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In chronic kidney disease, systemic inflammation and high serum phosphate (P) promote the de-differentiation of vascular smooth muscle cells (VSMC) to osteoblast-like cells, increasing the propensity for medial calcification and cardiovascular mortality. Vascular microRNA-145 (miR-145) content is essential to maintain VSMC contractile phenotype. Because vitamin D induces aortic miR-145, uremia and high serum P reduce it and miR-145 directly targets osteogenic osterix in osteoblasts, this study evaluated a potential causal link between vascular miR-145 reductions and osterix-driven osteogenic differentiation and its counter-regulation by vitamin D. Studies in aortic rings from normal rats and in the rat aortic VSMC line A7r5 exposed to calcifying conditions corroborated that miR-145 reductions were associated with decreases in contractile markers and increases in osteogenic differentiation and calcium (Ca) deposition. Furthermore, miR-145 silencing enhanced Ca deposition in A7r5 cells exposed to calcifying conditions, while miR-145 overexpression attenuated it, partly through increasing α-actin levels and reducing osterix-driven osteogenic differentiation. In mice, 14 weeks after the induction of renal mass reduction, both aortic miR-145 and α-actin mRNA decreased by 80% without significant elevations in osterix or Ca deposition. Vitamin D treatment from week 8 to 14 fully prevented the reductions in aortic miR-145 and attenuated by 50% the decreases in α-actin, despite uremia-induced hyperphosphatemia. In conclusion, vitamin D was able to prevent the reductions in aortic miR-145 and α-actin content induced by uremia, reducing the alterations in vascular contractility and osteogenic differentiation despite hyperphosphatemia.

BACKGROUND AND AIMS The prevalence of chronic kidney disease–associated pruritus (CKD-aP) found in different studies ranges from 40% to 90% in patients undergoing haemodialysis, and from 19% to 29% in non-dialysed patients. However, despite pruritus negatively affect the quality of life (QoL) and clinical outcomes as well as increase the risk of mortality, clinicians still tend to underestimate the number of patients with CKD-aP. This study was conducted to estimate the prevalence of pruritus and its impact in different dimensions of QoL in the Spanish population with CKD. METHOD A short survey was designed using seven questions included in several validated tools for pruritus assessment. The questionnaire was distributed by the Spanish Society of Nephrology to all their members in the framework of the Pruritus Week. Nephrologists visiting advanced CKD patients asked them to answer the questionnaires voluntarily. RESULTS A total of 1605 patients (haemodialysis 92%, peritoneal dialysis 5% and non-dialysis 3%) answered the questionnaire. A prevalence of CKD-aP of 50.5% was reported, 26.7% being moderate-to-severe. As shown in figure 1, the prevalence was higher in non-dialysis advanced CDK patients suggesting a benefit of dialysis in reducing itch. CKD-aP patients reported itching throughout their body and at any part of the day, but more at night. The percentage of patients with mood changes increased as the severity of itch increased, being anguish and lack of rest the parameters that were more highly affected. An increase in depression was also observed. Sexual function and desire impairment increased as severity of CKD-aP increased. Finally, CKD-aP patients reported higher sleeping disturbances than patients with no pruritus (difficulty to sleep, restless sleep and intake of sleep medication), which enhanced with the increase of pruritus severity. CONCLUSION CKD-aP is highly prevalent in patients with advanced CKD (non-dialysis and dialysis), which affects patients’ quality of life by inducing mood changes, including depression, impairing sexuality and affecting sleep.

