Surgical treatment of invasive fungal infection in pediatric oncology.

BACKGROUND: Invasive fungal disease (IFD) is typically aggressive and related with high mortality in children with a hematological malignancy. The association of medical and surgical treatment may ameliorate the outcome. The aim of this study was to analyze the surgical treatment of fungal infections in pediatric oncological populations. METHODS: Retrospective study (2000-2022) of a single-center experience. We reviewed the medical record of all patients with hematologic malignancies and IFD, analyzing the outcome. RESULTS: From the 70 pediatric cases of hematologic malignancies with the diagnosis IFD over 22 years, we included in the present study 44 cases who required surgical approaches for either diagnosis or treatment. Twenty-one patients were males and the mean age was 11 (range 1-23) years. The main indications for surgery were lack of improvement following medical treatment and/or progression of fungal infection (80%) and diagnosis confirmation (20%). Only five patients needed an emergency operation for rapid worsening of symptoms. The most common site of infection was the lung (80%) and the most frequently identified pathogen was Aspergillus (75%). The most common surgical procedures were lobectomy (performed in 17 patients) and atypical lung resection (10). Complications of surgery were mostly treated by medical approach. The mean time of resumption of oncological treatment was 40 (range 0-150) days. CONCLUSIONS: Surgery is an important step in the multimodal treatment of invasive fungal infection with excellent resolution rate. Overall mortality depends on the underlying malignancy.

Azole resistance mechanisms and population structure of the human pathogen Aspergillus fumigatus on retail plant products.

Aspergillus fumigatus is a ubiquitous saprotroph and human-pathogenic fungus that is life-threatening to the immunocompromised. Triazole-resistant A. fumigatus was found in patients without prior treatment with azoles, leading researchers to conclude that resistance had developed in agricultural environments where azoles are used against plant pathogens. Previous studies have documented azole-resistant A. fumigatus across agricultural environments, but few have looked at retail plant products. Our objectives were to determine if azole-resistant A. fumigatus is prevalent in retail plant products produced in the United States (U.S.), as well as to identify the resistance mechanism(s) and population genetic structure of these isolates. Five hundred twenty-five isolates were collected from retail plant products and screened for azole resistance. Twenty-four isolates collected from compost, soil, flower bulbs, and raw peanuts were pan-azole resistant. These isolates had the TR34/L98H, TR46/Y121F/T289A, G448S, and H147Y cyp51A alleles, all known to underly pan-azole resistance, as well as WT alleles, suggesting that non-cyp51A mechanisms contribute to pan-azole resistance in these isolates. Minimum spanning networks showed two lineages containing isolates with TR alleles or the F46Y/M172V/E427K allele, and discriminant analysis of principle components identified three primary clusters. This is consistent with previous studies detecting three clades of A. fumigatus and identifying pan-azole-resistant isolates with TR alleles in a single clade. We found pan-azole resistance in U.S. retail plant products, particularly compost and flower bulbs, which indicates a risk of exposure to these products for susceptible populations and that highly resistant isolates are likely distributed worldwide on these products.IMPORTANCEAspergillus fumigatus has recently been designated as a critical fungal pathogen by the World Health Organization. It is most deadly to people with compromised immune systems, and with the emergence of antifungal resistance to multiple azole drugs, this disease carries a nearly 100% fatality rate without treatment or if isolates are resistant to the drugs used to treat the disease. It is important to determine the relatedness and origins of resistant A. fumigatus isolates in the environment, including plant-based retail products, so that factors promoting the development and propagation of resistant isolates can be identified.

The first case of subcutaneous mycosis caused by Muyocopron laterale in China.

Muyocopron laterale is a type of endophytic fungus that parasitizes monocotyledonous plants. Cases of humans and other mammals being infected by M. laterale are very rare around the world. We report the first case of subcutaneous mycosis caused by M. laterale in China. A kidney transplant recipient was admitted for Pneumocystis carinii pneumonia and subsequently developed left calf redness and swelling due to a M. laterale infection. The patient was treated with sulfamethoxazole and voriconazole and underwent five surgical debridements and vacuum sealing drainage (VSD) applications with the left leg. The patient was eventually cured and discharged from the hospital.

