The CARBA-MAP study: national mapping of carbapenemases in Spain (2014-2018).

Introduction: Infections caused by carbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant Pseudomonas aeruginosa, including isolates producing acquired carbapenemases, constitute a prevalent health problem worldwide. The primary objective of this study was to determine the distribution of the different carbapenemases among carbapenemase-producing Enterobacterales (CPE, specifically Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae complex, and Klebsiella aerogenes) and carbapenemase-producing P. aeruginosa (CPPA) in Spain from January 2014 to December 2018. Methods: A national, retrospective, cross-sectional multicenter study was performed. The study included the first isolate per patient and year obtained from clinical samples and obtained for diagnosis of infection in hospitalized patients. A structured questionnaire was completed by the participating centers using the REDCap platform, and results were analyzed using IBM SPSS Statistics 29.0.0. Results: A total of 2,704 carbapenemase-producing microorganisms were included, for which the type of carbapenemase was determined in 2692 cases: 2280 CPE (84.7%) and 412 CPPA (15.3%), most often using molecular methods and immunochromatographic assays. Globally, the most frequent types of carbapenemase in Enterobacterales and P. aeruginosa were OXA-48-like, alone or in combination with other enzymes (1,523 cases, 66.8%) and VIM (365 cases, 88.6%), respectively. Among Enterobacterales, carbapenemase-producing K. pneumoniae was reported in 1821 cases (79.9%), followed by E. cloacae complex in 334 cases (14.6%). In Enterobacterales, KPC is mainly present in the South and South-East regions of Spain and OXA-48-like in the rest of the country. Regarding P. aeruginosa, VIM is widely distributed all over the country. Globally, an increasing percentage of OXA-48-like enzymes was observed from 2014 to 2017. KPC enzymes were more frequent in 2017-2018 compared to 2014-2016. Discussion: Data from this study help to understand the situation and evolution of the main species of CPE and CPPA in Spain, with practical implications for control and optimal treatment of infections caused by these multi-drug resistant organisms.

Infant gut microbiota colonization: influence of prenatal and postnatal factors, focusing on diet.

Maternal microbiota forms the first infant gut microbial inoculum, and perinatal factors (diet and use of antibiotics during pregnancy) and/or neonatal factors, like intra partum antibiotics, gestational age and mode of delivery, may influence microbial colonization. After birth, when the principal colonization occurs, the microbial diversity increases and converges toward a stable adult-like microbiota by the end of the first 3-5 years of life. However, during the early life, gut microbiota can be disrupted by other postnatal factors like mode of infant feeding, antibiotic usage, and various environmental factors generating a state of dysbiosis. Gut dysbiosis have been reported to increase the risk of necrotizing enterocolitis and some chronic diseases later in life, such as obesity, diabetes, cancer, allergies, and asthma. Therefore, understanding the impact of a correct maternal-to-infant microbial transfer and a good infant early colonization and maturation throughout life would reduce the risk of disease in early and late life. This paper reviews the published evidence on early-life gut microbiota development, as well as the different factors influencing its evolution before, at, and after birth, focusing on diet and nutrition during pregnancy and in the first months of life.

Effectiveness of Fosfomycin for the Treatment of Multidrug-Resistant Escherichia coli Bacteremic Urinary Tract Infections: A Randomized Clinical Trial.

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 parenteral 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 ∞ 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, -∞ 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. Trial Registration: ClinicalTrials.gov Identifier: NCT02142751.

The Nutrition in Early Life and Asthma (NELA) birth cohort study: Rationale, design, and methods.

BACKGROUND: Primary prevention strategies for asthma are lacking. Its inception probably starts in utero and/or during the early postnatal period as the developmental origins of health and disease (DOHaD) paradigm suggests. OBJECTIVES: The main objective of Nutrition in Early Life and Asthma (NELA) cohort study is to unravel whether the following factors contribute causally to the developmental origins of asthma: (1) maternal obesity/adiposity and foetal growth; (2) maternal and child nutrition; (3) outdoor air pollution; (4) endocrine disruptors; and (5) maternal psychological stress. Maternal and offspring biological samples are used to assess changes in offspring microbiome, immune system, epigenome and volatilome as potential mechanisms influencing disease susceptibility. POPULATION: Randomly selected pregnant women from three health areas of Murcia, a south-eastern Mediterranean region of Spain, who fulfilled the inclusion criteria were invited to participate at the time of the follow-up visit for routine foetal anatomy scan at 19-22 weeks of gestation, at the Maternal-Fetal Medicine Unit of the "Virgen de la Arrixaca" University Clinical Hospital over a 36-month period, from March 2015 to April 2018. DESIGN: Prospective, population-based, maternal-child, birth cohort study. METHODS: Questionnaires on exposures and outcome variables were administered to mothers at 20-24 gestation week; 32-36 gestation week; and delivery. Children were surveyed at birth, 3 and 18 months of age and currently at 5 years. Furthermore, physical examinations were performed; and different measurements and biological samples were obtained at these time points. PRELIMINARY RESULTS: Among the 1350 women invited to participate, 738 (54%) were finally enrolled in the study and 720 of their children were eligible at birth. The adherence was high with 612 children (83%) attending the 3 months' visit and 532 children (72%) attending the 18 months' visit. CONCLUSION: The NELA cohort will add original and unique knowledge to the developmental origins of asthma.

Adherence to the Mediterranean Diet and Determinants Among Pregnant Women: The NELA Cohort.

