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International audience; BACKGROUND: Voriconazole (VRC), a widely used triazole antifungal, exhibits significant inter- and intra-individual pharmacokinetic variability. The main metabolite voriconazole N-oxide (NOX) can provide information on the patient’s drug metabolism capacity. OBJECTIVES: Our objectives were to implement routine measurement of NOX concentrations and to describe the metabolic ratio (MR), and the contribution of the MR to VRC therapeutic drug monitoring (TDM) by proposing a suggested dosage-adjustment algorithm. PATIENTS AND METHODS: Sixty-one patients treated with VRC were prospectively included in the study, and VRC and NOX levels were assayed by LC-MS/MS. A mixed logistic model on repeated measures was implemented to analyze risk factors for the patient’s concentration to be outside the therapeutic range. RESULTS: Based on 225 measurements, the median and interquartile range were 2.4 μg/mL (1.2; 4.2), 2.1 μg/mL (1.5; 3.0), and 1.0 (0.6; 1.9) for VRC, NOX, and the MR, respectively. VRC C(min) 1.15 and

Magnusiomyces capitatus is an emerging opportunistic yeast, thus far mainly reported from the Western world where fungemia is the most frequent presentation in immunocompromised patients with high mortality. We described a rare case of Magnusiomyces capitatus infection from our hospital in China and reviewed six further cases published to date in Chinese literature. It is noted that half more of the cases (4/7) presented with fungemia in younger, immunosuppressed patients, whereas the remaining cases were with pneumonia in elderly, immunocompetent patients. All seven Chinese cases had favourable outcome with antifungal therapy. Based on the limited in vitro and clinical data, a combination of amphotericin B either with 5-fluorocytosine or voriconazole for fungemia in immunocompromised patients, and although fluconazole is not recommended as first-line therapy in the guideline, in our study, fluconazole alone or with 5-fluorocytosine for local pulmonary infection in immunocompetent patients is effective with good outcome.

Background In recent years, the rate of immunosuppressed patients has increased rapidly. Invasive fungal infections usually occur in these patients, especially those who have had hematological malignances and received chemotherapy. Fusariosis is a rare pathogenic fungus, it can lead to severely invasive Fusarium infections. Along with the increased rate of immune compromised patients, the incidence of invasive Fusarium infections has also increased from the past few years. Early diagnosis and therapy are important to prevent further development to a more aggressive or disseminated infection. Case summary We report a case of a 19-year-old male acute B-lymphocytic leukemia patient with fungal infection in the skin, eyeball, and knee joint during the course of chemotherapy. We performed skin biopsy, microbial cultivation, and molecular biological identification, and the pathogenic fungus was finally confirmed to be Fusarium solani. The patient was treated with oral 200 mg voriconazole twice daily intravenous administration of 100 mg liposomal amphotericin B once daily, and surgical debridement. Granulocyte colony-stimulating factor was administered to expedite neutrophil recovery. The disseminated Fusarium solani infection eventually resolved, and there was no recurrence at the 3 mo follow-up. Conclusion Our case illustrates the early detection and successful intervention of a systemic invasive Fusarium infection. These are important to prevent progression to a more aggressive infection. Disseminate Fusarium infection requires the systemic use of antifungal agents and immunotherapy. Localized infection likely benefits from surgical debridement and the use of topical antifungal agents.

Background Increasing incidence of invasive infections caused by rare fungi was observed over the recent years. Case Here, we describe the first reported case of an infection caused by the thermophilic mold Talaromyces thermophilus. Cultivation and, hence, identification of this fastidious organism is challenging since standard incubation conditions are not sufficient. Retrospective analysis of patient samples and in vitro experiments demonstrated that testing for fungal antigens, i.e., the cell wall components galactomannan and β-1,3-d-glucan, is a promising tool.

OBJECTIVES: Occurrence of invasive fungal respiratory superinfections in patients with COVID-19 has gained increasing attention in the latest studies. Yet, description of acute invasive fungal sinusitis with its management in those patients is still scarce. This study aims to describe this recently increasing clinical entity in relation to COVID-19 patients. STUDY DESIGN: Longitudinal prospective study. METHODS: Prospective longitudinal study included patients diagnosed with acute invasive fungal rhinosinusitis after a recent COVID-19 infection. Antifungal agents given included amphotericin B, voriconazole, and/or posaconazole. Surgical treatment was restricted to patients with PCR negative results for COVID-19. Endoscopic, open, and combined approaches were utilized to eradicate infection. Follow-up for survived patients was maintained regularly for the first postoperative month. RESULTS: A total of 36 patients with a mean age of 52.92 ± 11.30 years old were included. Most common associated disease was diabetes mellitus (27.8%). Mycological analysis revealed infection with Mucor and Aspergillus species in 77.8% and 30.6% of patients, respectively. Sino-nasal, orbital, cerebral, and palatine involvement was found in 100%, 80.6%, 27.8%, and 33.3% of patients, respectively. The most common reported symptoms and signs are facial pain (75%), facial numbness (66.7%), ophthalmoplegia, and visual loss (63.9%). All patients were treated simultaneously by surgical debridement with antifungal medications except for two patients with PCR-positive swab for COVID-19. These two patients received antifungal therapy alone. Overall survival rate was 63.89% (23/36). CONCLUSION: Clinical suspicion of acute invasive fungal sinusitis among COVID-19 patients and early management with antifungal therapy and surgical debridement is essential for better outcomes and higher survival. LEVEL OF EVIDENCE: IV Laryngoscope, 2021.

Introduction: Disease modifying treatments are commonly used in the treatment of multiple sclerosis. As different opportunistic infections have been reported, concerns are also raised regarding the risk of invasive fungal infections. Areas covered: Both clinical trials and observational studies on safety and efficacy of diseases modifying treatment for multiple sclerosis were reviewed and data regarding the occurrence of invasive fungal infections were reported. Papers evaluating the following drugs were reviewed: rituximab, ocrelizumab, alemtuzumab, fingolimod, natalizumab, dimethyl fumarate, interferon, glatiramer acetate, cladribine, teriflunomide. Expert opinion: Overall, the occurrence of invasive fungal infections was low, with most infective events reported among patients treated with monoclonal antibodies and fingolimod. Aspergillosis and cryptococcal meningitidis were the most representative fungal infections. Although not common, these infections may be difficult to diagnose and their fatality rate is often high. For this reason, screening protocols for fungal infections must be implemented in the clinical practice when managing patients with MS.

Background: Cryptococcal meningitis is one of the most devastating infections, particularly in HIV-infected individuals. The increased use of immunosuppressants led to an increase in the incidence of cryptococcosis in HIV-uninfected individuals. This study aimed to compare the characteristics between groups. Methods: This retrospective cohort study was conducted from 2011 to 2021 in northern Thailand. Individuals diagnosed with cryptococcal meningitis aged ≥15 years were enrolled onto the study. Results: Out of 147 patients, 101 were individuals infected with HIV and 46 were non-infected. Factors associated with being infected with HIV included age < 45 years (OR 8.70, 95% CI 1.78–42.62), white blood cells < 5000 cells/cu.mm. (OR 7.18, 95% CI 1.45–35.61), and presence of fungemia (OR 5.86, 95% CI 1.17–42.62). Overall, the mortality rate was 24% (18% in HIV-infected vs. 37% in HIV-uninfected individuals, p-value = 0.020). Factors associated with mortality included concurrent pneumocystis pneumonia (HR 5.44, 95% CI 1.55–19.15), presence of alteration of consciousness (HR 2.94, 95% CI 1.42–6.10), infection caused by members of C. gattii species complex (HR 4.19, 95% CI 1.39–12.62), and anemia (HR 3.17, 95% CI 1.17–8.59). Conclusions: Clinical manifestations of cryptococcal meningitis differed between patients with and without HIV-infection in some aspects. Increasing awareness in physicians of this disease in HIV-uninfected individuals may prompt earlier diagnosis and timely treatment.

