Pseudomonas aeruginosa bloodstream infections in children and adolescents: risk factors associated with carbapenem resistance and mortality.

BACKGROUND: Pseudomonas aeruginosa bloodstream infections (PA-BSIs) are a serious disease and a therapeutic challenge due to increasing resistance to carbapenems. Our objectives were to describe the prevalence and risk factors associated with carbapenem resistance (CR) and mortality in children with PA-BSI. METHODS: A retrospective, multi-centre study was carried out, including patients aged <20 years with PA-BSI in four tertiary hospitals in Madrid (Spain) during 2010-2020. Risk factors for CR PA-BSIs and 30-day mortality were evaluated in a multi-variable logistic regression model. RESULTS: In total, 151 patients with PA-BSI were included, with a median age of 29 months (interquartile range: 3.5-87.1). Forty-five (29.8%) cases were CR, 9.9% multi-drug resistant and 6.6% extensively drug resistant. The prevalence of CR remained stable throughout the study period, with 26.7% (12/45) of CR mediated by VIM-type carbapenemase. Patients with BSIs produced by CR-PA were more likely to receive inappropriate empiric treatment (53.3% vs 5.7%, P<0.001) and to have been previously colonized by CR-PA (8.9% vs 0%, P=0.002) than BSIs caused by carbapenem-susceptible P. aeruginosa. CR was associated with carbapenem treatment in the previous month (adjusted odds ratio (aOR) 11.15) and solid organ transplantation (aOR 7.64). The 30-day mortality was 23.2%, which was associated with mechanical ventilation (aOR 4.24), sepsis (aOR 5.72), inappropriate empiric antibiotic therapy (aOR 5.86), and source control as a protective factor (aOR 0.16). CONCLUSION: This study shows a concerning prevalence of CR in children with PA-BSIs, leading to high mortality. Inappropriate empiric treatment and sepsis were associated with mortality. The high prevalence of CR with an increased risk of inappropriate empiric treatment should be closely monitored.

Ethanolic extract of Artemisia campestris subsp. glutinosa (Besser) Batt. inhibits HIV-1 replication in vitro through the activity of terpenes and flavonoids on viral entry and NF-κB pathway.

ETHNO-PHARMACOLOGICAL RELEVANCE: The genus Artemisia spp. is well known for its anti-infectious properties and its high content in anti-infectious compounds, like the well-known sweet wormwood (Artemisia annua L.). Another Artemisia species, Artemisia campestris subsp. glutinosa (Besser) Batt., field wormwood, has been traditionally used as medicinal plant in the Mediterranean region. AIM OF THE STUDY: The aim of this study is to investigate the anti-HIV activity of field wormwood, to identify the compounds responsible for this activity and their structure and mechanism of action. MATERIALS AND METHODS: Antiviral activity of isolated compounds and extracts was evaluated in HIV-1 infections of lymphoblastoid cells. We also evaluated the mechanism of action of isolated compounds. Viral entry was studied comparing the inhibitory effect of isolated compounds on wild type HIV-1 and VSV pseudotyped HIV-1. To assess the viral transcriptional effect, plasmids encoding luciferase reporter genes under the control of the whole genome of HIV-1 or NF-κB or Sp1 transcription factors were transfected in the presence of the compounds under evaluation. Finally, antioxidant activity was assessed by quantitation of reduced and total glutathione in treated cell cultures. RESULTS: Ethanolic and aqueous extracts of Artemisia campestris subsp. glutinosa (Besser) Batt. subsp. glutinosa displayed anti-HIV activity in vitro, although ethanolic extract was more powerful (IC50 14.62 µg/mL). Bio-guided ethanolic extract fractionation leads to the isolation and characterization of two terpenes, damsin and canrenone, and four flavonoids, 6, 2', 4'-trimethoxyflavone, acerosin, cardamonin and xanthomicrol. All the isolated compounds inhibited HIV-1 replication in vitro with IC50 values between the middle nanomolar and the low micromolar range. Their anti-HIV mechanism of action is due to the bloking of viral entry and/or transcription inhibition, without correlation with the antioxidant activity, through interference with the cellular transcription factors NF-κB and Sp1, which are targets that are not currently reached by antiretroviral therapy. CONCLUSION: We describe here the anti-HIV activity of field wormwood, Artemisia campestris subsp. glutinosa (Besser) Batt., and the isolation and study of the mechanism of action of two terpenes and four flavonoids, responsible, at least in part, for its activity, through the inhibition of two different cellular targets affecting the HIV replication cycle. The activity of these compounds in cellular targets could explain why plant extracts can be used in the treatment of different diseases. Besides, the presence of several compounds with dual and different mechanisms of action could prove useful in the treatment of HIV-1 infection, since it could aid to overcome drug resistances and simplify drug therapy. This work is a further step in understanding the anti-infectious activity of wormwood species and their use in treating infectious diseases.

