Risk factors for gentamicin-resistant E. coli in children with community-acquired urinary tract infection.

According to many guidelines, gentamicin is the empirical parenteral treatment for children with community-acquired urinary tract infection (CA-UTI). However, increasing resistance rates are reported. The purpose of this study is to analyze risk factors for presenting with a UTI caused by a community-acquired gentamicin-resistant Escherichia coli in children in our hospital and to describe their clinical outcome. A retrospective case-control local study was performed in a tertiary care hospital from January 2014 to December 2016. Cases and controls were children below 14 years old diagnosed in the Emergency Department with febrile CA-UTI caused by gentamicin-resistant and gentamicin-susceptible febrile E. coli strains, respectively. During the study period, 54 cases were included and compared with 98 controls. Patients with chronic conditions were more likely to present with a UTI due to gentamicin-resistant E. coli (OR 3.27; 95% CI 1.37-7.8, p < 0.05), as well as children receiving antibiotic prophylaxis (OR 3.5; 95% CI 1.2-10.1, p < 0.05). Cases had longer hospital stays than controls (5.8 ± 5 days vs. 4.4 ± 4 days, p = 0.017). Gentamicin-resistant strains associated higher rates of cefuroxime (29% vs. 3%), cefotaxime (27% vs. 0%), and quinolone resistance (40.7% vs. 6%) (p < 0.01) and produced more frequently extended-spectrum beta-lactamases (ESBL) (20% vs. 0%, p < 0.01) and carbapenemases (7.4% vs. 0%; p = 0.015). All gentamicin-resistant strains were amikacin-sensitive. The presence of chronic conditions and antibiotic prophylaxis could be potential risk factors for gentamicin-resistant E. coli CA-UTI in children. Simultaneous resistance to cephalosporins, quinolones, and ESBL/carbapenemase production is frequent in these strains.

Mental Health in Children, Adolescents, and Youths Living with Perinatally Acquired HIV: At the Crossroads of Psychosocial Determinants of Health.

Here, we aim to describe mental health (MH) in a cohort of children, adolescents, and young adults living with perinatally acquired HIV (PHIV) in Spain and explore the treatment gap for mental disorders. We also aim to analyze the potential association between MH issues to psychosocial risk factors (PSRFs) and identify management priorities. We conducted a descriptive transversal study that included all cases of PHIV under follow-up in a reference hospital in Madrid. The study included patients undergoing follow-up in the pediatric outpatient clinic and youths transferred from pediatric to adult care units after 1997. Epidemiological, clinical, immunovirological, and treatment-related data were collected, including PSRF and adverse childhood experiences (ACEs). Of the 72 patients undergoing follow-up, 43 (59.7%) had already been transferred to the adult outpatient clinic. The patients' median age was 25 years (IQR 18-29), and 54.2% were women. Most patients were undergoing treatment (94.6%) and were virologically suppressed (84.7%). Although MH issues were present in 30 patients (41.7%), only 17 (56.7%) had been referred for evaluation to the Department of Mental Health, and only 9 (30%) had received a MH diagnosis. PSRFs were common (32% of participants had at least one PSRF) and were associated with MH issues and adherence issues (all p < 0.05). A multidisciplinary approach to address the psychological factors and social determinants of health is urgently needed, particularly during important life development stages, such as adolescence.

Immunogenicity of the Conjugate Meningococcal ACWY-TT Vaccine in Children and Adolescents Living with HIV.

BACKGROUND: Children and adolescents living with HIV (CALHIV) are at high risk of meningococcal infections and may present lower immune responses to vaccines. The objectives of this study were to assess the immunogenicity of the quadrivalent Men ACWY-TT vaccine (Nimenrix®) in CALHIV after a two-dose schedule and to describe possible HIV-related factors that may affect the immunogenic response. METHODS: A multicenter prospective study was designed, including CALHIV followed in five hospitals in Madrid, between 2019 and 2021. Two doses of the Men ACWY-TT vaccine were administered. Serum bactericidal antibody (SBA) assays using rabbit complement (rSBA) against serogroups C, W, and Y were used to determine seroprotection and vaccine response (the proportion achieving a putative protective titer of ≥eight or a ≥four-fold rise in titer from baseline). Serum was collected at baseline, and at 3 and 12 months after vaccination. RESULTS: There were 29 CALHIV included, 76% of whom were perinatally infected. All were receiving TAR and presented a good immunovirological and clinical status overall. At baseline, 45% of CALHIV had seroprotective titers to at least one serogroup, with individual seroprotection rates of 24%, 28%, and 32% against C, W, and Y, respectively. After a two-dose schedule, vaccine response was 83% for each serogroup, eliciting a vaccine response to all serogroups in 69% of them. One year after vaccination, 75% of CALHIV maintained seroprotective titers against the C serogroup, and 96% against W and Y. None of the HIV-related characteristics analyzed could predict vaccine response or antibody duration. CONCLUSIONS: CALHIV who received effective TAR and presented a good immuno-virological situation achieved an appropriate vaccine response after two doses of the Men ACWY-TT vaccine, and antibody-mediated protection against serogroups C, W, and Y was maintained in more than 70% of the patients one year after vaccination.

