Asma bronquial: IgE factor de riesgo en niños sanos

Tipo de estudio: prospectivo, transversal, analítico.Objetivo: Conocer los factores de riesgo para desarrollar enfermedades alérgicas y/o asma bronquial que elevan la Inmunoglobulina E total (IgE).Materiales y métodos: Se estudió la incidencia y los valores de riesgo de IgE en 203 niños sanos, de 2-26 meses, y se compararon entre los niños que tenían o no factores de riesgo. Para encontrar significancia estadística se usó la prueba chi2.Resultados: La IgE como factor de riesgo se encontró: en varones, hijos de madres asmáticas (p=0.005) y con <3Kg de peso al nacer (p<0.01); en niños alimentados con seno materno y fórmula (p<0.01); en presencia de alergenos intradomiciliarios (p=0.001) y en hijos de madres fumadoras (p<0.001). La incidencia de niveles elevados IgE fue del 80%.Conclusión: La alta incidencia de los valores de riesgo de IgE justifica la realización de nuevos estudios

Reporte de caso clínico: enfermedad de Menkes

La enfermedad de pelo ensortijado de Menkes es una patología congénita hereditaria, de pobre pronóstico, causada por una mutación de gen ATP7A localizado en el cromosoma X que codifica para las enzimas dependientes de cobre. Esta patología clínicamente está caracterizada por temprano retardo en el crecimiento, cabello frágil y ensortijado, degeneración arterial, cerebral y cerebelosa, lo que se explica por la disminución de la actividad de las cuproenzimas. Los severos daños neurológicos comienzan dentro del primero o segundo mes de vida y progresan rápidamente hasta la descerebración y muerte. El paciente objeto de estudio presentó desde los dos meses de edad crisis convulsivas focalizadas, que no ceden al tratamiento con anticonvulsivantes y que obligó a varias hospitalizaciones por su rápido y progresivo deterioro neurológico. La presencia además de un cabello acerado,frágil, escaso y despigmentado al igual que su piel, mejillas regordetas, frente olímpica, severa hipotonía muscular y el antecedente materno de cinco abortos, un hermano y dos tíos fallecidos tempranamente con convulsiones, permitió el diagnóstico clínico, que luego se corroboró con estudios complementarios

Infections in patients colonized with carbapenem-resistant Gram-negative bacteria in a medium Spanish city

