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1.
Ann Intern Med ; 176(4): 489-495, 2023 04.
Artículo en Inglés | MEDLINE | ID: mdl-36940442

RESUMEN

BACKGROUND: Candida auris is an emerging fungal threat that has been spreading in the United States since it was first reported in 2016. OBJECTIVE: To describe recent changes in the U.S. epidemiology of C auris occurring from 2019 to 2021. DESIGN: Description of national surveillance data. SETTING: United States. PATIENTS: Persons with any specimen that was positive for C auris. MEASUREMENTS: Case counts reported to the Centers for Disease Control and Prevention by health departments, volume of colonization screening, and antifungal susceptibility results were aggregated and compared over time and by geographic region. RESULTS: A total of 3270 clinical cases and 7413 screening cases of C auris were reported in the United States through 31 December 2021. The percentage increase in clinical cases grew each year, from a 44% increase in 2019 to a 95% increase in 2021. Colonization screening volume and screening cases increased in 2021 by more than 80% and more than 200%, respectively. From 2019 to 2021, 17 states identified their first C auris case. The number of C auris cases that were resistant to echinocandins in 2021 was about 3 times that in each of the previous 2 years. LIMITATION: Identification of screening cases depends on screening that is done on the basis of need and available resources. Screening is not conducted uniformly across the United States, so the true burden of C auris cases may be underestimated. CONCLUSION: C auris cases and transmission have risen in recent years, with a dramatic increase in 2021. The rise in echinocandin-resistant cases and evidence of transmission is particularly concerning because echinocandins are first-line therapy for invasive Candida infections, including C auris. These findings highlight the need for improved detection and infection control practices to prevent spread of C auris. PRIMARY FUNDING SOURCE: None.


Asunto(s)
Candida , Candidiasis , Humanos , Estados Unidos/epidemiología , Candida auris , Candidiasis/tratamiento farmacológico , Candidiasis/epidemiología , Candidiasis/diagnóstico , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Equinocandinas/uso terapéutico , Pruebas de Sensibilidad Microbiana
2.
Emerg Infect Dis ; 29(1): 110-117, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36573555

RESUMEN

Coccidioidomycosis is a fungal infection endemic to hot, arid regions of the western United States, northern Mexico, and parts of Central and South America. Sporadic cases outside these regions are likely travel-associated; alternatively, an infection could be acquired in as-yet unidentified newly endemic locales. A previous study of cases in nonendemic regions with patient self-reported travel history suggested that infections were acquired during travel to endemic regions. We sequenced 19 Coccidioides isolates from patients with known travel histories from that earlier investigation and performed phylogenetic analysis to identify the locations of potential source populations. Our results show that those isolates were phylogenetically linked to Coccidioides subpopulations naturally occurring in 1 of the reported travel locales, confirming that these cases were likely acquired during travel to endemic regions. Our findings demonstrate that genomic analysis is a useful tool for investigating travel-related coccidioidomycosis.


Asunto(s)
Coccidioidomicosis , Humanos , Estados Unidos/epidemiología , Coccidioidomicosis/epidemiología , Coccidioidomicosis/microbiología , Viaje , Filogenia , Enfermedad Relacionada con los Viajes , Coccidioides , Genómica
3.
Med Mycol ; 61(2)2023 Feb 03.
Artículo en Inglés | MEDLINE | ID: mdl-36715156

RESUMEN

Aspergillus fumigatus, an environmental mold, causes life-threatening infections. Studies on the phylogenetic structure of human clinical A. fumigatus isolates are limited. Here, we performed whole genome sequencing of 24 A. fumigatus isolates collected from 18 patients in U.S. healthcare facilities in California. Single-nucleotide polymorphism (SNP) differences between patient isolates ranged from 187 to 70 829 SNPs. For five patients with multiple isolates, we calculated the within-host diversities. Three patients had a within-host diversity that ranged from 4 to 10 SNPs and two patients ranged from 2 to 16 977 SNPs. Findings revealed highly diverse A. fumigatus strains among patients and two patterns of diversity for isolates that come from the same patient, low and extremely high diversity.


Aspergillus fumigatus is an environmental mold. It can cause a severe infection called aspergillosis in patients with weakened immune systems. We analyzed A. fumigatus DNA from patients at California hospitals. We described genetic diversity between samples from the same patients and among different patients. Our findings provide insight on using genomic sequencing to investigate aspergillosis in hospitals.