Transient Viral Rebound in Children with Perinatally Acquired HIV-1 Induces a Unique Soluble Immunometabolic Signature Associated with Decreased CD4/CD8 Ratio.

BACKGROUND: To determine by multi-omic analysis changes in metabolites, lipids, and proteins as a consequence of transient viral rebound (tVR) in children with perinatally acquired HIV-1 (PHIV). METHODS: Plasma samples from children with PHIV and with tVR (first episode of transient RNA-HIV viral load >20 copies/ml followed by suppression) on the time-point immediately before (pre-tVR) and after (post-tVR) the tVR were assessed. Multi-omic analyses were performed using nLC-Orbitrap, GC-qTOF-MS, and LC-qTOF-MS. RESULTS: Comparing pre- and post-tVR time-points, HIV-1 children with tVR (n = 5) showed a trend to a decrease in ratio CD4/CD8 (p = 0.08) but no significant differences were observed in plasma metabolites, lipids, or proteins. Post-tVR condition was compared with a reference group of children with PHIV with persistent viral control (n = 9), paired by sex, age, and time under antiretroviral treatment. A total of 10 proteins, 8 metabolites, and 2 lipids showed significant differences (p < 0.05): serotransferrin, clusterin, kininogen-1, succinic acid, threonine, 2-hydroxyisovaleric acid, methionine, 2-hydroxyglutaric, triacylglyceride 50:0 (TG50:0), and diacylglyceride 34:1 (DG34:1) were upregulated while alpha-2-macroglobulin, apolipoprotein A-II, carboxylic ester hydrolase, apolipoprotein D, coagulation factor IX, peptidase inhibitor 16, SAA2-SAA4 readthrough, oleic acid, palmitoleic acid, and D-sucrose downregulated on post-tVR time-point compared to the reference group. Ratio CD4/CD8 correlated with apolipoprotein A-II, DG34:1, and methionine (p = 0.004; ρ = 0.71, p = 0.016; ρ = -0.63; and p = 0.032; ρ = -0.57, respectively). Nadir CD4+ correlated inversely with kininogen-1 (p = 0.022; ρ = -0.60) and positively with D-sucrose (p = 0.001; ρ = 0.77). CONCLUSIONS: tVR followed by suppression implies changes in soluble proteins, lipids, and metabolites that correlate with immunological parameters, mainly ratio CD4/CD8, that decreased after tVR. These distinct soluble biomarkers could be considered potential biomarkers of immune progression.

Antimicrobial stewardship in hospitals: Expert recommendation guidance document for activities in specific populations, syndromes and other aspects (PROA-2) from SEIMC, SEFH, SEMPSPGS, SEMICYUC and SEIP.

In 2012, The Spanish Societies of Infectious Diseases and Clinical Microbiology (SEIMC), Hospital Pharmacy (SEFH), and Preventive Medicine, Public Health and Healthcare Management (SEMPSGS) lead a consensus document including recommendations for the implementation of antimicrobial stewardship (AMS) programs (AMSP; PROA in Spanish) in acute care hospitals in Spain. While these recommendations were critical for the development of these programs in many centres, there is a need for guidance in the development of AMS activities for specific patient populations, syndromes or other specific aspects which were not included in the previous document or have developed significantly since then. The objective of this expert recommendation guidance document is to review the available information about these activities in these patient populations or circumstances, and to provide guidance recommendations about them. With this objective the SEIMC, SEFH, SEMPSPGS, the Spanish Society of Intensive Care Medicine (SEMICYUC) and the Spanish Pediatric Infectious Disease Society (SEIP) selected a panel of experts who chose the different aspects to include in the document. Because of the lack of high-level evidence in the implementation of the activities, the panel opted to perform a narrative review of the literature for the different topics for which recommendations were agreed by consensus. The document was open to public consultation for the members of these societies for their comments and suggestions, which were reviewed and considered by the panel.

