Urinary tract infections and genital mycotic infections associated with SGLT­2 inhibitors: an analysis of the FDA Adverse Event Reporting System.

BACKGROUND: Sodium-glucose cotransporter-2 (SGLT-2) inhibitors are a class of antihyperglycemic agents, including canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin. Risk of urinary tract infections (UTIs) and genital mycotic infections (GMIs) associated with SGLT­2 inhibitors is of great clinical significance. The study aimed to assess the association between SGLT-2 inhibitors and occurrences of UTIs and GMIs using the FDA Adverse Event Reporting System (FAERS) database. METHODS: We used OpenVigil 2.1-MedDRA-v24 to query the FAERS database. Disproportionality analysis was performed to detect adverse event signals. Reporting Odds Ratio (ROR) and Proportional Reporting Ratio (PRR) were calculated to measure the disproportionality. RESULTS: A total of 45,256 reports related to the use of SGLT-2 inhibitors, including 1,714 UTI cases and 438 GMI cases, were retrieved. Potential positive signals for UTIs and GMIs were identified for canagliflozin, dapagliflozin, empagliflozin, and ertugliflozin in adult patients of all ages and both sexes. CONCLUSIONS: Data mining in the FAERS database suggests strong association between SGLT-2 inhibitors and UTIs/GMIs. These findings provide real-world evidence on the potential risk of UTIs/GMIs related to SGLT-2 inhibitors.

Infección micótica por Cladophialophora bantiana y desarrollo de feohifomicosis cerebral. Revisión sistemática de 58 informes de caso / Fungal infection by Cladophialophora bantiana and development of cerebral phaeohyphomycosis. A systematic review of 58 case reports

Introducción: Cladophialophora bantiana es un hongo filamentoso, denominado hongo dematiáceo por la presencia de melanina. Este hongo tiene importancia clínica por ser neurotrópico y causar feohifomicosis cerebral. Material y métodos. Se analizó la información científica disponible sobre el desarrollo de feohifomicosis cerebral provocada por Cladophialophora bantiana, seleccionando artículos de las bases de PubMed, Scopus y Google Scholar, que describen informes de caso sobre infección micótica de C. bantiana en adultos, considerando el análisis de la sintomatología, el historial clínico y los daños neuroanatómicos de los pacientes, además de considerar la mortalidad de la patología.ResultadosLa India y Estados Unidos fueron los países con más informes de caso, 32 y 11 casos, respectivamente. Asimismo, en cuanto a las lesiones neuroanatómicas, en su mayoría, los pacientes sufrieron lesiones mixtas (29%) y del lóbulo frontal (22%). De acuerdo con el estado de los pacientes, la patología tiene una mortalidad del 62%.ConclusionesSe concluye que la feohifomicosis cerebral tiene una alta mortalidad, no existe un tratamiento estandarizado y, en la mayoría de los casos, la infección fúngica del cerebro es mixta y afecta a varias partes del cerebro; además, si no se diagnostica y trata a tiempo, puede ocasionar la muerte de los pacientes. (AU)

INTRODUCTION: Cladophialophora bantiana is a filamentous fungus, known as a dematiaceous fungus because of the presence of melanin. This fungus is of clinical importance because it is neurotropic and causes cerebral phaeohyphomycosis. Material and methods. The available scientific information on the development of cerebral phaeohyphomycosis caused by Cladophialophora bantiana was analysed by selecting articles from the PubMed, Scopus and Google Scholar databases that describe case reports of fungal infection by C. bantiana in adults, taking into account the analysis of the patients’ symptomatology, clinical history and neuroanatomical damage, in addition to considering the mortality of the condition.RESULTSIndia and United States were the countries with most case reports, with 32 and 11 cases respectively. Moreover, in terms of neuroanatomical lesions, the majority of patients suffered mixed lesions (29%) and frontal lobe lesions (22%). In accordance with the patients’ condition, the pathology has a mortality rate of 62%.CONCLUSIONSIt is concluded that cerebral phaeohyphomycosis has a high mortality rate, there is no standardised treatment and, in most cases, the fungal infection of the brain is mixed and affects several different parts of it. Furthermore, if not diagnosed and treated in time, it can lead to the patients’ death. (AU)

Molecular Epidemiological Investigation of a Nosocomial Cluster of C. auris: Evidence of Recent Emergence in Italy and Ease of Transmission during the COVID-19 Pandemic.