Infección por rotavirus en un periodo de 6 años (2007.2012): consideraciones epidemiológicas / Rotavirus infection in a period of 6 years (2007.2012): epidemiological considerations

Introducción. Rotavirus es una causa importante de gastroenteritis aguda (GEA) en niños de hasta 5 años. El objetivo del trabajo fue investigar la incidencia de las infecciones nosocomiales y comunitarias por rotavirus, y analizar sus características epidemiológicas en estos pacientes en 2007-2012. Métodos. Se estudiaron las heces procesadas para detección de antígenos de rotavirus, mediante prueba inmunocromatográfica, de pacientes con GEA de hasta 5 años atendidos en el Hospital Infantil Universitario Niño Jesús, de Madrid. Resultados. Se procesaron para detección de rotavirus 4.590 heces de pacientes con GEA, detectándose rotavirus en 709 pacientes (808 heces): 52% pacientes con infección comunitaria y 48%, nosocomial. Cuarenta y dos episodios nosocomiales (12%) correspondieron a pacientes oncológicos. La distribución anual de pacientes en 2007-2012 fue 124 (18%), 98 (14%), 83 (12%), 138 (20%), 173 (24%) y 96 (14%), respectivamente. Un 86% de pacientes con GEA por rotavirus tenían≤1 año. La coinfección por rotavirus y adenovirus fue la más frecuente (65%). Conclusiones. Se detectó una elevada tasa de infección nosocomial y cambios en el patrón estacional, desde una marcada estacionalidad en 2007 a un patrón irregular en 2008-2012. Este cambio indica una transmisión viral sostenida que podría comprometer las medidas preventivas (AU)

Introduction. Rotavirus is a major cause of acute gastroenteritis (AGE) in children aged 5 years or under. The objective was to assess the incidence of nosocomial and community –acquired rotavirus infections, and its epidemiological characteristics in 2007-2012. Methods. Stools specimens were collected form children with AGE<5 years treated at the H.I.U Niño Jesús, Madrid, for the presence of rotavirus antigen by enzyme-linked immunosorbent assay. Results. A total of 4590 stools from patients with AGE were tested for rotavirus antigen. Rotavirus was detected in 709 patients (808 tools): 52% patients with community infections and 48% with nosocomial infections. Of these rotavirus nosocomial AGE, 12% were immunocompromised children. The number of patients with rotavirus in 2007-2012 was 124 (18%), 98 (14%), 83 (12%), 138 (20%), 173 (24%) and 93 (14%), respectively. Eighty-six percent of the patients with rotavirus AGE were ≤1 year of age. Rotavirus and adenovirus (65%) were the association most frequently detected. Conclusions. There are a high rate of nosocomial infection and changes in the seasonal pattern. From a marked seasonality in 2007, the pattern became irregular in 2008-2012. This change indicates a viral transmission more sustained which might reduce the efficiency of prevention measures (AU)

Implicación del grupo Bacteroides fragilis y otros anaerobios de importancia clínica en apendicitis aguda: ¿Es adecuado nuestro protocolo de terapia empírica? / Implication of the Bacteoirde fragilis group and other anaerobes of clinical improtance in acute apendicitis: Our empirical therapy schem is right?

