ABSTRACT
OBJECTIVES: To retrospectively describe the patterns of use of dalbavancin for treating infections in diabetic patients in Italian and Spanish standard clinical practice. METHODS: DALBADIA [NCT04959799] was a multicentre, observational, retrospective cohort study, conducted in Italy and Spain. The study enrolled 97 adults with type 1 or 2 diabetes mellitus, treated with dalbavancin as per standard clinical practice for a Gram-positive bacterial infection or the Gram-positive component of a mixed infection. RESULTS: Dalbavancin was used to treat cellulitis (18/92 patients, 19.6%), followed by prosthetic joint infection (14 patients, 15.2%), endocarditis (13 patients, 14.1%), and primary bacteraemia (10 patients, 10.9%); 78/92 (84.8%) patients had Gram-positive infections only, and 14 (15.2%) had mixed infections. The most frequently isolated microorganisms were Staphylococcus aureus in 43 (55.8% of the patients with microbial isolation), 25.6% of which methicillin-resistant; Staphylococcus epidermidis in 13 (16.9%), 53.8% of which methicillin-resistant; Enterococcus faecalis in 11 (14.3%). The main reason for the dalbavancin choice was the intent to simplify the antibiotic regimen (81.5% of cases). A multidisciplinary team participated in the treatment choice process for 53 (57.6%) patients. Dalbavancin was given as first-line antibiotic in 34 (37.0%) patients and administered as one infusion in 32 (34.8%), and as two infusions in 39 (42.4%). In total, 57/62 (91.9%) eligible patients with available assessment were judged clinically cured or improved at the end of observation. CONCLUSION: In clinical practice, dalbavancin was used in diabetic patients to treat ABSSSIs and other difficult-to-treat infections with a favourable safety profile and a high rate of positive clinical responses.
Subject(s)
Anti-Bacterial Agents , Diabetes Mellitus , Teicoplanin , Adult , Humans , Italy , Retrospective Studies , Spain , Teicoplanin/analogs & derivativesABSTRACT
La viruela del mono es una zoonosis que se contagia principalmente a través del contacto directo con los fluidos y las lesiones cutáneas de personas contagiadas con vesículas aun activas. Aunque el virus fue aislado por primera vez en 1958, y el primer caso humano se identificó en un niño en 1970, en la República Democrática del Congo, la enfermedad ha aumentado progresivamente su incidencia en África, alcanzando en mayo de 2022 transmisión sostenida fuera de este continente. Al ser un virus de nueva introducción en nuestro entorno sanitario, es necesario aprender el patrón epidemiológico en un medio diferente al de las zonas tradicionalmente endémicas y conocer los tratamientos antivirales a nuestro alcance, así como las medidas profilácticas que podrían plantearse, sabiendo que como virus emergente en nuestras regiones las evidencias científicas aun son limitadas. Existen antivirales que han demostrado en modelos animales combatir eficazmente la enfermedad con muy buena tolerancia clínica. Esta enfermedad también ha obligado a revisar las características de las vacunas frente a la viruela, ya que han demostrado un efecto protector frente a la viruela del mono. Por ello, es importante disponer de un documento que recopile toda la información científica publicada a este respecto.(AU)
Monkeypox is a zoonosis that is spread mainly through direct contact with fluids and skin lesions of infected people with vesicles still active. Although the virus was isolated for the first time in 1958 and the first human case was identified in a child in 1970, in the Democratic Republic of the Congo, the disease has progressively increased its incidence in Africa reaching in May 2022 sustained transmission outside this continent. As it is a newly introduced virus in our health system, it is necessary to learn the epidemiological pattern in a different environment from that of traditionally endemic areas and to know the available antiviral treatments, as well as the prophylactic measures that could be considered, knowing that as a virus emerging in our regions, scientific evidence is still limited. There are antivirals that have been shown, in animal models, to effectively combat the disease with very good clinical tolerance. This disease has also forced us to review the characteristics of smallpox vaccines, because they have shown a protective effect against monkeypox. For this reason, it is important to have a document that compiles all the scientific information published in this regard.(AU)
Subject(s)
Humans , Male , Female , Zoonoses/microbiology , Mpox (monkeypox)/drug therapy , Mpox (monkeypox)/immunology , Antiviral Agents , Vaccines , Cidofovir , Communicable Diseases , Microbiology , Microbiological Techniques , Mpox (monkeypox)/prevention & controlABSTRACT