Asunto(s)
Aspergilosis , Aspergillus fumigatus , Humanos , Antifúngicos/uso terapéutico , Aspergilosis/tratamiento farmacológico , Aspergilosis/veterinaria , Aspergillus fumigatus/genética , California , Genómica , Filogenia
4.
BMC Health Serv Res ; 23(1): 553, 2023 May 26.
Artículo en Inglés | MEDLINE | ID: mdl-37237256

RESUMEN

BACKGROUND: To support public health measures during the COVID-19 pandemic, oral opioid agonist treatment (OAT) take-home doses were expanded in Western countries with positive results. Injectable OAT (iOAT) take-home doses were previously not an eligible option, and were made available for the first time in several sites to align with public health measures. Building upon these temporary risk-mitigating guidelines, a clinic in Vancouver, BC continued to offer two of a possible three daily doses of take-home injectable medications to eligible clients. The present study explores the processes through which take-home iOAT doses impacted clients' quality of life and continuity of care in real-life settings. METHODS: Three rounds of semi-structured qualitative interviews were conducted over a period of seventeen months beginning in July 2021 with eleven participants receiving iOAT take-home doses at a community clinic in Vancouver, British Columbia. Interviews followed a topic guide that evolved iteratively in response to emerging lines of inquiry. Interviews were recorded, transcribed, and then coded using NVivo 1.6 using an interpretive description approach. RESULTS: Participants reported that take-home doses granted them the freedom away from the clinic to have daily routines, form plans, and enjoy unstructured time. Participants appreciated the greater privacy, accessibility, and ability to engage in paid work. Furthermore, participants enjoyed greater autonomy to manage their medication and level of engagement with the clinic. These factors contributed to greater quality of life and continuity of care. Participants shared that their dose was too essential to divert and that they felt safe transporting and administering their medication off-site. In the future, all participants would like more accessible treatment such as access longer take-home prescriptions (e.g., one week), the ability to pick-up at different and convenient locations (e.g., community pharmacies), and a medication delivery service. CONCLUSIONS: Reducing the number of daily onsite injections from two or three to only one revealed the diversity of rich and nuanced needs that added flexibility and accessibility in iOAT can meet. Actions such as licencing diverse opioid medications/formulations, medication pick-up at community pharmacies, and a community of practice that supports clinical decisions are necessary to increase take-home iOAT accessibility.


Asunto(s)
COVID-19 , Trastornos Relacionados con Opioides , Humanos , Analgésicos Opioides/uso terapéutico , Pandemias , Calidad de Vida , COVID-19/epidemiología , Colombia Británica , Trastornos Relacionados con Opioides/tratamiento farmacológico , Trastornos Relacionados con Opioides/prevención & control
5.
Emerg Infect Dis ; 28(9): 1924-1926, 2022 09.
Artículo en Inglés | MEDLINE | ID: mdl-35997504

RESUMEN

We characterized 2 clusters of blastomycosis cases in Minnesota, USA, using whole-genome sequencing and single-nucleotide polymorphism analyses. Blastomyces gilchristii was confirmed as the cause of infection. Genomic analyses corresponded with epidemiologic findings for cases of B. gilchristii infections, demonstrating the utility of genomic methods for future blastomycosis outbreak investigations.


Asunto(s)
Blastomicosis , Blastomyces/genética , Blastomicosis/epidemiología , Humanos , Minnesota/epidemiología , Epidemiología Molecular
6.
Ann Intern Med ; 174(11): 1554-1562, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34487450

RESUMEN

BACKGROUND: Candida auris, a multidrug-resistant yeast, can spread rapidly in ventilator-capable skilled-nursing facilities (vSNFs) and long-term acute care hospitals (LTACHs). In 2018, a laboratory serving LTACHs in southern California began identifying species of Candida that were detected in urine specimens to enhance surveillance of C auris, and C auris was identified in February 2019 in a patient in an Orange County (OC), California, LTACH. Further investigation identified C auris at 3 associated facilities. OBJECTIVE: To assess the prevalence of C auris and infection prevention and control (IPC) practices in LTACHs and vSNFs in OC. DESIGN: Point prevalence surveys (PPSs), postdischarge testing for C auris detection, and assessments of IPC were done from March to October 2019. SETTING: All LTACHs (n = 3) and vSNFs (n = 14) serving adult patients in OC. PARTICIPANTS: Current or recent patients in LTACHs and vSNFs in OC. INTERVENTION: In facilities where C auris was detected, PPSs were repeated every 2 weeks. Ongoing IPC support was provided. MEASUREMENTS: Antifungal susceptibility testing and whole-genome sequencing to assess isolate relatedness. RESULTS: Initial PPSs at 17 facilities identified 44 additional patients with C auris in 3 (100%) LTACHs and 6 (43%) vSNFs, with the first bloodstream infection reported in May 2019. By October 2019, a total of 182 patients with C auris were identified by serial PPSs and discharge testing. Of 81 isolates that were sequenced, all were clade III and highly related. Assessments of IPC identified gaps in hand hygiene, transmission-based precautions, and environmental cleaning. The outbreak was contained to 2 facilities by October 2019. LIMITATION: Acute care hospitals were not assessed, and IPC improvements over time could not be rigorously evaluated. CONCLUSION: Enhanced laboratory surveillance and prompt investigation with IPC support enabled swift identification and containment of C auris. PRIMARY FUNDING SOURCE: Centers for Disease Control and Prevention.