Prevalence of nonalcoholic fatty liver disease using noninvasive techniques among children, adolescents, and youths living with HIV.

OBJECTIVE: The prevalence of subclinical liver abnormalities is high among people with HIV, but data regarding perinatally HIV-infected children and adolescents (PHIV) are scarce. Noninvasive image techniques offer an opportunity to address nonalcoholic fatty liver disease (NAFLD) in a population in which the scores validated for adults have not been tested. DESIGN: Prospective cross-sectional study including PHIV and uninfected controls. METHODS: Noninvasive imaging techniques for the diagnosis of NAFLD and/or fibrosis were performed, and four scores to predict NAFLD were evaluated. RESULTS: Seventy-six participants (59.2% women) with a median of 19 years old (interquartile range: 15.5-25.6) were included, 38 were PHIV and 38 were age and sex-matched controls. All HIV participants were on ART at the moment of inclusion, and 86.8% were virologically suppressed. A total of 11 PHIV and three controls were diagnosed with NAFLD (28.9% vs. 7.9%; P = 0.02) by noninvasive imaging techniques. The performance of scores based on clinical and analytical parameters was very poor. Although nonsignificant, overweight was more common among participants with NAFLD, who had a significantly higher BMI. Differences in HIV-related parameters between the groups were nonsignificant, except for the CD4+/CD8+ T-cells ratio, decreased among PHIV diagnosed with NAFLD (P = 0.04). CONCLUSIONS: The prevalence of NAFLD was high (28.9%) among PHIV, and only partially explained by overweight and metabolic syndrome defining factors. The scores based on clinical and analytical parameters did not accurately identify participants at risk. Therefore, liver ultrasound assessment should be considered for the screening of NAFLD among PHIV in routine clinical practice.

Targeting the Gut Microbiota of Vertically HIV-Infected Children to Decrease Inflammation and Immunoactivation: A Pilot Clinical Trial.

Aims: Children with HIV exhibit chronic inflammation and immune dysfunction despite antiretroviral therapy (ART). Strategies targeting persistent inflammation are needed to improve health in people living with HIV. The gut microbiota likely interacts with the immune system, but the clinical implications of modulating the dysbiosis by nutritional supplementation are unclear. Methods: Pilot, double-blind, randomized placebo-controlled trial in which 24 HIV-infected on ART were randomized to supplementation with a daily mixture of symbiotics, omega-3/6 fatty acids and amino acids, or placebo four weeks, in combination with ART. We analyzed inflammatory markers and T-cell activation changes and their correlations with shifts in fecal microbiota. Results: Twenty-four HIV-infected children were recruited and randomized to receive a symbiotic nutritional supplement or placebo. Mean age was 12 ± 3.9 years, 62.5% were female. All were on ART and had HIV RNA < 50/mL. We did not detect changes in inflammatory (IL-6, IL-7, IP-10), microbial translocation (sCD14), mucosal integrity markers (IFABP, zonulin) or the kynurenine to tryptophan ratio, or changes in markers of the adaptive immune response in relation to the intervention. However, we found correlations between several key bacteria and the assessed inflammatory and immunological parameters, supporting a role of the microbiota in immune modulation in children with HIV. Conclusions: In this exploratory study, a four-week nutritional supplementation had no significant effects in terms of decreasing inflammation, microbial translocation, or T-cell activation in HIV-infected children. However, the correlations found support the interaction between gut microbiota and the immune system.

Effect of a Nutritional Intervention on the Intestinal Microbiota of Vertically HIV-Infected Children: The Pediabiota Study.

AIMS: The gut microbiota exerts a critical influence in the immune system. The gut microbiota of human virus immunodeficiency (HIV)-infected children remains barely explored. We aimed to characterize the fecal microbiota in vertically HIV-infected children and to explore the effects of its modulation with a symbiotic nutritional intervention. METHODS: a pilot, double blind, randomized placebo-controlled study including HIV-infected children who were randomized to receive a nutritional supplementation including prebiotics and probiotics or placebo for four weeks. HIV-uninfected siblings were recruited as controls. The V3-V4 region of the 16S rRNA gene was sequenced in fecal samples. RESULTS: 22 HIV-infected children on antiretroviral therapy (ART) and with viral load (VL) <50/mL completed the follow-up period. Mean age was 11.4 ± 3.4 years, eight (32%) were male. Their microbiota showed reduced alpha diversity compared to controls and distinct beta diversity at the genus level (Adonis p = 0.042). Patients showed decreased abundance of commensals Faecalibacterium and an increase in Prevotella, Akkermansia and Escherichia. The nutritional intervention shaped the microbiota towards the control group, without a clear directionality. CONCLUSIONS: Vertical HIV infection is characterized by changes in gut microbiota structure, distinct at the compositional level from the findings reported in adults. A short nutritional intervention attenuated bacterial dysbiosis, without clear changes at the community level. SUMMARY: In a group of 24 vertically HIV-infected children, in comparison to 11 uninfected controls, intestinal dysbiosis was observed despite effective ART. Although not fully effective to restore the microbiota, a short intervention with pre/probiotics attenuated bacterial dysbiosis.