Common variable immunodeficiency (CVID) is the most common symptomatic primary immunodeficiency characterized by decreased immunoglobulins and recurrent infections. Its aetiology remains unknown, and some patients present with severe non-infectious autoimmune or inflammatory complications with elevated associated morbimortality. Recently, intestinal dysbiosis has been proposed as a driver of immune dysregulation. In this study, we assessed the oral, respiratory, and gastrointestinal microbiota of 41 CVID patients (24 with dysimmune and 17 with infection complications) and 15 healthy volunteers using 16S rRNA gene sequencing to explore associations between microbiome profiles and CVID phenotypes. Profound differences in the composition of the microbiota in saliva, sputum, and stool were detected between dysimmune CVID patients and healthy individuals. Globally, respiratory species diversity and faecal bacterial richness were lower in CVID individuals with immune complications. Although a single species could not be identified as a robust predictor of dysimmunity, a combination of around 5-7 bacterial species in each type of sample could predict this severe phenotype with an accuracy of around 90% in the study population. Our study provides new insights into these previously unexplored but highly interrelated ecological niches among themselves and with patient profiles. Our data suggest that this disease-related systemic dysbiosis could be implicated in the immune dysregulation associated with severe cases of CVID.
Subject(s)
Common Variable Immunodeficiency , Gastrointestinal Microbiome , Humans , Dysbiosis , RNA, Ribosomal, 16S/genetics , Bacteria/geneticsABSTRACT
BACKGROUND AND OBJECTIVES: The increasing use of biologics in the treatment of inflammatory diseases has led to more cases of leishmaniasis in patients subjected to iatrogenic immunosuppression. The main objective was to describe the characteristics of the patients with cutaneous (CL) or mucocutaneous (MCL) leishmaniasis who were receiving a biological therapy at the time of diagnosis. PATIENTS AND METHODS: A multicenter retrospective study was design based on a cohort of patients diagnosed with CL or MCL. All patients who were being treated with biologicals were included. For each case, two matched non-exposed patients were included for comparison. RESULTS: 38 patients were diagnosed with CL or MCL while being treated with tumor necrosis factor alpha (TNF-α) inhibitors. Leishmaniasis presented more frequently as a plaque (58.3%) with a larger median lesion size (2.5 cm), ulceration (92.1%), and required a greater median number of intralesional meglumine antimoniate infiltrations (3 doses) (P < 0.05) than in non-exposed patients. We found no systemic involvement in patients being treated with anti-TNF-α. We did not find differences regarding the treatment characteristics whether biologic therapy was modified or not. CONCLUSIONS: Although management should be individualized, maintenance of biologic therapy does not seem to interfere with treatment of CL or MCL.
Subject(s)
Antiprotozoal Agents , Leishmaniasis, Cutaneous , Leishmaniasis, Mucocutaneous , Humans , Leishmaniasis, Mucocutaneous/diagnosis , Leishmaniasis, Mucocutaneous/drug therapy , Leishmaniasis, Cutaneous/diagnosis , Leishmaniasis, Cutaneous/drug therapy , Leishmaniasis, Cutaneous/pathology , Retrospective Studies , Tumor Necrosis Factor Inhibitors , Meglumine Antimoniate/therapeutic use , Immunologic Factors/therapeutic use , Antiprotozoal Agents/therapeutic useABSTRACT
INTRODUCTION: We developed a survey to obtain information on the monitoring practices of major systemic antifungals for treatment and prevention of serious fungal infection. METHODS: The survey included questions relating to methodology and practice and was distributed among 137 colleagues of the Study Group of Medical Mycology (GEMICOMED) from July to December 2019. RESULTS: Monitoring was routinely carried out by most respondents, mainly for voriconazole, and was more likely used to determine the efficacy of the dose administered and less for minimizing drug toxicity. Most responders did not follow the strategies of voriconazole dosage based on CYP2C19 genotyping. Monitoring of posaconazole, itraconazole, or other azole metabolites was not carried out or scarcely demanded. Most responders rarely used flucytosine in their clinical practice nor did they monitor it. According to the answers given by some responders, monitoring isavuconazole, amphotericin B, caspofungin and fluconazole exposure would be also interesting in daily clinical practice in selected patient populations. CONCLUSIONS: The survey reveals common practices and attitudes towards antifungal monitoring, sometimes not performed as per best recommendations, offering an opportunity for education and research. Appropriate use of therapeutic drug monitoring may be an objective of antifungal stewardship programmes.
