Six-year experience with GM test in hematological patients in a public Brazilian tertiary hospital

Abstract Invasive fungal infection (IFI) is frequent in patients with hematologic malignancies or submitted hematopoietic stem cell transplantation (HSCT). Objectives To evaluate the role of the GM (galactomannan) test in prescribing therapeutic antifungals; to determine invasive aspergillosis (IA) frequency, the factors associated with positive GM test, and the in-hospital mortality. Methods We conducted a retrospective observational study including patients aged 18 or over with hematological malignancy or submitted to HSCT. GM test was measured twice weekly. The hypothesis of IFI was considered in patients with neutropenia and persistent fever despite broad-spectrum antibiotics. Results A total of 496 patients were evaluated; the mean of GM tests performed per patient was 4.2 (+3.1), and 86 (17.3 %) had positive results. IFI was diagnosed in 166 (33.5 %) and IA in 22 (24.6 %) patients. Positive GM test was more frequent in patients with IFI (72.2 % and 25.1 %; OR 8.1; 95 % CI 4.8 - 13.8), and was associated with therapeutic antifungals prescription (52, 9 % and 20.5 %; OR 4.3, 95CI% 2.0 - 9.4), as well as lung abnormalities on HRCT (45.3% vs. 21.5 %; OR 3.0, 95 %CI 1.4 - 6.5). Mortality was 31.6 %. In the multivariate analysis, the variables associated with mortality were the hypothesis of IFI (OR 6.35; 95 % CI 3.63-11.12.0), lung abnormalities on HRCT (57.9 % and 26.9 %; OR 2 0.6; 95 % CI 1.5 - 4.4), and positive GM test (57.9 % and 26.9 %; OR 2.7 95 % CI 1.6 - 4.5). Conclusions Positive GM test was associated with lung abnormalities on HRCT and with the introduction of therapeutic antifungals. If adequate anti-mold prophylaxis is available, the GM test should not be used as screening, but to investigate IFI in high-risk patients. The diagnosis of IFI, positive GM test and lung abnormalities on HRCT were predictors of hospital mortality in patients with hematological malignancies or undergoing HSCT.

Mucormicosis maxilar asociado a COVID-19, tratamiento médico-quirúrgico y manejo multidisciplinario. Reporte de caso / Maxillary mucormycosis associated with COVID-19, medical-surgical treatment and multidisciplinary management. Case report

Resumen Introducción: Durante la actual pandemia de COVID-19 múltiples complicaciones se han desarrollado posterior a la enfermedad, dentro de las cuales se encuentran las infecciones fúngicas, como la mucormicosis, que puede resultar directamente de la infección por COVID-19 y/o como efecto secundario de los fármacos utilizados en su tratamiento. La mucormicosis es una infección causada por un grupo de hongos llamados mucormycetes; a nivel rinocerebral se presenta con celulitis facial, cefalea, proptosis, movilización del diente afectado y secreción nasal. Reporte de caso: Se presenta a un paciente femenino de 57 años con antecedente de neumonía grave por COVID-19 con posterior desarrollo de absceso periodontal que ameritó extracción del segundo molar superior derecho con posterior formación de fistula. Se toma TC de macizo facial donde se evidencia erosión ósea con pérdida de la morfología habitual y en pared anterior del seno maxilar derecho. Se realiza biopsia reportando tejido óseo con elementos micóticos (hifas aseptadas) morfológicamente compatibles con mucor sp. Se realizó tratamiento con anfotericina B y hemimaxilectomia derecha. Actualmente se encuentra en tratamiento con pozaconazol, y lavados quirúrgicos. Conclusión: La enfermedad de COVID-19 es una enfermedad muy común actualmente a nivel mundial, por lo que es importante identificar y llevar un seguimiento de aquellas personas con factores de riesgo para desarrollar mucormicosis; el diagnóstico y un plan de tratamiento temprano es fundamental para evitar complicaciones, las cuales pueden originar un desenlace fatal.