Objetivo. Debido a que existen pocos estudios sobre las implicaciones clínicas de la colonización por bacterias gramnegativas resistentes a carbapenémicos (BRC) se analizó ésta en frotis rectales (FR) y faríngeos (FF) y su relación con la capacidad de predecir infección/colonización. Material y métodos. Se realizó un estudio transversal, retrospectivo de los pacientes adultos hospitalizados entre enero del 2016 y diciembre del 2019. Los aislamientos fueron caracterizados mediante MicroScan y espectrometría de masas, aplicando los puntos de corte EUCAST 2018. La detección de carbapenemasas se realizó mediante PCR y secuenciación Sanger; se asignó el secuenciotipo mediante MLST. La relación genética entre los aislados se hizo mediante electroforesis de campo pulsado usando las enzimas Xbal, Spel o Apal. Resultados. Se detectaron 308 (86,03 %) FR y 50 (13,97%) FF positivos, teniendo el FR una sensibilidad del 85%, especificidad del 100%, VPP 100% y VPN 97%. En los FR se aislaron: 44% (n=135) Acinetobacter baumannii, 26% (n=80) Enterobacterales (20 KPC, 29 OXA-48, 22 VIM, 2 IMP, 7 NDM), 17% (n=53) Pseudomonas aeruginosa y 13% (n=40) Stenotrophomonas maltophilia. En los FF se aislaron un 44% (n=22) S. maltophilia, 40% (n=20) A. baumannii, 8% (n=4) P. aeruginosa y 8% (n=4) Enterobacterales (3 VIM, 1 OXA). De los pacientes con tomas simultáneas de FR y FF, 41 (40,6%) tuvieron positividad en ambos frotis, 45 (44,6%) sólo en FR y 15 (14,9%) sólo en FF. En el 81,3% (n=13) de los episodios la colonización precedió a la infección, existiendo asociación entre infección y colonización (p<0,001; χ2) y en todos en los que se conservó la información del pulsotipo los aislados de las muestras clínicas y de los frotis fueron similares. Conclusiones. La probabilidad de predecir la infección a través del colonizado por BRC en diferentes muestras clínicas es factible, teniendo el FR una mayor sensibilidad para detectar colonización.Objective. Because there are few studies on the clinical implications of colonization by carbapenem-resistant gram-negative bacteria (CRB) this was analyzed in rectal smears (RS) and pharyngeals (PS) and its ability to predict infection/ colonization. Methodology. A cross-sectional, retrospective study from adult inpatients between January 2016 and December 2019 was conducted. The isolates were characterized by MicroScan and spectrometry of masses applying EUCAST 2018 cutoff points. The detection of carbapenemases was performed by PCR and Sanger sequencing; sequencies was assigned by MLST. The genetic relationship between the clinical isolates was made by pulsed field electrophoresis using the enzymes Xbal, Spel or Apal. Results. A total of 308 (86.03%) RS and 50 (13.97%) positive PS were detected, the RS had a 85% sensibility, 100% specificity, 100% positive predictive value and 97% negative predictive value. In RS, the following were isolated: 44% (n =135) Acinetobacter baumannii, 26% (n =80) Enterobacterales (20 KPC, 29 OXA-48, 22 VIM, 2 IMP, 7 NDM), 17% (n=53) Pseudomonas aeruginosa and 13% (n=40) Stenotrophomonas maltophilia. In the PS were isolated 44% (n=22) S. maltophilia, 40% (n = 20) A. baumannii, 8% (n=4) P. aeruginosa and 8% (n=4) Enterobacterales (3 VIM, 1 OXA). From the patients with simultaneous RS and PS, 41 (40.6%) had positivity in both smears, 45 (44.6%) only in RS and 15 (14.9%) only in PS. Colonization preceded infection in 81.3% (n=13) of the isolates; association between infection and colonization was found (p<0.001; χ2); and the episodes where the information was found all the isolates from the clinical samples and from the smears were similar. Conclusions. The probability of predicting infection through the CRB colonized in different clinical samples is feasible. The RS has a major sensibility to detect colonization

Zika virus infection in pregnancy: a protocol for the joint analysis of the prospective cohort studies of the ZIKAlliance, ZikaPLAN and ZIKAction consortia

INTRODUCTION: Zika virus (ZIKV) infection in pregnancy has been associated with microcephaly and severe neurological damage to the fetus. Our aim is to document the risks of adverse pregnancy and birth outcomes and the prevalence of laboratory markers of congenital infection in deliveries to women experiencing ZIKV infection during pregnancy, using data from European Commission-funded prospective cohort studies in 20 centres in 11 countries across Latin America and the Caribbean. METHODS AND ANALYSIS: We will carry out a centre-by-centre analysis of the risks of adverse pregnancy and birth outcomes, comparing women with confirmed and suspected ZIKV infection in pregnancy to those with no evidence of infection in pregnancy. We will document the proportion of deliveries in which laboratory markers of congenital infection were present. Finally, we will investigate the associations of trimester of maternal infection in pregnancy, presence or absence of maternal symptoms of acute ZIKV infection and previous flavivirus infections with adverse outcomes and with markers of congenital infection. Centre-specific estimates will be pooled using a two-stage approach. ETHICS AND DISSEMINATION: Ethical approval was obtained at each centre. Findings will be presented at international conferences and published in peer-reviewed open access journals and discussed with local public health officials and representatives of the national Ministries of Health, Pan American Health Organization and WHO involved with ZIKV prevention and control activities

Understanding the relation between Zika virus infection during pregnancy and adverse fetal, infant and child outcomes: a protocol for a systematic review and individual participant data meta-analysis of longitudinal studies of pregnant women and their infants and children