Asunto(s)
Candidiasis/diagnóstico , Candidiasis/prevención & control , Atención Subaguda , Adulto , Anciano , Anciano de 80 o más Años , California/epidemiología , Candida auris/genética , Candidiasis/transmisión , Femenino , Humanos , Control de Infecciones , Cuidados a Largo Plazo , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Alta del Paciente , Instituciones de Cuidados Especializados de Enfermería , Secuenciación Completa del Genoma
7.
Mycopathologia ; 185(5): 917-923, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32860564

RESUMEN

BACKGROUND: Candida auris is an emerging multidrug-resistant yeast that causes outbreaks in healthcare settings around the world. In 2016, clinicians and public health officials identified patients with C. auris bloodstream infections (BSI) in Colombian healthcare facilities. To evaluate potential risk factors and outcomes for these infections, we investigated epidemiologic and clinical features of patients with C. auris and other Candida species BSI. METHODS: We performed a retrospective case-case investigation in four Colombian acute care hospitals, defining a case as Candida spp. isolated from blood culture during January 2015-September 2016. C. auris BSI cases were compared to other Candida species BSI cases. Odds ratio (OR), estimated using logistic regression, was used to assess the association between risk factors and outcomes. RESULTS: We analyzed 90 patients with BSI, including 40 with C. auris and 50 with other Candida species. All had been admitted to the intensive care unit (ICU). No significant demographic differences existed between the two groups. The following variables were independently associated with C. auris BSI: ≥ 15 days of pre-infection ICU stay (OR: 5.62, CI: 2.04-15.5), evidence of severe sepsis (OR: 3.70, CI 1.19-11.48), and diabetes mellitus (OR 5.69, CI 1.01-31.9). CONCLUSION: Patients with C. auris BSI had longer lengths of ICU stay than those with other candidemias, suggesting that infections are acquired during hospitalization. This is different from other Candida infections, which are usually thought to result from autoinfection with host flora.


Asunto(s)
Candida/aislamiento & purificación , Candidemia/epidemiología , Candidiasis/diagnóstico , Diagnóstico Diferencial , Adulto , Antifúngicos/uso terapéutico , Candidemia/diagnóstico , Candidemia/tratamiento farmacológico , Candidiasis/tratamiento farmacológico , Candidiasis/epidemiología , Colombia/epidemiología , Infección Hospitalaria/diagnóstico , Infección Hospitalaria/epidemiología , Complicaciones de la Diabetes/microbiología , Brotes de Enfermedades , Femenino , Humanos , Control de Infecciones , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Sepsis/complicaciones , Sepsis/microbiología , Resultado del Tratamiento , Adulto Joven
8.
Clin Infect Dis ; 68(1): 15-21, 2019 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-29788045

RESUMEN

Background: Candida auris is a multidrug-resistant yeast associated with hospital outbreaks worldwide. During 2015-2016, multiple outbreaks were reported in Colombia. We aimed to understand the extent of contamination in healthcare settings and to characterize the molecular epidemiology of C. auris in Colombia. Methods: We sampled patients, patient contacts, healthcare workers, and the environment in 4 hospitals with recent C. auris outbreaks. Using standardized protocols, people were swabbed at different body sites. Patient and procedure rooms were sectioned into 4 zones and surfaces were swabbed. We performed whole-genome sequencing (WGS) and antifungal susceptibility testing (AFST) on all isolates. Results: Seven of the 17 (41%) people swabbed were found to be colonized. Candida auris was isolated from 37 of 322 (11%) environmental samples. These were collected from a variety of items in all 4 zones. WGS and AFST revealed that although isolates were similar throughout the country, isolates from the northern region were genetically distinct and more resistant to amphotericin B (AmB) than the isolates from central Colombia. Four novel nonsynonymous mutations were found to be significantly associated with AmB resistance. Conclusions: Our results show that extensive C. auris contamination can occur and highlight the importance of adherence to appropriate infection control practices and disinfection strategies. Observed genetic diversity supports healthcare transmission and a recent expansion of C. auris within Colombia with divergent AmB susceptibility.