Chromoblastomycosis in French Guiana: Epidemiology and Practices, 1955-2023.

Chromoblastomycosis (CBM) is a chronic neglected fungal disease, usually met in tropical areas. French Guiana is a South American territory with limited epidemiological data. This retrospective study concerned all patients with CBM proven by at least one paraclinical examination and diagnosed in French Guiana between 1950 and 2023. In total, 23 patients were included, mostly males (87%) of Creole origin, living in the coastal region (87%) and involved in outdoor occupations (74%). Lesions were mostly observed on the lower limbs (78.3%), with a median time to diagnosis of four years. Laboratory tests included positive direct microscopic examinations (78.3%) and mycological cultures (69.6%), identifying 14 cases of Fonsecaea pedrosoi and one case of Exophiala janselmei. Various treatments were employed, including antifungals, surgery and combinations of both. In conclusion, CBM in French Guiana involves a different population than other subcutaneous mycoses such as Lobomycosis or Paracoccidioidomycosis, mostly found in the forest hinterland. Surgery should be recommended for recent and limited lesions. Itraconazole and terbinafine should systematically be proposed, either in monotherapy or in combination with surgery or cryotherapy.

Chromogenic, Biochemical and Proteomic Identification of Yeast and Yeast-like Microorganisms Isolated from Clinical Samples from Animals of Costa Rica.

Yeast infections are challenging human and animal medicine due to low rates of detection and the emergence of unknown ecology isolates. The aim of this study was to verify the biochemical identification of yeasts and yeast-like microorganisms obtained from animals comparing the results with chromogenic media and matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF MS). Between January and August 2023, yeast and yeast-like isolates from samples of animals with suspicion of mycosis were identified using Vitek® 2 Compact, Brilliance® Candida Agar and MALDI Biotyper® MSP. A total of 39 cases were included, and 45 isolations were obtained. Cryptococcus neoformans (15.5%, 7/45), Meyerozyma guilliermondii (13.3%, 6/45), Candida parapsilosis (11.1%, 5/45), Candida albicans and Candida tropicalis (8.9%, each one 4/45) were the most identified organisms. There was full agreement with the three identification methods in 71.1% (32/45) of the isolates, disagreement on species in 17.8% (8/45), disagreement on genus and species in 6.7% (3/45) and, in 4.4% (2/45), there was no matched pattern in MALDI-TOF to compare the results. Biochemical methods are a good option in laboratories where proteomics are not available, and chromogenic media enhances diagnostics by detecting mixed infections. Surveillance must be implemented to improve the detection of agents shared between humans and animals.

Challenging frontiers: Canine sporotrichosis due to Sporothrix brasiliensis, first case in Chile.

We report the first case of Sporothrix brasiliensis in a dog at Santiago, Chile. From an initial biopsy obtained from the patient, a histopathological study was performed that oriented a fungal infection. The molecular diagnosis from the isolated colony confirmed the identity of the S. brasiliensis agent. Although the literature indicates itraconazole as the first treatment option, the patient was treated with terbinafine followed by itraconazole, without achieving a clinical cure. S. brasiliensis that spread rapidly in Latin America, hence highlight the importance of timely diagnosis that contribute to maintaining human and animal health. 2012 Elsevier Ltd. All rights reserved.

Funding for research on cryptococcal disease: an analysis based on the G-finder report.

Members of the genus Cryptococcus are the causative agents of cryptococcal meningitis, a disease mainly associated with HIV-induced immunosuppression. Patients with cryptococcal meningitis are at a serious risk of death. Most patients suffering from cryptococcosis belong to neglected populations. With reduced support for research, new therapies are unlikely to emerge. In this essay, we used the Policy Cures/G-finder platform as a reference database for funding research on cryptococcal disease. Funding for cryptococcal research started being tracked by G-finder in 2013 and has continued to appear in the annual reports ever since. In total, 15 institutions were reported as major funders for research on cryptococcal disease over the years. The US National Institutes of Health (NIH) was the main funder, followed by the UK's Wellcome Trust. The annual analysis suggested slow yearly growth in funding from 2013 to 2021. The development of new tools to prevent and fight cryptococcal disease is urgent but requires improved funding.