IntroductionZika virus (ZIKV) infection during pregnancy is a known cause of microcephaly and other congenital and developmental anomalies. In the absence of a ZIKV vaccine or prophylactics, principal investigators (PIs) and international leaders in ZIKV research have formed the ZIKV Individual Participant Data (IPD) Consortium to identify, collect and synthesise IPD from longitudinal studies of pregnant women that measure ZIKV infection during pregnancy and fetal, infant or child outcomes.Methods and analysisWe will identify eligible studies through the ZIKV IPD Consortium membership and a systematic review and invite study PIs to participate in the IPD meta-analysis (IPD-MA). We will use the combined dataset to estimate the relative and absolute risk of congenital Zika syndrome (CZS), including microcephaly and late symptomatic congenital infections; identify and explore sources of heterogeneity in those estimates and develop and validate a risk prediction model to identify the pregnancies at the highest risk of CZS or adverse developmental outcomes. The variable accuracy of diagnostic assays and differences in exposure and outcome definitions means that included studies will have a higher level of systematic variability, a component of measurement error, than an IPD-MA of studies of an established pathogen. We will use expert testimony, existing internal and external diagnostic accuracy validation studies and laboratory external quality assessments to inform the distribution of measurement error in our models. We will apply both Bayesian and frequentist methods to directly account for these and other sources of uncertainty.Ethics and disseminationThe IPD-MA was deemed exempt from ethical review. We will convene a group of patient advocates to evaluate the ethical implications and utility of the risk stratification tool. Findings from these analyses will be shared via national and international conferences and through publication in open access, peer-reviewed journals.Trial registration numberPROSPERO International prospective register of systematic reviews (CRD42017068915).</jats:sec

Clinical, epidemiological characterization and risk factors for infection / colonization by carbapenemase-producing Enterobacterales