Asunto(s)
Anfotericina B/farmacología , Antifúngicos/farmacología , Candida/clasificación , Candida/efectos de los fármacos , Candidiasis/epidemiología , Candidiasis/microbiología , Farmacorresistencia Fúngica , Candida/genética , Candida/aislamiento & purificación , Portador Sano/epidemiología , Portador Sano/microbiología , Colombia/epidemiología , Microbiología Ambiental , Humanos , Pruebas de Sensibilidad Microbiana , Epidemiología Molecular , Tipificación Molecular , Técnicas de Tipificación Micológica , Secuenciación Completa del Genoma
9.
Emerg Infect Dis ; 25(9): 1780-1781, 2019 09.
Artículo en Inglés | MEDLINE | ID: mdl-31310230

RESUMEN

Four major clades of Candida auris have been described, and all infections have clustered in these 4 clades. We identified an isolate representative of a potential fifth clade, separated from the other clades by >200,000 single-nucleotide polymorphisms, in a patient in Iran who had never traveled outside the country.


Asunto(s)
Candida/aislamiento & purificación , Candidiasis/diagnóstico , Otomicosis/diagnóstico , Adolescente , Candida/genética , Candidiasis/tratamiento farmacológico , Candidiasis/microbiología , Femenino , Humanos , Irán , Otomicosis/tratamiento farmacológico , Otomicosis/microbiología , Viaje , Secuenciación Completa del Genoma
10.
Emerg Infect Dis ; 25(7)2019 07.
Artículo en Inglés | MEDLINE | ID: mdl-31211679

RESUMEN

Candida auris is an emerging multidrug-resistant fungus that causes hospital-associated outbreaks of invasive infections with high death rates. During 2015-2016, health authorities in Colombia detected an outbreak of C. auris. We conducted an investigation to characterize the epidemiology, transmission mechanisms, and reservoirs of this organism. We investigated 4 hospitals with confirmed cases of C. auris candidemia in 3 cities in Colombia. We abstracted medical records and collected swabs from contemporaneously hospitalized patients to assess for skin colonization. We identified 40 cases; median patient age was 23 years (IQR 4 months-56 years). Twelve (30%) patients were <1 year of age, and 24 (60%) were male. The 30-day mortality was 43%. Cases clustered in time and location; axilla and groin were the most commonly colonized sites. Temporal and spatial clustering of cases and skin colonization suggest person-to-person transmission of C. auris. These cases highlight the importance of adherence to infection control recommendations.


Asunto(s)
Candida , Candidiasis/epidemiología , Candidiasis/microbiología , Enfermedades Transmisibles Emergentes/epidemiología , Enfermedades Transmisibles Emergentes/microbiología , Infección Hospitalaria , Brotes de Enfermedades , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Candida/efectos de los fármacos , Candidemia/epidemiología , Candidemia/microbiología , Candidiasis/tratamiento farmacológico , Candidiasis/historia , Niño , Preescolar , Colombia/epidemiología , Enfermedades Transmisibles Emergentes/historia , Farmacorresistencia Fúngica , Femenino , Historia del Siglo XXI , Humanos , Lactante , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Mortalidad , Evaluación del Resultado de la Atención al Paciente , Vigilancia en Salud Pública , Estaciones del Año , Adulto Joven
11.
MMWR Morb Mortal Wkly Rep ; 68(21): 469-473, 2019 May 31.
Artículo en Inglés | MEDLINE | ID: mdl-31145717

RESUMEN

In August 2017, Hurricane Harvey caused unprecedented flooding and devastation to the Houston metropolitan area (1). Mold exposure was a serious concern because investigations after Hurricanes Katrina and Rita (2005) had documented extensive mold growth in flood-damaged homes (2,3). Because mold exposure can cause serious illnesses known as invasive mold infections (4,5), and immunosuppressed persons are at high risk for these infections (6,7), several federal agencies recommend that immunosuppressed persons avoid mold-contaminated sites (8,9). To assess the extent of exposure to mold and flood-damaged areas among persons at high risk for invasive mold infections after Hurricane Harvey, CDC and Texas health officials conducted a survey among 103 immunosuppressed residents in Houston. Approximately half of the participants (50) engaged in cleanup of mold and water-damaged areas; these activities included heavy cleanup (23), such as removing furniture or removing drywall, or light cleanup (27), such as wiping down walls or retrieving personal items. Among immunosuppressed persons who performed heavy cleanup, 43% reported wearing a respirator, as did 8% who performed light cleanup. One participant reported wearing all personal protective equipment (PPE) recommended for otherwise healthy persons (i.e., respirator, boots, goggles, and gloves). Immunosuppressed residents who are at high risk for invasive mold infections were exposed to mold and flood-damaged areas after Hurricane Harvey; recommendations from health care providers to avoid exposure to mold and flood-damaged areas could mitigate the risk to immunosuppressed persons.


