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Introduction: Carbapenemase-Producing Escherichia coli (CP-Eco) isolates, though less prevalent than other CP-Enterobacterales, have the capacity to rapidly disseminate antibiotic resistance genes (ARGs) and cause serious difficult-to-treat infections. The aim of this study is phenotypically and genotypically characterizing CP-Eco isolates collected from Spain to better understand their resistance mechanisms and population structure. Methods: Ninety representative isolates received from 2015 to 2020 from 25 provinces and 59 hospitals Spanish hospitals were included. Antibiotic susceptibility was determined according to EUCAST guidelines and wholegenome sequencing was performed. Antibiotic resistance and virulenceassociated genes, phylogeny and population structure, and carbapenemase genes-carrying plasmids were analyzed. Results and discussion: The 90 CP-Eco isolates were highly polyclonal, where the most prevalent was ST131, detected in 14 (15.6%) of the isolates. The carbapenemase genes detected were blaOXA-48 (45.6%), blaVIM-1 (23.3%), blaNDM-1 (7.8%), blaKPC-3 (6.7%), and blaNDM-5 (6.7%). Forty (44.4%) were resistant to 6 or more antibiotic groups and the most active antibiotics were colistin (98.9%), plazomicin (92.2%) and cefiderocol (92.2%). Four of the seven cefiderocol-resistant isolates belonged to ST167 and six harbored blaNDM. Five of the plazomicin-resistant isolates harbored rmt. IncL plasmids were the most frequent (45.7%) and eight of these harbored blaVIM-1. blaOXA-48 was found in IncF plasmids in eight isolates. Metallo-β-lactamases were more frequent in isolates with resistance to six or more antibiotic groups, with their genes often present on the same plasmid/integron. ST131 isolates were associated with sat and pap virulence genes. This study highlights the genetic versatility of CP-Eco and its potential to disseminate ARGs and cause community and nosocomial infections. [ABSTRACT FROM AUTHOR]

Infections caused by carbapenem-resistant Acinetobacter baumannii are a global threat causing a high number of fatal infections. This microorganism can also easily acquire antibiotic resistance determinants, making the treatment of infections a big challenge, and has the ability to persist in the hospital environment under a wide range of conditions. The objective of this work was to study the molecular epidemiology and genetic characteristics of two blaOXA24/40 Acinetobacter baumannii outbreaks (2009 and 2020-21) at a tertiary hospital in Northern Spain. Thirty-six isolates were investigated and genotypically screened by Whole Genome Sequencing to analyse the resistome and virulome. Isolates were resistant to carbapenems, aminoglycosides and fluoroquinolones. Multi-Locus Sequence Typing analysis identified that Outbreak 1 was mainly produced by isolates belonging to ST3Pas/ST106Oxf (IC3) containing blaOXA24/40, blaOXA71 and blaADC119. Outbreak 2 isolates were exclusively ST2Pas/ST801Oxf (IC2) blaOXA24/40, blaOXA66 and blaADC30, the same genotype seen in two isolates from 2009. Virulome analysis showed that IC2 isolates contained genes for capsular polysaccharide KL32 and lipooligosacharide OCL5. A 8.9 Kb plasmid encoding the blaOXA24/40 gene was common in all isolates. The persistance over time of a virulent IC2 clone highlights the need of active surveillance to control its spread. [ABSTRACT FROM AUTHOR]

Objectives: To describe and analyse erythromycin resistance trends in blood isolates of Staphylococcus aureus (EARS-Net Spain, 2004-2020) and the association of these trends with the consumption of macrolide, lincosamide, and streptogramin B (MLSB) antibiotics. To assess molecular changes that could be involved in erythromycin resistance trends by whole genome analysis of representative isolates. Materials and methods: We collected antibiotic susceptibility data for all firstblood S. aureus isolates in patients from 47 Spanish hospitals according to EARS-Net criteria. MLSB antibiotic consumption was obtained from the Spanish Agency for Medicines and Medical Devices (2008-2020). We sequenced 137 representative isolates for core genome multilocus sequence typing, resistome and virulome analysis. Results: For the 36,612 invasive S. aureus isolates, methicillin resistance decreased from 26.4% in 2004 to 22.4% in 2020. Erythromycin resistance in methicillin-susceptible S. aureus (MSSA) increased from 13.6% in 2004 to 28.9% in 2020 (p < 0.001); however, it decreased from 68.7 to 61.8% (p < 0.0001) in methicillinresistant S. aureus (MRSA). Total consumption of MLSB antibiotics increased from 2.72 defined daily doses per 1,000 inhabitants per day (DID) in 2014 to 3.24 DID in 2016. By WGS, the macrolide resistance genes detected were erm (59.8%), msrA (46%), and mphC (45.2%). The erm genes were more prevalent in MSSA (44/57, 77.2%) than in MRSA (38/80, 47.5%). Most of the erm genes identified in MSSA after 2013 differed from the predominant ermC gene (17/22, 77.3%), largely because ermT was significantly associated with MSSA after 2013 (11/29, 37.9%). All 13 ermT isolates in this study, except one, belonged to ST398 and came from 10 hospitals and six Spanish provinces. Conclusion: The significant increase in erythromycin resistance in blood MSSA correlated with the consumption of the MLSB antibiotics in Spain. These preliminary data seem support the hypothesis that the human ST398 MSSA clade with ermT-mediated resistance to erythromycin may be involved in this trend. [ABSTRACT FROM AUTHOR]

For a better understanding of the transmission cycles of mosquito-borne diseases, it is essential to explore the species composition and population dynamics, mainly during their peak abundance period. These investigations do not normally include peri-urban areas, despite their significant epidemiological interest. To address these gaps, an entomological survey was carried out in 2016 and 2017 in three aquatic ecosystems located on the outskirts of the city of Logroño, in northern Spain: the Iregua River and La Grajera (La Rioja) and Las Cañas Reservoirs (Navarra). Mosquitoes were captured using BG-Sentinel traps baited with CO2 and BG-lure, as well as through the human landing collection method. In total, 6793 mosquito specimens were captured, representing 24 taxa within six genera. A specific PCR based on the ITS2 gene was used to differentiate members of the Anopheles claviger complex, and all individuals were identified as An. claviger sensu stricto. La Grajera had the most diverse culicid fauna, with 19 taxa, followed by Las Cañas (n = 15) and the Iregua River (n = 13). The composition and abundance of Culicidae varied across the aquatic ecosystem. We observed that the different hydrological management practices of each environment could play a key role in determining the abundance of mosquito genera. The overall risk of mosquito bites in the study area is expected to be relatively low and will depend on the freshwater ecosystem and the time of year. [ABSTRACT FROM AUTHOR]