Candida auris is an emerging MDR pathogen raising major concerns worldwide. In Italy, it was first and only identified in July 2019 in our hospital (San Martino Hospital, Genoa), where infection or colonization cases have been increasingly recognized during the following months. To gain insights into the introduction, transmission dynamics, and resistance traits of this fungal pathogen, consecutive C. auris isolates collected from July 2019 to May 2020 (n = 10) were subjected to whole-genome sequencing (WGS) and antifungal susceptibility testing (AST); patients' clinical and trace data were also collected. WGS resolved all isolates within the genetic clade I (South Asian) and showed that all but one were part of a cluster likely stemming from the index case. Phylogenetic molecular clock analyses predicted a recent introduction (May 2019) in the hospital setting and suggested that most transmissions were associated with a ward converted to a COVID-19-dedicated ICU during the pandemic. All isolates were resistant to amphotericin B, voriconazole, and fluconazole at high-level, owing to mutations in ERG11(K143R) and TACB1(A640V). Present data demonstrated that the introduction of MDR C. auris in Italy was a recent event and suggested that its spread could have been facilitated by the COVID-19 pandemic. Continued efforts to implement stringent infection prevention and control strategies are warranted to limit the spread of this emerging pathogen within the healthcare system.

Genitourinary Complications of Diabetes Mellitus: An Overview of Pathogenesis, Evaluation, and Management.

BACKGROUND: Diabetes mellitus is a vastly prevalent metabolic disorder with escalating global health concerns. Particularly when mismanaged, chronic micro- and macrovascular complications may highly impair physiological systems while immunodeficiency disposes us to infection. OBJECTIVE: We investigate infections, localized complications, and neoplasms of the genitourinary system secondary to the chronic complications of diabetes mellitus in males and females. METHOD: A comprehensive MEDLINE® search was guided using key words relevant to diabetes mellitus and the genitourinary system. RESULTS: Pathogen-friendly environments may implicate the sequelae of urinary tract and genital mycotic infections, potentially generating necrosis, abscess, and other inflammatory complications, which may present concomitantly with neurogenic and/or vasculogenic dysfunction to further exacerbate an existing genitourinary condition. Manifestations of the adrenal, renal, and genital organs and tissues are discussed as they relate to vascular, immunodeficient, and other hyperglycemic complications of the diabetic state. Among those, chronic kidney disease and cystopathy are the most prevailing and detrimental. Though studies have connected diabetes to either an increased risk of developing or poor prognosis of bladder, renal, prostate, endometrial, and cervical cancers, the explicit biological relationships are as of yet inconclusive. CONCLUSION: Despite the availability of precise treatments to ameliorate most presently reviewed conditions, particularly urinary tract and genital mycotic infection-related sequelae, reversing permanent vascular damage remains a great challenge. Leading a healthier lifestyle and managing diabetes mellitus with a patient-centric approach from the outset are the most putative methods for preventing critical long-term genitourinary manifestations of diabetes mellitus.

The treatment f coccidioidomycosis / Tratamento da coccidioidomicose

SUMMARYTherapy of coccidioidomycosis continues to evolve. For primary pulmonary disease, antifungal therapy is frequently not required while prolonged courses of antifungals are generally needed for those in whom extrathoracic disseminated has occurred. Intravenous amphotericin B should be reserved for those with severe disease. Oral triazole antifungals have had a great impact on the management of coccidioidomycosis. Both fluconazole and itraconazole at 400 mg daily have been effective for various forms of coccidioidomycosis, including meningitis, although relapse after therapy is discontinued is a problem. Individuals with suppressed cellular immunity are at increased risk for symptomatic coccidioidomycosis and they include those with HIV infection, those on immunosuppressive medications, and those who have received a solid organ transplant. Pregnant women and African-American men have been identified as two other groups who are at an increased risk for symptomatic and severe infection.