MSG-15: Super-Bioavailability Itraconazole Versus Conventional Itraconazole in the Treatment of Endemic Mycoses-A Multicenter, Open-Label, Randomized Comparative Trial.

Background: Invasive fungal disease caused by dimorphic fungi is associated with significant morbidity and mortality. Super-bioavailability itraconazole (SUBA-itra) is a novel antifungal agent with pharmacokinetic advantages over currently available formulations. In this prospective comparative study, we report the outcomes of patients with endemic fungal infections (histoplasmosis, blastomycosis, coccidioidomycosis, and sporotrichosis). Methods: This open-label randomized trial evaluated the efficacy, safety, and pharmacokinetics SUBA-itra compared with conventional itraconazole (c-itra) treatment for endemic fungal infections. An independent data review committee determined responses on treatment days 42 and 180. Results: Eighty-eight patients were enrolled for IFD (SUBA-itra, n = 42; c-itra, n = 46) caused by Histoplasma (n = 51), Blastomyces (n = 18), Coccidioides (n = 13), or Sporothrix (n = 6). On day 42, clinical success was observed with SUBA-itra and c-itra on day 42 (in 69% and 67%, respectively, and on day 180 (in 60% and 65%). Patients treated with SUBA-itra exhibited less drug-level variability at days 7 (P = .03) and 14 (P = .06) of randomized treatment. The concentrations of itraconazole and hydroxyitraconazole were comparable between the 2 medications (P = .77 and P = .80, respectively). There was a trend for fewer adverse events (AEs; 74% vs 87%, respectively; P = .18) and serious AEs (10% vs 26%; P = .06) in the SUBA-itra-treated patients than in those receiving c-itra. Serious treatment-emergent AEs were less common in SUBA-itra-treated patients (12% vs 50%, respectively; P < .001). Conclusions: SUBA-itra was bioequivalent, well tolerated, and efficacious in treating endemic fungi, with a more favorable safety profile than c-itra. Clinical Trials Registration: NCT03572049.

Pictorial Review of Post COVID-19 Acute Invasive Fungal Sinusitis: Clinical Radiologists' Perspective.

Acute invasive fungal sinusitis (AIFS) is a rapidly progressive infection predominantly seen in immunocompromised patients. There is an increasing incidence of AIFS post COVID-19 infection. Yet, there is sparse literature regarding spectrum of cross-sectional imaging findings (CT and MRI) in these patients, which is prudent for appropriate timely surgical intervention. This study aims to highlight spectrum of imaging findings in patients with post-COVID-19 AIFS integrating the clinical details from presentation to follow-up. We retrospectively reviewed the demographics, clinical details and radiological imaging of 31 histopathological proven cases of post COVID-19 AIFS. MR and CT images of these patients were retrieved from the PACS and analysed. 90-day follow-up of these patients was obtained. Statistical analysis was performed using descriptive statistics. Cross-sectional imaging showed nasal cavity involvement in all patients, bilateral in (15, 48%) cases; predominant involvement of maxillary (31, 100%) followed by ethmoid sinuses (29, 93.5%) was seen. MR showed patchy/complete loss of normal mucosal enhancement in the turbinates and sinuses as predominant imaging finding. Maxillary sinus walls erosions were seen in 28 cases (90%). Rhino-orbital and rhino-orbito-cerebral mycosis was seen in 24 (77%) and 14 (45%) respectively. Optic nerve-sheath complex was involved in 15 (48%) cases. Cerebral involvement was seen in form of meningeal enhancement, cerebritis, ischemic changes, cavernous sinus and intracranial arterial thrombosis and aneurysms. Comprehensive knowledge of imaging features of AIFS and recognition of extent of their spread allows radiologists to play pivotal role in alerting the clinician for appropriate therapy to avoid protracted and fatal outcome.

