Unveiling the Hungarian landscape of laboratory and clinical management capacities for invasive fungal infections: navigating the frontlines against fungal menaces.

Background: Antifungal diagnostic capacity has been documented in various countries, there is a lack of comprehensive research on clinical mycology diagnostics and treatment in Hungary. Methods: We conducted an online survey encompassing questions that explored various aspects of the mycology diagnostic and antifungal therapy-related information. The survey aimed to gather details about institutional profiles, perceptions of invasive fungal infections (IFIs), and access to microscopy, culture, serology, antigen detection, molecular testing, and therapeutic drug monitoring. Results: As of May 2023, a total of 17 institutions responded to the questionnaire. Seven participants categorized the institutional incidence of IFI as 'very low', four as 'low', and six as 'mild'. The majority of centers identified Candida spp. (94%) and Aspergillus spp. (82%) as the most prevalent fungal pathogens. Nearly half of the laboratories (47%) reported using matrix-assisted laser desorption/ionization-time of flight mass spectrometry for identification. All institutions had access to microscopy and culture-based diagnostic approaches. A significant number of centers had access to antigen detection (71%) and various molecular assays (59%). Regarding antifungal agents, all reporting sites used at least one triazole, with voriconazole (77%) being the most common mold-active azole. Furthermore, 71% of the centers applied at least one formulation of amphotericin B, and 65% to one echinocandin. However, only 18% of the centers used 5-flucytosine. Conclusion: Resource availability for diagnosing and treating IFI in Hungary varies across hospitals based on location. Surveys help identify gaps and limitations in this area. To address these challenges, interregional cooperation within Hungary could be a facilitating strategy.

METHODS: We did an online survey with questions about how hospitals in Hungary handle fungal infections. We wanted to know about the hospitals' characteristics, how they see these infections, and what tools they use for diagnosis and treatment. RESULTS: As of May 2023, we got responses from 17 hospitals. Some said they hardly ever see these infections, while others said they see them a bit more. Most hospitals found Candida and Aspergillus as the most common fungal culprits. Many used a tool called MALDI-TOF MS for identification. All of them had ways to look at samples under a microscope and grow them in a dish. Many hospitals had tests to look for certain things in the blood (71%), and they also used different genetic tests (59%). When it came to medicines, they all had at least one kind of medicine called a triazole, with voriconazole being the most common one. They also had amphotericin B and echinocandins. But only a few had a medicine called 5-flucytosine. CONCLUSION: Hospitals in Hungary differ in how they handle fungal infections. Doing surveys like this can help find problems and limits. To fix these issues, hospitals in different parts of Hungary can work together.

Exploring how Hungary deals with serious fungal infections: facing fungal threats head-on Background: While various countries have looked into their ability to diagnose fungal infections, there hasn't been a comprehensive study on how Hungary deals with diagnosing and treating these infections.

Diagnosis and Treatment of Invasive Aspergillosis Caused by Non-fumigatus Aspergillus spp.

With increasing frequency, clinical and laboratory-based mycologists are consulted on invasive fungal diseases caused by rare fungal species. This review aims to give an overview of the management of invasive aspergillosis (IA) caused by non-fumigatus Aspergillus spp.-namely A. flavus, A. terreus, A. niger and A. nidulans-including diagnostic and therapeutic differences and similarities to A. fumigatus. A. flavus is the second most common Aspergillus spp. isolated in patients with IA and the predominant species in subtropical regions. Treatment is complicated by its intrinsic resistance against amphotericin B (AmB) and high minimum inhibitory concentrations (MIC) for voriconazole. A. nidulans has been frequently isolated in patients with long-term immunosuppression, mostly in patients with primary immunodeficiencies such as chronic granulomatous disease. It has been reported to disseminate more often than other Aspergillus spp. Innate resistance against AmB has been suggested but not yet proven, while MICs seem to be elevated. A. niger is more frequently reported in less severe infections such as otomycosis. Triazoles exhibit varying MICs and are therefore not strictly recommended as first-line treatment for IA caused by A. niger, while patient outcome seems to be more favorable when compared to IA due to other Aspergillus species. A. terreus-related infections have been reported increasingly as the cause of acute and chronic aspergillosis. A recent prospective international multicenter surveillance study showed Spain, Austria, and Israel to be the countries with the highest density of A. terreus species complex isolates collected. This species complex seems to cause dissemination more often and is intrinsically resistant to AmB. Non-fumigatus aspergillosis is difficult to manage due to complex patient histories, varying infection sites and potential intrinsic resistances to antifungals. Future investigational efforts should aim at amplifying the knowledge on specific diagnostic measures and their on-site availability, as well as defining optimal treatment strategies and outcomes of non-fumigatus aspergillosis.