We report a confirmed case of Candidatus Neoehrlichia mikurensis infection in a woman in Spain who had a previous hematologic malignancy. Candidatus N. mikurensis infections should be especially suspected in immunocompromised patients who exhibit persistent fever and venous thrombosis, particularly if they live in environments where ticks are prevalent. [ABSTRACT FROM AUTHOR]

Objectives. To describe participant characteristics associated with severe acute respiratory syndrome coronavirus 2 infection in Spain's first 2 COVID-19 waves per the Spanish National Seroepidemiological Survey of SARS-CoV-2 Infection (ENE–COVID). Methods. A representative cohort of the noninstitutionalized Spanish population, selected through stratified 2-stage sampling, answered a questionnaire and received point-of-care testing April to June 2020 (first wave: n = 68 287); previously seronegative participants repeated the questionnaire and test November 2020 (second wave: n = 44 451). We estimated seropositivity by wave and participant characteristics, accounting for sampling weights, nonresponse, and design effects. Results. We found that 6.0% (95% confidence interval [CI] = 5.7%, 6.4%) of Spain's population was infected by June and 3.8% (95% CI = 3.5%, 4.1%) more by November 2020. Both genders were equally affected. Seroprevalence decreased with age in adults 20 years and older in the second wave; socioeconomic differences increased. Health care workers were affected at 11.1% (95% CI = 9.0%, 13.6%) and 6.1% (95% CI = 4.4%, 8.5%) in the first and second waves, respectively. Living with an infected person increased infection risk to 22.1% (95% CI = 18.9%, 25.6%) in the first and 35.0% (95% CI = 30.8%, 39.4%) in the second wave. Conclusions. ENE–COVID characterized the first 2 pandemic waves, when information from surveillance systems was incomplete. (Am J Public Health. 2023;113(5):533–544. https://doi.org/10.2105/AJPH.2023.307233) [ABSTRACT FROM AUTHOR]

Data System. The Spanish National Seroepidemiological Survey of SARS-CoV-2 (or ENE-COVID; SARS-CoV-2 [severe acute respiratory syndrome coronavirus 2] is the causative agent of COVID-19) was funded by the Spanish Ministry of Health, the Instituto de Salud Carlos III, and the Spanish National Health System. Data Collection/Processing. A stratified 2-stage probability sampling was used to select a representative cohort of the noninstitutionalized population of Spain. ENE-COVID collected longitudinal data from epidemiological questionnaires and 2 SARS-CoV-2 IgG antibody tests. From April 27 to June 22, 2020, 68 287 participants (77.0% of contacted persons) received a point-of-care test and 61 095 (68.9%) also underwent a laboratory immunoassay. A second follow-up phase was conducted between November 16 and 30, 2020. Data Analysis/Dissemination. Analyses use weights to adjust for oversampling and nonresponse and account for design effects of stratification and clustering. ENE-COVID data for research purposes will be available upon request from the official study Web page. Public Health Implications. ENE-COVID, a nationwide population-based study, allowed monitoring seroprevalence of antibodies against SARS-CoV-2 at the national and regional levels, providing accurate figures by gender, age (from babies to nonagenarians), and selected risk factors; characterizing symptomatic and asymptomatic infections; and estimating the infection fatality risk during the first pandemic wave. (Am J Public Health. 2023;113(5):525–532. https://doi.org/10.2105/AJPH.2022.307167) [ABSTRACT FROM AUTHOR]

Coronary endothelial dysfunction and vasospasm are potential causes of ischemia in patients without obstructive coronary stenoses (INOCA). To evaluate the prevalence of endothelial dysfunction and the clinical profile of patients with INOCA in Spain, as well as to identify the predictors and the prognostic impact of endothelial dysfunction in this scenario. A total of 438 consecutive patients with INOCA in whom the acetylcholine test was performed were prospectively enrolled. Patients were followed up at 1 and 2 years. Mean age was 62 ± 11 years with 60% female. Clinical presentation comprised 52.6% angina at rest, 61.2% exertional angina, and 31.7% dyspnea. There were no major complications of the acetylcholine test. Endothelial dysfunction was observed in 198 (45%) of patients, with severe vasoconstriction (defined as over 70% constriction), being observed in 101 (23%). Multivariable regression analysis showed that endothelial dysfunction was predicted by the presence of exertional angina (OR 2.2; CI95%1.01–2.55; p = 0.02), prior coronary disease (OR 2.46; CI95% 1.57–3.89; p < 0.01), and coronary intramyocardial bridging (2.35; CI95% 1.02–5.60; p = 0.04). Patients with endothelial dysfunction presented with worsening angina compared to those without endothelial dysfunction (25.6% vs. 12.8%) and also presented with increased levels of minimal effort angina (40% vs. 26,7%, p = 0.03) more frequently during the follow up than those without endothelial dysfunction. Endothelial dysfunction was also an independent predictor of the occurrence of myocardial infarction or unstable angina at one year (OR 2.85, CI 95% 1.01–9.25; p = 0.03). Endothelial dysfunction is present in almost half of patients with INOCA and is associated with worsening symptoms, as well as with a higher rate of adverse events. [Display omitted] • Almost half of patients with INOCA have coronary endothelial dysfunction. • Exertional angina is a predictor of coronary endothelial dysfunction in INOCA. • Coronary endothelial dysfunction is a predictor of cardiovascular events in patients with INOCA. [ABSTRACT FROM AUTHOR]

