Evidence of Fluconazole-Resistant Candida parapsilosis Genotypes Spreading across Hospitals Located in Madrid, Spain and Harboring the Y132F ERG11p Substitution.

We have been monitoring the antifungal resistance in Candida parapsilosis isolates collected from inpatients at Madrid metropolitan area hospitals for the last 3 years. The study aimed to elucidate the presence of fluconazole-resistant C. parapsilosis genotypes in Madrid. From January 2019 to December 2021, a total of 354 C. parapsilosis isolates (n = 346 patients) from blood (76.6%) or intraabdominal samples were collected and genotyped using species-specific microsatellite markers. Antifungal susceptibilities to amphotericin B, the triazoles, micafungin, anidulafungin, and ibrexafungerp were performed according to EUCAST E.Def 7.3.2; the ERG11 gene was sequenced in fluconazole-resistant isolates. A total of 13.6% (n = 48/354) isolates (one per patient) were found to be resistant to fluconazole and non-wild-type to voriconazole but fully susceptible to ibrexafungerp. Resistant isolates were mostly sourced from blood (n = 45/48, 93.8%) and were detected in five hospitals. Two hospitals accounted for a high proportion of resistant isolates (n = 41/48). Resistant isolates harbored either the Y132F ERG11p amino acid substitution (n = 43) or the G458S substitution (n = 5). Isolates harboring the Y132F substitution clustered into a clonal complex involving three genotypes (one genotype accounted for n = 39/43 isolates) that were found in four hospitals. Isolates harboring the G458S substitution clustered into another genotype found in a fifth hospital. C. parapsilosis genotypes demonstrating resistance to fluconazole have been spreading across hospitals in Madrid, Spain. Over the last 3 years, the frequency of isolation of such isolates and the number of hospitals affected is on the rise.

Prevalence of SARS-CoV-2 in Spain (ENE-COVID): a nationwide, population-based seroepidemiological study.

BACKGROUND: Spain is one of the European countries most affected by the COVID-19 pandemic. Serological surveys are a valuable tool to assess the extent of the epidemic, given the existence of asymptomatic cases and little access to diagnostic tests. This nationwide population-based study aims to estimate the seroprevalence of SARS-CoV-2 infection in Spain at national and regional level. METHODS: 35 883 households were selected from municipal rolls using two-stage random sampling stratified by province and municipality size, with all residents invited to participate. From April 27 to May 11, 2020, 61 075 participants (75·1% of all contacted individuals within selected households) answered a questionnaire on history of symptoms compatible with COVID-19 and risk factors, received a point-of-care antibody test, and, if agreed, donated a blood sample for additional testing with a chemiluminescent microparticle immunoassay. Prevalences of IgG antibodies were adjusted using sampling weights and post-stratification to allow for differences in non-response rates based on age group, sex, and census-tract income. Using results for both tests, we calculated a seroprevalence range maximising either specificity (positive for both tests) or sensitivity (positive for either test). FINDINGS: Seroprevalence was 5·0% (95% CI 4·7-5·4) by the point-of-care test and 4·6% (4·3-5·0) by immunoassay, with a specificity-sensitivity range of 3·7% (3·3-4·0; both tests positive) to 6·2% (5·8-6·6; either test positive), with no differences by sex and lower seroprevalence in children younger than 10 years (<3·1% by the point-of-care test). There was substantial geographical variability, with higher prevalence around Madrid (>10%) and lower in coastal areas (<3%). Seroprevalence among 195 participants with positive PCR more than 14 days before the study visit ranged from 87·6% (81·1-92·1; both tests positive) to 91·8% (86·3-95·3; either test positive). In 7273 individuals with anosmia or at least three symptoms, seroprevalence ranged from 15·3% (13·8-16·8) to 19·3% (17·7-21·0). Around a third of seropositive participants were asymptomatic, ranging from 21·9% (19·1-24·9) to 35·8% (33·1-38·5). Only 19·5% (16·3-23·2) of symptomatic participants who were seropositive by both the point-of-care test and immunoassay reported a previous PCR test. INTERPRETATION: The majority of the Spanish population is seronegative to SARS-CoV-2 infection, even in hotspot areas. Most PCR-confirmed cases have detectable antibodies, but a substantial proportion of people with symptoms compatible with COVID-19 did not have a PCR test and at least a third of infections determined by serology were asymptomatic. These results emphasise the need for maintaining public health measures to avoid a new epidemic wave. FUNDING: Spanish Ministry of Health, Institute of Health Carlos III, and Spanish National Health System.