Pan-Indian Clinical Registry of Invasive Fungal Infections Among Patients in the Intensive Care Unit: Protocol for a Multicentric Prospective Study.

BACKGROUND: Fungal infections are now a great public health threat, especially in those with underlying risk factors such as neutropenia, diabetes, high-dose steroid treatment, cancer chemotherapy, prolonged intensive care unit stay, and so on, which can lead to mycoses with higher mortality rates. The rates of these infections have been steadily increasing over the past 2 decades due to the increasing population of patients who are immunocompromised. However, the data regarding the exact burden of such infection are still not available from India. Therefore, this registry was initiated to collate systematic data on invasive fungal infections (IFIs) across the country. OBJECTIVE: The primary aim of this study is to create a multicenter digital clinical registry and monitor trends of IFIs and emerging fungal diseases, as well as early signals of any potential fungal outbreak in any region. The registry will also capture information on the antifungal resistance patterns and the contribution of fungal infections on overall morbidity and inpatient mortality across various conditions. METHODS: This multicenter, prospective, noninterventional observational study will be conducted by the Indian Council of Medical Research through a web-based data collection method from 8 Advanced Mycology Diagnostic and Research Centers across the country. Data on age, gender, clinical signs and symptoms, date of admission, date of discharge or death, diagnostic tests performed, identified pathogen details, antifungal susceptibility testing, outcome, and so on will be obtained from hospital records. Descriptive and multivariate statistical methods will be applied to investigate clinical manifestations, risk variables, and treatment outcomes. RESULTS: These Advanced Mycology Diagnostic and Research Centers are expected to find the hidden cases of fungal infections in the intensive care unit setting. The study will facilitate the enhancement of the precision of fungal infection diagnosis and prompt treatment modalities in response to antifungal drug sensitivity tests. This registry will improve our understanding of IFIs, support evidence-based clinical decision-making ability, and encourage public health policies and actions. CONCLUSIONS: Fungal diseases are a neglected public health problem. Fewer diagnostic facilities, scanty published data, and increased vulnerable patient groups make the situation worse. This is the first systematic clinical registry of IFIs in India. Data generated from this registry will increase our understanding related to the diagnosis, treatment, and prevention of fungal diseases in India by addressing pertinent gaps in mycology. This initiative will ensure a visible impact on public health in the country. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54672.

Management of tinea capitis in infants and children in the United States: A national survey of pediatric dermatologists.

This study aimed to evaluate the current management of tinea capitis in the United States, specifically focusing on patients aged 0-2 months, 2 months to 2 years, and 2 years to 18 years. An online survey, distributed through the Pediatric Dermatology Research Alliance and the Society of Pediatric Dermatology, revealed the following preferences: fluconazole for those under 2 months, griseofulvin for those aged 2 months to 2 years, and terbinafine for those aged 2 years and older. There exists inter-provider variation in tinea capitis treatment regimens within the pediatric dermatology community.

Fungal thermotolerance revisited and why climate change is unlikely to be supercharging pathogenic fungi (yet).

Thermotolerance has been viewed as an uncommon characteristic among the fungi and one of the reasons that less than 1% of the described species operate as opportunistic pathogens of humans. Growth at 37°C is certainly a requirement for a fungus that invades the body core, but tens of thousands of nonpathogenic species are also able to grow at this temperature. Ergo, body temperature does not serve as a thermal barrier to the development of infections by many harmless fungi. The absence of other virulence factors must be more demanding. This observation raises questions about the hypothetical links between climate change and the increasing number of life-threatening human mycoses. Given the widespread distribution of fungal thermotolerance and the 1°C (2°F) increase in global temperature over the last 140 years it seems unlikely that the warming climate has driven the evolution of more virulent strains of fungi. More compelling explanations for the changes in the behavior of fungi as disease agents include their adaptation to the widening use of azole antifungals in hospitals and the wholesale application of millions of tons of the same class of heterocyclic chemicals in agriculture. On the other hand, climate change is having a significant effect on the spread of human mycoses by extending the geographical range of pathogenic fungi. A related increase in fungal asthma caused by spore inhalation is another likely consequence of planetary change.