Objectives: Little is known about IMP-producing Enterobacterales (IMP-Ent) in Europe. We analyzed at genomic and phenotypic level IMP-Ent isolates circulating in Spain in a 9-year period. Materials and methods: IMP-Ent isolates submitted to our reference laboratory were included. Antibiotic susceptibility was performed using microdilution method (EUCAST), and IMP-carbapenemase activity was measured with carbapenemase inhibitors, the ß-CARBA method, the modified Hodge test (MHT), and the modified carbapenemase inhibition method (mCIM). All isolates collected were sequenced for high-resolution single-nucleotide polymorphism (SNP) typing, core genome multilocus sequence typing (cgMLST), and resistome analysis. Results: Fifty IMP-Ent isolates, collected from 19 hospitals in 13 Spanish provinces, were detected: Klebsiella pneumoniae (IMP-Kpn) (24; 48%), Enterobacter roggenkampii (13; 26%), Enterobacter hormaechei (8, 16%), Klebsiella oxytoca (two; 4%), Enterobacter asburiae (one, 2%), Serratia marcescens (one; 2%) and Escherichia coli (one; 2%). All isolates were positive by the MHT and ß-CARBA tests; 48 (96%) were mCIM positive; 12 (24%) and 26 (52%) displayed positive inhibition with dipicolinic (meropenem) and EDTA (ertapenem), respectively. Five IMP-carbapenemase types were identified: IMP-8 (22; 44%), IMP-22 (17; 34%), IMP-13 (7; 14%), IMP-28 (two; 4%), and IMP-15 (two; 4%), predominating IMP-8 in K. pneumoniae and IMP-22 in E. roggenkampii. IMP-28 was exclusively identified in K. oxytoca and IMP-15 in E. hormaechei. Predominant STs were ST405 (29.2%), ST15 (25%) and ST464 (20.8%) in IMP-Kpn; ST96 (100%) in E. roggenkampii and ST182 (62.5%) in E. hormachei. Colistin and amikacin were the most active non-carbapenem antibiotics against IMP-Ent. Conclusion: IMP-Ent isolates remain infrequent in Spain, although in recent years have been circulating causing nosocomial outbreaks, being IMP-8-producing K. pneumoniae and IMP-22-producing E. roggenkampii the most frequently detected in this study. Inhibition with EDTA or dipicolinic acid presented false negative results in some IMP-producing strains. Active microbiological and molecular surveillance is essential for a better comprehension and control of IMP-Ent dissemination. [ABSTRACT FROM AUTHOR]

Simple Summary: Ixodid ticks and tick-borne diseases are expanding their geographical range, but surveillance activities vary among countries. We analysed the surveillance systems in place in the Netherlands, Spain and Italy, to identify ideal elements to monitor tick-borne diseases, by using a One Health evaluation protocol. We identified differences among the three surveillance systems, with the Dutch initiative showing a high level of transdisciplinary collaboration, good identification of the actors and engagement of the public in research and education. Measurable outcomes have been generated, such as the reduction in tick bites and the discovery of new pathogens and tick species. In Italy and Spain, surveillance systems are based on compulsory notification to health authorities; legislation seems relevant but law enforcement alongside the availability of economic resources is rather fragmented and limited to the most severe diseases. The non-scientific community is marginally considered and collaborations are limited to local initiatives. Research activities in both countries have mostly contributed to gaining knowledge on the distribution of tick species and the discovery of new pathogens. Although all TBD surveillance plans comply with the EU regulations, the initiatives characterised by trans-disciplinary collaboration may be more effective for the surveillance and prevention of tick-transmitted diseases. To identify ideal elements for the monitoring and prevention of tick-borne diseases (TBD), we analysed the surveillance systems in place in the Netherlands, Spain and Italy. We applied a semi-quantitative evaluation to identify outcomes and assess the degree of One Health implementation. Differences emerged in the surveillance initiatives, as well as the One Health scores. The Dutch surveillance is dominated by a high level of transdisciplinary and trans-sectoral collaboration, enabling communication and data sharing among actors. Different project-based monitoring, research and educational activities are centrally coordinated and the non-scientific community is actively involved. All this yielded measurable health outcomes. In Italy and Spain, TBD surveillance and reporting systems are based on compulsory notification. Law enforcement, alongside dedicated time and availability of economic resources, is fragmented and limited to the most severe health issues. Veterinary and human medicine are the most involved disciplines, with the first prevailing in some contexts. Stakeholders are marginally considered and collaborations limited to local initiatives. Research activities have mostly contributed to gaining knowledge on the distribution of tick vectors and discovery of new pathogens. Although all TBD surveillance plans comply with EU regulations, initiatives characterised by transdisciplinary collaboration may be more effective for the surveillance and prevention of TBD. [ABSTRACT FROM AUTHOR]

Simple Summary: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causing coronavirus disease-2019 (COVID-19) is a betacoronavirus (β-CoV) closely related to Severe Acute Respiratory Syndrome (SARS-CoV) and the Middle East Respiratory Syndrome Coronavirus (MERS-CoV), which have also caused severe outbreaks of disease in human populations. Human-to-animal transmission events during the COVID-19 pandemic have been documented in several countries. Different animal species have been proven to be susceptible to infection with SARS-CoV-2 both naturally and by experimental infection, including mustelids such as ferrets, otters, and American mink (Neogale vison). In this sense, infected farmed American mink develop respiratory signs associated with viral pneumonia. This study evaluates the presence of SARS-CoV-2 in European mink (Mustela lutreola) and American mink from Spain, by enzyme-linked immunosorbent assay (ELISA) using the receptor binding domain (RBD) of Spike protein antigen in serum samples and/or by RT-qPCR assays in oropharyngeal and rectal swabs. From January 2020 to February 2022, a total of 162 animals (127 European mink and 35 American mink) with no evidence of SARS-CoV-2 infection were included in the study. Of the 126 serum samples analysed by serology, anti-SARS-CoV-2 antibodies were not detected in the mink included in this study. In the same way, SARS-CoV-2 RNA has not been detected in any of the 160 swabs samples analysed by RT-qPCR. This study shows the absence of the wild mink exposure to SARS-CoV-2 in a geographic area seriously affected by COVID-19. With these results, it can be considered that the probability that the virus is circulating in wild mink is low. With this, the risk of virus transmission to humans by this route is also considered improbable. The impact of the SARS-CoV-2 pandemic on wildlife is largely unevaluated, and extended surveillance of animal species is needed to reach a consensus on the role of animals in the emergence and maintenance of SARS-CoV-2. This infection has been detected in farmed and domestic animals and wild animals, mainly in captivity. The interactions or shared resources with wildlife could represent a potential transmission pathway for the SARS-CoV-2 spill over to other wild species and could lead to health consequences or the establishment of new reservoirs in susceptible hosts. This study evaluated the presence of SARS-CoV-2 in European mink (Mustela lutreola) and American mink (Neogale vison) in Spain by enzyme-linked immunosorbent assay (ELISA) using the receptor binding domain (RBD) of Spike antigen in serum samples and/or by RT-qPCR assays in oropharyngeal and rectal swabs. From January 2020 to February 2022, a total of 162 animals (127 European mink and 35 American mink) with no evidence of SARS-CoV-2 infection were included in the study. Antibodies against the SARS-CoV-2 were not found in the serum samples analysed (n = 126), nor was the virus amplified by RT-qPCR (n = 160 swabs). Our results suggest that the potential role of wild mink and the European mink bred in captivity and released to the wild as dispersers of SARS-CoV-2 is so far low. However, wildlife surveillance for early detection of human and animal risks should be continued. In this sense, epidemiological monitoring measures, including serology and molecular analysis, are necessary. [ABSTRACT FROM AUTHOR]