Abstract Introduction: During the current pandemic of COVID-19 multiple complications have developed after the disease, among which are fungal infections, such as mucormycosis, which can result directly from COVID-19 infection and/or as a side effect of the drugs used in its treatment. Mucormycosis is an infection caused by a group of fungi called mucormycetes; at the rhinocerebral level it presents with facial cellulitis, headache, proptosis, mobilization of the affected tooth and nasal secretion. Case report: the following is a 57-year-old female patient with a history of severe pneumonia due to COVID-19 with subsequent development of periodontal abscess that merited extraction of the upper right second molar with subsequent fistula formation. The patient started an infection with the presence of purulent secretion in the extraction area of the right molar. A CT scan of the facial mass was taken showing bone erosion with loss of the usual morphology in the right upper maxillary bone and anterior wall of the right maxillary sinus, as well as a biopsy of the right maxilla reporting bone tissue with mycotic elements (aseptates hyphae) morphologically compatible with mucor sp. Treatment with amphotericin B and right hemimaxillectomy was performed. She is currently being treated with pozaconazole and surgical washings. Conclusion: COVID-19 disease is currently a very common disease worldwide, so it is important to identify and follow up those people with risk factors for developing mucormycosis; early diagnosis and treatment plan is essential to avoid complications, which can lead to a fatal outcome.

Infecciones fúngicas invasoras en niños con cáncer y portadores de aplasia medular severa en nueve hospitales de la red PINDA, Chile. 2016-2020

Introducción: La infección fúngica invasora (IFI) es una causa importante de morbilidad y mortalidad en pacientes oncológicos pediátricos y portadores de aplasia medular (AM) severa. Objetivo: Describir la epidemiología de la IFI desde el año 2016 al 2020 en niños con cáncer y AM para evaluar la necesidad de profilaxis antifúngica. Métodos: Estudio retrospectivo, multicéntrico, en pacientes pediátricos con cáncer y AM severa. Se incluyeron IFI probables y probadas. Resultados: Se diagnosticaron 57 casos de IFI, mediana de edad 9 años, 70% probadas y 30% probables. Hubo 42% de infecciones por levaduras y 56% por hongos filamentosos. Los sitios de infección más frecuentes fueron pulmón 38%, sangre 36% y rinosinusal 21%. La frecuencia global fue 5,4%; de ellas 21% en AM severa, 10% en leucemia mieloide aguda (LMA), 6,9% en recaída de LMA, 5,4% en recaída de leucemia linfática aguda (LLA), 3,8% en LLA. Las infecciones por hongos filamentosos predominaron en LMA, recaída de LMA. y AM severa. La mortalidad en pacientes con IFI fue de 11%. Conclusión: La frecuencia de IFI concuerda con la literatura médica. Recomendamos profilaxis antifúngica contra hongos filamentosos en pacientes con AM severa, LMA y recaída de LMA. Considerar en recaída de LLA de alto riesgo en etapa de inducción.

Background: Invasive fungal infections (IFIs) are an important cause of morbidity and mortality in pediatric oncology patients and severe aplastic anemia (SAA). Aim: To describe the epidemiology of IFI from 2016 to 2020 in children with cancer and SAA to assess the indication of antifungal prophylaxis. Methods: Multicenter, retrospective study of IFIs in pediatric oncology patients and SAA. Probable and proven IFIs were included. Results: Over the 5-year period, 57 IFIs were found, median age 9 years, 70% were proven and 30% were probable. Yeast infections were 42% and mold infections 56%. The most frequent infection sites were lung 38%, blood 36% and rhinosinusal 21%. The total IFI frequency was 5.4%, 21% in SAA, 10% in acute myeloid leukemia (AML), 6.9% in relapsed AML, 5.4% in relapsed acute lymphoblastic leukemia (ALL), 3.8% in ALL. Mold infections were predominant in AML, relapsed AML, and SAA. IFIs mortality was 11%. Conclusion: Frequency of IFI was consistent with the literature. We strongly recommend antifungal prophylaxis against mold infections in patients with SAA, AML, and relapsed AML. Would consider in high risk ALL relapse in induction chemotherapy.