A budget impact analysis of bezlotoxumab versus standard of care antibiotics only in patients at high risk of CDI recurrence from a hospital management perspective in Germany.

BACKGROUND: Clostridioides difficile infection (CDI) is one of the leading nosocomial infections, resulting in increased hospital length of stay and additional treatment costs. Bezlotoxumab, the first monoclonal antibody against CDI, has an 1 A guideline recommendation for prevention of CDI, after randomized clinical trials demonstrated its superior efficacy vs. placebo. METHODS: The budget impact analysis at hand is focused on patients at high risk of CDI recurrence. Treatment with standard of care (SoC) + bezlotoxumab was compared with current SoC alone in the 10 most associated Diagnosis Related Groups to identify, analyze, and evaluate potential cost savings per case from the German hospital management perspective. Based on variation in days to rehospitalization, three different case consolidation scenarios were assessed: no case consolidation, case consolidation for the SoC + bezlotoxumab treatment arm only, and case consolidation for both treatment arms. RESULTS: On average, the budget impact amounted to € 508.56 [range: € 424.85 - € 642.19] for no case consolidation, € 470.50 [range: € 378.75 - € 601.77] for case consolidation in the SoC + bezlotoxumab treatment arm, and € 618.00 [range: € 557.40 - € 758.41] for case consolidation in both treatment arms. CONCLUSIONS: The study demonstrated administration of SoC + bezlotoxumab in patients at high risk of CDI recurrence is cost-saving from a hospital management perspective. Reduced length of stay in bezlotoxumab treated patients creates free spatial and personnel capacities for the treating hospital. Yet, a requirement for hospitals to administer bezlotoxumab is the previously made request for additional fees and a successful price negotiation.

[Fever in Cancer Patients]. / Fieber bei Krebspatienten.

Fever in cancer patients is a medical emergency until a severe infection has been ruled out. In case of neutropenia prompt diagnostic work-up should be paralleled by empiric antibiotic treatment. Underlying malignancy as well as treatments may impair immune response and thus pave the way for less virulent pathogens. So the spectrum of infections comprises both pathogens that cause disease in immunocompetent patients and a variety of rarer organisms. After collecting two pairs of blood cultures, broad-spectrum antibiotic treatment should commence within one to two hours. Depending on the individual patient's risk antimicrobial prophylaxis should be considered.

The cost of treating mucormycosis with isavuconazole compared with standard therapy in the UK.

AIM: Mucormycosis is a fungal infection associated with high mortality. Until recently, the only licensed treatments were amphotericin B (AMB) formulations. Isavuconazole (ISAV) is a new mucormycosis treatment. A UK-based economic model explored treatment costs with ISAV versus liposomal AMB followed by posaconazole. MATERIALS & METHODS: As a matched case-control analysis showed similar efficacy for ISAV and AMB, a cost-minimization approach was taken. Direct costs - drug acquisition, monitoring and administration, and hospitalization costs - were estimated from the National Health Service perspective. RESULTS: Per-patient costs for ISAV and liposomal AMB + posaconazole were UK£26,810 and UK£41,855, respectively, with savings primarily driven by drug acquisition and hospitalization costs. CONCLUSION: ISAV may reduce costs compared with standard mucormycosis therapy.