Resumen: Introducción: Las alteraciones del metabolismo óseo y mineral son muy frecuentes en la enfermedad renal crónica (ERC). El aumento en los niveles de fósforo condiciona enfermedad ósea, riego de calcificación y mayor mortalidad, por lo que cualquier estrategia encaminada a su reducción debe ser bienvenida. El último fármaco incorporado al arsenal terapéutico para tratar la hiperfosforemia en la ERC es el oxihidróxido sucroférrico (OSF). Objetivo: Analizar la eficacia y seguridad de OSF en 3 cohortes de pacientes, una con ERC avanzada no en diálisis, otra en diálisis peritoneal y finalmente otra en hemodiálisis, seguidas durante 6 meses. Métodos: Estudio observacional multicéntrico, prospectivo, de práctica clínica. Se analizaron variables clínicas y epidemiológicas. Se valoró la evolución de parámetros relacionados con las alteraciones del metabolismo óseo y mineral y la anemia. Resultados: Se incluyeron en el estudio 85 pacientes (62 ± 12 años, 64% varones, 34% diabéticos), 25 con ERC avanzada no en diálisis, 25 en diálisis peritoneal y finalmente 35 en hemodiálisis. En 66 pacientes (78%) OSF fue el primer captor del fósforo; en los otros 19 se sustituyó un captor previo por OSF, por falta de tolerancia o eficacia. La dosis inicial de OSF fue 964 ± 323 mg/día. Globalmente los niveles séricos de fósforo experimentaron un descenso significativo a los 3 meses de tratamiento (19,6%; p

Island species are particularly vulnerable to environmental disturbances and introduced pathogens. Conducting health assessments of wild populations in the Galapagos improves the ability of wildlife managers and veterinarians to detect deteriorations in health status. Seabirds in particular are useful species to monitor due to their colonial breeding and wide migration range. Nazca boobies (Sula granti) in a breeding colony at Daphne Major (n = 30) were given physical examinations, and blood samples were collected for hematology and biochemistry using an iSTAT Portable Clinical Analyzer. Female boobies had longer wing length than males, as well as lower blood urea nitrogen, creatinine, and white blood cell counts. This could be attributed to sexual dimorphism or differences in foraging and mating strategies between the sexes. The time between capture and blood collection had a significant inverse relationship on plasma sodium, potassium, hemoglobin, anion gaps, and lymphocyte counts, suggesting that blood sampling in Nazca boobies should be done in less than 5 m to avoid the impacts of stress on hematological parameters. This is the first health assessment on the breeding colony of Nazca boobies at Daphne Major, and the results can inform future monitoring in this species as well as other sulids.

Island species are particularly vulnerable to environmental disturbances and introduced pathogens. Conducting health assessments of wild populations in the Galápagos improves the ability of wildlife managers and veterinarians to detect deteriorations in health status. Seabirds in particular are useful species to monitor due to their colonial breeding and wide migration range. Nazca boobies (

This study aimed at evaluating the clinical relevance of glycoprotein profiles during the earliest phases of rheumatoid arthritis (RA) as biomarkers of cardiovascular (CV) risk and treatment response. Then, GlycA and GlycB serum levels were measured using 1H-nuclear magnetic resonance in 82 early RA patients, 14 clinically-suspect arthralgia (CSA), and 28 controls. Serum glycosyltransferase activity was assessed by a colorimetric assay. Subclinical CV disease was assessed by Doppler-ultrasound. We found that GlycA and GlycB serum levels were increased in RA (both p &lt, 0.001), but not in CSA, independently of cardiometabolic risk factors. Increased serum glycosyltransferase activity paralleled GlycA (r = 0.405, p &lt, 0.001) and GlycB levels (r = 0.327, p = 0.005) in RA. GlycA, but not GlycB, was associated with atherosclerosis occurrence (p = 0.012) and severity (p = 0.001). Adding GlycA to the mSCORE improved the identification of patients with atherosclerosis over mSCORE alone, increasing sensitivity (29.7 vs. 68.0%) and accuracy (55.8 vs. 76.6%) and allowing reclassification into more appropriate risk categories. GlycA-reclassification identified patients with impaired lipoprotein metabolism. Finally, baseline GlycA levels predicted poor clinical response upon anti-rheumatic treatment at 6 and 12 months in univariate and multivariate analysis. In sum, increased GlycA levels during the earliest stage of RA can be considered a powerful biomarker for CV risk stratification and treatment response.