Perinatal HCV Transmission Rate in HIV/HCV Coinfected women with access to ART in Madrid, Spain.

BACKGROUND: Maternal HIV coinfection is a key factor for mother-to-child transmission (MTCT) of HCV. However, data about HCV MTCT in HIV/HCV-coinfected pregnant women on combined antiretroviral treatment (ART) are scarce. This study assessed the HCV MTCT rate in the Madrid Cohort of HIV-infected women. METHODS: Retrospective study within the Madrid Cohort of HIV-infected pregnant women (2000-2012). Epidemiological, clinical and treatment related variables were analysed for the mother and infant pairs. HCV MTCT rate was determined. RESULTS: Three hundred thirty-nine HIV/HCV-coinfected women and their exposed infants were recorded. A total of 227 (67%) paired mother-children had available data of HCV follow-up and were included for the analysis. Sixteen children (rate 7.0%, 95%CI 3.7-10.4%) were HCV infected by 18 months of age, none of them coinfected with HIV. HIV/HCV-coinfected pregnant women were mostly of Spanish origin with a background of previous injection drug use. HCV-genotype 1 was predominant. The characteristics of mothers that transmitted HCV were similar to those that did not transmit HCV with respect to sociodemographic and clinical features. A high rate (50%) of preterm deliveries was observed. Infants infected with HCV were similar at birth in weight, length and head circumference than those uninfected. CONCLUSION: MTCT rates of HCV among HIV/HCV-coinfected women on ART within the Madrid cohort were lower than previously described. However, rates are still significant and strategies to eliminate any HCV transmission from mother to child are needed.

Prognostic factors of a lower CD4/CD8 ratio in long term viral suppression HIV infected children.

BACKGROUND: Combination antiretroviral therapy (cART) is associated with marked immune reconstitution. Although a long term viral suppression is achievable, not all children however, attain complete immunological recovery due to persistent immune activation. We use CD4/CD8 ratio like a marker of immune reconstitution. METHODS: Perinatal HIV-infected children who underwent a first-line cART, achieved viral suppression in the first year and maintained it for more than 5 years, with no viral rebound were included. Logistic models were applied to estimate the prognostic factors, clinical characteristics at cART start, of a lower CD4/CD8 ratio at the last visit. RESULTS: 146 HIV-infected children were included: 77% Caucasian, 45% male and 28% CDC C. Median age at cART initiation was 2.3 years (IQR: 0.5-6.2). 42 (30%) children received mono-dual therapy previously to cART. Time of undetectable viral load was 9.5 years (IQR: 7.8, 12.5). 33% of the children not achieved CD4/CD8 ratio >1. Univariate analysis showed an association between CD4/CD8 <1 with lower CD4 nadir and baseline CD4; older age at diagnosis and at cART initiation; and a previous exposure to mono-dual therapy. Multivariate analysis also revealed relationship between CD4/CD8 <1 and lower CD4 nadir (OR: 1.002, CI 95% 1.000-1.004) as well as previous exposure to mono-dual therapy (OR: 0.16, CI 95% 0.003-0.720). CONCLUSIONS: CD4/CD8 >1 was not achieved in 33% of the children. Lower CD4 nadir and previous exposure to suboptimal therapy, before initiating cART, are factors showing independently association with a worse immune recovery (CD4/CD8 < 1).