RESUMOA terapia da coccidioidomicose continua a evoluir. Para a doença pulmonar primária, o tratamento antifúngico frequentemente não é necessário, enquanto períodos prolongados de tratamento antifúngico são geralmente necessários para aqueles nos quais houve disseminação extratorácica. A anfotericina B intravenosa deve ser reservada para pacientes com doença grave. Antifúngicos triazólicos orais têm tido um grande impacto no manejo da coccidioidomicose. Tanto fluconazol quanto itraconazol em doses diárias de 400 mg foram eficazes contra várias formas de coccidioidomicose, incluindo a meníngea, embora recaídas após a interrupção da terapia ainda constituam um problema. Indivíduos com supressão da imunidade celular apresentam risco aumentado para a coccidioidomicose sintomática, incluindo pacientes infectados pelo HIV, em uso de medicações imunossupressoras, e os que receberam transplantes de órgãos sólidos. Mulheres grávidas e homens afro-americanos foram identificados como dois outros grupos que apresentam risco aumentado de infecção sintomática e grave.

Tacrolimus does not alter the production of several cytokines and antimicrobial peptide in Malassezia furfur-infected-keratinocytes.

Topical immunosuppressant therapy is widely used in the treatment of inflammatory skin diseases, such as atopic dermatitis and psoriasis. Besides its beneficial therapeutic effects, application of topical anti-inflammatory drugs may render the epidermis more vulnerable to invading pathogens by suppressing innate immune responses in keratinocytes (KCs). Cytokines, chemokines and antimicrobial peptides (AMPs) produced by epithelial cells enable them to participate in innate and acquired immune responses. The aim of the present work was to study the influence of tacrolimus (FK506) on KCs infected with Malassezia furfur (M. furfur), evaluating the expression of pro-inflammatory cytokines IL-1α and IL-6, chemokine IL-8, anti-inflammatory cytokines transforming growth factor beta1 (TGF-ß1) and IL-10 and AMP ß-defensin-2. Human KCs were obtained from surgical specimens of normal adult skin. The expression of mRNAs in KCs: FK506-treated, FK506-treated and M. furfur-infected as well as only M. furfur-infected was quantified by real-time quantitative polymerase chain reaction. Next, the production of the AMP ß-defensin-2 and of the above-mentioned pro-inflammatory and anti-inflammatory cytokines was evaluated using enzyme-linked immunosorbent assay. In this study, FK506 did not alter cytokine and AMP production by KCs; this led us to hypothesise that it may not enhance the risk of mycotic skin infections.

The spectrum and aetiology of mycotic infections from a tertiary care hospital from Western part of India.

BACKGROUND: In the past few years, there has been an increase in infections caused by fungal aetiology. This is mainly due to increase in sizes of populations which are at risk. Also, fungi which were previously considered as non-pathogenic have been increasingly implicated. Hence, this study was taken up. AIM: To assess the magnitude of mycotic infections in this set up. To assess the spectrum of fungi which are involved in various infections. MATERIAL AND METHODS: Total 704 samples taken over two and half period were included. They consisted of various samples like sputum, blood, urine, sterile body fluids, corneal scrapings. These were processed by conventional mycological techniques. These included direct microscopy after Gram staining and KOH mount, culture on Sabouraud's dextrose agar (SDA), corn meal agar, brain heart infusion (BHI), brain heart infusion agar (BHIA) and others, as required. For non-albicans Candida, the automated Vitek 2 C system was used. Various moulds and yeasts were identified up to genus level and species level. RESULTS: Of 704 samples, 336 (48%) were positive for fungal culture. Of these, 244 isolates were yeast like fungi, 81 were moulds, 7 were yeasts and 4 were dimorphic. Among blood stream infections, non-albicans Candida were the commonest isolates. In the urine samples, C. albicans was the commonest isolate. From corneal scrapings, only moulds and dimorphic fungi were isolated. CONCLUSION: Incidence of non- albicans Candidal infections is increasing. Culture and identification of mycotic infections is essential for commencement of suitable antifungal therapy.

Clinical and pathological findings of concurrent poxvirus lesions and aspergillosis infection in canaries.