Inflammatory bowel disease and Clostridium difficile infection: contrasting views of international clinical professionals.

INTRODUCTION: In patients with inflammatory bowel disease (IBD), Clostridium difficile infection (CDI) is a risk factor for both morbidity and mortality. Currently, appropriate management is unclear. Guidance on best practice in the diagnosis and treatment of CDI in IBD patients is therefore needed. METHODS: A multidisciplinary group of clinicians involved in the treatment of patients with IBD and CDI developed 27 consensus statements. Respondents were asked to rate their agreement with each statement using a 4-point Likert scale. A modified Delphi methodology was used to review responses of 442 physicians from different specialties (including infectious disease specialists [n = 104], microbiologists [n = 95], and gastroenterologists [n = 73]). A threshold of 75 % agreement was predefined as consensus. RESULTS: Consensus was achieved for 17 of the 27 statements. Unprompted recognition of risk factors for CDI was low. Intensification of immunosuppressive therapy in the absence of clinical improvement was controversial. Clear definitions of treatment failure of antibiotic therapy in CDI and recurrence of CDI in IBD are needed. Respondents require further clarity regarding the place of fecal microbiota transplantation in CDI patients with IBD. Differences were observed between the perceptions of microbiologists and gastroenterologists, as well as between countries. CONCLUSIONS: Different perceptions both between specialties and geographical locations complicate the development of an internationally accepted algorithm for the diagnosis and treatment of CDI in patients with IBD. This study highlights the need for future studies in this area.

Epidemiology and prognosis of candidaemia in elderly patients.

The aim of the study was to analyse the epidemiology and prognosis of candidaemia in elderly patients. We performed a comparison of clinical presentation of candidaemia according to age and a study of hazard factors within a prospective programme performed in 29 hospitals. One hundred and seventy-six episodes occurred in elderly patients (>75 years), 227 episodes in middle-aged patients (61-75 years) and 232 episodes in younger patients (16-60 years). Central venous catheter, parenteral nutrition, neutropenia, immunosuppressive therapy and candidaemia caused by Candida parapsilosis were less frequent in elderly patients. These patients received inadequate antifungal therapy (57.3%) more frequently than middle-aged and younger patients (40.5% P < .001). Mortality during the first week (20%) and 30 days (42%) was higher in elderly patients. The variables independently associated with mortality in elderly patients during the first 7 days were acute renal failure (OR: 2.64), Pitt score (OR: 1.57) and appropriate antifungal therapy (OR: 0.132). Primary candidaemia (OR: 2.93), acute renal failure (OR: 3.68), Pitt score (OR: 1.38), appropriate antifungal therapy (OR: 0.3) and early removal of the central catheter (OR: 0.47) were independently associated with 30-day mortality.In conclussion, inadequate antifungal treatment is frequently prescribed to elderly patients with candidaemia and is related with early and late mortality.

Seroprevalence of anti-SARS-CoV-2 IgG antibodies: relationship with COVID-19 diagnosis, symptoms, smoking, and method of transmission.