Asunto(s)
Tormentas Ciclónicas , Desastres , Exposición a Riesgos Ambientales/estadística & datos numéricos , Hongos , Huésped Inmunocomprometido , Exposición a Riesgos Ambientales/efectos adversos , Humanos , Infecciones Fúngicas Invasoras/epidemiología , Medición de Riesgo , Texas/epidemiología
12.
Clin Microbiol Newsl ; 39(13): 99-103, 2017 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-29503491

RESUMEN

Candida auris is a newly emerging species that was first identified in Asia in 2009 but has rapidly spread across the world. C. auris differs from most other Candida species in that antifungal resistance is the norm rather than the exception, it is a commensal of human skin rather than the human gut, and it can be easily transmitted from person to person in a healthcare setting. This review discusses the emergence of C. auris, global epidemiology, identification, antifungal susceptibility testing, and precautions to be taken when it is identified from a patient specimen.

13.
MMWR Morb Mortal Wkly Rep ; 65(44): 1234-1237, 2016 Nov 11.
Artículo en Inglés | MEDLINE | ID: mdl-27832049

RESUMEN

Candida auris, an emerging fungus that can cause invasive infections, is associated with high mortality and is often resistant to multiple antifungal drugs. C. auris was first described in 2009 after being isolated from external ear canal discharge of a patient in Japan (1). Since then, reports of C. auris infections, including bloodstream infections, have been published from several countries, including Colombia, India, Israel, Kenya, Kuwait, Pakistan, South Africa, South Korea, Venezuela, and the United Kingdom (2-7). To determine whether C. auris is present in the United States and to prepare for the possibility of transmission, CDC issued a clinical alert in June 2016 informing clinicians, laboratorians, infection control practitioners, and public health authorities about C. auris and requesting that C. auris cases be reported to state and local health departments and CDC (8). This report describes the first seven U.S. cases of C. auris infection reported to CDC as of August 31, 2016. Data from these cases suggest that transmission of C. auris might have occurred in U.S. health care facilities and demonstrate the need for attention to infection control measures to control the spread of this pathogen.


Asunto(s)
Candida/aislamiento & purificación , Candidiasis/diagnóstico , Candidiasis/microbiología , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Candida/efectos de los fármacos , Candidiasis/tratamiento farmacológico , Enfermedades Transmisibles Emergentes , Farmacorresistencia Fúngica Múltiple , Resultado Fatal , Salud Global , Humanos , Estados Unidos
14.
Med Mycol ; 54(6): 584-92, 2016 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-27143633

RESUMEN

Environmental surveillance of the soil-dwelling fungus Coccidioides is essential for the prevention of Valley fever, a disease primarily caused by inhalation of the arthroconidia. Methods for collecting and detecting Coccidioides in soil samples are currently in use by several laboratories; however, a method utilizing current air sampling technologies has not been formally demonstrated for the capture of airborne arthroconidia. In this study, we collected air/dust samples at two sites (Site A and Site B) in the endemic region of Tucson, Arizona, and tested a variety of air samplers and membrane matrices. We then employed a single-tube nested qPCR assay for molecular detection. At both sites, numerous soil samples (n = 10 at Site A and n = 24 at Site B) were collected and Coccidioides was detected in two samples (20%) at Site A and in eight samples (33%) at Site B. Of the 25 air/dust samples collected at both sites using five different air sampling methods, we detected Coccidioides in three samples from site B. All three samples were collected using a high-volume sampler with glass-fiber filters. In this report, we describe these methods and propose the use of these air sampling and molecular detection strategies for environmental surveillance of Coccidioides.