Objetivo: Realizar una caracterización microbiológica, clínica, epidemiológica y de los factores de riesgo de la infección/colonización por Enterobacterales productores de carbapenemasas en Ecuador (EPC), en Ecuador y en un hospital de España, con especial atención a K. pneumoniae. Metodología: Para determinar la colonización por EPC, se obtuvo semanalmente frotis perineales e inguinales de pacientes ingresados en 7 unidades de cuidados intensivos, entre febrero y abril de 2016, en Guayaquil, Ecuador. Para el procesamiento, se utilizó el protocolo de laboratorio del CDC y CHROMOMagar mSuperCARBATM y PCR para confirmar carbapenemasas. El análisis genotípico se realizó mediante MLST y electroforesis de campo pulsado (PFEG). Se realizó análisis univariado y multivariado para determinar riesgo, así como análisis de coste. En un Hospital de Granada, España, se incluyeron pacientes con aislamientos positivos para Klebsiella pneumoniae blaKPC-3 ST 258, detectados entre octubre 2015 y marzo 2017; la sensibilidad antimicrobiana se determinó usando MicroScan y difusión en agar. Se usó PCR para codificar a los genes productores de carbapenemasas y MLST para la relación genética entre los aislados. En el hospital Virgen de las Nieves de Granada, España, se realizó un estudio transversal, retrospectivo de pacientes hospitalizados entre enero del 2016 y diciembre del 2019. Los aislamientos fueron caracterizados mediante MicroScan y espectrometría de masas, aplicando los puntos de corte EUCAST 2018. La detección de carbapenemasas se realizó mediante PCR y secuenciación Sanger; se asignó el secuenciotipo mediante MLST. La relación genética entre los aislados se hizo mediante PFEG usando las enzimas Xbal, Spel o Apal. Resultados: En Ecuador, el agar mSuper CARBATM mostró una sensibilidad del 93,05% y especificidad del 96.21% para la detección de EPC. Se incluyeron 665 pacientes, 255 colonizados/infectados por EPC y una prevalencia del 37,67%. K. pneumoniae blaKPC fue el microorganismo predominante. ST 258 fue el más frecuente. Los factores de riesgo independientes para la adquisición de EPC fueron: estancia prolongada en UCI (p <0,01), traqueotomía (p <0,01), hospitalización previa (p <0,01) y uso de vancomicina (p<0,01) y de macrólidos (p<0,01). En España se incluyeron 23 individuos con aislamientos de KPC-3 ST258, estos sólo fueron sensibles a gentamicina (CMI ≤ 2 mg/l), tigeciclina (CMI ≤ 1 mg/l) y colistina (CMI ≤ 2 mg/l). El gen blaKPC-3 estaba flanqueado por las secuencias de inserción Kpn6 y Kpn7 dentro Isoforma del transposón Tn4401a. En el estudio de colonización de bacterias gram-negativas resistentes a carbapenémicos (BRC), realizado en el hospital Virgen de las Nieves, en Granada, se detectaron 308 (10,7%) frotis rectales (FR) y 50 (8,9%) frotis faríngeos (FF) positivos. El FR mostró una sensibilidad del 85%, especificidad del 100%, VPP 100% y VPN 97% para la detección de colonización. De los pacientes con tomas simultáneas de FR y FF, 41(40,6%) tuvieron positividad en ambos frotis, 45(44,6%) sólo en FR y 15 (14,9%) sólo en FF. En el 81,3%(n=13) de los episodios la colonización precedió a la infección (p<0,001; χ2) y en todos en los que se conservó la información de pulsotipo los aislados de las muestras clínicas y de los frotis fueron similares. Conclusiones: El agar mSuper CARBATM es una alternativa útil y asequible para la detección de EPC.. Existe una alta prevalencia de EPC en las UCIs en Guayaquil, Ecuador y K. pneumoniae blaKPC es el microorganismo más frecuente. El uso de macrólidos y vancomicina se deben considerar como nuevos factores de riesgo para adquirir EPC. A su vez, se comunica por primera vez un brote de K. pneumoniae productor KPC-3 ST 258 en España. La probabilidad de predecir la infección a través del colonizado por BRC en diferentes muestras clínicas es factible, teniendo el FR una mayor sensibilidad para detectar colonización.Objective: To carry out a microbiological, clinical, epidemiological characterization and the risk factors of infection / colonization by carbapenemase-producing Enterobacterales (CPE) in Ecuador and a hospital in Spain. Methodology: To determine colonization by CPE, weekly perineal and inguinal swabs were obtained from patients admitted to 7 intensive units, between February and April 2016, in Guayaquil, Ecuador. We used the CDC laboratory protocol and CHROMOMagar mSuperCARBATMand PCR to confirm carbapenemases. Genotypic analysis was performed by MLST and pulsed field electrophoresis (PFEG). Univariate and multivariate analysis were performed to determine risk, as well as cost analysis. In a Hospital in Granada, Spain, patients with positive isolates for K. pneumoniae blaKPC-3 ST 258, detected between October 2015 and March 2017, were included, antimicrobial sensitivity was determined using MicroSan and agar diffusion. PCR was used to encode the carbapenemase producing genes and MLST for the genetic relationship between the isolates. A cross-sectional, retrospective study of hospitalized patients between January 2016 and December 2019, was carried out. The isolates were characterized by MicroScan and mass spectrometry, applying the EUCAST 2018 cut-off points. The detection of carbapenemases was performed by PCR and Sanger sequencing; Sequenciotype was assigned by MLST. The genetic relationship between the isolates was made by PFEG using the enzymes Xbal, Spel or Apal. Results: In Ecuador, MSuper CARBATM agar showed a sensitivity of 93,05%, specificity of 96,21% for the detection of CPE. 665 patients were included, 255 colonized / infected by CPE and a prevalence of 37,67%. K. pneumoniae blaKPC was the predominant organism. ST 258 was the most frequent. The independent risk factors for the acquisition of CPE were prolonged stay in the ICU (p <0,01), tracheostomy (p <0,01), previous hospitalization (p <0,01), use of vancomycin (p <0,01) and macrolides (p <0,01). In Spain, 23 individuals with isolates of KPC-3 ST258 were included; these were only sensitive to gentamicin (MIC ≤ 2 mg/l), tigecycline (MIC ≤ 1 mg/l) and colistin (MIC ≤ 2 mg/l). The blaKPC-3 gene was flanked by the Kpn6 and Kpn7 insertion sequences within the Isoform of the Tn4401 a transposon. In the study of colonization of gram-negative carbapenem-resistant bacteria (BRC), 308 (10,7%) positive (rectal swab) RS and 50 (8,9%) positive (pharyngeal swab) ) PS were detected. RS had a sensitivity of 85%, specificity of 100%, PPV 100% and NPV 97% to detect colonization. Of 101 patients with simultaneous RS and PS intake, 41 (40,6%) had positivity in both smears, 45 (44,6 %) only in RS and 15 (14,9%) only in PS. In 81.3% (n=13) of the episodes, colonization preceded infection (p<0,001; χ2) and in all the isolations which the pulsotipe was kept, the clinical samples were similar to the swabs. Conclusions: MSuper CARBATM agar is a useful and affordable alternative for the detection of CPE . There is a high prevalence of CPE in ICUs in Guayaquil, Ecuador, K. pneumoniae blaKPC is the most frequent microorganism. The use of macrolides and vancomycin should be considered as new risk factors for acquiring CPE. An outbreak of K. pneumoniae producer KPC-3 ST 258 is reported for the first time in Spain. The probability of predicting infection through the colonized by BRC in different clinical samples is feasible, with the RS having a higher sensitivity to detect colonization.Tesis Univ. Granada

