Aspectos epidemiológicos, clínicos y de laboratorio de la candidemia en el siglo XXI

Candida spp. es responsable de alrededor del 80% de todas las infecciones fúngicas nosocomiales. Ocupa el cuarto lugar entre los microorganismos causantes de infección en el torrente circulatorio en EEUU y el séptimo en Europa. Existen numerosos estudios epidemiológicos sobre candidemia, efectuados en escenarios muy diversos, durante cortos periodos de tiempo y elaborados con distintos diseños, que coinciden en señalar que se ha producido un incremento significativo de las candidemias en las últimas dos décadas. La magnitud del incremento descrito podría obedecer a diferentes motivos. No se dispone de información que proporcione una mayor perspectiva en el tiempo que incluya un importante número de candidemias en pacientes no seleccionados, diagnosticados y tratados por un mismo equipo de profesionales, de acuerdo con una misma metodología que nos pueda proporcionar una interpretación más realista sobre los cambios producidos. La candidemia es una infección con una mortalidad que oscila entre el 29-76%, pudiendo llegar la mortalidad relacionada con la infección hasta el 49%. La evolución clínica depende no sólo de la adecuación del tratamiento sino de la gravedad de las enfermedades de base y del estado clínico del paciente. Se ha señalado que los nuevos métodos diagnósticos y terapéuticos apenas han modificado la mortalidad de forma relevante. Es necesario conocer si se ha producido algún cambio en los factores de riesgo de mortalidad de acuerdo a datos clínicos recientes y analizar si las diferencias en el abordaje de las candidemias en distintos periodos de tiempo han tenido alguna repercusión en el pronóstico. Las recomendaciones sobre el manejo de las candidemias en pacientes con catéter vascular incluyen la retirada del mismo siempre que sea posible. Aunque existen resultados contradictorios, hay publicaciones que demuestran que la retirada precoz tiene importancia pronóstica, no solo en las candidemias por catéter sino también en las primarias aunque no es infrecuente que se incluyan como candidemias primarias a infecciones que en realidad están producidas por catéter pero no se dispone de cultivo del mismo..

Community-based screening of Chagas disease among Latin American migrants in a non-endemic country: an observational study

Background: Chagas disease is a parasitic disease endemic to Latin America, but it has become a disease of global concern due to migration flows. Asymptomatic carriers may host the parasite for years, without knowing they are infected. The aim of this study is to assess prevalence of Chagas disease and evaluate the participants' level of knowledge between Latin American migrants attending a community-based screening campaign. Methods: Three community-based campaigns were performed in Alicante (Spain) in 2016, 2017 and 2018, including educational chats and blood tests for Trypanosoma cruzi serology. Participants completed a questionnaire assessing knowledge about the mechanisms of transmission, disease presentation, diagnosis, and treatment. People seropositive for T. cruzi underwent diagnostic confirmation by two different tests. Results were analyzed by multivariable logistic regression and expressed as adjusted odds ratios (aORs), adjusting for age, sex, and time in Spain. Results: A total of 596 participants were included in the study; 17% were aged under 18 years. Prevalence in adults was 11% [54/496; 95% confidence interval (CI): 8.3-14.5%] versus 0% among children. All but one case were in Bolivians. Diagnosis was independently associated with having been born in Bolivia (aOR: 102, 95% CI: 13-781) and a primary school-level education (aOR: 2.40, 95% CI: 1.14-5.06). Of 54 people diagnosed with Chagas disease (most of whom were asymptomatic), 42 (77.7%) returned to the clinic at least once, and 24 (44.4%) received treatment. Multivariable analysis showed that coming from Argentina (aOR: 13, 95% CI: 1.61-1188) or Bolivia (aOR: 1.90, 95% CI: 1.19-3.39) and having received information about Chagas disease in Spain (aOR: 4.63, 95% CI: 2.54-8.97) were associated with a good level of knowledge on the disease. Having primary level studies (aOR: 0.59, 95% CI: 0.34-0.98) and coming from Ecuador (aOR: 4.63, 95% CI: 2.52-847) were independently associated with a lower level of knowledge. Conclusions: Community-based interventions are a good strategy for diagnosing neglected diseases such as Chagas disease in non-endemic countries and for identifying and treating infected, asymptomatic individuals.This study was partially supported by the third call for research grants (J-M.R.-R.) from the Institute of Health and Biomedical Research of Alicante (ISABIAL)/FISABIO Foundation (III convocatoria de ayudas a proyectos de investigación del Instituto de Investigación Sanitaria y Biomédica de Alicante (ISABIAL) – Fundación FISABIO) (UGP-16-158); and by the collaborative agreement between ISABIAL/Fundación FISABIO and Fundación Mundo Sano-Spain, in accordance with the Sponsorship Law. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S

Asymptomatic Strongyloidiasis among Latin American Migrants in Spain: A Community-Based Approach