Asunto(s)
Microbiología del Aire , Coccidioides/aislamiento & purificación , Técnicas Microbiológicas/métodos , Reacción en Cadena de la Polimerasa/métodos , Reacción en Cadena en Tiempo Real de la Polimerasa/métodos , Arizona , Coccidioides/clasificación , Coccidioides/genética , Microbiología del Suelo
15.
PLoS Pathog ; 8(4): e1002620, 2012.
Artículo en Inglés | MEDLINE | ID: mdl-22496647

RESUMEN

Tuberculosis (TB) disease in HIV co-infected patients contributes to increased mortality by activating innate and adaptive immune signaling cascades that stimulate HIV-1 replication, leading to an increase in viral load. Here, we demonstrate that silencing of the expression of the transcription factor nuclear factor of activated T cells 5 (NFAT5) by RNA interference (RNAi) inhibits Mycobacterium tuberculosis (MTb)-stimulated HIV-1 replication in co-infected macrophages. We show that NFAT5 gene and protein expression are strongly induced by MTb, which is a Toll-like receptor (TLR) ligand, and that an intact NFAT5 binding site in the viral promoter of R5-tropic HIV-1 subtype B and subtype C molecular clones is required for efficent induction of HIV-1 replication by MTb. Furthermore, silencing by RNAi of key components of the TLR pathway in human monocytes, including the downstream signaling molecules MyD88, IRAK1, and TRAF6, significantly inhibits MTb-induced NFAT5 gene expression. Thus, the innate immune response to MTb infection induces NFAT5 gene and protein expression, and NFAT5 plays a crucial role in MTb regulation of HIV-1 replication via a direct interaction with the viral promoter. These findings also demonstrate a general role for NFAT5 in TLR- and MTb-mediated control of gene expression.


Asunto(s)
Infecciones por VIH/metabolismo , VIH-1/fisiología , Mycobacterium tuberculosis/metabolismo , Transducción de Señal/inmunología , Receptores Toll-Like/metabolismo , Factores de Transcripción/metabolismo , Tuberculosis/metabolismo , Replicación Viral/inmunología , Células Cultivadas , Femenino , Regulación de la Expresión Génica/inmunología , Infecciones por VIH/inmunología , Humanos , Inmunidad Innata , Quinasas Asociadas a Receptores de Interleucina-1/inmunología , Quinasas Asociadas a Receptores de Interleucina-1/metabolismo , Masculino , Mycobacterium tuberculosis/inmunología , Factor 88 de Diferenciación Mieloide/inmunología , Factor 88 de Diferenciación Mieloide/metabolismo , Regiones Promotoras Genéticas/inmunología , Receptores Toll-Like/inmunología , Factores de Transcripción/inmunología , Tuberculosis/inmunología , Péptidos y Proteínas Asociados a Receptores de Factores de Necrosis Tumoral/inmunología , Péptidos y Proteínas Asociados a Receptores de Factores de Necrosis Tumoral/metabolismo
16.
mSphere ; 9(2): e0057723, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38299868

RESUMEN

Since 2016, in Colombia, ongoing transmission of Candida auris has been reported in multiple cities. Here, we provide an updated description of C. auris genomic epidemiology and the dynamics of antifungal resistance in Colombia. We sequenced 99 isolates from C. auris cases with collection dates ranging from June 2016 to January 2021; the resulting sequences coupled with 103 previously generated sequences from C. auris cases were described in a phylogenetic analysis. All C. auris cases were clade IV. Of the 182 isolates with antifungal susceptibility data, 67 (37%) were resistant to fluconazole, and 39 (21%) were resistant to amphotericin B. Isolates predominately clustered by country except for 16 isolates from Bogotá, Colombia, which grouped with isolates from Venezuela. The largest cluster (N = 166 isolates) contained two subgroups. The first subgroup contained 26 isolates, mainly from César; of these, 85% (N = 22) were resistant to fluconazole. The second subgroup consisted of 47 isolates from the north coast; of these, 81% (N = 38) were resistant to amphotericin B. Mutations in the ERG11 and TAC1B genes were identified in fluconazole-resistant isolates. This work describes molecular mechanisms associated with C. auris antifungal resistance in Colombia. Overall, C. auris cases from different geographic locations in Colombia exhibited high genetic relatedness, suggesting continued transmission between cities since 2016. These findings also suggest a lack of or minimal introductions of different clades of C. auris into Colombia. IMPORTANCE: Candida auris is an emerging fungus that presents a serious global health threat and has caused multiple outbreaks in Colombia. This work discusses the likelihood of introductions and local transmission of C. auris and provides an updated description of the molecular mechanisms associated with antifungal resistance in Colombia. Efforts like this provide information about the evolving C. auris burden that could help guide public health strategies to control C. auris spread.