Subject(s)
Antifungal Agents , Mycoses , Humans , Antifungal Agents/therapeutic use , Voriconazole/therapeutic use , Itraconazole/therapeutic use , Mycoses/drug therapy , Mycoses/microbiology , Fluconazole/therapeutic useABSTRACT
Monkeypox is a zoonosis that is spread mainly through direct contact with fluids and skin lesions of infected people with vesicles still active. Although the virus was isolated for the first time in 1958 and the first human case was identified in a child in 1970, in the Democratic Republic of the Congo, the disease has progressively increased its incidence in Africa reaching in May 2022 sustained transmission outside this continent. As it is a newly introduced virus in our health system, it is necessary to learn the epidemiological pattern in a different environment from that of traditionally endemic areas and to know the available antiviral treatments, as well as the prophylactic measures that could be considered, knowing that as a virus emerging in our regions, scientific evidence is still limited. There are antivirals that have been shown, in animal models, to effectively combat the disease with very good clinical tolerance. This disease has also forced us to review the characteristics of smallpox vaccines, because they have shown a protective effect against monkeypox. For this reason, it is important to have a document that compiles all the scientific information published in this regard.
Subject(s)
Mpox (monkeypox) , Smallpox Vaccine , Child , Animals , Humans , Mpox (monkeypox)/drug therapy , Mpox (monkeypox)/epidemiology , Mpox (monkeypox)/prevention & control , Monkeypox virus , Smallpox Vaccine/therapeutic use , Africa , IncidenceABSTRACT
Introduction: We developed a survey to obtain information on the monitoring practices of major systemic antifungals for treatment and prevention of serious fungal infection. Methods: The survey included questions relating to methodology and practice and was distributed among 137 colleagues of the Study Group of Medical Mycology (GEMICOMED) from July to December 2019. Results: Monitoring was routinely carried out by most respondents, mainly for voriconazole, and was more likely used to determine the efficacy of the dose administered and less for minimizing drug toxicity. Most responders did not follow the strategies of voriconazole dosage based on CYP2C19 genotyping. Monitoring of posaconazole, itraconazole, or other azole metabolites was not carried out or scarcely demanded. Most responders rarely used flucytosine in their clinical practice nor did they monitor it. According to the answers given by some responders, monitoring isavuconazole, amphotericin B, caspofungin and fluconazole exposure would be also interesting in daily clinical practice in selected patient populations. Conclusions: The survey reveals common practices and attitudes towards antifungal monitoring, sometimes not performed as per best recommendations, offering an opportunity for education and research. Appropriate use of therapeutic drug monitoring may be an objective of antifungal stewardship programmes.(AU)
Introducción: Describimos los resultados de una encuesta diseñada para obtener información sobre prácticas de monitorización de los principales antifúngicos sistémicos utilizados en el tratamiento y la prevención de la infección fúngica grave en España. Métodos: La encuesta, que incluye preguntas relacionadas tanto con metodología como con su uso práctico, se distribuyó entre 137 compañeros del Grupo de Estudio de Micología Médica (GEMICOMED), de la Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. Resultados: La mayoría de los encuestados respondieron utilizar la monitorización de antifúngicos de forma rutinaria, principalmente para voriconazol, y en especial para evaluar la eficacia de la dosis administrada y menos para minimizar su toxicidad. La mayoría de ellos no siguieron las estrategias de dosificación de voriconazol basadas en el conocimiento previo del genotipo CYP2C19, relacionado con su metabolización. Por el contrario, la monitorización de posaconazol, itraconazol o de algunos de sus metabolitos no se realizó o apenas se solicitó. La mayoría de los encuestados rara vez usan 5-fluocitosina en su práctica clínica y por tanto tampoco monitorizan su exposición. Un alto porcentaje consideraría de utilidad poder evaluar la exposición a isavuconazol, anfotericina B, caspofungina y fluconazol en determinadas situaciones en la práctica clínica. Conclusiones: La encuesta revela prácticas y actitudes hacia la monitorización de antifúngicos que en ocasiones no se realizan según las principales recomendaciones, lo que ofrece una oportunidad para la educación y la investigación. Abordar esta formación podría convertirse en objetivo de los programas racionales del uso de antimicrobianos a nivel nacional.(AU)