OBJECTIVES Elderly patients show a higher incidence of ischemic and bleeding events after percutaneous transluminal coronary intervention (PCI). We sought to investigate outcomes in elderly patients treated with antithrombotic strategy guided by bleeding and ischemic risks after revascularization with last generation everolimus-eluting stent (EES). METHODS Prospective multicenter registry including patients over 75 years revascularized with EES and antithrombotic therapy guided by clinical presentation, PCI complexity and PRECISE DAPT score. Co-primary safety endpoints were: (1) composite of cardiac death, myocardial infarction and stent thrombosis and; (2) bleeding (BARC 2-5). Primary efficacy endpoint was target lesion revascularization. A matched group of patients revascularized with current drug-eluting stents and no such tailored antithrombotic therapy was used as control. RESULTS Finally, 1064 patients were included in SIERRA-75 cohort, 80.8 ± 4.2 years, 36.6% women, 71% acute coronary syndromes (ACS) and 53.6% complex PCI. Co-primary safety endpoint of major adverse cardiovascular events was met in 6.2%, coprimary safety endpoint of bleeding in 7.8% and primary efficacy endpoint of TKLR in 1.5%. The multivariable adjusted model showed no significant association of the prescribed short/long dual antiplatelet therapy (DAPT) durations with any endpoint suggesting a well tailored therapy. No stent thrombosis reported in the subgroup with 1-3 months DAPT duration. As compared to control group, bleeding BARC 2-5 was significantly lower in SIERRA-75 group (7.4% vs. 10.2%, P = 0.04) as well as the net safety-efficacy endpoint (14.3% vs. 18.5%, P = 0.02). CONCLUSIONS In elderly population, the application of this risks-adjusted antithrombotic protocol after revascularization with last generation EES seems to be associated with an improved prognosis in terms of ischemic and bleeding outcomes. [ABSTRACT FROM AUTHOR]

Blood culture negative endocarditis (BCNE) is frequent in infective endocarditis (IE). One of the causes of BCNE is fastidious microorganisms, such as Bartonella spp. The aim of this study was to describe the epidemiologic, clinical characteristics, management and outcomes of patients with Bartonella IE from the "Spanish Collaboration on Endocarditis-Grupo de Apoyo al Manejo de la Endocarditis infecciosa en España (GAMES)"cohort. Here we presented 21 cases of Bartonella IE. This represents 0.3% of a total of 5590 cases and 2% of the BCNE from the GAMES cohort. 62% were due to Bartonella henselae and 38% to Bartonella quintana. Cardiac failure was the main presenting form (61.5% in B. hensalae, 87.5% in B. quintana IE) and the aortic valve was affected in 85% of the cases (76% in B. henselae, 100% in B. quintana IE). Typical signs such as fever were recorded in less than 40% of patients. Echocardiography showed vegetations in 92% and 100% of the patients with B. henselae and B. quintana, respectively. Culture was positive only in one patient and the remaining were diagnosed by serology and PCR. PCR was the most useful tool allowing for diagnosis in 16 patients (100% of the studied valves). Serology, at titers recommended by guidelines, only coincided with PCR in 52.4%. Antimicrobial therapy, in different combinations, was used in all cases. Surgery was performed in 76% of the patients. No in-hospital mortality was observed. One-year mortality was 9.4%. This article remarks the importance for investigating the presence of Bartonella infection as causative agent in all BCNE since the diagnosis needs specific microbiological tools and patients could benefit of a specific treatment. [ABSTRACT FROM AUTHOR]

During recent decades, a tick-borne rickettsial syndrome, characterized by eschar and painful lymphadenopathy after Dermacentor marginatus-bite, has been described as an emerging rickettsiosis in Europe. Our group named it DEBONEL (Dermacentor-borne-necrosis-erythema-lymphadenopathy), regarding the vector and the main infection signs. Other groups called it TIBOLA (tick-borne-lymphadenophathy) and, later, SENLAT (scalp-eschar-and-neck-lymphadenopathy-after-tick-bite), expanding, in the latter, the etiological spectrum to other pathogens. Objective: To investigate the etiology of DEBONEL agents in our area, and to compare their epidemiological/clinical/microbiological characteristics. During 2001–2020, 216 patients clinically diagnosed of DEBONEL (the largest series from one center) in La Rioja (northern Spain) were examined. Rickettsia spp. were amplified in 14/104 (13.46%) blood samples, 69/142 (48.59%) eschar swabs, 7/7 (100%) biopsies, and 71/71 (100%) D. marginatus from patients. For samples in which Rickettsia was undetected, no other microorganisms were found. 'Candidatus Rickettsia rioja', Rickettsia slovaca, Rickettsia raoultii, and Rickettsia DmS1 genotype were detected in 91, 66, 4, and 3 patients, respectively. DEBONEL should be considered in patients with clinical manifestations herein described in areas associated to Dermacentor. The most frequently involved agent in our environment is 'Ca. R. rioja'. The finding of Rickettsia sp. DmS1 in ticks attached to DEBONEL patients suggests the implication of other rickettsia genotypes. [ABSTRACT FROM AUTHOR]

Pets from COVID‐19 owners were screened for SARS‐CoV‐2 (April–May 2020). From 23 pets, an asymptomatic cat showed positive RT‐qPCRs results from oropharyngeal swab (negative rectal swab). Remaining pets were negative. This suggests that cats can contract the virus from their infected owners and may act as potential hosts for SARS‐CoV‐2. Their role in carrying live or infectious viruses and disseminating them needs more investigation. [ABSTRACT FROM AUTHOR]