The swallow-tailed gull, Creagrus furcatus, is a seabird endemic to the Galápagos archipelago. In general health, blood chemistry and haematology, parameters have not been published for this species. Blood analyses were run on samples drawn from 58 clinically healthy swallow-tailed gulls captured at Islote Pitt on San Cristóbal Island in July 2016 (28) and South Plaza Island in June 2017 (30). A point of care blood analyzer (iSTAT) was used in the field to obtain results for HCO3−, pH, pCO2, pO2, TCO2, anion gap, chloride, creatinine, glucose, haematocrit, haemoglobin, ionized calcium, potassium, sodium and urea nitrogen. A portable Lactate Plus™ analyzer was used to measure lactate. The baseline data reported is valuable for comparisons amongst different populations in the archipelago and to detect changes in health status of Galápagos swallow-tailed gulls.

Background and Aims The stratification of early cardiovascular (CV) risk is a major unmet need in chronic kidney disease (CKD). Since angiogenic T-cells are emerging mediators of vascular homeostasis and have been linked to CV disease (CVD), this study evaluated the frequency of circulating angiogenic T-cells in CKD patients undergoing peritoneal dialysis (CKD-5D) and their potential as predictive biomarkers of CVD. Method In 30 peritoneal dialysis patients and 16 matched healthy controls (HC), we quantified: Vascular calcification (by Kauppila Index); left carotid intima media thickness (lc-IMT by ultrasound), carotid adventitial vasa vasorum density (an early marker of atherosclerosis stage, by Superb Microvascular Ultrasound Image), pulse wave velocity (a marker of vascular stiffness and dysfunction, using the Complior Analyzer), angiogenic T cell frequency in blood (by Flow cytometry) and the traditional 10-year CVD risk (using the SCORE chart). Results As expected, CKD-5D patients exhibited higher Kauppila index (p0.05) and did not correlate with Kauppila (r=-0.350, p=0.080) or lcIMT (r=-0.154, p=0.600), but strongly associated negatively with both pulse wave velocity (r=-0.734, p Conclusion Angiogenic-T cell frequency was decreased in CKD-5D patients and could be considered as biomarkers of vascular dysfunction and early atherosclerosis stage.

OBJECTIVE. Eicosanoids modulate inflammation via complex networks involving different pathways and downstream mediators, including oxylipins. Although altered eicosanoids are linked to rheumatoid arthritis (RA), suggesting that metabolization is enhanced, the role of oxylipins in disease stratification remains unexplored. This study was undertaken to characterize oxylipin networks during the earliest stages of RA and evaluate their associations with clinical features and treatment outcomes. METHODS. In total, 60 patients with early RA (according to the American College of Rheumatology/European League Against Rheumatism 2010 criteria), 11 individuals with clinically suspect arthralgia (CSA), and 28 healthy control subjects were recruited. Serum samples were collected at the time of onset. In the early RA group, 50 patients who had not been exposed to disease-modifying antirheumatic drug (DMARD) or glucocorticoid treatment at the time of recruitment were prospectively followed up at 6 and 12 months after having received conventional synthetic DMARDs. A total of 75 oxylipins, mostly derived from arachidonic, eicosapentanoic, and linoleic acids, were identified in the serum by liquid chromatography tandem mass spectrometry. RESULTS. Univariate analyses demonstrated differences in expression patterns of 14 oxylipins across the RA, CSA, and healthy control groups, with each exhibiting a different trajectory. Network analyses revealed a strong grouping pattern of oxylipins in RA patients, whereas in individuals with CSA, a fuzzy network of oxylipins with higher degree and closeness was found. Partial least-squares discriminant analyses yielded variable important projection scores of >1 for 22 oxylipins, which allowed the identification of 2 clusters. Cluster usage differed among the groups (P = 0.003), and showed associations with disease severity and low rates of remission at 6 and 12 months in RA patients who were initially treatment-naive. Pathway enrichment analyses revealed different precursors and pathways between the groups, highlighting the relevance of the arachidonic acid pathway in individuals with CSA and the lipooxygenase pathway in patients with early RA. In applying distinct oxylipin signatures, subsets of seropositive and seronegative RA could be identified. CONCLUSION. Oxylipin networks differ across stages during the earliest phases of RA. These distinct oxylipin networks could potentially elucidate pathways with clinical relevance for disease progression, clinical heterogeneity, and treatment response.