We present the case of a man with acute lymphoblastic leukemia and prolonged profound neutropenia, who developed an invasive infection by Fusarium graminearum, acquired via non-cutaneous entry, with gastrointestinal symptoms, sigmoid perforation and liver abscesses due to portal dissemination. The etiologic agent was identified using the 18S-ITS1-5.8S-ITS2-28S rRNA sequence gene, from a liver biopsy. The infection was resolved with surgical drainage and antifungal treatment based on voriconazole. As far as we know, there are no previous reports in the literature of cases of human infection due to Fusarium graminearum.

Mucormycosis is one of the most aggressive invasive mycoses. The mortality rate of patients with mucormycosis, depending on clinical form and background disease, varies from 30% to 100%. This article provides the first description of mucormycosis in Russia after infection caused by SARS-CoV-2, as well as a review of literature reports on mucormycosis in patients with COVID-19 (as of September 2021).

Background Commercially available, noninvasive testing options for histoplasmosis are limited outside of the United States. Objectives To describe the diagnostic performance of a novel Histoplasma antigen enzyme immunoassay (IM EIA) for the diagnosis of histoplasmosis in dogs. Animals Twenty dogs with histoplasmosis, 79 dogs without histoplasmosis, and 11 unclassified dogs providing 202 urine samples. Methods This a prospective study using stored urine samples. Samples were analyzed with the IM EIA and with the commercially available Histoplasma antigen EIA (MV EIA). Dogs were classified based on final proven diagnosis and performance of the IM EIA was described and compared with the MiraVista enzyme immunoassay (MV EIA). Results The diagnostic sensitivity (DSe), specificity (DSp), and accuracy (DAc) of the IM EIA were 70% (51%-89%), 99% (97%-100%), and 93% (81%-100%), respectively. The DSe, DSp, and DAc for the MV EIA were 95% (85%-100%), 99% (97%-100%), and 98% (95%-100%), respectively. The area under the receiver operator characteristic curve was significantly smaller for IM EIA (0.87) as compared with MV EIA (0.97, P = .03). This was primarily due to 6 false negative IM EIA results, 4 from dogs with disease localized to the gastrointestinal tract. The MV EIA was positive in 5/6 of these dogs. Conclusions and clinical importance The IM EIA might be useful for the diagnosis of disseminated histoplasmosis in dogs, but clinical usefulness will be limited in dogs with histoplasmosis localized to the GI tract.

Invasive infections are a major complication before liver transplantation (LT) and in the early phase after surgery. There has been an increasing prevalence of invasive fungal disease (IFD), especially among the sickest patients with decompensated cirrhosis and acute-on-chronic liver failure, who suffer from a profound state of immune dysfunction and receive intensive care management. In such patients, who are listed for LT, development of an IFD often worsens hepatic and extra-hepatic organ dysfunction, requiring a careful evaluation before surgery. In the post-transplant setting, the burden of IFD has been reduced after the clinical advent of antifungal prophylaxis, even if several major issues still remain, such as duration, target population and drug type(s). Nevertheless, the development of IFD in the early phase after surgery significantly impairs graft and patient survival. This review outlines presentation, prophylactic and therapeutic strategies, and outcomes of IFD in LT candidates and recipients, providing specific considerations for clinical practice.

Occurrence of invasive fungal infections has gained significant attention during recent times in patients with COVID-19. Patients with severe form of COVID-19, such as those treated in the intensive care unit with prolonged steroid use, are particularly vulnerable to secondary bacterial and fungal infections. Disseminated systemic mycosis is a life-threatening condition, especially in immunocompromised patients. Here, we report a case of a recovered severe COVID-19 patient, who presented with persistent fever. 18F-FDG-labeled leukocyte scan revealed focal accumulation of radiotracer in the small intestine and right lung lower lobe. Subsequently, performed biopsy revealed mucormycosis.

Background Non-Aspergillus mould infections such as those caused by Scedosporium apiospermum or Lomentospora prolificans are an emerging threat. Few studies have monitored their long-term incidence. Objectives To analyse the epidemiology, risk factors, clinical features and incidence of patients with proven and probable infections. Patients/methods Patients admitted to Gregorio Maranon Hospital between 1998 and 2017 and from whom Scedosporium/Lomentospora was isolated were studied. Subjects were classified as having a probable/proven invasive fungal infection or colonization. Molecular identification and antifungal susceptibility testing of isolates causing infection were performed, as well as a description of the patients and incidence of infection. Results One or more Scedosporium/Lomentospora isolates were identified in 67 patients. Sixteen (23.9%) patients had developed infection: 11 scedosporiosis and 5 lomentosporiosis. Stable incidence was observed throughout the study period. Most patients were immunosuppressed and the most common underlying diseases were haematologic malignancy (25%), solid organ transplantation (25%) and chronic corticoid therapy (25%). Breakthrough infection occurred in four patients, 2/11 (18.2%) cases of scedosporiosis and 2/5 (40%) of lomentosporiosis. Overall mortality was 54.5% (6/11) and 80% (4/5) in subjects with scedosporiosis and lomentosporiosis, respectively. High MICs of amphotericin B and remarkable inter-species susceptibility variability to triazoles was observed for most isolates. Conclusions In contrast to previous studies, the incidence of scedosporiosis and lomentosporiosis has not increased at our hospital over the years. The tendency to cause disseminated infection and a reduced susceptibility to most antifungal agents leads to high mortality.

Summary Fluconazole is one of the most commonly used drugs for antifungal prophylaxis in childhood leukaemia. However, its interaction with vincristine may induce neuropathy and the emergence of antifungal drug resistance contributes to substantial mortality caused by invasive fungal infections (IFIs). In a retrospective single‐centre study, we compared tolerability and outcome of different antifungal prophylaxis strategies in 198 children with acute leukaemia (median age 5·3 years). Until 2010, antifungal prophylaxis with fluconazole was offered to most of the patients and thereafter was replaced by liposomal amphotericin‐B (L‐AMB) and restricted to high‐risk patients only. Vincristine‐induced neurotoxicity was significantly reduced under L‐AMB, as the percentage of patients with severe constipation decreased (15·4% vs. 3·7%, before vs. after 31 December·2010, P = 0·01) and stool frequency increased by up to 38% in polyene‐treated patients (P = 0·005). Before 2011, 10 patients developed confirmed IFIs, most of them were infected with Aspergillus species. After risk adaption in 2011, IFIs were completely prevented (P = 0·007). L‐AMB prophylaxis is beneficial in childhood leukaemia patients, as it offers effective antifungal activity with improved tolerability as compared to fluconazole. The potential impact of our risk‐adapted antifungal treatment should be included in current prophylaxis guidelines for childhood leukaemia.