Aims: The study of SARS-CoV-2 antibodies in the population is a crucial step towards overcoming the COVID-19 pandemic. Seroepidemiological studies allow an estimation of the number of people who have been exposed to the virus, as well as the number of people who are still susceptible to infection. Methods: In total, 13 560 people from Arganda del Rey, Madrid (Spain) were assessed between January and March 2021 for the presence of IgG antibodies, using rapid tests and histories of symptoms compatible with COVID-19. Results: 24.2% of the participants had IgG antibodies and 9% had a positive COVID-19 diagnosis. Loss of smell/taste was the most discriminating symptom of the disease. The main transmitters of infection were found to be household members. Unexpectedly, in smokers, the incidence of positive COVID-19 diagnoses was significantly lower. Additionally, it was found that there was a discrepancy between COVID-19 diagnosis and the presence of IgG antibodies. Conclusions: Rapid anti-IgG tests are less reliable in detecting SARS-CoV-2 infection at an individual level, but are functional in estimating SARS-CoV-2 infection rates at an epidemiological level. The loss of smell/taste is a potential indicator for establishing COVID-19 infection.

Longitudinal survey of humoral and cellular response to SARS-CoV-2 infection in children.

BACKGROUND: Data regarding humoral and cellular response against SARS-CoV-2 in children are scarce. We analysed seroconversion rate, decrease of anti-RBD IgG antibodies over time and T-cell response in paediatric patients who suffered COVID-19. METHODS: Longitudinal study of paediatric patients COVID-19 diagnosed by positive molecular assay in nasopharyngeal swabs. Blood samples were drawn 1-2 months and 6-7 months after acute infection. Anti-RBD IgG were determined using the Alinity® SARS-CoV-2 IgG II Quant assay (Abbott). Cellular immune response was analysed by T-SPOT® SARS-CoV-2 assay kit (Oxford Immunotec Ltd.). RESULTS: 27/39 (69,2%) patients seroconverted. Despite a significant decrease in antibody levels over time (p < 0,01), no children seroreverted between first and second visits. Only 6/16 (37,2%) children under 6 years-old were seropositive compared to 21/23 (91,3%) over 6 years-old (p < 0,01). Highest antibody levels were found in seropositive younger children (p = 0,036). Thirteen (33,3%) children showed T-cell response. Among participants showing humoral response, no cellular response was detected in 14 (51,9%). CONCLUSIONS: Anti-RBD IgG antibodies persistence at 6-7-months after SARS-CoV-2 infection was observed. A different IgG response was found depending on age. As measured by T-SPOT, most patients did not display cellular response 6-7 months after infection.

Global Emergence of Resistance to Fluconazole and Voriconazole in Candida parapsilosis in Tertiary Hospitals in Spain During the COVID-19 Pandemic.

Background: Candida parapsilosis is a frequent cause of candidemia worldwide. Its incidence is associated with the use of medical implants, such as central venous catheters or parenteral nutrition. This species has reduced susceptibility to echinocandins, and it is susceptible to polyenes and azoles. Multiple outbreaks caused by fluconazole-nonsusceptible strains have been reported recently. A similar trend has been observed among the C. parapsilosis isolates received in the last 2 years at the Spanish Mycology Reference Laboratory. Methods: Yeast were identified by molecular biology, and antifungal susceptibility testing was performed using the European Committee on Antimicrobial Susceptibility Testing protocol. The ERG11 gene was sequenced to identify resistance mechanisms, and strain typing was carried out by microsatellite analysis. Results: We examined the susceptibility profile of 1315 C. parapsilosis isolates available at our reference laboratory between 2000 and 2021, noticing an increase in the number of isolates with acquired resistance to fluconazole, and voriconazole has increased in at least 8 different Spanish hospitals in 2020-2021. From 121 recorded clones, 3 were identified as the most prevalent in Spain (clone 10 in Catalonia and clone 96 in Castilla-Leon and Madrid, whereas clone 67 was found in 2 geographically unrelated regions, Cantabria and the Balearic Islands). Conclusions: Our data suggest that concurrently with the coronavirus disease 2019 pandemic, a selection of fluconazole-resistant C. parapsilosis isolates has occurred in Spain, and the expansion of specific clones has been noted across centers. Further research is needed to determine the factors that underlie the successful expansion of these clones and their potential genetic relatedness.

Clinitest rapid COVID-19 antigen test for the diagnosis of SARS-CoV-2 infection: A multicenter evaluation study.