The red-footed booby ( Sula sula) is a widely distributed sulid native to the Galápagos archipelago. Hematology and blood chemistry parameters have been published for this species, but not from the San Cristóbal rookery. Analyses were run on blood samples drawn from 31 manually restrained red-footed boobies that were captured by hand from their nests at Punta Pitt on San Cristóbal Island. A portable blood analyzer (iSTAT) was used to obtain near immediate field results for pH, partial pressure of oxygen, partial pressure of carbon dioxide, bicarbonate, hematocrit, hemoglobin, sodium, potassium, ionized calcium, and glucose. Blood lactate was measured using a portable Lactate Plus™ analyzer. Average heart rate, respiratory rate, body weight, body temperature, and biochemistry and hematology parameters were comparable to those of healthy individuals of other sulids. The reported results provide baseline data that can be used for comparisons among populations and in detecting changes in health status among Galápagos red-footed boobies.

Alterations in bone and mineral metabolism are very common in chronic kidney disease (CKD). The increase in phosphate levels leads to bone disease, risk of calcification and greater mortality, so any strategy aimed at reducing them should be welcomed. The latest drug incorporated into the therapeutic arsenal to treat hyperphosphataemia in CKD is sucroferric oxyhydroxide (SFO).To analyse the efficacy and safety of SFO in 3 cohorts of patients, one with advanced CKD not on dialysis, another on peritoneal dialysis and the last on haemodialysis, followed for 6 months.A prospective, observational, multicentre study in clinical practice. Clinical and epidemiological variables were analysed. The evolution of parameters relating to alterations in bone and mineral metabolism and anaemia was analysed.Eighty-five patients were included in the study (62±12 years, 64% male, 34% diabetic), 25 with advanced CKD not on dialysis, 25 on peritoneal dialysis and lastly, 35 on haemodialysis. In 66 patients (78%), SFO was the first phosphate binder; in the other 19, SFO replaced a previous phosphate binder due to poor tolerance or efficacy. The initial dose of SFO was 964±323mg/day. Overall, serum phosphate levels saw a significant reduction at 3 months of treatment (19.6%; P.001). There were no differences in the efficacy of the drug when the different populations analysed were compared. Over the course of the study, there were no changes to levels of calcium, PTHi, ferritin, transferrin saturation index or haemoglobin, although there was a tendency for the last 2 to increase. Twelve patients (14%) withdrew from follow-up, 10 due to gastrointestinal adverse effects (primarily diarrhoea) and 2 were lost to follow-up (kidney transplant). The mean dose of the drug that the patients received increased over time, up to 1,147±371mg/day.SFO is an effective option for the treatment of hyperphosphataemia in patients with CKD both in the advanced phases of the disease and on dialysis. We found similar efficacy across the 3 groups analysed. The higher their baseline phosphate level, the greater the reduction in the serum levels. A notable reduction in phosphate levels can be achieved with doses of around 1,000mg/day. Diarrhoea was the most common side effect, although it generally was not significant.