There is scarce information on the actual incidence of candidemia in COVID-19 patients. In addition, comparative studies of candidemia episodes in COVID-19 and non-COVID-19 patients are heterogeneous. Here, we assessed the real incidence, epidemiology, and etiology of candidemia in COVID-19 patients, and compared them with those without COVID-19 (2020 vs. 2019 and 2020, respectively). We also genotyped all C. albicans, C. parapsilosis, and C. tropicalis isolates (n = 88), causing candidemia in both groups, providing for the first time a genotypic characterization of isolates gathered in patients with either COVID-19 or non-COVID-19. Incidence of candidemia was higher in patients with COVID-19 than non-COVID-19 (4.73 vs. 0.85 per 1000 admissions; 3.22 vs. 1.14 per 10,000 days of stay). No substantial intergroup differences were found, including mortality. Genotyping proved the presence of a low number of patients involved in clusters, allowing us to rule out rampant patient-to-patient Candida transmission. The four patients, involved in two clusters, had catheter-related candidemia diagnosed in the first COVID-19 wave, which demonstrates breaches in catheter management policies occurring in such an overwhelming situation. In conclusion, the incidence of candidemia in patients with COVID-19 is significantly higher than in those without COVID-19. However, genotyping shows that this increase is not due to uncontrolled intrahospital transmission.

We describe a vaccinated lung transplant recipient who experienced a fatal outcome associated with coronavirus disease 2019 (COVID-19). Tocilizumab was administered. The patient exhibited clinical and radiographic evidence of colitis during the course of multiple secondary infections. This report emphasizes the need for more conservative precautions to prevent COVID-19 infection in transplant recipients.

Introduction Invasive fungal infections have always been a major cause of mortality and morbidity and are especially prevalent in the immunosuppressed groups of patients. Members of the Mucoracea family have an increasing incidence and prevalence. It has always been difficult to diagnose this condition due to various reasons. Materials and Methods This was an observational study carried out jointly by the Department of Microbiology and the Department of Pathology for a duration of one year. All patients who presented in various clinical departments with a high index of clinical suspicion for mucormycosis were included in this study. A total of 186 samples were received from suspected cases of mucormycosis and were all subjected to direct microscopy by potassium hydroxide (KOH), fungal culture, and histopathological examination. Results Mucormycosis was documented in 33 out of 186 cases on direct microscopy, whereas 21 were positive on fungal culture. Histopathological positivity was reduced with only 11 cases showing aseptate hyphae suggestive of mucormycosis. Conclusion As these organisms generally do not grow well on routine culture media and with the histopathological results also being not suggestive clearly of mucormycosis, direct microscopy thus becomes more important and essential in the rapid diagnosis of this deadly condition.

Molds are ubiquitous in the environment, and immunocompromised patients are at substantial risk of morbidity and mortality due to their underlying disease and the resistance of pathogenic molds to currently recommended antifungal therapies. This combination of weakened-host defense, with limited antifungal treatment options, and the opportunism of environmental molds renders patients at risk and especially vulnerable to invasive mold infections such as Aspergillus and members of the Order Mucorales. Currently, available antifungal drugs such as azoles and echinocandins, as well as combinations of the same, offer some degree of efficacy in the prevention and treatment of invasive mold infections, but their use is often limited by drug resistance mechanisms, toxicity, drug-drug interactions, and the relative paucity of oral treatment options. Clearly, there is a need for agents that are of a new class that provides adequate tissue penetration, can be administered orally, and have broad-spectrum efficacy against fungal infections, including those caused by invasive mold organisms. Ibrexafungerp, an orally bioavailable glucan synthase inhibitor, is the first in a new class of triterpenoid antifungals and shares a similar target to the well-established echinocandins. Ibrexafungerp has a very favorable pharmacokinetic profile for the treatment of fungal infections with excellent tissue penetration in organs targeted by molds, such as the lungs, liver, and skin. Ibrexafungerp has demonstrated in vitro activity against Aspergillus spp. as well as efficacy in animal models of invasive aspergillosis and mucormycosis. Furthermore, ibrexafungerp is approved for use in the USA for the treatment of women with vulvovaginal candidiasis. Ibrexafungerp is currently being evaluated in clinical trials as monotherapy or in combination with other antifungals for treating invasive fungal infections caused by yeasts and molds. Thus, ibrexafungerp offers promise as a new addition to the clinician's armamentarium against these difficult-to-treat infections. Experiments reported in this manuscript were funded by Scynexis and support for mucormycosis research was provided by the NIH/NIAID under Contract No. HHSN272201700039I (Task order A34-HHSN27200003). Sí

Invasive infections with emerging yeasts such as Geotrichum, Saprochaete/Magnusiomyces, Trichosporon, and other species are associated with high morbidity and mortality rates. Due to the rarity and heterogeneity of these yeasts, medical mycology has lacked guidance in critical areas affecting patient management. Now, physicians and life scientists from multiple disciplines and all world regions have united their expertise to create the “Global guideline for the diagnosis and management of rare yeast infections: an initiative of the European Confederation of Medical Mycology in cooperation with the International Society for Human and Animal Mycology and the American Society for Microbiology.” Recommendations are stratified for high- and low-resource settings and are therefore applicable worldwide. The advantages and disadvantages of various diagnostic methods and treatment options are outlined. This guideline reflects the current best-practice management for invasive rare yeast infections in a range of settings, with the intent of establishing a global standard of care for laboratorians and clinicians alike.

Candida parapsilosis can cause invasive fungal infection which is associated with significant morbidity and mortality. Timely management of this uncommon Candida pathogen is essential to prevent peritoneal dialysis patients from succumbing to the infectious complications of peritonitis related to it. We present a 75-year-old Caucasian female with end-stage renal disease, on peritoneal dialysis at home, who presented with peritonitis features found to be related to this rare Candida species. She was treated with four weeks course of oral fluconazole and was switched to incenter hemodialysis. Physicians need to be aware of this notorious Candida species in peritoneal dialysis patients and prompt management is essential in successful patient outcomes.

The ability to predict invasive fungal infections (IFI) in patients with hematological malignancies is fundamental for successful therapy. Although gut dysbiosis is known to occur in hematological patients, whether airway dysbiosis also contributes to the risk of IFI has not been investigated. Nasal and oropharyngeal swabs were collected for functional microbiota characterization in 173 patients with hematological malignancies recruited in a multicenter, prospective, observational study and stratified according to the risk of developing IFI. A lower microbial richness and evenness were found in the pharyngeal microbiota of high-risk patients that were associated with a distinct taxonomic and metabolic profile. A murine model of IFI provided biologic plausibility for the finding that loss of protective anaerobes, such as Clostridiales and Bacteroidetes, along with an apparent restricted availability of tryptophan, is causally linked to the risk of IFI in hematologic patients and indicates avenues for antimicrobial stewardship and metabolic reequilibrium in IFI. This work was supported by FunMeta Project (ERC-2011-AdG 293714), MicroTher(ERC-2018-PoC-813099), and Gilead (IN-IT-131-4525-518872.9) to L.R. and the GrantAgency of the Czech Republic (GACR No 17-24592Y) and the Czech Ministry ofEducation, Youth and Sports (CETOCOEN PLUS CZ.02.1.01/0.0/0.0/15_003/0000469;LM2015051 and CETOCOEN EXCELLENCE Teaming 2 project CZ.02.1.01/0.0/0.0/18_046/0015975; and Horizon2020 project 857560) to Z.S.