Carbapenemase producing Enterobacteriaceae in intensive care units in Ecuador: Results from a multicenter study.

Carbapenemase-producing Enterobacteriaceae (CPE) are of global concern due to the growing number of patients who acquire them and their association with high mortality rates. Although there are some reports of endemicity in developing countries, little is known about this microorganism, and Ecuador is not an exception. Subsequently, our objective was to clinically and molecularly characterize carbapenemase producing-Enterobacteriaceae in intensive care units (ICUs) in Guayaquil, Ecuador. To determine CPE colonization, we obtained perineal and inguinal swabs from patients admitted to seven intensive-care adult units in Guayaquil-Ecuador between February and April 2016. The Centers for Disease Control and Prevention (CDC) laboratory protocol and chromogenic agar were used to process the cultures. Polymerase chain reaction was used to confirm carbapenemase production. Genotypic analysis was performed by Multilocus Sequence Typing (MLST) and pulsed-field electrophoresis (PFEG). Demographic and clinical data were obtained from the electronic charts and patient's relatives. Six hundred seventy-seven patients were included in the study, of whom 255 were colonized/infected by CPE. The CPE prevalence was 37.67%. Previous use of antimicrobials, use of invasive procedures and being burned at admission were associated with CPE. The most frequent infection was found after a surgical procedure. Klebsiella pneumoniae (n=249) was the predominant microorganism harbouring blaKPC, followed by Enterobactercloacae (n=8), Klebsiella aerogenes (n=4), Escherichia coli (n=4) and Klebsiella oxytoca (n=1). NDM was present in Proteus mirabilis. The strains were distributed in 19 sequence types (ST), and 10 were not reported previously in Ecuador. ST 258 was the sequence type isolated most frequently. This study shows a high prevalence of CPE in ICUs, particularly K. pneumoniae blaKPC ST 258. The identification of KPC alleles may help to understand the routes of dissemination and control spread within ICUs in Guayaquil, Ecuador

