylaxis in LT recipients. Limited antifungal use in a major living liver donor transplantation (LDLT) group, with low MELD scores and immunosuppression protocols, could be feasible. Future multicenter studies can improve understanding and develop prophylaxis algorithms for LT settings. Full article

Background: Invasive fungal infections (IFIs) are a major complication in patients with acute myeloid leukemia (AML), particularly during chemotherapy-induced neutropenia. Posaconazole is the standard drug for primary antifungal prophylaxis (PAP), but its use is limited by oral bioavailability and CYP3A4 interactions. Study Objective: This study aims to evaluate the clinical efficacy and safety of intravenous caspofungin versus oral posaconazole as PAP in AML patients during their first cycle of chemotherapy and assess their subsequent impact on clinical outcomes. Methods: A retrospective, monocentric study was conducted on 75 consecutive AML patients treated at the Federico II University Medical School of Naples, Italy (2021–2025). Patients received either caspofungin or posaconazole as PAP based on the drug–drug interaction risk or clinical conditions. IFIs were diagnosed using EORTC/MSG criteria. Logistic and Cox regression models were used to assess risk factors and overall survival (OS). Results: IFI incidence was 13.3% overall (9.4% proven/probable). No significant difference was found between the caspofungin and posaconazole groups (six vs. four IFIs; p = 0.878). Post-chemotherapy refractory AML (OR = 11.9; p = 0.003) and liver disease (OR = 30.4; p = 0.004) independently predicted IFI development. Median OS did not significantly differ in patients receiving caspofungin versus posaconazole (29.3 vs. 32.1 months, p = 0.6). Conclusions: Caspofungin appears clinically comparable to posaconazole for PAP in AML during the induction phase, especially when azole use is contraindicated. Prospective studies are warranted to refine prophylactic strategies in the era of new AML therapies. Full article

Background: Myelotoxicity, usually manifested by moderate leukopenia (particularly neutropenia), is a well-known adverse drug reaction to azathioprine (AZA) therapy. Thiopurine methyltransferase (TMPT) and nucleoside diphosphate-linked moiety X-type motif 15 (NUDT15) genotyping are not routinely performed in patients starting AZA therapy due to their low cost-effectiveness. Additionally, the concomitant use of xanthine oxidase inhibitors and 5-aminosalicylates may slow the metabolism of 6-mercaptopurine. Case Description: We describe a case of a 26-year-old Caucasian man with Crohn’s disease and psoriatic arthritis treated with mesalazine and AZA (100 mg daily) who developed prolonged bone marrow aplasia and neutropenic fever after increasing the daily dose of AZA from 100 to 150 mg (from 44 to 66 mg/m²), without frequent total blood count monitoring. Discontinuation of AZA, multiple transfusions of red blood cells and platelet concentrate, filgrastim, empirical antibiotic therapy, and antiviral and antifungal prophylaxis were obtained after 11 days complete recovery of bone marrow aplasia. Methods: Genomic DNA genotyping of coding regions of TPMT (exons 2–9) and NUDT15 (exons 1–3). Results: Heterozygous alleles in the untranslated region (c.460G>A and c.719A>G) associated with TPMT deficiency and a benign variant (c.*7G>A) in the 3′-UTR of NUDT15 with no effect on enzyme activity were found. Conclusions: This case highlights the importance of monitoring the total blood count frequently during the first weeks of treatment with moderate-to-high doses of AZA. Furthermore, the interaction between AZA and mesalazine may play a significant role in the development of prolonged bone marrow aplasia. Full article

Introduction: The consumption of systemic antifungals is on the rise. However, a significant proportion of systemic antifungal prescriptions is inappropriate. Inappropriately prescribed antifungals are problematic, but there has been minimal emphasis on ensuring the appropriate prescription of systemic antifungals. Local studies regarding the patterns and appropriateness of antifungal prescriptions are also lacking. Materials and Methods: In this retrospective, single-centre, observational study, every in-patient prescription order of systemic antifungals in a regional hospital in Hong Kong between 1 May and 31 July 2023 was reviewed via electronic patient records. The appropriateness of a systemic antifungal prescription was assessed by its indication, dosage, duration and antifungal–concomitant drug interactions by a single reviewer. Results: A total of 177 prescriptions orders were collected. Itraconazole, micafungin and fluconazole were the most prescribed systemic antifungals. The haematology team, infectious disease team and ICU were the major systemic antifungal prescribers in this study. The overall appropriateness of systemic antifungal prescriptions was 27.7% (49/177), with an appropriateness of 72.9% (129/177) for indications, 57.1% (101/177) for dosage, 91.5% (162/177) for duration and 71.6% (127/177) for antifungal–concomitant drug interactions. Triazole antifungals had an overall prescription appropriateness of only 15% and were more likely to be prescribed inappropriately than non-triazole antifungals (p < 0.001). Common prescription pitfalls include (i) starting a systemic antifungal for sputum culture that grew Candida spp., (ii) debatable prophylaxis with itraconazole capsules, (iii) overlooking potentially serious antifungal–drug interactions. Conclusions: Inappropriate systemic antifungal prescription is not uncommon in Hong Kong. Establishing an antifungal stewardship programme in public hospitals may be beneficial. Full article