Pulmonary endemic mycoses.

While rare, the likelihood of encountering a case of a pulmonary endemic mycosis (PEM) in the UK is increasing. Diagnosis may be challenging, often leading to considerable delay to appropriate treatment. Clinical suspicion must be present for respiratory disease, particularly in the immunocompromised or in those not responding to empiric treatment approaches, and an extended travel history should be obtained. This article summarises the epidemiology of PEM, key clinical features, diagnostic strategies and management.

Mycological Methods for Routine Air Sampling and Interpretation of Results in Operating Theaters.

Many infectious diseases are transmitted via the air and are, therefore, particularly difficult to combat. These infections include various invasive mycoses caused by molds. The usual route of infection is the inhalation of conidia. In hospitals, infection can also occur through the deposition of conidia in otherwise sterile anatomical sites during surgical and other invasive procedures. Therefore, knowledge of airborne mold concentrations can lead to measures to protect patients from fungal infections. The literature on this topic contains insufficient and sometimes ambiguous information. This is evidenced by the fact that there are no international recommendations or guidelines defining the methodology of air sampling and the interpretation of the results obtained. Surgical departments, intensive care units and medical mycology laboratories are, therefore, left to their own devices, leading to significant differences in the implementation of mycological surveillance in hospitals. The aim of this mini-review is to provide an overview of the current methods of air sampling and interpretation of results used in medical mycology laboratories.

Oral mucosa sporotrichosis: Report of a rare case acquired by direct inoculation.

Sporotrichosis is a rare type of fungal infection caused by Sporothrix fungus. Transmissions are commonly by traumatic inoculation of the fungus through the skin and subcutaneous tissue either from environmental exposure or contact with infected animals. Due to its mode of transmission, it is commonly affecting the upper limbs. Definitive diagnosis can be obtained by fungal culture test on secretion fluids, pus, bloods or tissue biopsy. We report a rare presentation of this disease appearing as a solitary chronic ulcer of the lip which was successfully treated with itraconazole.

Deep cutaneous mycoses in kidney transplant recipients: Diagnostic and therapeutic challenges.

Deep cutaneous mycoses (DCMs) are rare infections that extend throughout the dermis and subcutis, often occurring after inoculation with pathogenic fungi. Trends toward a growing incidence have been observed that may be partially related to an increasing population of solid organ transplant patients. The aim of this study is to describe the diagnostics and the outcomes of DCM among kidney transplant recipients so as to optimize their management. We performed a retrospective review of cases of DCM occurring among kidney transplant recipients in our institution over 12 years. Twenty cases were included. Lesions were only located on the limbs and presented mainly as single (10/20, 50%) nodular lesions (15/20, 75%), with a mean size of 3 cm. Direct mycological examination was positive for 17 patients (17/20, 85%) and the cultures were consistently positive. Thirteen different fungal species were observed, including phaehyphomycetes (n = 8), hyalohyphomycetes (n = 3), dermatophytes (n = 1), and mucorale (n = 1). The (1-3) beta-D-glucan antigen (BDG) was also consistently detected in the serum (20/20, 100%). Systematic imaging did not reveal any distant infectious lesions, but locoregional extension was present in 11 patients (11/14, 79%). Nineteen patients received antifungal treatment (19/20, 95%) for a median duration of 3 months, with surgery for 10 (10/20, 50%). There is a great diversity of fungal species responsible for DCMs in kidney transplant recipients. The mycological documentation is necessary to adapt the antifungal treatment according to the sensitivity of the species. Serum BDG positivity is a potentially reliable and useful tool for diagnosis and follow-up.

Is milbemycin a game changer against antifungal drug-resistant mycoses?