Introducción. Nuestro objetivo es estudiar la implicación de anaerobios, especialmente del grupo Bacteroides fragilis (B. fragilis), en los procesos de apendicitis aguda y determinar su patrón de resistencia antibiótica en vista a evaluar la adecuación de la terapia empírica empleada. Métodos. La identificación de los microorganismos se realizó mediante pruebas bioquímicas habituales y el estudio de sensibilidad mediante microdilución en caldo. Resultados. En el Hospital Infantil U. Niño Jesús de Madrid, 2007-2011, fueron procesados 596 exudados peritoneales de apendicitis aguda, 320 (54%) muestras fueron positivas, recuperándose 1.052 patógenos. 468 (45%9 anaerobios. El grupo B. fragilis fue el más frecuentemente aislado (67%). Los agentes más activos frente anaerobios son imipenem, metronidazol y la combinación agente β-lactámico/inhibidor de β-lactamasas. Sin embargo, metronidazol no muestra actividad frente a Porphromonas spp. Y Peptococus spp./eptostreptococcus spp. Las tasas de resistencia a cefoxitina y clindamicina del grupo B. fragilis fueron 19% y 48% respectivamente, cuestionando la adecuación del uso empírico de cefoxitina. Mientras la resistencia del grupo B. fragilis a clindamicina no cambia apreciablemente durante el periodo 2007-2010, se observa un progresivo descenso en la resistencia a cefoxitina. Conclusiones. Otros tratamientos empíricos (amoxicilina/ácido clavulánico o metronidazol) serían más apropiados en las infecciones intraabdominales (AU)

Introduction. Our objective is to analyze the involvement of anaerobes, with emphasis on the Bacteroides fragilis (B. fragilis) group, collected from appendicitis and t determine the antimicrobial reistance profile in order to evaluate the adequacy of our empirical therapy scheme. Methods. Microorganisms were identified by standard biochemical methods. Antimicrobial susceptibility was performed using a broth microdilution methods. Results. During 2007-2011, 596 peritoneal exudates of acute appendicitis were received at Hospital U. Infantil Niño Jesús of Madrid, 320 (54%) specimens from 309 patients were positive and 1052 pathogens were recovered: 468 (45%) anaerobe. B. fragilis roup was the most commonly isolated anaerobic organism 867&). Thea gents most active against anaerobic bacteria are imipenem, metronidazole and combination of β-lactam/β-lactamase inhibitor. However, metronidazole does not have activity against Porphyromonas spp. And Peptococcus spp./peptostreptococus spp. The rates of cefoxitin and clindamycin-resistant B. fragilis group were 19% and 48% respectively, which may raise questions about the appropriateness of the empirical use of cefoxitine. While the B. fragilis group resistance to clindamycin does not change significantly during 2007-2010 period, a progressive decrease was found in the resistance rates to cefoxitin. Conclusions. Other empirical treatments (amoxicillin/clavulanic acid or Metronidazole) would be most appropriate in intra-abdominal infections (AU)

[Staphylococcus aureus infections in the intensive care unit: clinical and epidemiological characteristics]. / Infecciones por Staphylococcus aureus en cuidados intensivos: características clínicas y epidemiológicas.