Trichosporon species are some of the most common pathogenic yeasts in Asia, and many are resistant to echinocandin antifungal drugs. Effective treatment of fungal infections requires the selection of appropriate antifungals and the accurate identification of the causal organism. However, in histopathological specimens Trichosporon spp. are often misidentified as Candida species due to morphological similarities. In situ hybridization (ISH) is a useful technique for identifying fungal species in formalin-fixed and paraffin-embedded (FFPE) tissue sections. Although many novel probes for ISH are available, the practical use of ISH for identification of fungi remains limited, in part due to the lack of adequate verifications. We conducted a two-center retrospective observational study in which the ISH technique was used to differentiate Trichosporon spp. and C. albicans in FFPE tissue from autopsy specimens. The study included 88 cases with blood stream yeast infection without Cryptococci extracted from 459 autopsy files of cases with proven invasive fungal infection (IFI). Positive signals for the Trichosporon spp. protein nucleic acid (PNA) probe and C. albicans PNA probe were seen for 7 and 35 cases, respectively, whereas the remaining 46 were negative for both. For the Trichosporon spp.- positive specimens, 5/7 were reported as candidiasis in autopsy records. Our results suggested that accurate histological identification of fungal infections remains challenging, but ISH may be a suitable approach to support histological findings. In addition, this retrospective study suggested that trichosporonosis may have high prevalence among cases of bloodstream yeast infections in Japan.

Limited information exists regarding the optimal dose of posaconazole delayed-release tablet for the treatment of invasive mold infection. Here, we report the case of a previously healthy 44-year-old Thai man who developed coexisting invasive pulmonary aspergillosis and mucormycosis following a car accident. He was treated with posaconazole delayed-release tablet. This report describes the pharmacokinetic/pharmacodynamic study, safety profile, and determination of the appropriate dosage of posaconazole delayed-release tablet in a patient with coexisting invasive aspergillosis and mucormycosis. Posaconazole exposure was analyzed by noncompartmental model. Ratio of area under the plasma concentration-time curve over the minimum inhibitory concentration (AUC/MIC) was applied to maximize the efficacy of posaconazole. The loading dose of 300 mg q 12 hrs was found to be potentially insufficient for achieving the AUC/MIC target for treatment of invasive mold infection with minimum inhibitory concentrations >0.01 mg/L. Early therapeutic drug monitoring to detect the drug concentration of posaconazole delayed-release tablet is necessary so that dosing adjustments can be made, as needed. In addition, a maintenance dose of either 400 or 300 mg once daily could achieve the AUC/MIC targets. These maintenance dosing regimens effectuated a successful clinical outcome with minimal adverse events.

International audience; Invasive aspergillosis (IA) occurs in up to 23% of allogeneic hematopoietic stem cell transplantation (HSCT) patients. Although transplant procedures have changed over time, more late cases of IA are being observed. The objective of this study was to identify the pre-and post-transplant factors of IA in a large cohort of HSCT patients mainly transplanted with reduced-intensity conditioning. This multicenter, case-control study was carried out using data collected between 2005 and 2010 by the Surveillance des Aspergilloses Invasives en France program (Institut Pasteur, Paris) and the European Society for Blood and Marrow Transplantation ProMISe registry. Four control subjects without IA were individually matched to each case based on the center, patient age, and year of the transplant. We identified 185 cases of probable and proven IA and 651 control subjects. The median date of IA after the transplant was 133 days, with 35 cases (19%) of early IA (before day 40), 33 cases (18%) of late IA (days 40 to 100), and 117 cases (63%) cases of very late IA (after day 100). In the multivariate analysis early IA was significantly associated with a lack of engraftment, whereas late and very late IA were significantly associated with more than grade II acute graft-versus-host disease (GVHD); very late IA was also significantly associated with relapse and secondary neutropenia. Two-thirds of IA cases occurred more than 100 days after HSCT with different risk factors from those occurring earlier. Prophylactic strategies should consider the specific risk factors for late and very late IA, especially GVHD, relapse after transplant, and secondary neutropenia.

Paediatric invasive fungal infections have significantly increased over the past few decades, in particular among the immunocompromised population. Candida and Aspergillus spp. are still the most commonly isolated organisms. Image-based assessment of fungal infections can indeed be challenging especially in oncologic al patients where the differential diagnosis relative to other infections and neoplastic lesions cannot be often obvious. Therefore, the knowledge of the main radiological features associated with fungal infections is crucial to achieve an early correct diagnosis and address the most appropriate therapeutic approach. Thus, our aim was to review the main radiological features of paediatric fungal infections with particular focus on positron emission tomography/magnetic resonance imaging (PET/MRI), referring to the experience of our tertiary level hospital.

Objective: To determine if there was an increase in the rate of cases presenting with rhino-orbital-cerebral mucormycosis (ROCM) to a tertiary care center during the first wave of the coronavirus disease 2019 (COVID-19) pandemic and the characteristics of the presenting cases.Methods: Retrospective observational study reviewing ROCM cases presenting from March 25 until September 25, 2020. Cases fulfilling the clinical, radiological, and pathological/microbiological criteria for diagnosis with ROCM were included. The number of cases presenting during the designated interval, their COVID-19 status, comorbidities, and clinical presentation were analyzed. The number of cases during the corresponding interval in the previous 3 years was used as reference to detect if there was a recent spike.Results: Of the 12 ROCM cases identified, 5 had a concurrent positive reverse transcription PCR (RT-PCR) test result for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), 1 had a prior positive result, and 6 did not have concurrent nor prior positive test results. Nine of the 12 cases had poorly controlled diabetes mellitus, and 2 cases had a hematological malignancy. All cases had orbital invasion, and eight cases had cerebral invasion. The number of cases identified during the interval is much higher than the numbers presenting in the prior 3 years during equivalent intervals (range, one to two cases) than those reported in the literature in different settings in the pre-pandemic era.Conclusions: There is an increased rate of ROCM cases presenting to our center during the first wave of the COVID-19 pandemic. This is a preliminary report, and further studies are needed to corroborate the findings and explain possible underlying links.

Certain Penicillium species are emerging opportunistic pathogens. While these can be common causes of airborne contamination of clinical cultures, an increasing number of reports describe clinically significant disease in the immunocompromised population, particularly in patients with hematologic malignancy. The typical site of infection is respiratory, but disseminated infection is also reported with some frequency. Therefore, culture growth of Penicillium in respiratory and other clinical samples from immunocompromised patients requires thorough investigation with clinical correlation. Here we report a case of angioinvasive Penicillium cluniae infection of the right shin in a patient with acute myeloid leukemia and review reported cases of invasive Penicillium infection (excluding Talaromyces marneffei) in hematologic malignancy patients to characterize the emerging pathogen in this vulnerable population.

�������������������� ��� �������� ���� ���������������� �������������������� ���������������������� ������������������������ ����������������. ���������������������� �������������� ���������������������������������� ������������������������ ������������������ 100%. �� ������������ ���������������������� ������������ �� �������� ������������ ������������������������������������ ����������������������, ���������������������������� Lichtheimia ornata. ���������� �������������������������������� ������������ �������������� �������������������� ���� Lichtheimia-����������������������., Mucormycosis is one of the most aggressive mycotic in-fections. The mortality rate of patients with disseminated mucormycosis reaches 100%. The article presents the world's first case of disseminated mucormycosis caused by Lichtheim-ia ornata. We analyzed data of the scientific literature on Lichtheimia-mucormycosis.