Clinicopathological association of mucormycosis in COVID 19 pandemic

Context: Coinfection and superadded infections in patients with coronavirus disease 2019 (COVID-19) has been reported on multiple series. The emerging second wave of the pandemic has come with a lot of changes, especially in developing countries like India. One of such changes is sudden, significant rise in mucormycosis cases. Aims: To find out clinicopathological association of invasive mucormycosis with COVID-19 infection status and immunocompromised state. Settings and Design: A cross-sectional study done at a tertiary care centre. Methods and Material: All cases admitted in the dedicated mucormycosis ward between 1-06-2021 and 15-06-2021 were included in the study. The cases were admitted with suspicion of mucormycosis. The histopathological results were correlated with KOH mount and radiological reports. The clinicopathological association of occurrence of mucormycosis in post-covid and non-COVID patients along with other risk factors. Statistical Analysis Used: Odds ratio, chi square test were used to find the association using MS Excel 2010 and SPSS. Results: Thirty-six (81.82%) cases were of the post-COVID status, and 8 cases were non-COVID status. Out of 36 post-COVID patients, 33 (91.67%) showed evidence of invasive mucormycosis and of 8 non-COVIDpatients, 7 had evidence of mucormycosis (odds ratio = 1.57). Out of the total diagnosed cases of mucormycosis, 21 (52.5%) patients were known cases of diabetes mellitus (DM), and 7 (17.5%) cases of newly diagnosed hyperglycemia. Thirty (75%) patients out of 40 had some form of immunocompromised state. This shows statistically significant association of DM and immunocompromised state with the occurrence of mucormycosis in post-COVID patients (chi square value2 = 6.891, P value = 0.008). Twenty-five patients had the history of steroid use during the treatment of COVID-19. Conclusions: The infection with COVID-19 definitely increases the odds of contracting mucormycosis, but most of the cases had diabetes mellitus. So, it is possible that COVID-19 virus predisposes individuals to invasive fungal infection by precipitating DM.

Advances in anti-invasive fungal drug delivery systems / 浙江大学学报·医学版

Currently, the first-line drugs for invasive fungal infections (IFI), such as amphotericin B, fluconazole and itraconazole, have drawbacks including poor water solubility, low bioavailability, and severe side effects. Using drug delivery systems is a promising strategy to improve the efficacy and safety of traditional antifungal therapy. Synthetic and biomimetic carriers have greatly facilitated the development of targeted delivery systems for antifungal drugs. Synthetic carrier drug delivery systems, such as liposomes, nanoparticles, polymer micelles, and microspheres, can improve the physicochemical properties of antifungal drugs, prolong their circulation time, enhance targeting capabilities, and reduce toxic side effects. Cell membrane biomimetic drug delivery systems, such as macrophage or red blood cell membrane-coated drug delivery systems, retain the membrane structure of somatic cells and confer various biological functions and specific targeting abilities to the loaded antifungal drugs, exhibiting better biocompatibility and lower toxicity. This article reviews the development of antifungal drug delivery systems and their application in the treatment of IFI, and also discusses the prospects of novel biomimetic carriers in antifungal drug delivery.

GATA2 variants in patients with non-tuberculous mycobacterial or fungal infections without known immunodeficiencies

ABSTRACT Introduction Haploinsufficiency of the hematopoietic transcription factor GATA2 is associated with a broad spectrum of diseases, including infection susceptibility and neoplasms. We aimed to investigate GATA2 variants in patients with non-tuberculous mycobacterial (NTM) and/or fungal infections (FI) without known immunodeficiencies. Method We performed GATA2 genotyping in patients with NTM and/or FI. Results Twenty-two patients were enrolled (seventeen FI, four NTM and one with both infections). The pathogenic variant NG_029334.1:g.16287C>T was found in one patient (4.5%) and two asymptomatic offsprings. We also found the likely-benign variant NG_029334.1:g.12080G>A (rs2335052), the benign variant NG_029334.1:g.16225C>T (rs11708606) and the variant of uncertain significance NG_029334.1:g.16201G>A (rs369850507) in 18.2%, 27.3%, and 4.5% of the cases, respectively. Malignant diseases were additionally diagnosed in six patients. Conclusion Although detected in 45.4% of the patients, most GATA2 variants were benign or likely benign. Identifying a pathogenic variant was essential for driving both the patient's treatment and familial counseling. Pathogenic variants carriers should receive genetic counseling, subsequent infection prevention measures and malignancies surveillance. Additionally, case-control genotyping should be carried out in Brazil to investigate whether the observed variants may be associated with susceptibility to opportunistic infections and/or concurrent neoplasms.

Efficacy and safety of continuous pump versus intermittent infusion of amphotericin B in the treatment of invasive fungal infection：a meta-analysis / 中国药房