The pandemic of Zika virus in 2016 and other arboviruses prompted La Rioja Government in Spain to implement an entomological surveillance program of mosquitoes (Diptera; Culicidae) in the region of La Rioja. The morphological identification was supported by genetic analysis using the COI (cytochrome c oxidase subunit I) and the ITS2 (internal transcribed spacer 2) genes. In total, we identified 24 species arranged in 6 genera: Aedes (7 species), Anopheles (4 species), Coquillettidia (1 species), Culex (7 species), Culiseta (4 species), and Uranotaenia (1 species). Aedes sticticus and Aedes geniculatus are newly reported for La Rioja region. In total, 465 COI sequences were analyzed for Culicinae and Anophelinae and 54 ITS2 sequences for Anophelinae; all individuals identified as the same species clustered together in the Neighbor Joining trees. The levels of sequence divergence based on COI ranged between 0% and 2.62%, while the interspecific genetic divergence ranged from 3.05% to 20.07%. Within the genus Culiseta, certain specimens of Culiseta annulata, Culiseta litorea, and Culiseta subochrea were morphologically misidentified due to variation in the main diagnostic characters. The interspecific genetic divergence based on the ITS2 ranged from 0% to 2.98%. An accurate identification of mosquito vectors is the first step to establish a vector surveillance program for preventing pathogen transmission. [ABSTRACT FROM AUTHOR]

Objectives: NDM carbapenemases have spread worldwide. However, little information exists about the impact of NDM-producing Enterobacteriaceae in Spain. By WGS, we sought to elucidate the population structure of NDM-like-producing Klebsiella pneumoniae and Escherichia coli in Spain and to determine the plasmids harbouring blaNDM-like genes.Methods: High-resolution SNP typing, core-genome MLST and plasmid reconstruction (PlasmidID) were performed on 59 NDM-like-producing K. pneumoniae and 8 NDM-like-producing E. coli isolated over an 8 year period in Spain.Results: Five major epidemic clones of NDM-producing K. pneumoniae caused five important nationwide outbreaks: ST437/NDM-7, ST437/NDM-1, ST147/NDM-1, ST11/NDM-1 and ST101/NDM-1; in contrast, the spread of NDM-producing E. coli was polyclonal. Three blaNDM types were identified: blaNDM-1, 61.2%; blaNDM-7, 32.8%; and blaNDM-5, 6%. Five K. pneumoniae isolates co-produced other carbapenemases (three blaOXA-48 and two blaVIM-1). The average number of acquired resistance genes was higher in K. pneumoniae than in E. coli. The plasmids encoding blaNDM-like genes belonged to IncFII, IncFIB, IncX3, IncR, IncN and IncC types, of which IncF, IncR and IncC were associated with MDR. The genetic surroundings of blaNDM-like genes showed a highly variable region upstream of ISAba125.Conclusions: In recent years NDM-producing K. pneumoniae and E. coli have emerged in Spain; the spread of a few high-risk K. pneumoniae clones such as ST437/NDM-7, ST437/NDM-1, ST147/NDM-1, ST11/NDM-1 and ST101/NDM-1 have caused several interregional outbreaks. In contrast, the spread of NDM-producing E. coli has been polyclonal. Plasmid types IncFII, IncFIB, IncX3, IncR, IncN and IncC carried blaNDM, and the same IncX3 plasmid was detected in K. pneumoniae and E. coli. [ABSTRACT FROM AUTHOR]

Background Outpatient parenteral antibiotic treatment (OPAT) has proven efficacious for treating infective endocarditis (IE). However, the 2001 Infectious Diseases Society of America (IDSA) criteria for OPAT in IE are very restrictive. We aimed to compare the outcomes of OPAT with those of hospital-based antibiotic treatment (HBAT). Methods Retrospective analysis of data from a multicenter, prospective cohort study of 2000 consecutive IE patients in 25 Spanish hospitals (2008–2012) was performed. Results A total of 429 patients (21.5%) received OPAT, and only 21.7% fulfilled IDSA criteria. Males accounted for 70.5%, median age was 68 years (interquartile range [IQR], 56–76), and 57% had native-valve IE. The most frequent causal microorganisms were viridans group streptococci (18.6%), Staphylococcus aureus (15.6%), and coagulase-negative staphylococci (14.5%). Median length of antibiotic treatment was 42 days (IQR, 32–54), and 44% of patients underwent cardiac surgery. One-year mortality was 8% (42% for HBAT; P <.001), 1.4% of patients relapsed, and 10.9% were readmitted during the first 3 months after discharge (no significant differences compared with HBAT). Charlson score (odds ratio [OR], 1.21; 95% confidence interval [CI], 1.04–1.42; P =.01) and cardiac surgery (OR, 0.24; 95% CI,.09–.63; P =.04) were associated with 1-year mortality, whereas aortic valve involvement (OR, 0.47; 95% CI,.22–.98; P =.007) was the only predictor of 1-year readmission. Failing to fulfill IDSA criteria was not a risk factor for mortality or readmission. Conclusions OPAT provided excellent results despite the use of broader criteria than those recommended by IDSA. OPAT criteria should therefore be expanded. [ABSTRACT FROM AUTHOR]

Tick-borne rickettsioses, most of them belonging to the spotted fever group (SFG), have been recognized as important emerging vector-borne zoonotic diseases. In order to determine the presence of Rickettsia spp. in questing ticks from north-western Spain, 1056 Ixodes ricinus, 19 Dermacentor marginatus, 17 Dermacentor reticulatus and one Ixodes acuminatus were processed. Rickettsia DNA was detected by PCR targeting rOmpA and rOmpB genes. A total of 219 (20.7%) I. ricinus, 19 (100%) D. marginatus and four D. reticulatus (23.5%) were positive. The prevalence was significantly higher in I. ricinus from coastal areas and in winter. Five species were identified: Rickettsia felis, Rickettsia monacensis, Rickettsia raoultii, Rickettsia slovaca and "Candidatus Rickettsia rioja". Our results reveal a significant presence of some pathogenic Rickettsia species in questing tick populations from this area which involves a noticeable risk of rickettsiosis. As R. raoultii, R. slovaca and "Ca. R. rioja" DNA were identified in I. ricinus, considered an unusual vector for these Rickettsia species, further studies are needed to unravel the role of that tick species in the maintenance and transmission of these three Rickettsia species in north-western Spain. [ABSTRACT FROM AUTHOR]