This is a Scoping Review on the Management and Outcomes of Intracranial Fungal infections in Africa

Introduction: Rhino-orbito-cerebral mucormycosis is a fatal disease caused by saprophytic fungi seen almost exclusively in diabetic and immunocompromised patients. Aim: To describe various imaging findings of mucormycosis, and to emphasise the importance of imaging in its diagnosis and management. Materials and Methods: A retrospective, observational, single centre study was done including patients with clinical and microbiological evidence of rhino-orbito-cerebral mucormycosis, who had a history of Coronavirus Disease 2019 (COVID-19) infection and had undergone Computed Tomography (CT) and/ or Magnetic Resonance Imaging (MRI) scan of the head, orbit, and paranasal sinuses during the period of one month from 1st-31st May 2021. The clinical and imaging data of 67 such cases were interpreted and analysed by two radiologists. Results: The study included 67 patients out of which 44 were male and 23 were female, and the average age of patients was 49±13 years. During their treatment for COVID-19, 55 (82.08%) patients had a history of hospitalisation and administration of supplemental oxygen, all 67 (100%) patients had taken broad spectrum antibiotics, 56 (83.58%) patients had taken steroids, 20 (29.85%) patients previously had a history of diabetes with worsening of glycaemic control during COVID-19 infection, and 47 (70.15%) patients were diagnosed with new onset hyperglycaemia. On imaging i.e., on CT and/or MRI with or without contrast, the infection was found to primarily affect the sino-nasal region. There was unilateral or bilateral involvement of single or multiple paranasal sinuses in all 67 patients with involvement of nasal cavity in 42 patients. Maxillary sinus was the most common and consistently involved sinus seen in all 67 patients, followed by ethmoid sinus seen in 54 patients. Additionally, 56 patients had extra-sinus disease with spread along vessels, nerves, or via bone erosion. CT showed soft tissue thickening, oedema, and fat stranding with or without bone erosion as the predominant finding in involved areas, while MRI showed Short Tau Inversion Recovery (STIR) hyperintense soft tissue thickening and postcontrast enhancement as the main finding. Conclusion: There is a complex interplay of various COVID-19 infection and treatment related factors that are responsible for increased susceptibility to mucormycosis infection. Imaging plays an important role in aiding the diagnosis, determining the extent and spread of infection, guiding the extent of the surgical intervention, and determining the prognosis of these patients. The contrast enhanced MRI along with plain CT should be the preferred choice of imaging.

Infection is a major complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT) especially cytomegalovirus (CMV) infection and invasive fungal infection (IFI). Taiwan is a high CMV seroprevalence area. Our study aimed to evaluate the incidence, risk factors, the impact on survival of CMV infection (including reactivation and disease) and the association of CMV infection and IFI in recipients after allo-HSCT during the first 100 days after transplantation. This was a retrospective study including 180 recipients of allo-HSCT. A total of 99 patients had CMV reactivation, and nine patients had CMV diseases. There were more mismatched donors, more ATG usage and more transplantation from CMV IgG-negative donor in patients with CMV reactivation. There was no survival difference in patients with or without CMV reactivation. A total of 34 patients had IFIs, and IFI after allo-HSCT was associated with significantly inferior survival. Patients with CMV reactivation did not increase the incidence of overall IFI, but they did result in more late-onset (>40 days) IFI (p = 0.056). In this study, we demonstrated real-world data of CMV infection and IFI from a high CMV seroprevalence area.

Objectives Effective antifungal therapy is important to reduce mortality in patients with invasive fungal infections (IFIs). Numerous factors affect pharmacokinetic/pharmacodynamic (PK/PD) parameters in critically-ill patients. To guide individualised administration in critically-ill patients, it is of great significance to determine the population pharmacokinetics of caspofungin. Methods A prospective study in 42 ICU patients with IFIs was conducted in China. A population pharmacokinetic model of caspofungin was established using a non-linear mixed-effects model, which was utilised to investigate the effects of demographic indices, liver function and kidney function on pharmacokinetics. Additionally, appropriate dosages of caspofungin under various scenarios were determined based on MICs and probability of target attainment (PTA) at specific dosages. Results In critically-ill Chinese patients, clearance (CL), volume of distribution (V) and area under the curve at steady-state (AUCss) of caspofungin were 0.32 L/h, 6.77 L and 135.47 mg•h/L, respectively. Blood albumin and total bilirubin levels were factors affecting CL, while body weight was the only factor affecting V among Chinese people with relatively low weight compared with other populations. A maintenance dose of 50 mg caspofungin achieved a high PTA for treating IFIs caused by Candida albicans (MIC ≤ 0.06 mg/L) and Candida glabrata (MIC ≤ 0.125 mg/L). The maintenance dose of caspofungin should be adjusted to 70–200 mg for IFIs caused by C. albicans (MIC, 0.06–0.125 mg/L). For IFIs caused by Candida parapsilosis, an MIC > 0.03 mg/L is associated with a very low PTA, but higher doses of caspofungin or alternative antifungals need to be further studied. Conclusion The population pharmacokinetic model established here described well the PK/PD characteristics of caspofungin in critically-ill Chinese patients. These results could guide the formulation of individualised caspofungin dosing regimens for critically-ill patients.

Objective: The aim of the study was to observe the clinical efficacy and safety of intravenous and oral sequential treatment with voriconazole for Candida central nervous system (CNS) infection in premature infants. Methods: The study included retrospective analysis of the clinical data of six premature infants with Candida CNS infection admitted to the neonatology department in Shanghai Children’s Hospital between November 2016 and November 2019. By reviewing the characteristics of voriconazole based on the literature, it showed that infants without gastrointestinal dysfunction could be effectively treated by intravenous and oral sequential therapy with voriconazole (both 7 mg/kg/dose, every 12 h). Clinical manifestations, the time required for the cerebrospinal fluid (CSF), blood culture, nonspecific infection markers such as platelets and C-reactive protein (CRP) to turn normal, and drug-related side effects were observed and recorded in the process of treatment. All data were statistically analyzed by T test and Mann–Whitney U test. Results: A total of six premature infants were diagnosed with Candida CNS infection, two cases were diagnosed by a positive CSF culture and four cases were clinically diagnosed. Blood culture was positive for Candida in five cases. Among the 6 patients, 4 cases were Candida albicans and 2 cases were Candida parapsilosis. All the six cases were cured. After 3–5 days of treatment, symptoms such as lethargy, apnea, and feeding intolerance were improved and disappeared; a repeated blood culture turned negative in 3–7 days; CSF returned to normal in 15 ± 9 days on an average. Brain abscess, meningeal inflammation, and other infectious lesions were cleared on cranial magnetic resonance imaging (MRI) after treatment. The average total course of voriconazole was 61 ± 29 days, and the average oral treatment was 28 ± 15 days. No Candida recurrence was found during the treatment, and no drug-related side effects such as skin rash, liver and kidney function impairment, or visual abnormalities were found. The white blood cells, CSF glucose/plasma glucose ratio, and protein in CSF were significantly improved after the treatment (p < 0.05). No statistically significant difference was identified in the liver and kidney function indexes (p > 0.05). Conclusion: Voriconazole is a relatively safe and effective alternative treatment for Candida CNS infection in preterm infants. No severe drug-related side effects were detected.