The Galápagos shearwater

Inflammation is central to chronic kidney disease (CKD) pathogenesis and vascular outcomes, but the exact players remain unidentified. Since low density granulocytes (LDGs) are emerging mediators in inflammatory conditions, we aimed to evaluate whether LDGs may be altered in CKD and related to clinical outcomes as biomarkers. To his end, LDGs subsets were measured in peripheral blood by flow cytometry and confocal microscopy in 33 CKD patients undergoing peritoneal dialysis and 15 healthy controls (HC). Analyses were replicated in an additional cohort. DEF3 (marker of early granulopoiesis) gene expression on PBMCs was quantified by qPCR. Total CD15+ LDGs and both CD14lowCD16+ and CD14−CD16− subsets were expanded in CKD. The relative frequency of the CD14−CD16− subpopulation was higher among the CD15+ pool in CKD. This alteration was stable over-time. The increased CD14−CD16−CD15+ paralleled Kauppila scores and DEF3 expression, whereas no association was found with CD14lowCD16+ CD15+. Both subsets differed in their CD11b, CD10, CD35, CD31, CD62L, IFNAR1 and CD68 expression, FSC/SSC features and nuclear morphology, pointing to different origins and maturation status. In conclusion, LDGs were expanded in CKD showing a skewed distribution towards a CD14−CD16−CD15+ enrichment, in association with vascular calcification. DEF3 expression in PBMC can be a marker of LDG expansion. Fil: Rodríguez Carrio, Javier. Hospital Universitario Central de Asturias. Instituto de Investigación Sanitaria del Principado de Asturias (ISPA). Bone and Mineral Research Unit; España. Universidad de Oviedo; España Fil: Carrillo López, Natalia. Hospital Universitario Central de Asturias; España Fil: Ulloa, Catalina. Hospital Universitario Central de Asturias; España Fil: Seijo, Mariana. Hospital Universitario Central de Asturias; España. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Inmunología, Genética y Metabolismo. Universidad de Buenos Aires. Facultad de Medicina. Instituto de Inmunología, Genética y Metabolismo; Argentina Fil: Rodríguez García, Minerva. Hospital Universitario Central de Asturias; España Fil: Rodríguez Suárez, Carmen. Hospital Universitario Central de Asturias; España Fil: Díaz-Corte, Carmen. Hospital Universitario Central de Asturias; España Fil: Cannata Andía, Jorge B.. Universidad de Oviedo; España. Hospital Universitario Central de Asturias; España Fil: Suárez, Ana. Universidad de Oviedo; España Fil: Dusso, Adriana. Hospital Universitario Central de Asturias; España

In chronic kidney disease (CKD), hyperphosphatemia-induced inflammation aggravates vascular calcification (VC) by increasing vascular smooth muscle cell (VSMC) osteogenic differentiation, ADAM17-induced renal and vascular injury, and TNFα-induction of neutral-sphingomyelinase2 (nSMase2) to release pro-calcifying exosomes. This study examined anti-inflammatory β-glucans efficacy at attenuating systemic inflammation in health, and renal and vascular injury favoring VC in hyperphosphatemic CKD. In healthy adults, dietary barley β-glucans (Bβglucans) reduced leukocyte superoxide production, inflammatory ADAM17, TNFα, nSMase2, and pro-aging/pro-inflammatory STING (Stimulator of interferon genes) gene expression without decreasing circulating inflammatory cytokines, except for γ-interferon. In hyperphosphatemic rat CKD, dietary Bβglucans reduced renal and aortic ADAM17-driven inflammation attenuating CKD-progression (higher GFR and lower serum creatinine, proteinuria, kidney inflammatory infiltration and nSMase2), and TNFα-driven increases in aortic nSMase2 and calcium deposition without improving mineral homeostasis. In VSMC, Bβglucans prevented LPS- or uremic serum-induced rapid increases in ADAM17, TNFα and nSMase2, and reduced the 13-fold higher calcium deposition induced by prolonged calcifying conditions by inhibiting osteogenic differentiation and increases in nSMase2 through Dectin1-independent actions involving Bβglucans internalization. Thus, dietary Bβglucans inhibit leukocyte superoxide production and leukocyte, renal and aortic ADAM17- and nSMase2 gene expression attenuating systemic inflammation in health, and renal injury and aortic calcification despite hyperphosphatemia in CKD. A grant to A.S.D. and M.J.M. from IRBLleida and Agrotecnio Research collaborative projects from the Consell Social at Lleida University supported initial work, Instituto de Salud Carlos III and co-funded by European Union (ERDF/FEDER) (FIS PI11/00259, PI14/01452, PI17/02181), Plan de Ciencia, Tecnología e Innovación 2013–2017 y 2018–2022 del Principado de Asturias (GRUPIN14-028, IDI-2018-000152), RedInRen from ISCIII (ISCIII-RETIC REDINREN RD16/0009). Investigator support included: NC-L by GRUPIN14-028 and IDI-2018-000152, LM-A by GRUPIN14-028, SP by FICYT; MVA and PV by Educational Grant 2 A/2015 from ERA-EDTA CKD-MBD Working Group; PV and AC by ERA-EDTA fellowships 2011 and 2012; JR-C by MINECO (“Juan de la Cierva” program, FJCI-2015-23849); A.S.D. by Asociación Investigación de Fisiología Aplicada. A.S.D. and M.J.M. are members of the Campus Iberus (Ebro Valley Campus of International Excellence).