OBJECTIVE To compare efficacy and safety of continuous pump versus intermittent infusion of amphotericin B in the treatment of invasive fungal infection， and to provide evidence-based reference for clinical treatment. METHODS Retrieved from PubMed， the Cochrane Library， Web of Science， Embase， Wanfang， CNKI， CBM and VIP database， randomized controlled trial （RCT） and cohort study about 24 h continuous pump （trial group） versus intermittent infusion （control group） of amphotericin B were collected from the inception to Jan. 2023. After literature screening and data extraction， the quality of RCT was evaluated with modified Jadad scale， and the quality of cohort study was evaluated with Newcastle-Ottawa scale. Meta-analysis and sensitivity analysis were performed by using RevMan 5.4 software. RESULTS A total of 7 literature were included， involving 1 RCT and 6 cohort studies with a total of 767 patients. The results of meta-analysis showed that the clinical effective rate [RR＝1.44， 95%CI （1.13，1.83）， P＝0.003] of trial group was significantly higher than that of control group， and all-cause mortality rate [RR＝0.37， 95%CI（0.19，0.72），P＝0.003] and the incidence rate of infusion reaction [RR＝0.28，95%CI（0.18，0.43）， P＜0.000 01] were significantly lower than control group； there was no statistical significance in the incidence rate of renal impairment between 2 groups [RR＝0.71，95%CI（0.45，1.11），P＝0.13] . The sensitivity analysis results showed that the results obtained in this study were robust. CONCLUSIONS The efficacy and safety of 24 h continuous pump of amphotericin B are better than those of intermittent infusion in the treatment of invasive fungal infection.

Zygomycosis of the Oral Cavity in a Main Referral Centre in Malaysia: A Case Series (1967-2021)

@#Zygomycosis is a rare opportunistic fungal infection caused by fungi in the phylum Mucoromycota, subphylum Mucoromycotina and order Mucorales. Immunocompromised patients may harbour the disease by inhalation of the spores from the environment into the paranasal sinuses. Rhino-orbital-cerebral is the most common form which extends into the oral cavity, especially to the palate. We present twelve cases of zygomycosis diagnosed in the Stomatology Unit, Institute for Medical Research (IMR), Malaysia. Most of the patients are immunocompromised and presented as the rhino-orbital-cerebral form. Routine haematoxylin and eosin (H&E) staining were used for all cases while selected cases required additional special staining. The characteristic histological features of broad, non-septate, branched, amphophilic fungal hyphae are seen. We aim to report this rare occurrence to contribute to the literature and raise awareness about this condition among clinicians. To date, this is the first compilation of oral zygomycosis cases known to be reported in Malaysia.

Risk Prediction Model for Pulmonary Fungal Infections in Patients with Lung Cancer / 中山大学学报(医学科学版)

ObjectiveTo investigate the risk factors for pulmonary fungal infection in lung cancer patients， construct and validate a risk prediction model using available clinical data to predict the risk of pulmonary fungal infections in patients with lung cancer. MethodsWe conducted a retrospective study and collected information of 390 lung cancer patients treated at Zhongshan People's Hospital from January 2021 to March 2023. Demographic and clinical characteristics of the patients with and without pulmonary fungal infections were used to construct column line graphs to predict the occurrence of pulmonary fungal infections. All enrolled patients were randomly assigned to training set and internal validation set in the ratio of 7：3. For the modelling group， LASSO regression was applied to screen variables and select predictors， and multivariate logistic regression with a training set was used to construct the Noe column line graph model. The judgment ability of the model was determined by calculating the area under the curve （AUC）， and in addition， calibration analysis and decision curve analysis （DCA） were performed on the model. ResultsLASSO regression identified 14 potential predictive factors， and further logistic regression analysis showed that hepatic injury， surgery， anemia， hypoalbuminemia， illness course， invasive operation， hospital stay at least 2 weeks and glucocorticoid used for at least 2 weeks were independent predictors for the occurrence of pulmonary fungal infection in lung cancer patients. A predictive model was established based on these variables， with an AUC95%CI of 0.980 （0.973， 0.896） for the training set and an AUC95%CI of 0.956 （0.795， 1.000） for internal validation， indicating high discriminative ability. The calibration curves for both the training set and validation set were distributed along the 45°line， and the decision curve analysis （DCA） showed net benefit for threshold probabilities greater than 0.03. ConclusionsThe construction and validation of a predictive model for the risk of lung fungal infections in lung cancer patients will help clinical practitioners to identify high-risk groups and give timely intervention or adjust treatment decisions.

Investigation and analysis of superficial fungal infection and drug use among naval trainees / 药学实践杂志

Objective To investigate the pathogenesis of superficial mycosis among naval trainees, and observe the efficacy of a novel antifungal drug. Methods A questionnaire survey was conducted on the onset, medication and recurrence of superficial fungal infection among the trainees from January, 2020 to July, 2020. At the same time, the new antifungal drug sulconazole nitrate spray was provided for treatment and the drug efficacy was observed. Results The participants generally lacked understanding and attention to superficial fungal infections. The incidence rate of superficial fungal infection was 52%, of which 76.2% of patients had recurrence of superficial fungal infection. The sulconazole nitrate spray showed great effect against these infections. Conclusion The trainees should understand the causes of superficial fungal infection through health education and seek medical treatment and medication in time. The cure rate of superficial fungal infections could only be improved through the collaborative management of the school, hospital, and trainees to reduce the impact of these infections on naval trainees’ work and life.