Milbemycin oximes are macrocyclic lactones that have a broad spectrum of activity against nematode infection in animals. They are known to block drug efflux, which increases the susceptibility of fungi to azoles. We investigated the effects of milbemycin on the azole susceptibility of fungi (Aspergillus fumigatus, Candida albicans, C. auris, Cryptococcus neoformans, and Trichophyton rubrum). To screen for changes in azole susceptibility, fungal growth was tested on a culture medium containing 1 µg/ml milbemycin. The results showed that milbemycin increased the azole susceptibility of azole-resistant strains of C. albicans, C. auris, C. neoformans, and T. rubrum. Thus, milbemycin might be useful against antifungal drug-resistant strains.

Milbemycin blocks drug efflux and increases the azole susceptibility of azole-resistant strains of Candida albicans, C. auris, Cryptococcus neoformans, and Trichophyton rubrum. This drug is expected to be a game changer against antifungal drug-resistant infections.

Pericardial effusion in an immunocompetent host- a unique presentation of histoplasmosis.

Histoplasma capsulatum infection is infrequently considered in the differential diagnoses for acute pericarditis in immunocompetent hosts when presenting with tamponade physiology, given its gradual infective nature. We describe a case of a young male presenting solely with acute pericarditis with pericardial effusion and early cardiac tamponade physiology secondary to a pulmonary histoplasmosis infection. Our patient had no pulmonary symptoms; the only pulmonary manifestation of histoplasmosis included incidental findings of subcarinal lymphadenopathy and a left lingular nodule abutting the pericardium. Given failure of symptom improvement with pericardiocentesis and first-line therapy for idiopathic/viral pericarditis, further workup of the pulmonary nodule was pursued. Histopathologic analysis of tissue showed caseating granulomas and fungal Grocott-Gömöri's methenamine silver stain revealed yeast consistent with Histoplasma species. The patient improved with itraconazole therapy. Learning objective: Pulmonary histoplasmosis has potential to present as a pericardial effusion in the immunocompetent individual. In addition to pericardiocentesis, antifungal therapy can be curative.

Case Report: Diagnosing Dermatophytoses in Children.

Dermatophytoses of the skin and scalp are common disorders in the pediatric population. The resemblance of the clinical presentation to other dermatoses can make fungal infections challenging to diagnose. We present three cases of dermatophytoses in children. The presence of fungi within skin lesions was confirmed in all cases. The diagnoses were "id" reaction in response to Trichophyton tonsurans infection, Kerion celsi because of Microsporum canis infection, and hair loss during microsporosis. Based on our review and clinical experience, we suggest diagnostic paths and treatments for dermatophytoses in children.

Infectious Complications of Pulmonary Sarcoidosis.

In this review, the infectious complications observed in sarcoidosis are considered from a practical point of view to help the clinician not to overlook them in a difficult context, as pulmonary sarcoidosis makes the recognition of superinfections more difficult. An increased incidence of community-acquired pneumonia and of opportunistic pneumonia has been reported, especially in immunosuppressed patients. Pulmonary destructive lesions of advanced sarcoidosis increase the incidence of chronic pulmonary aspergillosis and infection by other agents. Screening and treatment of latent tuberculosis infection are crucial to prevent severe tuberculosis. Severity in COVID-19 appears to be increased by comorbidities rather than by sarcoidosis per se. The diagnosis of infectious complications can be challenging and should be considered as a potential differential diagnosis when the exacerbation of sarcoidosis is suspected. These complications not only increase the need for hospitalizations, but also increase the risk of death. This aspect must be carefully considered when assessing the overall health burden associated with sarcoidosis. The impact of immune dysregulation on infectious risk is unclear except in exceptional cases. In the absence of evidence-based studies on immunosuppressants in the specific context of pulmonary sarcoidosis, it is recommended to apply guidelines used in areas outside sarcoidosis. Preventive measures are essential, beginning with an appropriate use of immunosuppressants and the avoidance of unjustified treatments and doses. This approach should take into account the risk of tuberculosis, especially in highly endemic countries. Additionally, parallel emphasis should be placed on vaccinations, especially against COVID-19.