Objectives: Tropheryma whipplei has been detected in 3.5% of the blood culture-negative cases of endocarditis in Spain. Experience in the management of T. whipplei endocarditis is limited. Here we report the long-term outcome of the treatment of previously reported patients who were diagnosed with infective endocarditis (IE) caused by T. whipplei from the Spanish Collaboration on Endocarditis-Grupo de Apoyo al Manejo de la Endocarditis Infecciosa en España (GAMES) and discuss potential options for antimicrobial therapy for IE caused by T. whipplei.Patients and Methods: Seventeen patients with T. whipplei endocarditis were recruited between 2008 and 2014 in 25 Spanish hospitals. Patients were classified according to the therapeutic regimen: ceftriaxone and trimethoprim/sulfamethoxazole, doxycycline + hydroxychloroquine and other treatment options.Results: Follow-up data were obtained from 14 patients. The median follow-up was 46.5 months. All patients completed the antibiotic treatment prescribed, with a median duration of 13 months. Six patients were treated with ceftriaxone and trimethoprim/sulfamethoxazole (median duration 13 months), four with doxycycline + hydroxychloroquine (median duration 13.8 months) and four with other treatment options (median duration 22.3 months). The follow-up after the end of the treatments was between 5 and 84 months (median 24 months).Conclusions: All treatment lines were effective and well tolerated. Therapeutic failures were not detected during the treatment. None of the patients died or experienced a relapse during the follow-up. Only six patients received antibiotic treatment in accordance with guidelines. These data suggest that shorter antimicrobial treatments could be effective. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to characterize the bacterial microbiome of hard ticks with affinity to bite humans in La Rioja (North of Spain). Methods: A total of 88 adult ticks (22 Rhipicephalus sanguineus sensu lato, 27 Haemaphysalis punctata, 30 Dermacentor marginatus and 9 Ixodes ricinus) and 120 I. ricinus nymphs (CRETAV collection, La Rioja, Spain), representing the main anthropophilic species in our environment, were subjected to a metagenomic analysis of the V3-V4 region of the 16S rRNA gene using an Illumina MiSeq platform. Data obtained with Greengenes database were refined with BLAST. Four groups of samples were defined, according to the four tick species. Results: Proteobacteria was the predominant phylum observed in all groups. Gammaproteobacteria was the most abundant class, followed by Alphaproteobacteria for R. sanguineus, H. punctata and D. marginatus but the relative abundance of reads for these classes was reversed for I. ricinus. This tick species showed more than 46% reads corresponding to ‘not assigned’ OTUs (Greengenes), and >97% of them corresponded to ‘Candidatus Midichloriaceae’ using BLAST. Within Rickettsiales, ‘Candidatus Midichloria’, Rickettsia, Ehrlichia, ‘Candidatus Neoehrlichia’ and Wolbachia were detected. I. ricinus was the most alpha-diverse species. Regarding beta-diversity, I. ricinus and H. punctata samples grouped according to their tick species but microbial communities of some R. sanguineus and D. marginatus specimens clustered together. Conclusions: The metagenomics approach seems useful to discover the spectrum of tick-related bacteria. More studies are needed to identify and differentiate bacterial species, and to improve the knowledge of tick-borne diseases in Spain. [ABSTRACT FROM AUTHOR]

Objectives: We analysed the microbiological traits and population structure of KPC-producing Enterobacteriaceae isolates collected in Spain between 2012 and 2014. We also performed a comparative WGS analysis of the three major KPC-producing Klebsiella pneumoniae clones detected.Methods: Carbapenemase and ESBL genes were sequenced. The Institut Pasteur MLST scheme was used. WGS data were used to construct phylogenetic trees, to identify the determinants of resistance and to de novo assemble the genome of one representative isolate of each of the three major K. pneumoniae clones.Results: Of the 2443 carbapenemase-producing Enterobacteriaceae isolates identified during the study period, 111 (4.5%) produced KPC. Of these, 81 (73.0%) were K. pneumoniae and 13 (11.7%) were Enterobacter cloacae. Three major epidemic clones of K. pneumoniae were identified: ST11/KPC-2, ST101/KPC-2 and ST512/KPC-3. ST11/KPC-2 differed from ST101/KPC-2 and ST512/KPC-3 by 27 819 and 6924 SNPs, respectively. ST101/KPC-2 differed from ST512/KPC-3 by 28 345 SNPs. Nine acquired resistance genes were found in ST11/KPC-2, 11 in ST512/KPC-3 and 13 in ST101/KPC-2. ST101/KPC-2 had the highest number of virulence genes (20). An 11 bp deletion at the end of the mgrB sequence was the cause of colistin resistance in ST512/KPC-3.Conclusions: KPC-producing Enterobacteriaceae are increasing in Spain. Most KPC-producing K. pneumoniae isolates belonged to only five clones: ST11 and ST512 caused interregional spread, ST101 caused regional spread and ST1961 and ST678 produced independent hospital outbreaks. ST101/KPC-2 had the highest number of resistance and virulence genes. ST101/KPC-2 and ST512/KPC-3 were recently implicated in the spread of KPC in Italy. [ABSTRACT FROM AUTHOR]