Background Pneumocystis pneumonia (PCP) is an important cause of acute respiratory failure (ARF) in immunocompromised patients, yet no actual clinical tool suitably identifies patients at risk. Recently, a multivariable prediction model has been proposed for haematology patients with ARF requiring intensive care unit (ICU) admission to assess the risk of PCP (PCP score). However, it has not yet been validated externally. Methods To validate the PCP score, a retrospective cohort study was conducted in two large designated haematology centres in Korea. One-hundred and forty haematology patients with ARF were admitted to ICU. They underwent aetiologic evaluations between July 2016 and June 2019. The predictive ability of the score was assessed with the receiver operating characteristic (ROC) curve analysis for both the discrimination and calibration of the score. Results Among the 141 patients, 13 (9.2%) were finally diagnosed of PCP. Although the median of PCP score in PCP group was higher than in non-PCP group (3.0 [interquartile range 0.0–4.0] vs. 2.0 [0.5–4.0]), the difference was not statistically significant (P = 0.679). The area under the ROC curve of the PCP score in our cohort was 0.535 (95% CI, 0.449–0.620), indicating no discriminatory ability. When using a cut-off of 3.0 the score, the result was 38.5% (95% CI, 13.9–68.4) sensitive and 7.03% (95% CI, 61.6–78.1) specific. The negative predictive value was 58.8% and positive predictive value was 59.8% for a 10% prevalence of PCP. Conclusions In this study, the PCP score was not useful to predict the risk of PCP in haematology patients with ARF. Further prospective validation studies are needed to validate the score’s use in routine clinical practice for the early diagnosis of PCP in haematology patients.

Background: Invasive fungal infection (IFI) is one of the most common nosocomial infections. However, data on the epidemiology of IFI and susceptibility to antifungal agents in China are quite limited, and in particular, no current data exist on the microbiological, and clinical characteristics of IFI patients in Northeast China.\ud\udObjectives: The purpose of this study was to provide a retrospective review of the clinical characteristics, laboratory test results, and risk factor predictions of inpatients diagnosed with IFI. Multivariate regression analysis was used to assess prognostic factors associated with the mortality of these patients.\ud\udMethods: We retrospectively analyzed the results from 509 patients with IFI extracted from the First Hospital of China Medical University from January 2013 to January 2018.\ud\udResults: Neutrophil numbers, total bilirubin, length of stay in the ICU, renal failure, use of immunosuppressants within the past 30 days, stomach tube placement and septic shock were risk factors for death from IFI. Recent surgery (within 2 weeks) and drainage tube placement did not increase mortality in these IFI patients. Increased serum levels of PCT (AUC 0.601, 95% CI 0.536–0.665, P = 0.003) and CRP (AUC 0.578, 95% CI 0.512–0.644, P = 0.020) provided effective predictors of 30-day mortality rates.\ud\udConclusions: We report for the first time epidemiological data on invasive fungal infections in Northeast China over the past 5 years. Despite the limited available clinical data, these findings will greatly aid clinical health care workers with regard to the identification, prevention, and treatment of IFI in hospitalized patients.

To determine the dynamic changes of pathogenic yeast prevalence and antifungal susceptibility patterns in tertiary hospitals in China, we analyzed 527 yeast isolates preserved in the Research Center for Medical Mycology at Peking University, Beijing, China, between Jan 2010 and Dec 2019 and correctly identified 19 yeast species by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF-MS) and ribosomal DNA sequencing. Antifungal susceptibility testing was performed following a Sensititre YeastOne colorimetric microdilution panel with nine clinically available antifungals. The Clinical and Laboratory Standards Institute (CLSI)-approved standard M27-A3 (S4) and newly revised clinical breakpoints or species-specific and method-specific epidemiological cutoff values were used for the interpretation of susceptibility test data. In this study, although Candida albicans was the predominant single species, non-C. albicans species constituted >50% of isolates in 6 out of 10 years, and more rare species were present in the recent 5 years. The non-C. albicans species identified most frequently were Candida parapsilosis sensu stricto, Candida tropicalis, and Candida glabrata. The prevalence of fluconazole and voriconazole resistance in the C. parapsilosis sensu stricto population was

In patients with hematologic malignancies due to immune system disorders, especially persistent febrile neutropenia, invasive fungal infections (IFI) occur with high mortality. Aspergillosis, candidiasis, fusariosis, mucormycosis, cryptococcosis and trichosporonosis are the most important infections reported in patients with hematologic malignancies that undergo hematopoietic stem cell transplantation. These infections are caused by opportunistic fungal pathogens that do not cause severe issues in healthy individuals, but in patients with hematologic malignancies lead to disseminated infection with different clinical manifestations. Prophylaxis and creating a safe environment with proper filters and air pressure for patients to avoid contact with the pathogens in the surrounding environment can prevent IFI. Furthermore, due to the absence of specific symptoms in IFI, rapid and accurate diagnosis reduces the mortality rate of these infections and using molecular techniques along with standard mycological methods will improve the diagnosis of disseminated fungal infection in patients with hematologic disorders. Amphotericin B products, extended-spectrum azoles, and echinocandins are the essential drugs to control invasive fungal infections in patients with hematologic malignancies, and according to various conditions of patients, different results of treatment with these drugs have been reported in different studies. On the other hand, drug resistance in recent years has led to therapeutic failures and deaths in patients with blood malignancies, which indicates the need for antifungal susceptibility tests to use appropriate therapies. Life-threatening fungal infections have become more prevalent in patients with hematologic malignancies in recent years due to the emergence of new risk factors, new species, and increased drug resistance. Therefore, in this review, we discuss the different dimensions of the most critical invasive fungal infections in patients with hematologic malignancies and present a list of these infections with different clinical manifestations, treatment, and outcomes.

Purpose To assess and compare the efficacy and safety of posaconazole with fluconazole for the prevention of invasive fungal infections in children who were undergoing induction therapy for acute lymphoblastic leukemia (ALL). To develop an approach to predict invasive fungal infections in ALL patients who accepted posaconazole prophylaxis. Methods This was a single-center, retrospective cohort study of patients with newly diagnosed ALL, comparing invasive fungal infections in patients who received no prophylaxis, posaconazole prophylaxis, or fluconazole prophylaxis during induction therapy. A propensity score-weighted logistic regression model was used to adjust for confounders. Hepatotoxicity was assessed according to the Common Terminology Criteria for Adverse Events (CTCAE) criteria. Results Out of the 155 ALL patients, 60 received no prophylaxis, 70 received posaconazole prophylaxis, and 25 received fluconazole prophylaxis. Posaconazole prophylaxis reduced the odds of invasive fungal infections by > 60%, prolonged infection-free survival significantly, and did not increase the risk of hepatotoxicity. Additionally, we found that the combination of age at diagnosis, clinically documented bacterial infection in the first 15 days of induction therapy, and absolute neutrophil count (ANC) curve enabled significant prediction of the susceptibility to infections after receiving posaconazole prophylaxis. Conclusions Our findings supported using targeted prophylaxis with posaconazole in ALL children undergoing induction chemotherapy. Age, clinically documented bacterial infection and ANC are important predictors of invasive fungal infections in patients with posaconazole prophylaxis.