Feasibility and effectiveness of posaconazole prophylaxis in combination with micafungin bridging for patients undergoing allogeneic stem cell transplantation: a 6-yr analysis from the cologne cohort for neutropenic patients.

INTRODUCTION: Invasive fungal diseases (IFDs) are an important cause of morbidity and mortality in patients undergoing allogeneic stem cell transplantation (SCT). METHODS: To compare the effectiveness of two prophylactic antifungal regimens used as standard of care (SOC) in the setting of SCT during the periods of May 2006 - September 2009 (oral posaconazole, POS) and October 2009 - July 2011 (oral posaconazole with intravenous micafungin bridging, POS-MIC), data from the Cologne Cohort of Neutropenic Patients (CoCoNut) study were analyzed after nearest-neighbor matching. Endpoints were occurrence of breakthrough probable/proven IFD under prophylaxis, incidence and duration of persistent febrile neutropenia, incidence of unspecific pneumonic infiltrates, possible IFD, positive galactomannan tests, as well as fungal-free and overall survival. RESULTS: Of 291 patients with 307 SCTs observed during the study period, 212 fulfilled the inclusion criteria and were included into the analysis. Patients receiving POS-MIC were less likely to develop a pneumonic infiltrate (RR 0.71, 95% CI 0.51-1.00) or possible IFD (RR 0.36, 95% 0.15-0.87). They also demonstrated improved fungal-free survival at day 100 (P = 0.009). No significant differences were observed for the incidence of probable or proven IFD, positive galactomannan tests, persistent febrile neutropenia, duration of hospitalization and overall mortality. There was no grade III or IV CTCAE (Common Terminology Criteria for Adverse Events) toxicity related to antifungal prophylaxis. CONCLUSION: Our results suggest that both prophylactic regimens, POS and POS-MIC are feasible, safe and effective. Our data suggest that bridging with intravenous micafungin could indeed improve exposure to antifungal prophylaxis, which may explain the reduced incidence of pneumonia and IFD in the bridging group.

Clinically defined chemotherapy-associated bowel syndrome predicts severe complications and death in cancer patients.

BACKGROUND: Neutropenic patients are at risk of abdominal complications and yet the incidence and impact of these complications on patients' morbidity and mortality have not been sufficiently evaluated. We aimed to assess a clinical rule for early detection of abdominal complications leading to death or transfer to intensive care in patients with chemotherapy-associated neutropenia. DESIGN AND METHODS: This observational multicenter study was carried out in seven German hematology-oncology departments. For inclusion, neutropenia of at least 5 consecutive days was required. Risk factors for "transfer to intensive care" and "death" were assessed by backward-stepwise binary logistic regression analyses. Chemotherapy-associated bowel syndrome was defined as a combination of fever (T ≥37.8 °C) and abdominal pain and/or lack of bowel movement for 72 hours or more. Five hundred and twenty-one neutropenic episodes were documented in 359 patients. RESULTS: The incidence of chemotherapy-associated bowel syndrome was 126/359 (35%) in first episodes of neutropenia. Transfer to intensive care occurred in 41/359 (11%) and death occurred in 17/359 (5%) first episodes. Chemotherapy-associated bowel syndrome and duration of neutropenia were identified as risk factors for transfer to intensive care (P<0.001; OR 4.753; 95% CI 2.297-9.833, and P=0.003; OR 1.061/d; 95% CI 1.021-1.103). Chemotherapy-associated bowel syndrome and mitoxantrone administration were identified as risk factors for death (P=0.005; OR 4.611; 95% CI 1.573-13.515 and P=0.026; OR 3.628; 95% CI 1.169-11.256). CONCLUSIONS: The occurrence of chemotherapy-associated bowel syndrome has a significant impact on patients' outcome. In future interventional clinical trials, this definition might be used as a selection criterion for early treatment of patients at risk of severe complications.