Asunto(s)
Antifúngicos , Candidiasis , Humanos , Antifúngicos/farmacología , Antifúngicos/uso terapéutico , Anfotericina B , Candida auris , Fluconazol , Colombia/epidemiología , Candida/genética , Candidiasis/microbiología , Filogenia , Genómica
17.
Microbiol Spectr ; 12(7): e0354023, 2024 Jul 02.
Artículo en Inglés | MEDLINE | ID: mdl-38842332

RESUMEN

Candida auris, initially identified in 2009, has rapidly become a critical concern due to its antifungal resistance and significant mortality rates in healthcare-associated outbreaks. To date, whole-genome sequencing (WGS) has identified five unique clades of C. auris, with some strains displaying resistance to all primary antifungal drug classes. In this study, we presented the first WGS analysis of C. auris from Bangladesh, describing its origins, transmission dynamics, and antifungal susceptibility testing (AFST) profile. Ten C. auris isolates collected from hospital settings in Bangladesh were initially identified by CHROMagar Candida Plus, followed by VITEK2 system, and later sequenced using Illumina NextSeq 550 system. Reference-based phylogenetic analysis and variant calling pipelines were used to classify the isolates in different clades. All isolates aligned ~90% with the Clade I C. auris B11205 reference genome. Of the 10 isolates, 8 were clustered with Clade I isolates, highlighting a South Asian lineage prevalent in Bangladesh. Remarkably, the remaining two isolates formed a distinct cluster, exhibiting >42,447 single-nucleotide polymorphism differences compared to their closest Clade IV counterparts. This significant variation corroborates the emergence of a sixth clade (Clade VI) of C. auris in Bangladesh, with potential for international transmission. AFST results showed that 80% of the C. auris isolates were resistant to fluconazole and voriconazole, whereas Clade VI isolates were susceptible to azoles, echinocandins, and pyrimidine analogue. Genomic sequencing revealed ERG11_Y132F mutation conferring azole resistance while FCY1_S70R mutation found inconsequential in describing 5-flucytosine resistance. Our study underscores the pressing need for comprehensive genomic surveillance in Bangladesh to better understand the emergence, transmission dynamics, and resistance profiles of C. auris infections. Unveiling the discovery of a sixth clade (Clade VI) accentuates the indispensable role of advanced sequencing methodologies.IMPORTANCECandida auris is a nosocomial fungal pathogen that is commonly misidentified as other Candida species. Since its emergence in 2009, this multidrug-resistant fungus has become one of the five urgent antimicrobial threats by 2019. Whole-genome sequencing (WGS) has proven to be the most accurate identification technique of C. auris which also played a crucial role in the initial discovery of this pathogen. WGS analysis of C. auris has revealed five distinct clades where isolates of each clade differ among themselves based on pathogenicity, colonization, infection mechanism, as well as other phenotypic characteristics. In Bangladesh, C. auris was first reported in 2019 from clinical samples of a large hospital in Dhaka city. To understand the origin, transmission dynamics, and antifungal-resistance profile of C. auris isolates circulating in Bangladesh, we conducted a WGS-based surveillance study on two of the largest hospital settings in Dhaka, Bangladesh.


Asunto(s)
Antifúngicos , Candida auris , Candidiasis , Pruebas de Sensibilidad Microbiana , Filogenia , Secuenciación Completa del Genoma , Bangladesh/epidemiología , Humanos , Antifúngicos/farmacología , Candidiasis/microbiología , Candidiasis/epidemiología , Candida auris/genética , Candida auris/efectos de los fármacos , Candida auris/aislamiento & purificación , Farmacorresistencia Fúngica , Genoma Fúngico , Polimorfismo de Nucleótido Simple , Candida/genética , Candida/efectos de los fármacos , Candida/clasificación , Candida/aislamiento & purificación , Fluconazol/farmacología , Femenino
18.
Open Forum Infect Dis ; 11(6): ofae264, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38835496

RESUMEN

Background: Reports of fluconazole-resistant Candida parapsilosis bloodstream infections are increasing. We describe a cluster of fluconazole-resistant C parapsilosis bloodstream infections identified in 2021 on routine surveillance by the Georgia Emerging Infections Program in conjunction with the Centers for Disease Control and Prevention. Methods: Whole-genome sequencing was used to analyze C parapsilosis bloodstream infections isolates. Epidemiological data were obtained from medical records. A social network analysis was conducted using Georgia Hospital Discharge Data. Results: Twenty fluconazole-resistant isolates were identified in 2021, representing the largest proportion (34%) of fluconazole-resistant C parapsilosis bloodstream infections identified in Georgia since surveillance began in 2008. All resistant isolates were closely genetically related and contained the Y132F mutation in the ERG11 gene. Patients with fluconazole-resistant isolates were more likely to have resided at long-term acute care hospitals compared with patients with susceptible isolates (P = .01). There was a trend toward increased mechanical ventilation and prior azole use in patients with fluconazole-resistant isolates. Social network analysis revealed that patients with fluconazole-resistant isolates interfaced with a distinct set of healthcare facilities centered around 2 long-term acute care hospitals compared with patients with susceptible isolates. Conclusions: Whole-genome sequencing results showing that fluconazole-resistant C parapsilosis isolates from Georgia surveillance demonstrated low genetic diversity compared with susceptible isolates and their association with a facility network centered around 2 long-term acute care hospitals suggests clonal spread of fluconazole-resistant C parapsilosis. Further studies are needed to better understand the sudden emergence and transmission of fluconazole-resistant C parapsilosis.