Objectives: Rapid and reliable exclusion of invasive fungal infections (IFI) by markers able to avoid unnecessary empirical antifungal treatment is still a critical unmet clinical need. We investigated the diagnostic performance of a newly available β-d-Glucan (BDG) quantification assay, focusing on the optimisation of the BDG cut-off values for IFI exclusion. Methods: BDG results by Wako β-glucan assay (lower limit of detection [LLOD]=2.16pg/mL, positivity≥11pg/mL) on two consecutive serum samples were retrospectively analysed in 170 patients, admitted to haematological wards (N=42), intensive care units (ICUs; N=80), or other wards (N=48), exhibiting clinical signs and/or symptoms suspected for IFI. Only patients with proven IFI (EORTC/MSG criteria) were considered as true positives in the assessment of BDG sensitivity, specificity and predictive values. Results: Patients were diagnosed with no IFI (69.4%), proven IFI (25.3%) or probable IFI (5.3%). Two consecutive BDG values7.7pg/mL, could be a promising diagnostic approach to confidently rule out an IFI in both ICU and non-ICU patients. The poor specificity in the ICU setting remains a concern, due to the difficulty to interpret positive results in this fragile population.

Highlights • Invasive pulmonary aspergillosis should be considered in critically ill patients without neutropenia or obvious systemic immunosuppression. • Patients with cirrhosis have a weakened immune system and are at risk for invasive fungal diseases including pulmonary aspergillosis. • Algorithms for diagnosing invasive fungal infections provide useful guidance but should not replace clinical suspicion., Aspergillus molds are ubiquitous environmental molds that can cause devastating invasive infections in immunocompromised patients. These infections often go unrecognized in critically ill patients. This case describes a 68 year-old female resident of a long-term nursing facility with history of dementia, nonalcoholic fatty liver disease with cirrhosis, chronic kidney disease stage III and insulin-dependent type 2 diabetes who presented with vomiting, diarrhea and leg swelling. She developed hypotension and was treated for sepsis but found to have negative routine infectious workup. Chest imaging showed nodular densities and bilateral opacities. She developed acute renal failure and hypoxic respiratory failure followed by acute decompensated cirrhosis with refractory volume overload and hypotension and was eventually transitioned to comfort care measures. Autopsy ultimately showed invasive pulmonary aspergillosis. Here we review the diagnosis and management of invasive fungal infections in critically ill patients without typical risk factors or clinical findings for invasive fungal disease. Invasive fungal infections are frequently missed and carry high mortality rates, therefore warranting consideration in critically ill populations.

Purpose: Due to limitations of traditional microbiological techniques, standardised fungal biomarker tests such as Galactomannan Index (GMI) and 1,3-beta-D-glucan (BDG) are being preferred for diagnosis of invasive fungal infections (IFIs). These tests have been extensively used in developed countries but seldom in developing countries. The present study was performed to evaluate these tests for the diagnosis of IFIs in immunocompromised patients at an Indian tertiary care centre. Materials and Methods: A retrospective hospital-based study was done in immunocompromised patients with clinical suspicion of IFI. The demographic, clinical, radiological and mycological details of the patients were recorded. The patients were categorised into proven, probable and no IFI (as per European Organization for Research and Treatment of Cancer/Mycoses Study Group criteria). The sensitivity and specificity of BDG Fungitell and Platelia Aspergillus antigen assays was estimated. Results: A total of 70 consecutive patients were included, of which 41 had IFI (10 proven and 31 probable) while 29 had no IFI. A significant association was found between IFI and the presence of a central venous line (P = 0.035) and history of intake of T-cell immunosuppressants (P = 0.001). Median BDG values (pg/ml) in patients with proven IFI, probable IFI and no IFI were 300 (range: 70–500), 165 (range: 53–500) and 45 (range: 31–500), respectively. The receiver operating characteristic (ROC) curve analysis for BDG revealed an area under the curve of 0.995, sensitivity: 97.4% and specificity: 96.6% for IFI diagnosis. The ROC curve analysis of GMI revealed an AUC of 0.75 and 90% patients with invasive aspergillosis (IA) had positive GMI. Conclusion: BDG has good sensitivity and specificity for distinguishing IFI from no IFIs and GMI may be used for diagnosing IA.

Aim: Invasive mold diseases (IMDs) are associated with significant morbidity and mortality. Approved treatments include voriconazole (VORI), liposomal amphotericin B (L-AMB), posaconazole (POSA) and isavuconazole (ISAV). A UK-based economic model was developed to explore the cost of treating IMDs with ISAV versus L-AMB followed by POSA. Materials & methods: As indirect comparisons have demonstrated similar efficacy between the comparators, a cost-minimization approach was taken. Drug acquisition, administration & monitoring, and hospitalization costs were evaluated from the healthcare system perspective. Results: Per-patient costs were UK£14,842 with ISAV versus UK£18,612 with L-AMB followed by POSA. Savings were driven by drug acquisition, and administration & monitoring costs. Conclusion: ISAV has the potential to reduce IMD treatment costs relative to L-AMB followed by POSA.

Cryptococcus neoformans is a fungal pathogen that infects the lungs and then often disseminates to the central nervous system, causing meningitis. How Cryptococcus is able to suppress host immunity and escape the antifungal activity of macrophages remains incompletely understood. We reported that the F-box protein Fbp1, a subunit of the SCF(Fbp1) E3 ligase, promotes Cryptococcus virulence by regulating host-Cryptococcus interactions. Our recent studies demonstrated that the fbp1Δ mutant elicited superior protective Th1 host immunity in the lungs and that the enhanced immunogenicity of heat-killed fbp1Δ yeast cells can be harnessed to confer protection against a subsequent infection with the virulent parental strain. We therefore examined the use of heat-killed fbp1Δ cells in several vaccination strategies. Interestingly, the vaccine protection remains effective even in mice depleted of CD4+ T cells. This finding is particularly important in the context of HIV/AIDS-induced immune deficiency. Moreover, we observed that vaccinating mice with heat-killed fbp1Δ induces significant cross-protection against challenge with diverse invasive fungal pathogens, including C. neoformans, C. gattii, and Aspergillus fumigatus, as well as partial protection against Candida albicans. Thus, our data suggest that the heat-killed fbp1Δ strain has the potential to be a suitable vaccine candidate against cryptococcosis and other invasive fungal infections in both immunocompetent and immunocompromised populations. IMPORTANCE Invasive fungal infections kill more than 1.5 million people each year, with limited treatment options. There is no vaccine available in clinical use to prevent and control fungal infections. Our recent studies showed that a mutant of the F-box protein Fbp1, a subunit of the SCF(Fbp1) E3 ligase in Cryptococcus neoformans, elicited superior protective Th1 host immunity. Here, we demonstrate that the heat-killed fbp1Δ cells (HK-fbp1) can be harnessed to confer protection against a challenge by the virulent parental strain, even in animals depleted of CD4+ T cells. This finding is particularly important in the context of HIV/AIDS-induced immune deficiency. Moreover, we observed that HK-fbp1 vaccination induces significant cross-protection against challenge with diverse invasive fungal pathogens. Thus, our data suggest that HK-fbp1 has the potential to be a broad-spectrum vaccine candidate against invasive fungal infections in both immunocompetent and immunocompromised populations.