OBJECTIVES: RT-PCR assay is the reference method for diagnosis of COVID-19, but it is also a laborious and time-consuming technic, limiting the availability of testing. Rapid antigen-detection tests are faster and less expensive; however, the reliability of these tests must be validated before they can be used widely. The objective of this study was to determine the performance of the Clinitest Rapid COVID-19 Antigen Test (ClinitestRT) (SIEMENS) for SARS-CoV-2 in nasopharyngeal swab specimens. METHODS: This prospective multicenter study was carried out in three Spanish university hospitals including individuals with clinical symptoms or epidemiological criteria for COVID-19. Only individuals with ≤7 days from the onset of symptoms or from exposure to a confirmed case of COVID-19 were included. Two nasopharyngeal samples were taken to perform the ClinitestRT, as a point-of-care test, and a diagnostic RT-PCR test. RESULTS: Overall sensitivity and specificity for the ClinitestRT among the 450 patients studied were 93.3% (CI 95%: 89.7-96.8) and 99.2% (CI 95%: 97.2-99.8), respectively. Sensitivity in participants with ≤5 days of the clinical course was 93.6% (CI 95%: 89.2-96.3), and in participants who had a CT < 25 for the RT-PCR test was 98.4% (CI 95%: 94.5-99.6). Agreement between techniques was 96.7% (kappa score: 0.93; CI 95%: 0.90-0.97). CONCLUSIONS: The ClinitestRT provides good clinical performance, with more reliable results for patients with a higher viral load. The results must be interpreted based on the local epidemiological context.

[Seroprevalence and vertical transmission of Chagas disease in a cohort of Latin-american pregnant women in a tertiary hospital in Madrid]. / Seroprevalencia y transmisión vertical de enfermedad de Chagas en una cohorte de gestantes latinoamericanas en un hospital terciario de Madrid.

BACKGROUND: Chagas disease, caused by Trypanosoma cruzi (T. cruzi), is endemic in Latin-America and is emerging in Spain due to immigration. The vertical transmission rate is around 5%. A routine prenatal screening with serology of all pregnant women from endemic areas is recommended to identify infected newborns, allowing early treatment and cure. OBJECTIVE: The aim of this study was to estimate the prevalence of positive Chagas serology in a cohort of pregnant women from Latin-America and its vertical transmission. PATIENTS AND METHODS: An observational, prospective, follow-up study was conducted on women with positive serology to T. cruzi, as well as their newborns, from January 2013 to April 2015. Congenital Chagas was ruled out using a PCR technique at birth and at 1 month, and with serology at 9-12 months old. A child was considered infected when PCR was positive, and uninfected when PCR was negative, and/or it had a negative serology. RESULTS: Screening was performed on 1244 pregnant women from Latin-America, and there were positive results in 40 (prevalence 3.2%, 95% CI: 2.4-4.4%), with 85% of them from Bolivia. There was only one infected newborn (rate of vertical transmission 2.8% (95% CI: 0-15%)), who had a positive PCR at birth. Relative studies enabled an 8-year-old sister with an asymptomatic disease to be diagnosed and treated. Both were treated successfully with benznidazole (later the PCR and serology were negative). CONCLUSION: Screening during pregnancy in Latin-American women helped to detect those with Chagas disease. The rate of vertical transmission was 2.8%, in keeping with literature. Screening led to the detection and treatment of previously unidentified familial cases.

Decentralization of health systems in low and middle income countries: a systematic review.

OBJECTIVES: A substantial number of low and middle income countries (LMICs) have implemented health sector reforms in the last 40 years, and the majority of them have included some degree of decentralization of the health system as part of the wider reform. This review will provide an updated and comprehensive assessment of the effects of decentralization in LMICs. METHODS: We conducted a systematic review of published and grey literature till May 2015, following standard methods. RESULTS: 54 qualitative, quantitative and mixed methods studies conducted in 26 countries were included in the review. We found positive and negative effects of decentralization of health systems in LMICs. Whereas decentralization of governance, financing and service delivery, have been shown to have positive effects on the system; decentralization of resource management has been challenging in several settings. CONCLUSIONS: Overall, lessons learned from LMICs suggest that factors such as adequate mix of technical skills at the local level to perform decentralized tasks, effective decentralization of decision-making to the periphery, and political leadership are key factors for a successful decentralization.