Antimicrobial stewardship in hospitals: Expert recommendation guidance document for activities in specific populations, syndromes and other aspects (PROA-2) from SEIMC, SEFH, SEMPSPGS, SEMICYUC and SEIP / Programas de optimización del uso de antimicrobianos en hospitales: guía de recomendaciones de expertos para actividades en poblaciones específicas, síndromes y otros aspectos (PROA-2) de la SEIMC, SEFH, SEMPSPGS y SEIP

In 2012, The Spanish Societies of Infectious Diseases and Clinical Microbiology (SEIMC), Hospital Pharmacy (SEFH), and Preventive Medicine, Public Health and Healthcare Management (SEMPSGS) lead a consensus document including recommendations for the implementation of antimicrobial stewardship (AMS) programs (AMSP; PROA in Spanish) in acute care hospitals in Spain. While these recommendations were critical for the development of these programs in many centres, there is a need for guidance in the development of AMS activities for specific patient populations, syndromes or other specific aspects which were not included in the previous document or have developed significantly since then. The objective of this expert recommendation guidance document is to review the available information about these activities in these patient populations or circumstances, and to provide guidance recommendations about them. With this objective the SEIMC, SEFH, SEMPSPGS, the Spanish Society of Intensive Care Medicine (SEMICYUC) and the Spanish Pediatric Infectious Disease Society (SEIP) selected a panel of experts who chose the different aspects to include in the document. Because of the lack of high-level evidence in the implementation of the activities, the panel opted to perform a narrative review of the literature for the different topics for which recommendations were agreed by consensus. The document was open to public consultation for the members of these societies for their comments and suggestions, which were reviewed and considered by the panel.(AU)

En 2012, las Sociedades Españolas de Enfermedades Infecciosas y Microbiología Clínica (SEIMC), Farmacia Hospitalaria (SEFH) y Medicina Preventiva, Salud Pública y Gestión Sanitaria (SEMPSPGS) lideraron un documento de consenso que incluía recomendaciones para la implementación de Programas de optimización del uso de antimicrobianos (PROA) en hospitales de agudos en España. Si bien estas recomendaciones fueron críticas para el desarrollo de estos programas en muchos centros, actualmente es necesario establecer unas guías para la implementación de las actividades de los PROA en determinadas poblaciones de pacientes, síndromes clínicos y otros aspectos específicos que no se incluyeron en el documento previo o que desde entonces se han desarrollado significativamente. El objetivo de esta guía de recomendaciones de expertos es revisar la información disponible acerca de esas actividades en estas poblaciones o circunstancias de pacientes y proporcionar unas recomendaciones que sirvan de guía sobre ellas. Con este objetivo, la SEIMC, la SEFH y la SEMPSPGS, así como la Sociedad Española de Medicina Intensiva, Crítica y Unidades Coronarias (SEMICYUC) y la Sociedad Española de Infectología Pediátrica (SEIP), seleccionaron un panel de expertos que eligieron los diferentes aspectos a incluir en el documento. Debido a la ausencia de evidencia de alto nivel en la implementación de las diferentes actividades, el panel optó por realizar una revisión narrativa de la literatura de los diferentes aspectos, en los que las recomendaciones se acordaron por consenso. El documento se abrió para consulta pública a los miembros de estas sociedades para sus comentarios y sugerencias, que fueron revisadas y consideradas por el panel.(AU)

Oseltamivir treatment for influenza in hospitalized children without underlying diseases.

AIM: To determine whether the treatment with oseltamivir improves the outcome of children with confirmed influenza infection and no other underlying disease. METHODS: Multicentric, retrospective study performed in 10 hospitals of Madrid between September 2010 and June 2012. All children admitted to the hospitals with confirmed influenza infections were eligible. Children with risk factors for serious disease and nosocomial influenza infections were excluded. Asthma was not considered an exclusion factor. The study compared patients treated and untreated with oseltamivir. Fever duration, oxygen support, antibiotics administration, length of hospital stay, intensive care admission and bacterial complications were analyzed. To compare variables, χ(2) test, Fisher exact test, ANOVA or Mann-Whitney U test were used. RESULTS: Two hundred eighty-seven children were included and 93 of them were treated with oseltamivir (32%). There were no significant differences between treated and untreated patients in days of fever after admission (1.7 ± 2; 2.1 ± 2.9, P > 0.05), length of stay (5.2 ± 3.6; 5.5 ± 3.4, P > 0.05), days of hypoxia (1.6 ± 2.3; 2.1 ± 2.9, P > 0.05), diagnosis of bacterial pneumonia (10%; 17%, P > 0.05), intensive care admission (6.5%; 1.5%,P > 0.05) or antibiotic prescription (44%; 51%, P > 0.05). There were no differences when the population was stratified by age (below or over 1 year) or by the presence or absence of asthma. CONCLUSIONS: There were no proven benefits of treatment with oseltamivir in hospitalized pediatric patients without the underlying diseases or risk factors for developing a serious illness, including those with asthma.

Síndrome sepsis-like y meningoencefalitis aguda por parechovirus tipo 3 / Sepsis-like syndrome and acute meningoencephalitis due to parechovirus type 3

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