Subject(s)
Humans , Male , Female , 34628 , Antifungal Agents , Mycoses , Surveys and Questionnaires , SpainABSTRACT
Monkeypox is a zoonosis that is spread mainly through direct contact with fluids and skin lesions of infected people with vesicles still active. Although the virus was isolated for the first time in 1958 and the first human case was identified in a child in 1970, in the Democratic Republic of the Congo, the disease has progressively increased its incidence in Africa reaching in May 2022 sustained transmission outside this continent. As it is a newly introduced virus in our health system, it is necessary to learn the epidemiological pattern in a different environment from that of traditionally endemic areas and to know the available antiviral treatments, as well as the prophylactic measures that could be considered, knowing that as a virus emerging in our regions, scientific evidence is still limited. There are antivirals that have been shown, in animal models, to effectively combat the disease with very good clinical tolerance. This disease has also forced us to review the characteristics of smallpox vaccines, because they have shown a protective effect against monkeypox. For this reason, it is important to have a document that compiles all the scientific information published in this regard.
ABSTRACT
Common variable immunodeficiency (CVID) is the most frequent symptomatic primary immunodeficiency (PID) in general population. PID are genetic diseases that share a dysfunction in the immune system entailing a greater risk of both chronic and recurrent infections. These patients can also develop chronic gastrointestinal infections caused by norovirus with persistent viral dissemination, which can be detect ed months after primoinfection. Additionally, a proportion of CVID patients show a typical severe enteropathy presenting with recurrent diarrhoea, intestinal malabsorption, inflammatory lesions, and villous atrophy. Some studies have related this enteropathy with chronic intestinal infection caused by norovirus. (AU)
Subject(s)
Humans , Common Variable Immunodeficiency/complications , Common Variable Immunodeficiency/pathology , Caliciviridae Infections , Diarrhea , Gastrointestinal DiseasesABSTRACT
The indiscriminate and massive antibiotic use in the clinical practice and in agriculture or cattle during the past few decades has produced a serious world health problem that entails high morbidity and mortality: the antibiotic multi-drug resistance. In 2017 and 2019, the World Health Organization published a list of urgent threats and priorities in the context of drug resistance, which only included Gram-negative bacteria and specially focused on carbapenem-resistant Acinetobacter baumannii and Pseudomonas aeruginosa, as well as carbapenem and third generation cephalosporin-resistant Enterobacteriaceae. This scenario emphasizes the need of developing and testing new antibiotics from different families, such as new beta-lactams, highlighting cefiderocol and its original mechanism of action; new beta-lactamase inhibitors, with vaborbactam or relebactam among others; new quinolones such as delafloxacin, and also omadacycline or eravacycline, as members of the tetracycline family. The present work reviews the importance and impact of Gram-negative bacterial infections and their resistance mechanisms, and analyzes the current therapeutic paradigm as well as the role of new antibiotics with a promising future in the era of multi and pan-drug resistance. (AU)
Subject(s)
Humans , History, 21st Century , beta-Lactam Resistance , Anti-Bacterial Agents , Gram-Negative Bacterial Infections , Acinetobacter baumannii , Pseudomonas aeruginosa , World Health OrganizationABSTRACT