Seroprevalencia y transmisión vertical de enfermedad de Chagas en una cohorte de gestantes latinoamericanas en un hospital terciario de Madrid / Seroprevalence and vertical transmission of Chagas disease in a cohort of Latin-american pregnant women in a tertiary hospital in Madrid

Introducción: La enfermedad de Chagas, causada por Trypanosoma cruzi (T. cruzi), es endémica en Latinoamérica y emergente en España, ligada a inmigración. La transmisión vertical se estima de alrededor del 5%. Se recomienda cribado selectivo en el embarazo para identificar al recién nacido infectado, permitiendo tratamiento precoz y curación de la enfermedad. Objetivo: El objetivo de este estudio fue estimar la prevalencia de serología positiva para T. cruzi en una cohorte de gestantes latinoamericanas y la tasa de transmisión vertical de la misma. Pacientes y métodos: Estudio observacional prospectivo de gestantes con serología positiva para T. cruzi en hospital terciario, desde enero del 2013 hasta abril del 2015. El seguimiento de recién nacidos se realizó con PCR al nacimiento, repetida al mes, y serología a los 9-12 meses. Se consideró infectado al niño con PCR positiva y no infectado al niño con PCR negativa y/o negativización de anticuerpos. Resultados: Se realizó cribado en 1.244 gestantes latinoamericanas, siendo positivas 40 (prevalencia 3,2%, IC del 95%: 2,4-4,4%), 85% procedentes de Bolivia. Solo un niño resultó infectado (transmisión vertical 2,8%, IC del 95%: 0-15%) con PCR positiva al nacimiento. La detección de la embarazada permitió estudiar a los hermanos, detectándose caso asintomático en paciente de 8 años. Ambos tratados con benznidazol con buena tolerancia, evolución favorable y negativización de PCR y anticuerpos. Conclusión: El cribado de embarazadas latinoamericanas ha permitido la detección de gestantes con enfermedad de Chagas. La transmisión vertical fue del 2,3%, coincidente con la literatura. El cribado ha permitido la detección y el tratamiento de casos familiares no identificados previamente (AU)

Background: Chagas disease, caused by Trypanosoma cruzi (T. cruzi), is endemic in Latin-America and is emerging in Spain due to immigration. The vertical transmission rate is around 5%. A routine prenatal screening with serology of all pregnant women from endemic areas is recommended to identify infected newborns, allowing early treatment and cure. Objective: The aim of this study was to estimate the prevalence of positive Chagas serology in a cohort of pregnant women from Latin-America and its vertical transmission. Patients and methods: An observational, prospective, follow-up study was conducted on women with positive serology to T. cruzi, as well as their newborns, from January 2013 to April 2015. Congenital Chagas was ruled out using a PCR technique at birth and at 1 month, and with serology at 9-12 months old. A child was considered infected when PCR was positive, and uninfected when PCR was negative, and/or it had a negative serology. Results: Screening was performed on 1244 pregnant women from Latin-America, and there were positive results in 40 (prevalence 3.2%, 95% CI: 2.4-4.4%), with 85% of them from Bolivia. There was only one infected newborn (rate of vertical transmission 2.8% (95% CI: 0-15%)), who had a positive PCR at birth. Relative studies enabled an 8-year-old sister with an asymptomatic disease to be diagnosed and treated. Both were treated successfully with benznidazole (later the PCR and serology were negative). Conclusion: Screening during pregnancy in Latin-American women helped to detect those with Chagas disease. The rate of vertical transmission was 2.8%, in keeping with literature. Screening led to the detection and treatment of previously unidentified familial cases (AU)

Osteomielitis esternal y mediastinitis por Fusobacterium necrophorum / Sternal osteomyelitis and mediastinitis due to Fusobacterium necrophorum

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Dolor dorsolumbar y adenopatías supraclaviculares en un varón de 67 años / No disponible

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