The Mediterranean diet represents one of the most studied dietary patterns; however, there is no single tool for measuring the grade of adherence and no single set of criteria for adapting these indices to pregnant women. We characterized the adherence to the Mediterranean diet (MDA) of pregnant women participating in the NELA (Nutrition in Early Life and Asthma) cohort and identified the sociodemographic determinants and lifestyle habits associated with a higher risk of a low MDA. Maternal diet during gestation was assessed by a validated Food Frequency Questionnaire (FFQ) (n = 665). We estimated the Relative Mediterranean Diet score (rMED), Alternative Mediterranean Diet score (aMED), and the Alternate Healthy Eating Index-2010 (AHEI-2010). Multivariate regression models were performed to identify the sociodemographic and lifestyle factors associated with each index. Mothers with a lower age and more previous deliveries had a greater probability of low MDA (p < 0.05). For the aMED index only, mothers with university education and/or who practiced sport activities for two or more hours per week had a lower probability of a low MDA (p < 0.01). The three indices classified the NELA cohort as having a medium level of adherence. These results may be improved by designing intervention strategies and dietary recommendations for both maternal and offspring health.

Impact of Pneumococcal Vaccination in the Nasopharyngeal Carriage of Streptococcus pneumoniae in Healthy Children of the Murcia Region in Spain.

BACKGROUND: An epidemiological study of Streptococcus pneumoniae nasopharyngeal carriage in healthy children was carried out five years after the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13). OBJECTIVES: Study the impact of pediatric vaccination with PCV13, and other associated epidemiological factors on the status of nasopharyngeal carriage, the circulating pneumococcal serotypes, and the antibiotic susceptibility to more frequently used antibiotics. METHODS: A multi-center study was carried out in Primary Health Care, which included 1821 healthy children aged 1 to 4 years old. All isolates were sent to the Spanish Pneumococcal Reference Laboratory for serotyping and antimicrobial susceptibility testing. RESULTS: At least one dose of PCV13 had been received by 71.9% of children and carriage pneumococcal prevalence was 19.7%. The proportion of PCV13 serotypes was low (14.4%), with an observed predominance of non-vaccine serotypes, 23B, 11A, 10A, 35B/F, and 23A were the five most frequent. A high rate of resistance to penicillin, erythromycin, and trimethoprim sulfamethoxazole was found. CONCLUSIONS: A low proportion of PCV13 serotypes were detected, confirming the impact of pediatric vaccination for reducing the serotypes vaccine carriage. High resistance rates to clinically important antibiotics were observed.

Sondas de gastrostomía: indicaciones y complicaciones infecciosas en un hospital terciario / Gastrostomy tubes: indications and infectious complications in a tertiary hospital

Introducción. La sonda de gastrostomía es la modalidad de elección para nutrición enteral de larga duración. Entre sus limitaciones, las infecciones representan la complicación menor de mayor prevalencia. Nuestro objetivo se centra en conocer el número y tipo de sondas de gastrostomía (SG), así como, las características de los pacientes y la prevalencia y tipo de complicaciones infecciosas en nuestro hospital. Métodos. Estudio retrospectivo observacional desde enero de 2010 a julio de 2015 mediante revisión de la historia clínica electrónica y el software de gestión del laboratorio de microbiología de nuestro hospital. Se ha analizado la identificación y la sensibilidad antibiótica de todos los aislados microbianos de pacientes con SG durante el periodo de estudio. Resultados. Se realizó gastrostomía endoscópica percutánea en 203 pacientes (70,5%) y gastrostomía quirúrgica en 85 (29,5%). La principal razón identificada para iniciar nutrición enteral a través de SG fue la neoplasia maligna (33,3%), destacando el cáncer de labio, cavidad oral y faringe (11,8%) y el de los diferentes órganos digestivos (8,7%). La prevalencia global de infección del orificio de gastrostomía fue del 16,6%. Los aislados bacterianos más frecuentes fueron: Staphylococcus aureus (21,3%), Pseudomonas aeruginosa (13,1%) y Escherichia coli (9,8). La tasa de aislados multirresistentes fue del 3,1%. Conclusión. Las indicaciones y el tipo de SG, así como, la prevalencia y microorganismos responsables de complicaciones infecciosas son similares a las publicadas en la literatura. Este estudio permite la adaptación de los protocolos de profilaxis, así como de tratamiento antibiótico empírico al conocer la etiología y la sensibilidad antibiótica de los microorganismos responsables de infección (AU)

Introduction. Gastrostomy tube is the best option for long-term enteral nutrition. Among its limitations, infections represent the most frequent minor complication. Our aim is the knowledge of the number and type of gastrostomy tubes and its main indication in our hospital. In addition, prevalence of infectious complications was studied paying attention to the main etiologic agents and their antibiotic susceptibility. Methods. Observational retrospective study from January 2010 to July 2015 through the electronic clinical history and the clinical microbiology laboratory software. Identification and antibiotic susceptibility of clinically significant isolates from patients with suspicion of gastrostomy tube infection have been analysed. Results. Percutaneous endoscopic gastrostomy was performed in 203 patients (70.5%) and surgical gastrostomy in 85 (29.5%). The main reason identified for starting enteral nutrition through gastrostomy tube was malignant neoplasy, above all, lip, oral cavity and pharynx cancer (11.8%) and that from digestive organs (8.7%). Global prevalence of gastrostomy tube infection was 16.6%. The most common bacterial pathogens isolated were Staphylococcus aureus (21.3%), Pseudomonas aeruginosa (13.1%), and Escherichia coli (9.8%). The percentage of multi resistant isolates was 3.1%. Conclusions. Gastrostomy tube indications and type, and also, prevalence and microorganisms isolated from culture in infectious complications are similar to those described previously in the literature. The study allows the adaptation of the antibiotic prophylaxis and empirical antibiotic treatment thanks to the knowledge of the etiologic agents and their antibiotic susceptibility (AU)

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