Clinical characteristics and treatment of central nervous system aspergillosis: an analysis of 37 cases / 中华神经科杂志

Objective:To summarize the clinical characteristics and therapeutic efficacy of central nervous system (CNS) aspergillosis.Methods:The clinical manifestations, laboratory examination, neuroimaging features, treatment and prognosis of 37 cases of CNS aspergillosis diagnosed and treated in the First Medical Center of People′s Liberation Army General Hospital from January 2000 to January 2021 were retrospectively analyzed. According to the correlation between intracranial lesions and paranasal sinus lesions, they were divided into two groups: rhino-cerebral aspergillosis (RA, n=21) group and cerebral aspergillosis (CA, n=16) group. Results:Only 16.2% (6/37) of CNS aspergillosis patients had a clear background of immunosuppression, but 35.1% (13/37) were complicated with diabetes. The most common clinical manifestations were headache (73.0%, 27/37), cranial nerve involvement (59.5%, 22/37) and fever (37.8%, 14/37). Cerebrospinal fluid characteristics included increased pressure (53.8%, 14/26), increased white blood cell count (46.7%, 14/30), decreased glucose (30.0%, 9/30), increased protein (70.0%, 21/30), and high positive results of the metagenomic next-generation sequencing (mNGS) of pathogenic microorganism (7/10). Cranial magnetic resonance imaging showed that commonly involved sites were sinus, orbital apex, posterior orbit, cavernous sinus (43.2%, 16/37) and cerebral lobes (27.0%, 10/37). Treatment options included antifungal drugs alone (64.9%, 24/37), combination of drugs and surgery (27.0%, 10/37) and surgery alone (8.1%, 3/37). Compared with the CA group, RA group had fewer males [47.6% (10/21) vs 14/16, χ2=6.34, P=0.012] and older age [(54.2±19.4) years vs (38.4±18.4) years, t=2.50, P=0.017], and was more prone to headache [85.7% (18/21) vs 9/16, χ2=4.00, P=0.046) and cranial nerve involvement [81.0% (17/21) vs 5/16, χ 2=9.31, P=0.006]. The misdiagnosis rate of these patients in the early stage was 73.0% (27/37). A total of 29 patients (85.3%, 29/34) were treated with voriconazole successively, and the course of treatment was 3.0 (0.5, 10.4) months. Compared with salvage therapy, the mortality of primary therapy was lower (4/17 vs 9/12, χ2=7.54, P=0.006). All patients were followed up to December 2021, and 17 patients died, with a mortality rate of 45.9% (17/37). Conclusions:CNS aspergillosis may have no definite immunosuppressive background. Some of CNS aspergillosis patients are complicated with diabetes, and the clinical manifestations of the disease lack specificity, with high misdiagnosis rate in the early stage, no inflammatory changes in cerebrospinal fluid, and high positive rate of mNGS for pathogenic microorganism. Early and long-term application of voriconazole can significantly reduce the mortality rate.

Evaluation of interactions of silibinin with the proteins ALS3 and SAP5 against Candida albicans / Avaliação das interações da silibinina com as proteínas ALS3 e SAP5 contra Candida albicans

Objective: to evaluate the molecular interaction of silibinin with the targets ALS3 and SAP5. Methodology: Molecular docking protocols were conducted to analyze the binding interaction of silibinin with ALS3 and SAP5. Results: Eleven interactions of ALS3 with silibinin and four with fluconazole were found, while six interactions were observed of SAP5 with silibinin and four with fluconazole. Conclusion: Molecular docking between silibinin and ALS3 identified important interactions, but no significant interactions were observed with SAP5, even though silibinin can exhibit affinity and interactions with other SAP5 sites.

Objetivo: Avaliar a interação molecular da silibinina com os alvos ALS3 e SAP5. Metodologia: Protocolos de docking molecular foram conduzidos para analisar a interação de ligação da silibinina com ALS3 e SAP5. Resultados: Foram encontradas onze interações de ALS3 com silibinina e quatro com fluconazol, enquanto seis interações foram observadas de SAP5 com silibinina e quatro com fluconazol. Conclusão: Docking molecular entre silibinina e ALS3 identificou interações importantes, mas não foram observadas interações significativas com SAP5, embora a silibinina possa apresentar afinidade e interações com outros sítios SAP5.