OBJECTIVE: To investigate clinical, pathological and mycological findings in canaries, in which pox lesions and Aspergillus fumigatus (A. fumigatus) infection were observed simultaneously. METHODS: This study was performed on a breeding colony (about 100 canaries) affected by fatal wasting disease. Necropsy was undertaken on 10 severely affected canaries, and gross lesions were recorded. Samples from internal organs displaying lesions were obtained for histopathological evaluation. Tracheal swap samples of internal organs of the all infected animals with lesions at necropsy were cultured in Sabouraud Dextrose Agar for mycological examination. RESULTS: At necropsy, caseous foci were determined in the lungs, on the air sacs, liver, spleen, heart. Swelling of the eyelids, diffuse hemorrhages in the subcutaneous tissue with small papular lesions of the skin were other typical necropsy findings. Histopathologically, pathognomonic eosinophilic intracytoplasmic inclusion bodies, which called Bollinger bodies, in both skin cells and vacuolated air way epithelial cells confirmed canary pox infection. Moreover, histopathological examination of the white-yellowish caseous foci revealed necrotic granulomatous reaction consisting of macrophages, heterophil leukocytes and giant cells encapsulated with a fibrous tissue. After the culture of the tissue samples, the formation of bluish green colonies confirmed A. fumigatus infection. CONCLUSIONS: Canary pox has been known as the disease that can result in high losses in a short time, as a re-emerging disease that has not been present during recent years in canary flocks in Iran. So, the current paper provides useful information to prevent misdiagnosed of canary pox disease which can cause secondary mycotic infection.

Clinical and pathological findings of concurrent poxvirus lesions and aspergillosis infection in canaries

Objective:To investigate clinical, pathological and mycological findings in canaries, in which pox lesions and Aspergillus fumigatus (A. fumigatus) infection were observed simultaneously. Methods:This study was performed on a breeding colony (about 100 canaries) affected by fatal wasting disease. Necropsy was undertaken on 10 severely affected canaries, and gross lesions were recorded. Samples from internal organs displaying lesions were obtained for histopathological evaluation. Tracheal swap samples of internal organs of the all infected animals with lesions at necropsy were cultured in Sabouraud Dextrose Agar for mycological examination. Results: At necropsy, caseous foci were determined in the lungs, on the air sacs, liver, spleen, heart. Swelling of the eyelids, diffuse hemorrhages in the subcutaneous tissue with small papular lesions of the skin were other typical necropsy findings. Histopathologically, pathognomonic eosinophilic intracytoplasmic inclusion bodies, which called Bollinger bodies, in both skin cells and vacuolated air way epithelial cells confirmed canary pox infection. Moreover, histopathological examination of the white-yellowish caseous foci revealed necrotic granulomatous reaction consisting of macrophages, heterophil leukocytes and giant cells encapsulated with a fibrous tissue. After the culture of the tissue samples, the formation of bluish green colonies confirmed A. fumigatus infection. Conclusions:Canary pox has been known as the disease that can result in high losses in a short time, as a re-emerging disease that has not been present during recent years in canary flocks in Iran. So, the current paper provides useful information to prevent misdiagnosed of canary pox disease which can cause secondary mycotic infection.

Clinical and pathological findings of concurrent poxvirus lesions and aspergillosis infection in canaries

<p><b>OBJECTIVE</b>To investigate clinical, pathological and mycological findings in canaries, in which pox lesions and Aspergillus fumigatus (A. fumigatus) infection were observed simultaneously.</p><p><b>METHODS</b>This study was performed on a breeding colony (about 100 canaries) affected by fatal wasting disease. Necropsy was undertaken on 10 severely affected canaries, and gross lesions were recorded. Samples from internal organs displaying lesions were obtained for histopathological evaluation. Tracheal swap samples of internal organs of the all infected animals with lesions at necropsy were cultured in Sabouraud Dextrose Agar for mycological examination.</p><p><b>RESULTS</b>At necropsy, caseous foci were determined in the lungs, on the air sacs, liver, spleen, heart. Swelling of the eyelids, diffuse hemorrhages in the subcutaneous tissue with small papular lesions of the skin were other typical necropsy findings. Histopathologically, pathognomonic eosinophilic intracytoplasmic inclusion bodies, which called Bollinger bodies, in both skin cells and vacuolated air way epithelial cells confirmed canary pox infection. Moreover, histopathological examination of the white-yellowish caseous foci revealed necrotic granulomatous reaction consisting of macrophages, heterophil leukocytes and giant cells encapsulated with a fibrous tissue. After the culture of the tissue samples, the formation of bluish green colonies confirmed A. fumigatus infection.</p><p><b>CONCLUSIONS</b>Canary pox has been known as the disease that can result in high losses in a short time, as a re-emerging disease that has not been present during recent years in canary flocks in Iran. So, the current paper provides useful information to prevent misdiagnosed of canary pox disease which can cause secondary mycotic infection.</p>

Destructive aspergillosis.