Surveillance System. A network of 32 Spanish hospitals, serving approximately 9.6 million persons, submitted antimicrobial-susceptibility data on 7,098 invasive Escherichia coli species (2001-2003). Resistance to ampicillin, cotrimoxazole, ciprofloxacin, gentamicin, and tobramycin was found at rates of 59.9%, 32.6%, 19.3%, 6.8%, and 5.3%, respectively. Resistance to multiple drugs increased from 13.8% in 2001 to 20.6% in 2003 (p <0.0001). Antimicrobial consumption data were obtained from the Spanish National Health System. In spite of decreased cephalosporin and beta-lactam use, overall extended-spectrum beta-lactamase production increased from 1.6% (2001) to 4.1% (2003) (p <0.0001), mainly due to the rising prevalence of cefotaximases. Resistance to ciprofloxacin significantly increased, mostly in community-onset infections, which coincided with a rise in community quinolone use. Cotrimoxazole resistance remained stable at approximately 30%, even though its use was dramatically reduced. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study was to analyse the microbiological traits and the population structure of carbapenemase-producing (CP) Escherichia coli isolates collected in Spain between 2012 and 2014.Methods: Two-hundred-and-thirty-nine E. coli isolates non-susceptible to carbapenems were studied. The carbapenemase genes and the phylogenetic groups were characterized using PCR. MLST was carried out using the typing schemes of the University of Warwick and the Institut Pasteur. The diversity of the population structure was estimated by calculating a simple diversity index (SDI).Results: One-hundred-and-twenty-one isolates (50.6%) produced carbapenemases, of which 87 (71.9%) were OXA-48, 27 (22.3%) were VIM-1, 4 (3.3%) were KPC-2, 2 (1.7%) were NDM and 1 (0.8%) was IMP-22; 4 isolates were collected in 2012, 40 in 2013 and 77 in 2014. Ertapenem was more sensitive than imipenem or meropenem for screening for OXA-48-producing E. coli. Using the Warwick typing scheme, 59 different STs were identified, the most prevalent being ST131 (16.5%). The population diversity was higher among VIM-1-producing isolates (SDI = 81.5%) than among OXA-48-producing isolates (SDI = 44.8%). The Pasteur scheme had a higher discrimination capability (SDI = 55.4%) than the Warwick scheme (SDI = 48.8%).Conclusions: A progressive increase in the prevalence of CP E. coli was observed, mainly due to the dissemination of OXA-48 producers. The most sensitive method for detecting decreased susceptibility of CP E. coli to carbapenems was disc diffusion with ertapenem using the EUCAST screening cut-offs. The spread of CP E. coli was due to a polyclonal population. The Pasteur scheme showed the highest discrimination power. Surveillance is crucial for the early detection of CP E. coli. [ABSTRACT FROM AUTHOR]

Objectives: The global emergence of OXA-48-producing Klebsiella pneumoniae clones is a significant threat to public health. We used WGS and phylogenetic analysis of Spanish isolates to investigate the population structure of blaOXA-48-like-expressing K. pneumoniae ST11 and ST405 and to determine the distribution of resistance genes and plasmids encoding blaOXA-48-like carbapenemases.Methods: SNPs identified in whole-genome sequences were used to reconstruct phylogenetic trees, identify resistance determinants and de novo assemble the genomes of 105 blaOXA-48-like-expressing K. pneumoniae isolates.Results: Genome variation was generally lower in outbreak-associated isolates compared with those associated with sporadic infections. The relatively limited variation observed within the outbreak-associated isolates was on average 7-10 SNPs per outbreak. Of 24 isolates from suspected sporadic infections, 7 were very closely related to isolates causing hospital outbreaks and 17 were more diverse and therefore probably true sporadic cases. On average, 14 resistance genes were identified per isolate. The 17 ST405 isolates from sporadic cases of infection had four distinct resistance gene profiles, while the resistance gene profile differed in all ST11 isolates from sporadic cases. Sequence analysis of 94 IncL/M plasmids carrying blaOXA-48-like genes revealed an average of two SNP differences, indicating a conserved plasmid clade.Conclusions: Whole-genome sequence analysis enabled the discrimination of outbreak and sporadic isolates. Significant inter-regional spread within Spain of highly related isolates was evident for both ST11 and ST405 K. pneumoniae. IncL/M plasmids carrying blaOXA-48-like carbapenemase genes were highly conserved geographically and across the outbreaks, sporadic cases and clones. [ABSTRACT FROM AUTHOR]

Background: Most available information on carbapenemase-producing Enterobacteriaceae (CPE) is usually associated with specific types of infection or patient or with descriptions of outbreaks. The aim of this study was to comprehensively analyse the clinical epidemiology, clinical features and outcomes of colonisation and infections due to CPE in Spain.Methods: A multicentre prospective cohort study was carried out in 34 Spanish hospitals from February to May 2013. All new patients testing positive for CPE in clinical samples were included. Logistic regression was used to identify predictors of mortality.Results: Overall, 245 cases were included. The most frequent organism was Klebsiella pneumoniae (74%) and the carbapenemases belonged to the OXA-48 (74%), metallo-β-lactamase (MBL) (24%) and KPC (2%) groups. Acquisition was nosocomial in 145 cases (60%) and healthcare-associated (HCA) in 91 (37%); 42% of the latter were nursing home residents, in whom OXA-48-producing K. pneumoniae ST405 predominated. MBLs and OXA-48 predominated in ICU and medical patients, respectively. Overall, 67% of patients had infections. The most frequent infections identified in this study were urinary tract (43%) and skin structure (21%) infections, and 10% of infections were bacteraemic. Crude mortality was 20%. Inappropriate antibiotic therapy was independently associated with an increased risk of death (OR = 3.30; 95% CI: 1.34-8.11).Conclusions: We found some differences in the epidemiology of CPE depending on the type of carbapenemase produced. Although a low proportion of CPE infections were bacteraemic, active antibiotic therapy was a protective factor for reducing mortality. [ABSTRACT FROM AUTHOR]

The article describes the repair works undertaken by the Spanish Highway Department of the Ministry of Development at the two dual-lane Niévares tunnels on the Cantabria Motorway, close to Gijon (Asturias). Both tunnels revealed a series of problems due to the presence of carbonate materials, and where the dissolution and run-off of the same led to blockages in the drainage and the production of additional stress on the tunnel lining (ten years after the tunnels had come into operation), both in the side walls and on the tunnel floor. This article describes the anomalies detected and the work carried out to strengthen and drain the lining and to improve the system for the removal of collected water, as well as the initiation of a study into the mitigating effect of polyaspartic acid in the limestone deposits. These works have all been carried out by alternately closing each tunnel off to traffic. [ABSTRACT FROM AUTHOR]

Background 'Candidatus Neoehrlichia mikurensis' is a tick-borne bacteria implicated in human health. To date, 'Ca. Neoehrlichia mikurensis' has been described in different countries from Africa, Asia and Europe, but never in Spain. However, according to the epidemiological features of the main vector in Europe, Ixodes ricinus, its circulation in our country was suspected. Methods A total of 200 I. ricinus ticks collected in the North of Spain were analyzed. DNAs were extracted and used as templates for PCRs targeting fragment genes for Anaplasma/Ehrlichia detection. The amplified products were sequenced and analyzed. Results 'Ca. Neoehrlichia mikurensis' was amplified in two specimens. Furthermore, Anaplasma phagocytophilum was detected in 61 samples analyzed. Conclusions The detection of 'Ca. Neoehrlichia mikurensis' in I. ricinus ticks from Spain indicates its circulation and the potential risk of contracting a human infection in this country. [ABSTRACT FROM AUTHOR]