COVID-19 associated with disseminated histoplasmosis in a kidney transplant patient / COVID-19 asociado a histoplasmosis diseminada en un paciente trasplantado renal

Abstract We report a case of disseminated histoplasmosis and COVID-19 infection in a renal transplant recipient in Argentina. The patient exhibited respiratory symptoms, and a chest computed tomography scan (CT) showed multiple bilateral centrilobular opacities with a tree-in-bud pattern in both lobes. The patient was initially treated as having bacterial community-acquired pneumonia, and then tuberculosis. A month later, histoplasmosis was diagnosed, and Histoplasma capsulatum LAmB clade was isolated from sputum, skin and oral lesions. The patient was hospitalized and treatment was started with intravenous liposomal amphotericin B. During the course of the antifungal therapy the respiratory symptoms worsened, a new chest CT showed a unilateral lesion with a ground glass appearance and SARS-CoV-2 was detected in a new nasopharyngeal sample. In addition, plasma therapy was administered, and the immunosuppressive regimen was adjusted (everolimus was interrupted, mycophenolate mofetil reduced, and meprednisone increased). Finally, the patient's progress was favorable and was discharged after five days on oral itraconazole treatment for histoplasmosis.

Resumen Se presenta un caso de histoplasmosis diseminada e infección por COVID-19 en un paciente trasplantado renal en Argentina. El paciente presentó un cuadro clínico respiratorio, y la tomografía computarizada (TC) de tórax mostró múltiples opacidades centrolobulillares bilaterales con patrón de árbol en brote. El paciente fue tratado inicialmente con antibióticos para agentes causantes de neumonía bacteriana adquirida en la comunidad y luego como tuberculosis. Un mes después se le diagnosticó una histoplasmosis diseminada y el hongo fue aislado del esputo, la piel y la mucosa oral. El hongo fue tipificado molecularmente como Histoplasma capsulatum clado LAmB. El paciente fue hospitalizado y se inició tratamiento con anfoteric-ina B liposomal vía intravenosa. Durante el transcurso de la terapia antifúngica los síntomas respiratorios del paciente empeoraron, una nueva TC de tórax mostró una lesión unilateral con apariencia de vidrio esmerilado y se detectó SARS-CoV-2 en el hisopado nasofaríngeo. El paciente fue tratado con plasmoterapia y se modificó el régimen de inmunosupresión (se interrumpió everolimus, se redujo micofenolato de mofetilo y se incrementó la meprednisona). La evolución del paciente fue favorable y fue dado de alta con tratamiento oral con itraconazol.

Mucormicosis asociada a COVID-19. Un caso en Argentina / COVID-19 associated mucormycosis. A case in Argentina

Resumen La enfermedad COVID-19 provocada por el virus SARS-CoV-2 presenta una gravedad variable. Recientemente se ha observado un aumento en el número de casos informados de mucormicosis asociada a COVID-19 (CAM), principalmente en personas con diabetes mellitus, cetoacidosis diabética o en tratamiento con esteroides. El mayor número de casos ha sido notificado en India, en donde la prevalencia de CAM en pacientes hospitalizados en el año 2020 fue de 0.27%, lo que implica un aumento en la prevalencia de mucormicosis de 2.1 veces respecto del año 2019. Si bien el tratamiento con corticoides reduce la mortalidad en pacientes con COVID-19 grave, su uso prolongado, en combinación con otros factores clínicos e inmunológicos, puede aumentar el riesgo de infección fúngica invasiva. Comunicamos un caso de CAM en Argentina. El presente informe representa una alerta para fundar sospecha de infección fúngica invasiva en pacientes con COVID-19.

Abstract SARS-CoV-2 virus disease presents variable severity. Recently, an increasing report of cases of COVID-19 associated mucormycosis (CAM) has been observed, mainly in patients with diabetes mellitus, diabetic ketoacidosis or under steroids treatment. The highest number of cases have been reported in India, with a prevalence of 0.27 % in hospitalized patients with COVID-19 during year 2020, which implies a 2.1-fold increase in the prevalence of mucormycosis compared to year 2019. Although corticosteroids treatment reduces mortality in patients with severe COVID-19, its prolonged use, in combination with other clinical and immunological factors, could increase the risk of invasive fungal infection. We report a case of CAM in Argentina. This report represents a warning for considering the diagnosis of invasive fungal infection in patients with severe COVID-19.