Strongyloides stercoralis infection is frequently underdiagnosed since many infections remain asymptomatic. Aim: To estimate the prevalence and characteristics of asymptomatic S. stercoralis infection in Latin American migrants attending a community-based screening program for Chagas disease in Spain. Methodology: Three community-based Chagas disease screening campaigns were performed in Alicante (Spain) in 2016, 2017, and 2018. Serological testing for S. stercoralis infection was performed using a non-automatized IVD-ELISA detecting IgG (DRG Instruments GmbH, Marburg, Germany). Results: Of the 616 migrants from Central and South America who were screened, 601 were included in the study: 100 children and adolescents (<18 years of age) and 501 adults. Among the younger group, 6 participants tested positive (prevalence 6%, 95% confidence interval [CI] 2.5% to 13.1%), while 60 adults did so (prevalence 12%, 95% CI 9.3% to 15.3%). S. stercoralis infection was more common in men than in women (odds ratio adjusted [ORa] 2.28, 95% CI 1.289 to 4.03) and in those from Bolivia (ORa 2.03, 95% CI 1.15 to 3.59). Prevalence increased with age (ORa 1.02, 95% CI 0.99 to 1.05). In contrast, a university education had a protective effect (ORa 0.29, 95% CI 0.31 to 0.88). Forty-one (41/66; 62.1%) of the total cases of S. stercoralis infection were treated at the health care center. Positive stool samples were observed in 19.5% of the followed-up positive cases. Conclusion: Incorporating serological screening for S. stercoralis into community-based screening for Chagas disease is a useful intervention to detect asymptomatic S. stercoralis infection in Central and South American migrants and an opportunity to tackle neglected tropical diseases in a transversal way. The remaining challenge is to achieve patients' adherence to the medical follow-up.This study was partially supported by the 3rd call for research project grants for the Institute of Health and Biometric Research of Alicante (ISABIAL)/FISABIO Foundation (UGP-16-158), and by the collaboration agreement regulated under the Law of Patronage between ISABIAL/FISABIO and the Foundation Mundo Sano, Spain.S

Effectiveness of Fosfomycin for the Treatment of Multidrug-Resistant Escherichia coli Bacteremic Urinary Tract Infections

IMPORTANCE The consumption of broad-spectrum drugs has increased as a consequence of the spread of multidrug-resistant (MDR) Escherichia coli. Finding alternatives for these infections is critical, for which some neglected drugs may be an option. OBJECTIVE To determine whether fosfomycin is noninferior to ceftriaxone or meropenem in the targeted treatment of bacteremic urinary tract infections (bUTIs) due to MDR E coli. DESIGN, SETTING, AND PARTICIPANTS This multicenter, randomized, pragmatic, open clinical trial was conducted at 22 Spanish hospitals from June 2014 to December 2018. Eligible participants were adult patients with bacteremic urinary tract infections due to MDR E coli; 161 of 1578 screened patients were randomized and followed up for 60 days. Data were analyzed in May 2021. INTERVENTIONS Patients were randomized 1 to 1 to receive intravenous fosfomycin disodium at 4 g every 6 hours (70 participants) or a comparator (ceftriaxone or meropenem if resistant; 73 participants) with the option to switch to oral fosfomycin trometamol for the fosfomycin group or an active oral drug or pa renteral ertapenem for the comparator group after 4 days. MAIN OUTCOMES AND MEASURES The primary outcome was clinical and microbiological cure (CMC) 5 to 7 days after finalization of treatment; a noninferiority margin of 7% was considered. RESULTS Among 143 patients in the modified intention-to-treat population (median [IQR] age, 72 [62-81] years; 73 [51.0%] women), 48 of 70 patients (68.6%) treated with fosfomycin and 57 of 73 patients (78.1%) treated with comparators reached CMC (risk difference, -9.4 percentage points; 1-sided 95% CI, -21.5 to infinity percentage points; P = .10). While clinical or microbiological failure occurred among 10 patients (14.3%) treated with fosfomycin and 14 patients (19.7%) treated with comparators (risk difference, -5.4 percentage points; 1-sided 95% CI. -infinity to 4.9; percentage points; P = .19), an increased rate of adverse event-related discontinuations occurred with fosfomycin vs comparators (6 discontinuations [8.5%] vs 0 discontinuations; P = .006). In an exploratory analysis among a subset of 38 patients who underwent rectal colonization studies, patients treated with fosfomycin acquired a new ceftriaxone-resistant or meropenem-resistant gram-negative bacteria at a decreased rate compared with patients treated with comparators (0 of 21 patients vs 4 of 17 patients [23.5%]; 1-sided P = .01). CONCLUSIONS AND RELEVANCE This study found that fosfomycin did not demonstrate noninferiority to comparators as targeted treatment of bUTI from MDR E coli; this was due to an increased rate of adverse event-related discontinuations. This finding suggests that fosfomycin may be considered for selected patients with these infections

A metabolic readout of the urine metabolome of COVID-19 patients

Analysis of urine samples from COVID-19 patients by 1H NMR reveals important metabolic alterations due to SAR-CoV-2 infection. Previous studies have identified biomarkers in urine that reflect metabolic alterations in COVID-19 patients. We have used 1H NMR to better define these metabolic alterations since this technique allows us to obtain a broad profile of the metabolites present in urine. This technique offers the advantage that sample preparation is very simple and gives us very complete information on the metabolites present. To detect these alterations, we have compared urine samples from COVID-19 patients (n = 35) with healthy people (n = 18). We used unsupervised (Robust PCA) and supervised (PLS-LDA) multivariate analysis methods to evaluate the differences between the two groups: COVID-19 and healthy controls. The differences focus on a group of metabolites related to energy metabolism (glucose, ketone bodies, glycine, creatinine, and citrate) and other processes related to bacterial flora (TMAO and formic acid) and detoxification (hippuric acid). The alterations in the urinary metabolome shown in this work indicate that SARS-CoV-2 causes a metabolic change from a normal situation of glucose consumption towards a gluconeogenic situation and possible insulin resistance.This work has been financed by the Universidad de Alicante (POSTCOVID-10-09)