This study presents important morphometric and health parameters of 55 great frigatebirds from two locations on the Galápagos archipelago. All of the animals were robust, clinically healthy and behaving normally. This data adds to baseline health assessment values and provides reference blood parameter intervals., The great frigatebird, Fregata minor, is a widely distributed seabird native to the Galápagos archipelago. Haematology and blood chemistry parameters have been published for this species but not from the San Cristóbal and North Seymour great frigatebird breeding colonies. Analyses were run on blood samples drawn from 25 great frigatebirds captured by hand at their nests at Punta Pitt on San Cristóbal Island and 30 birds on North Seymour Island, Galápagos Islands. A portable blood analyser (iSTAT) was used to obtain near immediate field results for pH, pO2, pCO2, TCO2, HCO3−, haematocrit (Hct), haemoglobin (Hb), sodium (Na), potassium (K), chloride (Cl), ionized calcium (iCa), creatinine, urea nitrogen, anion gap and glucose. Blood lactate was measured using a portable Lactate Plus™ analyser. Average heart rate, respiratory rate, body weight, body temperature, biochemistry and haematology parameters were comparable to healthy individuals of other Fregatidae. The reported results provide baseline data that can be used for comparisons among populations and in detecting changes in health status among Galápagos great frigatebirds.

The Galapagos shearwater, Puffinus subalaris, is a seabird endemic to the Galapagos archipelago. Hematology, blood chemistry, and general health parameters have not been published for this species. Analyses were run on blood samples drawn from 20 clinically healthy Galapagos shearwaters captured by hand at their nests at Islote Pitt on San Cristobal Island in July 2016. A portable blood analyzer (iSTAT) was used to obtain near immediate field results for pH, pO2, pCO2, TCO2, HCO3–, hematocrit, hemoglobin, sodium, potassium, chloride, ionized calcium, creatinine, urea nitrogen, anion gap, and glucose. Blood lactate was measured using a portable Lactate Plus analyzer. The reported results provide baseline data that can be used for comparisons among populations and in detecting changes in health status among Galapagos shearwaters.

Objective: The aim of this study was to analyze the NP/OP S. pneumoniae serotype distribution and potential vaccine coverage in Costa Rican children with Otitis Media (OM) before the introduction of PCV-7 in the National Immunization Program (NIP). Methods: Between 2002 and 2006, NP and OP samples were obtained from 641 children from 6 to 79 months of age, at the time of OM diagnosis. S. pneumoniae serotyping and antimicrobial susceptibility were performed. Results: 386 S. pneumoniae isolates were recovered. The most common S. pneumoniae serotypes (ST) were: ST 6B, ST 14, ST 19F. Penicillin non-susceptibility was observed among 57% of the isolates obtained from children < 24 months of age. 15% strains were multidrug resistant. Potential vaccine coverage was: PCV-7: 60%; PCV-10: 62%; and PCV-13: 76% and against penicillin non-susceptible and multidrug resistant isolates was: PCV-7; 59% and 83%, respectively; PCV-10: 60% and 85%, respectively and PCV-13: 74% and 96%, respectively. Conclusions: S. pneumoniae was isolated from the NP and/or OP in the majority (59%) of studied children with OM. At a statistical significant level, only serotype 3 was more frequently isolated among children >24 months of age. Antibiotic non-susceptibility and MDR were significantly higher in children