Purpose We aimed to implement and to assess the impact of the antifungal stewardship programme (AFSp) on prescription appropriateness of antifungals, management and outcomes of candidaemia patients, and antifungal consumption and costs at our solid organ transplant (SOT) institute. Methods Local epidemiology of invasive fungal infections (IFIs) from 2009 to 2017 was analysed in order to prepare an effective AFSp, implemented in January 2018. It included suspension of empirical antifungal prescriptions after 72 hours (antifungal time-out), automated alert and infectious disease (ID) consult for empirical prescriptions and for every patient with IFI, and indication for step-down to oral fluconazole when possible. We used process measures and results measures to assess the effects of the implemented programme. Results The ASFp led to significant improvements in selection of the appropriate antifungal (40.5% in pre-AFS vs 78.6% in post-AFS), correct dosing (51.2% vs 79.8%), correct length of treatment (55.9% vs 75%) and better management of patients with candidaemia. Analysis of prescribed empirical antifungal revealed that defined daily doses (DDDs) per 100 patient days decreased by 36.7% in 2018 compared to the average of pre-AFSp period, with important savings in costs. Conclusion This AFSp led to a better use of antifungal drugs in terms of appropriateness and consumption, with stable clinical and microbiological outcomes in patients with IFI.

Background Posaconazole is a triazole with limited pharmacokinetic information in children. This study assessed the correlation between posaconazole oral solution daily dosage/kg/body weight and trough plasma level. Methods A total of 97 hematology-oncology pediatric patients with ≥1 posaconazole plasma concentration level (PPC) assessment in the first 6 weeks after the start of posaconazole treatment were included. Results Posaconazole was used as prophylaxis in 84 of 97 (87%) patients and as therapy in 13 of 97 (13%). The median daily dose/kg/bw ranged from 10 to 12 mg in the prophylaxis group and 12.5 to 16.5 mg in the therapy group. The median value of PPC for the prophylaxis group was 0.9 and 0.8 μg/mL at the first and second/third determinations, respectively. Posaconazole prophylaxis failed in 4 of 84 patients (5%). The median value of PPC for the therapy group was 1.5 and 1.4 μg/mL at the first/second and the third determination, respectively. Posaconazole-related side effects were reported in 6 patients and all regressed with the suspension of the drug. In the prophylaxis group, the use of proton-pump inhibitors was significantly associated with a lower PPC, P = 0.04. Conclusions Posaconazole may be a valuable antifungal agent in children despite the incomplete knowledge of its pharmacokinetic characteristics.

Background COVID-19 co-infections have been described with different pathogens, including filamentous and yeast fungi. Methodology A retrospective case series study conducted from February to December 2020, at a Brazilian university hospital. Data were collected from two hospital surveillance systems: Invasive fungal infection (IFI) surveillance (Mycosis Resistance Program - MIRE) and COVID-19 surveillance. Data from both surveillance systems were cross-checked to identify individuals diagnosed with SARS-CoV-2 (by positive polymerase chain reaction (PCR)) and IFI during hospital stays within the study period. Results During the study period, 716 inpatients with COVID-19 and 55 cases of IFI were identified. Fungal co-infection with SARS-CoV-2 was observed in eight (1%) patients: three cases of aspergillosis; four candidemia and one cryptococcosis. The median age of patients was 66 years (IQR 58-71 years; range of 28-77 years) and 62.5% were men. Diagnosis of IFI occurred a median of 11.5 days (IQR 4.5-23 days) after admission and 11 days (IQR 6.5-16 days) after a positive PCR result for SARS-CoV-2. In 75% of cases, IFI was diagnosed in the intensive care unit (ICU). Cases of aspergillosis emerged earlier than those of candidemia: an average of 8.6 and 28.6 days after a positive PCR for SARS-CoV-2, respectively. All the patients with both infections ultimately died. Conclusion A low rate of COVID-19 co-infection with IFI was observed, with high mortality. Most cases were diagnosed in ICU patients. Aspergillosis diagnosis is highly complex in this context and requires different criteria.

Introduction Data suggests that invasive fungal infections (IFI) might complicate COVID-19. Our goal was to describe characteristics of IFI among critically ill COVID-19 adults. Methods A retrospective observational case-series analysis was done between March–July 2020. Consecutive patients with critical COVID-19 were eligible, and have been included when proven or putative/probable IFI could be confirmed during their course. For COVID-19 diagnosis, ECDC definitions and WHO severity criteria were followed. Candidaemia was diagnosed according to the ESCMID 2012 guideline. Invasive pulmonary aspergillosis (IPA) was defined following EORTC/MSG, ECMM/ISHAM and modified AspICU criteria. Outcome variables were rates of IFIs, in-hospital all-cause mortality, rate and time to negative respiratory SARS-CoV-2 PCR. Results From 90 eligible patients, 20 (22.2%) fulfilled criteria for IFI. Incidence rate for IFI was 2.02 per 100 patient-days at ICU. Patients were mostly elderly males with significant comorbidities, requiring mechanical ventilation because of ARDS. IFI could be classified as candidaemia in 7/20 (40%), putative/probable IPA in 16/20 (80.0%). Isolated species of candidaemia episodes were Candida albicans (4/9, 44.4%), Candida glabrata (3/9, 33.3%), Candida parapsilosis (1/9, 11.1%), Candida metapsilosis (1/9, 11.1%). Mold isolates from lower respiratory tract were Aspergillus fumigatus, BAL galactomannan positivity was prevalent (16/20, 80.0%). Mortality was 12/20 (60.0%) with a median time to death of 31.0±37.0 (5–89) days. Only 9/20 (45.0%) patients reached SARS-CoV-2 PCR negativity after a median time of 20.0±12.0 (3–38) days. Conclusion In this small cohort of critically ill COVID-19 adults, morbidity and mortality related to invasive fungal infections proved to be significant.

International audience; Fungemia presents high morbi-mortality and thus rapid microbiological diagnosis may contribute to appropriate patient management. In the last decade, kits based on molecular technologies have become available and health care institutes are increasingly facing critical investment choices. Although all these tools aim to achieve rapid fungal detection and species identification, they display different inherent characteristics. Areas covered: Considering technologies allowing detection and identification of fungal species in a sepsis context, the market proposes either tests on positive blood culture or tests on patient's whole blood. In this review, the authors describe and compare the ePlex® Blood Culture Identification Fungal Pathogen (BCID-FP) test, a fully automated one-step single-use cartridge assay that has been designed to detect identify frequent or rare but emerging, fungal species, from positive blood culture. A comparison with the competing kits is provided. Expert commentaries: The ePlex BCID-FP test provides a diversified and rather relevant panel. Its easy-to-use cartridges allow flexible use around the clock. Nevertheless, prospective clinical studies assessing the time-to-result benefit on antifungal stewardship and on hospital length of stay are not available yet. New tools aim to benefit clinicians and patients, but they should be accompanied by supervision of result interpretation and adaptation of antifungal stewardship.

Invasive fungal infections (IFIs) are serious infections that develop in conjunction with neutropenia after chemotherapy for acute leukemia or with hematopoietic stem cell transplantation. Conventionally, empirical antifungal therapy was recommended to treat IFIs for patient safety despite a lack of evidence of fungal infections. However, many studies have indicated that antifungals were not necessary for over half of patients, and several detriments of empirical therapy were noted, e.g., antifungals caused adverse reactions, an increase in drug-resistant fungi was a possibility, and medical costs soared. β-D-glucan (BDG) is a component of clinically important fungi such as Aspergillus and Candida. The G-test was developed in Japan as a way to measure BDG in serum using a coagulation factor from the blood of the horseshoe crab. Pre-emptive antifungal therapy based upon serodiagnosis with a BDG or galactomannan assay and CT imaging has been introduced. With pre-emptive antifungal therapy, the prognosis is equivalent to that with empirical therapy, and the dose of the antifungal has been successfully reduced. Measurement of BDG has been adopted widely as a method of diagnosing IFIs and is listed in the key guidelines for fungal infections and febrile neutropenia.