The incidence of mycotic infections of paranasal sinuses is on the rise. Aspergillosis is the commonest fungal infection involving the nose and paranasal sinuses. This disease has a varied presentation ranging from the allergic form to the more deadly invasive or destructive form. Destructive fungal disease is almost regarded as synonymous with mucormycosis. The destructive potential of aspergillosis has not been highlighted in the medical literature. We here report a case of aspergillosis, which caused massive destruction of maxilla in an apparently healthy patient.

Coloración de Papanicolaou y su importancia en el diagnóstico de las infecciones cervicovaginales / Papanicolaou-stained smears: its importance in the diagnosis of cervicovaginal infections

La coloración de Papanicolaou, además de la detección temprana del carcinoma de cuello uterino, brinda información sobre el estado hormonal y es orientativa al diagnóstico de infecciones cervicovaginales. La importancia de su detección y tratamiento radica en que pueden evitarse complicaciones posteriores, como enfermedad pélvica inflamatoria, ruptura prematura de membranas, abortos, sepsis del recién nacido, esterilidad. Se procesaron 251 muestras. Se estudió la correlación entre la información brindada por la coloración de Papanicolaou y el examen microbiológico (observación en fresco y coloración de Gram), con el fin de verificar la utilidad que puede brindar la coloración de Papanicolaou como alerta de las infecciones cervicovaginales. Para clasificar las muestras como vaginosis bacterianas se aplicaron los criterios de Amsel. Sobre el total de las muestras se obtuvo para las vaginosis 80% de correlación. En el caso de las infecciones micóticas el porcentaje representa 69%, valor que asciende a 75% si se consideran las muestras inflamatorias. Para Trichomonas vaginalis se obtuvo 100% de concordancia. La comparación de estos dos procedimientos revela un alto porcentaje de correlación, siendo el examen de Papanicolaou un valioso auxiliar para el diagnóstico de ciertas infecciones cervicovaginales.

The Papanicolaou (Pap) smearis not only a mean of early detection of cervical cancer, but also a cytologic screening which reports on the hormonal condition and helps in the diagnosis of cervicovaginal infections. The importance of the early detection and management of this kind of infections is based on the possibility of preventing from later complications such as pelvic inflammatory disease, early breaking of water, abortions, neonatal sepsis and infertility. In order to prove the uses of the Pap-stained smears as a way of diagnosis on potential cervicovaginal infections, 251 samples have been studied focusing on the correlation between the results of Pap-stained smears and those of wet preparations and Gram-stained. The Amsel criteria has been used to classify the samples as Bacterial Vaginosis cases. Taking the Vaginosis cases, 80% of them showed correlation between cytologic and bacteriological techniques. Mycotic infections were detected in 69% of the samples, rate which increased to 75% considering the inflammatory samples. The correlation between the Pap-stained smears and wet preparations/Gram-stained was of 100% for Trichomonas vaginalis samples. In conclusion, there is a high correlation between these two methods that proves the importance of the Pap-stained smears as an auxiliary process for diagnosing specific cervicovaginal infections.

A Review of Systemic Antifungal Agents.

Résumé- Cet article est une revue des antifongiques systémiques communément utilisés. Sont présentés les origines des diverses substances, leur pharmacocinétique, leur mode d'action, leurs effets secondaires et enfin, leurs indications en médecine vétérinaire. [Hill, P.B., Moriello, K.A., Shaw, S.E. A review of systemic antifungal agents (Antifongiques systémiques: une revue). Abstract- This paper is a review of commonly used systemic antifungal antibiotics. Included is a review of the origins of the drugs, pharmacokinetics, modes of action, adverse effects and clinical uses in veterinary medicine.