Rhino-orbital-cerebral mucormycosis: An epidemiological study from a tertiary care referral center in Western India

Purpose: Rhino?orbital?cerebral mucormycosis (ROCM) is a rare opportunistic fungal infection with a fulminant course and an often fatal outcome. It can occur in immune?compromised patients such as those having uncontrolled diabetes, on long?term corticosteroid or immunosuppressive therapy, with COVID?19 infection, renal failure, AIDS, malignancy, or organ transplant. The aim of our study was to study the epidemiology of mucormycosis in COVID?19 patients and identify its risk factors. Methods: Ours was an epidemiological study wherein we gathered the demographic, clinical, histopathological, and radiological data of 458 patients of mucormycosis who presented to us between August 2020 and May 2021. Mucormycosis was defined through clinical and radiological findings or positive culture reports. Results: Out of all, 20.74% of patients did not have any past or concurrent history of COVID?19. The most common symptom of mucormycosis was orbital/facial pain (38.64%) and the most common sign was periocular/facial edema (50.74%). Mucormycosis involving the nose and sinuses (94.54%) was most common followed by rhino?orbital (45.41%) and brain involvement (10.04%). The most common risk factor for mucormycosis was diabetes [81.92%], followed by corticosteroid use [79.69%] and supplemental oxygen [48.90%]. Most of the patients received similar treatment with IV amphotericin B [88.64%] and local debridement [80.74%]. Conclusion: With the third wave of COVID?19 still lurking, a fatal fungal infection should be kept in mind in COVID?19 active as well as recovered patients, especially those who have co?morbid medical conditions such as uncontrolled diabetes and who are treated with large doses of corticosteroids.

Importancia de la monitorización de concentraciones plasmáticas de voriconazol y dificultad en ajuste de dosis en un paciente pediátrico / Voriconazole monitorization in pediatric patients, difficulties in dose adjustment

Resumen Presentamos el caso de un escolar de 10 años, con el diagnóstico de una recaída de una leucemia mieloide aguda que cursó con un episodio de una neutropenia febril de alto riesgo, posterior a un ciclo intensivo de quimioterapia, evolucionando con una infección fúngica invasora demostrada por histopatología. Se inició tratamiento con voriconazol intravenoso, evolucionando con concentraciones plasmáticas erráticas que requirieron sucesivos ajustes de dosis, lo que también ocurrió con la administración oral del medicamento. Finalmente, tuvo una respuesta favorable al tratamiento, a pesar de la dificultad de la dosificación para alcanzar niveles terapéuticos. La búsqueda activa y la terapia antifúngica anticipada, así como la monitorización seriada de concentraciones terapéuticas de voriconazol, permitieron un tratamiento antifúngico óptimo y oportuno, mejorando el pronóstico del paciente.

Abstract We present a 10-year-old male patient with a diagnosis of relapsed acute myeloid leukemia (AML), presenting with high-risk febrile neutropenia (HRFN), after a cycle of intensive chemotherapy, evolving with an invasive fungal infection demonstrated by histopathology. Treatment with intravenous voriconazole was started, with erratic plasmatic levels, which require successive dose adjustments which also occurred with oral administration. Finally, he had a favorable response to treatment, despite of the dosing difficulties to reach therapeutic levels. Active search as well as preemptive antifungal therapy, together with plasmatic level monitorization of voriconazole allowed a prompt recovery and improved the patient prognosis.

Acute invasive fungal rhinosinusitis in pediatric patients with oncohematological diseases

Abstract Introduction Invasive fungal diseases represent important causes of morbidity and mortality among pediatric oncohematological patients. Acute invasive fungal rhinosinusitis is a rare and aggressive disease that occurs mainly in immunocompromised patients. The mortality rate is high and therefore, accurate and early diagnosis is essential. Objectives The aim of this study was to describe the frequency of acute invasive fungal rhinosinusitis among pediatric oncohematological patients and characterize them with confirmed diagnoses. Methods This was a retrospective study that analyzed the medical records of pediatric patients diagnosed with oncohematological diseases and suspected fungal infections, who were included after obtaining informed consent, from January to December 2017, in the pediatric unit of a tertiary university hospital. Data collected from medical record analysis included the following: underlying diagnosis, absolute neutrophil count, clinical presentation, culture and biopsy results, surgical procedures performed, survival and mortality. Results A total of 27 patients were evaluated, with three suspected cases of acute invasive fungal rhinosinusitis. Histopathological and microbiological analyses confirmed two cases. In both cases, the pathogen isolated in the culture was Fusarium sp. The two confirmed cases were female, aged 12 and 14 years, both with an absolute neutrophil count of 10 cells/μL. The underlying disease of the first patient was acute myeloid leukemia (subtype M5), whereas the second patient presented idiopathic bone marrow aplasia. Conclusion Both confirmed cases of acute invasive fungal rhinosinusitis presented with constitutional symptoms and signs of nasal and sinusital inflammation. This demonstrates the importance of fever as a symptom in immunocompromised patients and it should prompt otorhinolaryngological investigation.