19.
PLoS One ; 19(1): e0291406, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38241320

RESUMEN

Candida auris is a newly emerged multidrug-resistant fungus capable of causing invasive infections with high mortality. Despite intense efforts to understand how this pathogen rapidly emerged and spread worldwide, its environmental reservoirs are poorly understood. Here, we present a collaborative effort between the U.S. Centers for Disease Control and Prevention, the National Center for Biotechnology Information, and GridRepublic (a volunteer computing platform) to identify C. auris sequences in publicly available metagenomic datasets. We developed the MetaNISH pipeline that uses SRPRISM to align sequences to a set of reference genomes and computes a score for each reference genome. We used MetaNISH to scan ~300,000 SRA metagenomic runs from 2010 onwards and identified five datasets containing C. auris reads. Finally, GridRepublic has implemented a prospective C. auris molecular monitoring system using MetaNISH and volunteer computing.


Asunto(s)
Candida , Candidiasis , Humanos , Candida/genética , Candidiasis/microbiología , Candida auris , Estudios Prospectivos , Metagenómica , Antifúngicos/uso terapéutico
20.
Lancet Microbe ; 5(3): e282-e290, 2024 03.
Artículo en Inglés | MEDLINE | ID: mdl-38432234

RESUMEN

BACKGROUND: Zoonotic sporotrichosis is a neglected fungal disease, whereby outbreaks are primarily driven by Sporothrix brasiliensis and linked to cat-to-human transmission. To understand the emergence and spread of sporotrichosis in Brazil, the epicentre of the current epidemic in South America, we aimed to conduct whole-genome sequencing (WGS) to describe the genomic epidemiology. METHODS: In this genomic epidemiology study, we included Sporothrix spp isolates from sporotrichosis cases from Brazil, Colombia, and the USA. We conducted WGS using Illumina NovaSeq on isolates collected by three laboratories in Brazil from humans and cats with sporotrichosis between 2013 and 2022. All isolates that were confirmed to be Sporothrix genus by internal transcribed spacer or beta-tubulin PCR sequencing were included in this study. We downloaded eight Sporothrix genome sequences from the National Center for Biotechnology Information (six from Brazil, two from Colombia). Three Sporothrix spp genome sequences from the USA were generated by the US Centers for Disease Control and Prevention as part of this study. We did phylogenetic analyses and correlated geographical and temporal case distribution with genotypic features of Sporothrix spp isolates. FINDINGS: 72 Sporothrix spp isolates from 55 human and 17 animal sporotrichosis cases were included: 67 (93%) were from Brazil, two (3%) from Colombia, and three (4%) from the USA. Cases spanned from 1999 to 2022. Most (61 [85%]) isolates were S brasiliensis, and all were reported from Brazil. Ten (14%) were Sporothrix schenckii and were reported from Brazil, USA, and Colombia. For S schenckii isolates, two distinct clades were observed wherein isolates clustered by geography. For S brasiliensis isolates, five clades separated by more than 100 000 single-nucleotide polymorphisms were observed. Among the five S brasiliensis clades, clades A and C contained isolates from both human and cat cases, and clade A contained isolates from six different states in Brazil. Compared with S brasiliensis isolates, larger genetic diversity was observed among S schenckii isolates from animal and human cases within a clade. INTERPRETATION: Our results suggest that the ongoing epidemic driven by S brasiliensis in Brazil represents several, independent emergence events followed by animal-to-animal and animal-to human transmission within and between Brazilian states. These results describe how S brasiliensis can emerge and spread within a country. FUNDING: Coordenação de Aperfeiçoamento de Pessoal de Nível Superior, Brazil; the São Paulo Research Foundation; Productivity in Research fellowships by the National Council for Scientific and Technological Development, and Ministry of Science and Technology of Brazil.


Asunto(s)
Sporothrix , Esporotricosis , Animales , Humanos , Esporotricosis/epidemiología , Esporotricosis/veterinaria , Esporotricosis/microbiología , Brasil/epidemiología , Filogenia , Brotes de Enfermedades , Genómica , Sporothrix/genética
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