et al., Malignant progression in cancer requires populations of tumor-initiating cells (TICs) endowed with unlimited self renewal, survival under stress, and establishment of distant metastases. Additionally, the acquisition of invasive properties driven by epithelial-mesenchymal transition (EMT) is critical for the evolution of neoplastic cells into fully metastatic populations. Here, we characterize 2 human cellular models derived from prostate and bladder cancer cell lines to better understand the relationship between TIC and EMT programs in local invasiveness and distant metastasis. The model tumor subpopulations that expressed a strong epithelial gene program were enriched in highly metastatic TICs, while a second subpopulation with stable mesenchymal traits was impoverished in TICs. Constitutive overexpression of the transcription factor Snai1 in the epithelial/ TIC-enriched populations engaged a mesenchymal gene program and suppressed their self renewal and metastatic phenotypes. Conversely, knockdown of EMT factors in the mesenchymal-like prostate cancer cell subpopulation caused a gain in epithelial features and properties of TICs. Both tumor cell subpopulations cooperated so that the nonmetastatic mesenchymal-like prostate cancer subpopulation enhanced the in vitro invasiveness of the metastatic epithelial subpopulation and, in vivo, promoted the escape of the latter from primary implantation sites and accelerated their metastatic colonization. Our models provide new insights into how dynamic interactions among epithelial, self-renewal, and mesenchymal gene programs determine the plasticity of epithelial TICs., T. Celià-Terrassa is a recipient of a doctoral fellowship from the CSIC. Ó. Meca-Cortés, A. Arnal-Estapé, and C. Estarás are recipients of doctoral fellowships and F. Mateo of a Juan de la Cierva postdoctoral fellowship from the Ministerio de Ciencia e Innovación (MICINN). R.R. Gomis is a researcher of the Institució Catalana de Recerca i Estudis Avançats. Financial support was provided to T.M. Thomson by MICINN (SAF2008-04136-C02-01 and SAF2011-24686), the Agència de Gestió d’Ajuts Universitaris i de Recerca (2009SGR1482), the Agencia Española de Cooperación Internacional y Desarrollo (A/023859/09), and the Xarxa de Referencia en Biotecnologia; to P.L. Fernández by MICINN (FIS-PI080274), the Fondo de Investigaciones de la Seguridad Social (PI080274), the Spanish National Biobank Network, the Instituto de Salud Carlos III (ISCIII-RETIC RD06/0020), the Xarxa de Bancs de Tumours de Catalunya-Pla Director d’Oncologia, and the Fondo Europeo de Desarrollo Regional (FEDER) — Unión Europea “Una manera de hacer Europa”; and to R.R. Gomis by the BBVA Foundation and MICINN (SAF2007-62691).

Otitis media (OM) is one of the most common infections in children, Streptococcus pneumoniae and nontypable Haemophilus influenzae being the two most common pathogens isolated in the middle ear fluid (MEF) of children with OM. Cefditoren is a third-generation cephalosporin with broad-spectrum antibacterial activity, including activity against those pathogens commonly causing OM, with enhanced stability against common β-lactamases. The main objective of this study was to evaluate the in vitro activity of cefditoren against pathogens collected from the MEF of Costa Rican children with OM between 2006 and 2011. A total of 715 samples were analyzed. Among the 89 S. pneumoniae strains that were penicillin-nonsusceptible, only 7% were cefditoren-resistant according to Spanish Regulatory Agency criteria; among the H. influenza and M. catarrhalis isolates obtained, 100 and 90% of the isolates, respectively, were cefditoren-susceptible. MIC50/90 against the 207 PCV-13 S. pneumoniae serotyped strains and the 79 serotypes not covered by PCV-13 for cefditoren were 0.03/1 and 0.03/0.12 mg/l, respectively. For both amoxicillin-susceptible and resistant H. influenzae strains, the MIC range against cefditoren was from ≤0.015 to 0.06 mg/l as well. In conclusion, the confirmation of the wide spectrum of activity of cefditoren and its intrinsic strength against resistant strains allows us to suggest that cefditoren might be included as one of the best choices among antibiotics that are widely used in empiric therapy for OM in pediatric patients.