Effects of nystatin oral care combined with health education in preventing oral fungal infection in patients with severe hepatitis / 中国实用护理杂志

Objective:To explore the risk factors of oral fungal infection in patients with severe hepatitis, and the prevention role of nystatin oral care combined with precision health education on oral fungal infection.Methods:A total of 150 patients with severe hepatitis who were hospitalized for diagnosis and treatment in the First Affiliated Hospital of Zhengzhou University from February 2018 to February 2020 were selected as the research objects. According to the random number table method, they were divided into the observation group (given nystatin oral care combined with precision health education intervention) and the control group (given routine oral care combined with precision health education intervention), 75 cases in each group. The incidence of oral fungal infections in the two groups after the intervention were compared.Results:The fungal infection rate in the observation group at 1 week, 2 weeks and 4 weeks after intervention were 2.67% (2/75), 4.00% (3/75), 8.00% (6/75), which were significantly lower than 12.00% (9/75), 18.67% (14/75), 25.33% (19/75) in the control group ( χ2=4.81, 8.03, 8.11, all P<0.05). Four weeks after the intervention, among the 6 patients with fungal infection in the observation group, there were 5 cases of oral leukoplakia and foreign body sensation in the pharynx, and 1 patient with oral leukoplakia; among the 19 patients with fungal infection in the control group, all had oral mucosal leukoplakia. There were 17 cases of leukoplakia and pharyngeal foreign body sensation, and 2 cases of oral leukoplakia. Conclusions:Nystatin oral care combined with precision health education is of great significance in patients with severe hepatitis, and can effectively reduce the incidence of oral fungal infections.

Lesions caused by human and domestic and wild animal bites

ABSTRACT Animal bites are a common problem in the emergency room. There are many reports of isolated cases (mainly of domestic mammals); however, texts with more comprehensive and general guidance on these kinds of bite injuries are necessary, including those caused by wild mammals, reptiles, and even fish. This review aims to update knowledge on this problem, which includes human and domestic and wild animal bites. Health teams in emergency care centers should be aware of the initial and late measures required to control this problem.

Study on the relationship between blood concentration and efficacy of voriconazole in the treatment of pediatric invasive fungal infection / 药学实践杂志

Objective To explore the correlation between dose, blood concentration and efficacy of voriconazole in the treatment of invasive fungal infection in children. Methods 68 children treated with voriconazole during January 2019 to December 2019 were collected. The plasma concentration of voriconazole was assayed by high performance liquid chromatography (HPLC). The correlation between blood concentration and clinical efficacy was statistically analyzed. Results Different drug blood concentrations were obtained with different dosages: <4.0 mg/kg (6 cases) with the trough concentration ranged from 0.4 to 3.31 μg/ml (r=0.613, P=0.195). (4.0 - 7.0) mg/kg (44 cases), ranged from 0.35 to 7.02 μg/ml (r=0.325, P=0.018); >7.0 mg/kg (18 cases), ranged from 1.46 to 12.45 μg/ml (r=0.584，P＜0.023). There was a difference between the three groups (F=7.270, P=0.026). The relationship between the drug blood concentration and the therapeutic effect was obvious. In the <1.0 μg/ml group of 14 cases, 10 cases (71.4%) were effective, and 4 cases were ineffective. In the 1.0 - 5.5 μg/ml group of 48 cases, 44 cases (91.7%) were effective, and 4 cases were ineffective. In the >5.5 μg/ml group of 6 cases, 4 cases (66.7%) were effective and 2 cases ineffective. The difference among the three groups was obvious (χ2=5.360, P=0.039). Among the 68 cases, 58 cases (85.3%) were effective, and 10 cases (14.7%) were ineffective. Adverse reactions occurred in 10 cases (14.7%) with mild liver function injury, which did not affect the treatment and recovered with liver protection treatment. Conclusion This study showed that voriconazole was generally safe and effective in the treatment of invasive fungal infections in children. There was a significant dose-blood concentration and efficacy correlation. Further studies on pharmacokinetics and efficacy should be carried out to optimize the individualized treatment.