Reporte de caso clínico: enfermedad de Menkes

La enfermedad de pelo ensortijado de Menkes es una patología congénita hereditaria, de pobre pronóstico, causada por una mutación de gen ATP7A localizado en el cromosoma X que codifica para las enzimas dependientes de cobre. Esta patología clínicamente está caracterizada por temprano retardo en el crecimiento, cabello frágil y ensortijado, degeneración arterial, cerebral y cerebelosa, lo que se explica por la disminución de la actividad de las cuproenzimas. Los severos daños neurológicos comienzan dentro del primero o segundo mes de vida y progresan rápidamente hasta la descerebración y muerte. El paciente objeto de estudio presentó desde los dos meses de edad crisis convulsivas focalizadas, que no ceden al tratamiento con anticonvulsivantes y que obligó a varias hospitalizaciones por su rápido y progresivo deterioro neurológico. La presencia además de un cabello acerado,frágil, escaso y despigmentado al igual que su piel, mejillas regordetas, frente olímpica, severa hipotonía muscular y el antecedente materno de cinco abortos, un hermano y dos tíos fallecidos tempranamente con convulsiones, permitió el diagnóstico clínico, que luego se corroboró con estudios complementarios

Colistin resistance screening by 3 μg/ml colistin agar in Carbapenemase-producing Enterobacterales.

In low- and middle-income countries, the use of colistin in therapeutic regimens is common, to treat infections produced for Carbapenemase-producing Enterobacterales (CPE) due to limited access to the recently discovered-approved antibiotics. Furthermore, the technical limitations to perform colistin susceptibility tests make it difficult to assess the suitability of this treatment for each patient, as well as to monitor the rates of resistance. In the present study, we describe the use of agar dilution using a unique colistin concentration of 3 μg/ml to discriminate isolates with colistin resistance in CPE obtained from clinical samples. Clinical Laboratory Standards Institute (CLSI) colistin broth microdilution method and dilution agar with a colistin concentration of 3 μg/ml were performed in 168 isolates of CPE obtained from clinical samples in Guayaquil, Ecuador. Broth microdilution was considered our gold standard using CLSI breakpoints as reference (≤2 μg/ml intermediate and ≥4 μg/ml resistant). Categorical agreement was defined as obtaining a reading within the same category with both methodologies. Isolates obtained from respiratory samples were the most prevalent (26.19%; n = 44). Klebsiella pneumoniae was the predominant specie (94.04%; n = 158). KPC-like carbapenemase was present in all the isolates, and interestingly, colistin resistance was not mediated by MCR-1 production. Categorical agreement between both methods resulted in 97.02%. We propose the use of dilution agar with a colistin concentration of 3 μg/ml, as a valid method for screening colistin resistance in low- and middle-income countries to monitor resistance and to perform epidemiological studies

Risk factors associated with colistin resistance in carbapenemase-producing Enterobacterales: a multicenter study from a low-income country

Abstract Purpose The aim of this study was to assess the risk factors for colistin-resistant carbapenemase-producing Enterobacterales (CR-CPE), and describe the mortality associated with this organism, in a low-income country. Methods A descriptive, observational, and prospective multicenter study was carried out in Guayaquil, Ecuador. All patients with carbapenem-resistant Enterobacterales admitted between December 2021 and May 2022 were enrolled. Infection definitions were established according to the Centers for Disease Control and Prevention (CDC) protocols. The presence of carbapenemase-producing Enterobacterales was confirmed with a multiplex PCR for bla KPC, bla NDM, bla OXA-48, bla VIM, and bla IMP genes. MCR-1 production was studied molecularly, and MLST assays were carried out. Results Out of 114 patients enrolled in the study, 32 (28.07%) had at least one positive sample for CR-CPE. Klebsiella pneumoniae ST512-KPC-3 was the most frequent microorganism isolated. Parenteral feeding, β-lactamase inhibitor use, recent hemodialysis, and renal failure were all considered independent risk factors for carrying CR-CPE. A mortality of 41.22% was detected, but we could not find any difference between colistin-resistant and colistin-susceptible CPE. MCR-1 production was not detected in any of the isolates studied. Conclusion A significant burden for CR-CPE was found in a South American country that was mainly caused by the high-risk clone K. pneumoniae ST512-KPC-3 and not mediated by mcr-1 production. Its acquisition involved parenteral feeding, β-lactamase inhibitor use, recent hemodialysis, and renal failure as independent risk factors, demonstrating the critical need for infection prevention and stewardship programs to avoid dissemination to other countries in the region