INTRODUCTION: There has been an increase in invasive Staphylococcus Aureus infections over the last few years, which have required admission to the pediatric intensive care unit (PICU). PATIENTS AND METHODS: All patients with S. aureus infection who were admitted to PICU were enrolled in a retrospective study (January 2006-June 2010). The patients were classified into 2 groups: community-acquired infection (Group 1) and nosocomial infection (Group 2). We recorded epidemiological data, type of S. aureus (methicillin-susceptible S. aureus [MSSA], methicillin-resistant S. aureus [MRSA]), risk factors, site of infection, presence of hemodynamic instability, respiratory support, and mortality. RESULTS: A total of 51 patients were enrolled, 21 belonging to Group 1 and 30 to Group 2. The median age was lower in Group 1 (1.6 years vs 3.2 years; P=.009). MSSA was isolated in 88% of cases. MRSA was detected in 6/51 (12%) of cases, which were isolated in the later study period (January 2009-June 2010). The risk factors for infection were: immunosuppression, venous catheter, institutionalization, mechanical ventilation, previous surgery, previous trauma and chronic osteomyelitis. A large majority (83%) of the patients with MRSA infection had risk factors. The type of infection was varied, with respiratory tract infection being the most common (75%). Hemodynamic instability was observed in 43% of patients. Most patients (86%) required respiratory support. One patient in Group 1 died of necrotizing pneumonia caused by MSSA. CONCLUSIONS: Infections by S. aureus in children are severe and have a high morbidity. Respiratory infection was the most common in our series. Isolation of MSSA is common in these infections, although, an increase in the number of infections by MRSA was observed during the latter part of the study.

Infeccion invasora por Blastoschizomyces capitatus / Invasive infection due to Blastoschizomyces capitatus

No disponible

A mouse model to study the alterations in haemostatic and inflammatory parameters induced by Lonomia achelous caterpillar haemolymph.

A mouse model was established to reproduce the haemorrhagic syndrome which occurs in humans after accidental contact with the hairs of the caterpillar Lonomia achelous (LA) and measures the haemostatic and inflammatory alterations that occur as a result of this contact. Mice were injected intradermally with different doses (0.4, 0.8 and 1.6 mg/animal) of L. achelous haemolymph (LAH). Haematological (haemoglobin, haematocrit, platelet count, differential leukocyte count), haemostatic (fibrinogen, plasminogen, factor XIII [FXIII], fibrinolytic activity) and inflammatory parameters (tumour necrosis factor alpha [TNF-α], nitric oxide [NO]) were measured at different times up to 48 h. C57BL/6 mice responded to LAH injection, in terms of these parameters, in a manner similar to that seen in humans, whereas the BALB/c mice were unresponsive. In C57BL/6 mice injected with LAH, time course measurements showed: a) a reduction in the haemoglobin, haematocrit, fibrinogen, FXIII and plasminogen levels, b) no effect on the platelet count and c) immediate leukocytosis and an increase in the fibrinolytic activity in plasma. An inflammatory response (TNF-α) was observed within 1 h post-injection, followed by a more persistent increase in serum NO. These findings suggest that C57BL/6 mice represent a useful model of the haemorrhagic syndrome observed in humans who have suffered contact with the caterpillar, permitting a deeper understanding of the role of the inflammatory response in the haematological and haemostatic manifestations of this syndrome.

Ellagitannins from Tuberaria lignosa as entry inhibitors of HIV.

Screening of plants from the Iberian Peninsula for anti-human immunodeficiency virus (-HIV) activity revealed that aqueous extract of Tuberaria lignosa gave positive results. Following an activity-guided procedure, the crude extract was counterextracted, and the subsequent fractions obtained tested for their anti-HIV activity in vitro. The bioassay-guided fractionation of the extract afforded an ellagitannin enriched fraction (EEF) isolated for the first time from this species. This EEF exhibited antiviral activity against HIV in MT-2 infected cells, with an IC(50) value of 2.33mug/ml (selectivity index greater than 21). Inhibition of HIV infection by EEF appears to be mediated by CD4 down-regulation, the main receptor for HIV entry. CXCR4 and CCR5 receptors were not affected by EEF, explaining why EEF is able to inhibit R5 and X4 infections.

Preliminary study of the anti-inflammatory activity of hexane extract and fractions from Bursera simaruba (Linneo) Sarg. (Burseraceae) leaves.