BACKGROUND: Both fidaxomicin and bezlotoxumab (used in combination with an antibiotic against Clostridioides difficile) achieve reductions in recurrence rates of C. difficile infection (CDI). However, the two strategies have never been compared. METHODS: Data from two retrospective cohorts of 'real-life' use of fidaxomicin and bezlotoxumab in combination with a standard anti-C. difficile antibiotic were used to compare the rates of recurrence of both strategies. Since the two cohorts were not identical, we used a propensity score analysis. RESULTS: Three hundred and two patients were included: 244 in the fidaxomicin cohort and 78 in the bezlotoxumab cohort. A history of renal failure or immunosuppression was more frequent in patients receiving bezlotoxumab (39.7% and 66.7% versus 26.6% and 38.9%; Pâ=â0.03 and Pâ<â0.001, respectively), but the severity and number of previous CDI episodes were similar in both cohorts. We observed that 19.3% of the patients in the fidaxomicin cohort experienced recurrence, compared with 14.1% in the bezlotoxumab cohort (OR 1.45; 95% CI 0.71-2.96; Pâ=â0.29) but the difference remained non-significant after propensity score matching using previously defined variables (OR 1.24; 95% CI 0.50-3.07; Pâ=â0.64). Moreover, the multivariate analysis did not show differences depending on the drug used. CONCLUSIONS: We observed that fidaxomicin and bezlotoxumab are prescribed in similar clinical scenarios, although those treated with bezlotoxumab have greater comorbidity. The proportion of recurrences was numerically lower in those treated with bezlotoxumab, although the propensity analysis did not find significant differences between the two drugs.
Subject(s)
Clostridium Infections , Vancomycin , Anti-Bacterial Agents/therapeutic use , Antibodies, Monoclonal , Broadly Neutralizing Antibodies , Clostridium Infections/drug therapy , Cohort Studies , Fidaxomicin/therapeutic use , Humans , Recurrence , Retrospective Studies , Treatment Outcome , Vancomycin/therapeutic useABSTRACT
Patients with a compromised immune system suffer awide variety of insults. Pulmonary complications remain amajor cause of both morbidity and mortality in immunocompromised patients. When such individuals present with radiographic infiltrates, the clinician faces a diagnostic challenge.The differential diagnosis in this setting is broad and includesboth infectious and non-infectious conditions. Evaluation ofthe immunocompromised host with diffuse pulmonary infiltrates can be difficult, frustrating, and time-consuming. Thiscommon and serious problem results in significant morbidityand mortality, approaching 90%. Infections are the most common causes of both acute and chronic lung diseases leading torespiratory failure. Non-invasive diagnostic methods for evaluation are often of little value, and an invasive procedure (suchas bronchoalveolar lavage, transbronchial biopsy or even openlung biopsy) is therefore performed to obtain a microbiologicand histologic diagnosis. Bronchoscopy allows certain identification of some aetiologies, and often allows the exclusion ofinfectious agents. Early use of computed tomography scanning is able to demonstrate lesions missed by conventionalchest X-ray. However, even when a specific diagnosis is made,it might not impact patients overall survival and outcomes (AU)
Subject(s)
Humans , Animals , Pneumonia/diagnosis , Pneumonia/drug therapy , Pneumonia/etiology , Immunocompromised Host , Lung Diseases/diagnosis , Lung Diseases/microbiology , Lung Diseases/mortalityABSTRACT
OBJECTIVE: The aim of this study was to analyze which are the main factors that could influence the result of a CT guided biopsy in vertebral osteomyelitis (VO) patients. METHODS: A single center retrospective observational study was performed including adult patients who had been diagnosed with VO and undergone CT guided needle biopsy from January 2010 to January 2020. Demographical features, concurrent diseases, laboratory findings, microbiological diagnosis, radiological data, medical complications, antibiotic exposure were compiled. Multivariate analysis was performed with a logistic regression comparing the patients depending on the culture result. RESULTS: Seventy-seven patients were included in the study. Baseline characteristics were comparable between groups. Sample culture was positive in 43 cases (56%). Microorganism isolated were gram+(72%), gram-(14%), mycobacteria (7%) and fungi (7%). Delay in the procedure, antibiotic exposure and blood culture positivity were also similar among both groups. The biopsy results were not influenced by the CRP value, the presence of fever nor antibiotic exposure. The longer duration of back pain was associated to a lower probability of a positive culture. CONCLUSIONS: In conclusion, our study displays an acceptable reliability of CT guided needle biopsy in VO patients, even in cases under antibiotic treatment. The presence of fever or CRP values did not predict a positive culture. Delay in diagnosis could impact negatively on culture yield.