Bursera simaruba (L.) Sarg. leaves hexane extracts display anti-inflammatory activity on the adjuvant-carrageenan-induced inflammation in rats. In order to isolate and identify the active compounds of the hexane extract, we performed a preliminary phytochemical study and a bioassay-directed fractionation using the carrageenan-induced paw oedema test in mice. From the nine fractions (A-I) obtained, of an initial chromatographic separation, fractions A and E (doses equivalents to 1.50 g dry plant/kg body weight) showed the strongest anti-inflammatory activity comparable to that of the reference drug phenylbutazone (80 mg/kg). The isolation and characterization of 3-methylene-7,11,15-trimethylhexadec-1-ene (neophytadiene) (1), ergost-5-en-3beta-ol (2), 24S-stigmast-5,22E-dien-3beta-ol (3), 24S-stigmast-5-en-3beta-ol (4) and alpha-amyrin (5), from these fractions is reported.

COX-2 and sPLA2 inhibitory activity of aqueous extract and polyphenols of Rhizophora mangle (red mangrove).

The aqueous extract of Rhizophora mangle bark and its polyphenolic fractions showed remarkable in vitro antiinflammatory activity in a preliminary study. The low molecular weight fraction exhibited cyclooxygenase-2 inhibitory activity while the total aqueous extract and the low molecular weight fraction showed secretory phospholipase A(2) inhibitory activity.

Anti-inflammatory activity of four Bolivian Baccharis species (Compositae).

Hexanic, dichloromethanic, ethanolic and aqueous extracts from Baccharis obtusifolia HBK, Baccharis latifolia (R. et P.) Pers., Baccharis pentlandii D.C. and Baccharis subulata Wedd., plants used in the traditional medicine of South America have been studied for their in vitro anti-inflammatory activity in cellular systems. Calcium ionophore A23187-stimulated mouse peritoneal macrophages were validated as a source of cyclooxygenase-1 (COX-1) (prostaglandin E2, PGE2) and 5-lipoxygenase (5-LOX) (leukotriene C4, LTC4), and mouse peritoneal macrophages stimulated with Escherichia coli lipopolysaccharide (LPS) were used for testing cyclooxygenase-2 (COX-2) (PGE2), nitric oxide (NO) and tumour necrosis factor-alpha (TNF-alpha) activity. Most of the extracts tested were active in all assays.

Kingella kingae como causa de infección en dos niños menores de dos años / Kingella kingae infections in two children younger than two years old

Kingella kingae es un cocobacilo gramnegativo, aerobio, pertenenciente a la familia de las Neisseriaceae. Presentamos dos casos clínicos de infección por Kingella kingae: bacteriemia y artritis séptica, diagnosticados en nuestro centro en el intervalo de un mes. Kingella kingae forma parte de la flora orofaríngea habitual, pudiendo ser la puerta de entrada de las infecciones sistémicas. Desde la administración de la vacuna frente a Haemophilus influenzae tipo b, Kingella kingae está siendo la principal bacteria gramnegativa implicada en infecciones osteoarticulares en niños menores de tres años. Kingella kingae es muy sensible a los antibióticos que normalmente se utilizan de forma empírica. Las infecciones por Kingella kingae habitualmente siguen un curso clínico benigno, y se han descrito casos de resolución espontánea. Queremos hacer hincapié en el hecho de que este microorganismo no es sospechado o buscado en infecciones en pacientes pediátricos. Kingella kingae es un microorganismo de difícil aislamiento, poco resistente en condiciones adversas, por lo que es importante inocular la muestra de sangre o líquido articular en frasco de hemocultivo (AU)

Screening of selected plant extracts for in vitro inhibitory activity on human immunodeficiency virus.

As part of our screening of anti-AIDS agents from natural sources, extracts of 15 medicinal plants widely used in the folk medicines of North America and Europe were evaluated in vitro. Most of the extracts tested were relatively nontoxic to human lymphocytic MT-2 cells, but only the extracts of Hysopp officinalis and Dittrichia viscosa exhibited anti-HIV activity in an in vitro MTT assay. The 50% hydroalcohol extract of Hysopp officinalis and the aqueous extract of Dittrichia viscosa showed inhibitory effects against HIV-1 induced infections in MT-2 cells at concentrations ranging from 50 to 100 microg/mL and 25 to 400 microg/mL, respectively. Both extracts showed no appreciable cytotoxicity at these concentrations.