Subject(s)
Image-Guided Biopsy , Osteomyelitis , Adult , Biopsy, Needle , Humans , Osteomyelitis/diagnosis , Reproducibility of Results , Tomography, X-Ray ComputedABSTRACT
Objective: The aim of this study was to analyze which are the main factors that could influence the result of a CT guided biopsy in vertebral osteomyelitis (VO) patients. Methods: A single center retrospective observational study was performed including adult patients who had been diagnosed with VO and undergone CT guided needle biopsy from January 2010 to January 2020. Demographical features, concurrent diseases, laboratory findings, microbiological diagnosis, radiological data, medical complications, antibiotic exposure were compiled. Multivariate analysis was performed with a logistic regression comparing the patients depending on the culture result. Results: Seventy-seven patients were included in the study. Baseline characteristics were comparable between groups. Sample culture was positive in 43 cases (56%). Microorganism isolated were gram+(72%), gram−(14%), mycobacteria (7%) and fungi (7%). Delay in the procedure, antibiotic exposure and blood culture positivity were also similar among both groups. The biopsy results were not influenced by the CRP value, the presence of fever nor antibiotic exposure. The longer duration of back pain was associated to a lower probability of a positive culture. Conclusions: In conclusion, our study displays an acceptable reliability of CT guided needle biopsy in VO patients, even in cases under antibiotic treatment. The presence of fever or CRP values did not predict a positive culture. Delay in diagnosis could impact negatively on culture yield.(AU)
Objetivo: El propósito del presente estudio es analizar qué factores pueden influir en el resultado del cultivo de las muestras obtenidas por punción guiada por TC en pacientes con osteomielitis vertebral. Métodos: Se realizó un estudio en un único centro, retrospectivo y observacional en pacientes diagnosticados de osteomielitis vertebral, que fueron subsidiarios de punción-biopsia entre enero de 2010 y enero de 2020. Se recogieron para su análisis, variables demográficas, comorbilidades, resultados de laboratorio, radiología, el tratamiento previo con antibióticos y la demora previa a la realización de la técnica. Se realizó un análisis multivariante mediante regresión logística. Resultados: Se incluyó a un total de 77 pacientes que fueron sometidos a la técnica. Sus características basales fueron similares. El cultivo fue positivo en 43 casos (56%). Los microorganismos aislados fueron gram + (72%), gram (14%), micobacterias (7%) y hongos (7%). El retraso en la ejecución de la técnica y el tratamiento previo con antibióticos fue similar en ambos grupos. Ni el valor de PCR, la presencia de fiebre ni la antibioterapia tuvieron influencia en el resultado del cultivo. Se observó que una mayor duración del dolor lumbar se relacionó con una menor probabilidad de obtener un resultado positivo en el cultivo. Conclusiones: Incluso bajo exposición antibiótica, la punción asistida por TC mostró una rentabilidad aceptable. La presencia de fiebre o valores elevados de PCR no fueron predictivos de positividad del cultivo. El retraso diagnóstico sí podría impactar negativamente en la rentabilidad diagnóstica del cultivo procedente de la biopsia.(AU)
Subject(s)
Humans , Male , Female , Spinal Puncture , Biopsy , Image-Guided Biopsy , Osteomyelitis/diagnosis , Tomography, X-Ray Computed , Anti-Bacterial Agents , Discitis , Reproducibility of Results , Retrospective Studies , RheumatologySubject(s)
Chagas Disease , Trypanosoma cruzi , Vasculitis , Autoimmunity , Chagas Disease/complications , Chronic Disease , HumansABSTRACT
INTRODUCTION: We developed a survey to obtain information on the monitoring practices of major systemic antifungals for treatment and prevention of serious fungal infection. METHODS: The survey included questions relating to methodology and practice and was distributed among 137 colleagues of the Study Group of Medical Mycology (GEMICOMED) from July to December 2019. RESULTS: Monitoring was routinely carried out by most respondents, mainly for voriconazole, and was more likely used to determine the efficacy of the dose administered and less for minimizing drug toxicity. Most responders did not follow the strategies of voriconazole dosage based on CYP2C19 genotyping. Monitoring of posaconazole, itraconazole, or other azole metabolites was not carried out or scarcely demanded. Most responders rarely used flucytosine in their clinical practice nor did they monitor it. According to the answers given by some responders, monitoring isavuconazole, amphotericin B, caspofungin and fluconazole exposure would be also interesting in daily clinical practice in selected patient populations. CONCLUSIONS: The survey reveals common practices and attitudes towards antifungal monitoring, sometimes not performed as per best recommendations, offering an opportunity for education and research. Appropriate use of therapeutic drug monitoring may be an objective of antifungal stewardship programmes.
ABSTRACT
Candida auris is an emergent multidrug-resistant fungal pathogen considered a severe global threat due to its capacity to cause nosocomial outbreaks and deep-seated infections with high transmissibility and mortality. However, evidence on its pathogenicity and the complex host-pathogen interactions is still limited. This study used the in vivo invertebrate model in Galleria mellonella to assess its virulence, exploring the mortality kinetics, melanization response, and morphological changes after fungal infection compared to Candida albicans and Candida parapsilosis, with known high and low pathogenicity, respectively. All C. auris isolates presented less virulence than C. albicans strains but higher than that induced by C. parapsilosis isolates. Increased pathogenicity was observed in nonaggregative phenotypes of C. auris, while the melanization response of the larvae to fungal infection was homogeneous and independent of the causing species. C. auris was able to filament in the in vivo animal model G. mellonella, with aggregative and nonaggregative phenotypes presenting various pseudohyphal formation degrees as pathogenicity determinants in a strain-dependent manner. Histological invasiveness of C. auris mimicked that observed for C. albicans, with effective dissemination since the early stages of infection both in yeast and filamented forms, except for a remarkable respiratory tropism not previously observed in other yeasts. These characteristics widely differ between strains and advocate the hypothesis that the morphogenetic variability of C. auris is an indicator of its flexibility and adaptability, contributing to its emergence and rising worldwide prevalence. IMPORTANCE Candida auris is an emergent fungus that has become a global threat due to its multidrug resistance, mortality, and transmissibility. These unique features make it different from other Candida species, but we still do not fully know the degree of virulence and, especially, the host-pathogen interactions. In this in vivo insect model, we found that it presents an intermediate degree of virulence compared to known high- and low-virulence Candida species but with significant variability between aggregative and nonaggregative strains. Although it was previously considered unable to filament, we documented in vivo filamentation as an important pathogenic determinant. We also found that it is able to disseminate early through the host, invading both the circulatory system and many different tissues with a remarkable respiratory tropism not previously described for other yeasts. Our study provides new insights into the pathogenicity of an emergent fungal pathogen and its interaction with the host and supports the hypothesis that its morphogenetic variability contributes to its rising global prevalence.
Subject(s)
Candida auris/physiology , Candida auris/pathogenicity , Candidiasis/microbiology , Moths/microbiology , Animals , Candida auris/genetics , Candida auris/growth & development , Disease Models, Animal , Larva/growth & development , Larva/microbiology , Moths/growth & development , Phenotype , VirulenceABSTRACT
Infections caused by mucorales, with an increasing incidence after candidiasis and aspergillosis, are characterized by the fast angioinvasion of blood vessels and invasion of neighboring organs or structures. Mucorales most commonly cause rhinocerebral, pulmonary, cutaneous, digestive or disseminated infections, and their spread is favored by certain underlying diseases (diabetes, kidney failure) and risk factors (neutropenia, immunosuppression, iron overload). These infections have a high mortality rate, over 40% in many series, and the key to their cure depends on both an early diagnosis and an antifungal treatment, associated in most cases with extensive surgical debridement and other adjunctive therapies. Currently, there are international guidelines, not only local ones, for the management of mucormycosis, in which it is considered by consensus and with a strong recommendation that first-line treatment with high-dose liposomal amphotericin B is the best choice. The combined antifungal treatment of polyene agents with triazoles or candins remains in open debate.