Infective endocarditis (IE) is a severe and life-threatening disease. Identification of infectious etiology is essential for establishing the appropriate antimicrobial treatment and decreasing mortality. The aim of this study was to explore the potential utility of metataxonomics for improving microbiological diagnosis of IE. Here, next-generation sequencing (NGS) of the V3–V4 region of the 16S rRNA gene was performed in 27 heart valve tissues (18 natives, 5 intravascular devices, and 4 prosthetics) from 27 patients diagnosed with IE (4 of them with negative blood cultures). Metataxonomics matched with conventional diagnostic techniques in 24/27 cases (88.9%). The same bacterial family was assigned to 24 cases; the same genus, to 23 cases; and the same species, to 13 cases. In 22 of them, the etiological agent was represented by percentages > 99% of the reads and in two cases, by ~70%. Staphylococcus aureus was detected in a previously microbiological undiagnosed patient. Thus, microbiological diagnosis with 16S rRNA gene targeted-NGS was possible in one more sample than using traditional techniques. The remaining two patients showed no coincidence between traditional and 16S rRNA gene-targeted NGS microbiological diagnoses. In addition, 16S rRNA gene-targeted NGS allowed us to suggest coinfections that were supported by clinical data in one patient, and minority records also verified mixed infections in three cases. In our series, metataxonomics was valid for the identification of the causative agents, although more studies are needed before implementation of 16S rRNA gene-targeted NGS for the diagnosis of IE. [ABSTRACT FROM AUTHOR]

Objectives To describe the molecular and population-level characterization of a selected group of OXA-48-like-producing Klebsiella pneumoniae isolates collected in Spain between January 2011 and May 2012. Methods During the study period, 151 OXA-48-like-producing K. pneumoniae isolates were collected from 10 hospitals in six different Spanish regions. From these, a representative sample of 21 isolates that caused hospital outbreaks and single infections was selected for further in-depth analysis. Molecular epidemiology was investigated using PFGE and multilocus sequence typing (MLST). Resistance genes were characterized by PCR and sequencing. Plasmids carrying blaOXA-48-like were studied by PFGE with S1 nuclease digestion. Results All 21 isolates had ertapenem MICs ≥1 mg/L, but 47.6% remained susceptible to imipenem and meropenem; blaOXA-48 was identified in 19 isolates (90.5%) and the novel blaOXA-244 and blaOXA-245 genes were detected in 1 isolate each. With one exception, all isolates that contained blaOXA-48-like also contained blaCTX-M-15. PFGE typing revealed six clusters comprising isolates that belonged to MLST types ST11, ST16, ST392, ST405, ST437 and ST663, respectively. Two main clusters were identified: PFGE cluster 1 (12 isolates, belonging either to ST405 or ST663, from seven hospitals), and PFGE cluster 2 (4 ST16 isolates from two hospitals). Six of seven donor isolates conjugated successfully; blaOXA-48-like (but not blaCTX-M-15) was carried on ∼60 kb Inc L/M plasmids. Conclusions Multidrug-resistant K. pneumoniae producing OXA-48-like carbapenemase are emerging as important pathogens in Spain due to intra- and inter-hospital, clonal and non-clonal dissemination. [ABSTRACT FROM PUBLISHER]

Purpose: To define and validate a pharmacokinetic (PK) model for tacrolimus (TAC) that includes patient pathophysiology and has clinical applicability in the first 2 weeks post-liver transplantation (PLT). Methods: Routine monitoring records [dose, trough levels (C), demographics, biochemistry] from 75 patients treated with TAC (Prograf®) PLT were used to develop a population PK model (employing NONMEM®) testing for predictors of oral clearance (CL/F) according to bedside evidence and primarily with aspartate aminotransferase (AST), albumin (ALB), and hematocrit (HCT). Patients were catergorized into subgroups with above and below 'normal' thresholds for AST (500 U/L), ALB (2.5 g/dL), and HCT (28 %), respectively. The model was validated with ten patients from the same period and 15 more recent patients. An empirical Bayes method was developed and applied to the prediction of individual profiles serving as a dose adjustment tool. Results: The number of days PLT (Days PLT) was a key variable during the first 2 weeks, with a dichotomy in the mono-compartmental parameters for 0-3 Days PLT and 4-15 Days PLT. During 0-3 Days PLT, AST levels, indicative of allograft functionality (and TAC metabolism), were crucial predictors of elimination. Three groups were identified with the following clearances: CL/F = 8.93 L/h for AST ≥500 U/L and CL/F = 11.0 L/h for AST <500 U/L. During 4-15 Day PLT, low values of ALB (<2.5 g/dL) and HCT (<28 %) combined were determinant of a patient subgroup with a tendency to underexposure and complexity in empirical dose adjustment. The CL/F = 25.1 L/h for this subgroup compared to CL/F = 17.1 L/h for the others in that period. The elimination half-life for individual patients varied over tenfold so that a large number of subjects were not at steady state, making the use of a PK model necessary to achieve rapidly and safely the target concentration for TAC in LT. Validation of the model demonstrated that both bias and precision were within acceptable limits. Conclusion: For TAC therapy, covariate models using mixed effects methods are most useful when combined with patient-specific biochemical assays as well as clinical evidence. In such cases, the observed C and Bayes methods can provide the most likely individual PK parameters, hence the optimal next dose to reach individualized target levels for each patient. [ABSTRACT FROM AUTHOR]

We amplified gene sequences from Anaplasma phagocytophilum, Borrelia garinii, B. valaisiana, B. turdi, Rickettsia monacensis, R. helvetica, R. sibirica sibirica, and Rickettsia spp. (including Candidatus Rickettsia vini) in ticks removed from birds in Spain. The findings support the role of passerine birds as possible dispersers of these tick-borne pathogens. [ABSTRACT FROM AUTHOR]

Objectives To describe the clinical presentation and prognosis of elderly adults hospitalized with pandemic 2009 A(H1N1) influenza infection and to compare these data with those of younger patients. Design Prospective, observational, multicenter study. Setting Thirteen hospitals in Spain. Participants Adults admitted to the hospital with confirmed pandemic 2009 A(H1N1) influenza infection. Measurements Demographic, clinical, laboratory, radiological, and outcome variables. Results Between June 12 and November 10, 2009, 585 adults with confirmed 2009 A(H1N1) influenza were hospitalized, of whom 50 (8.5%) were aged 65 and older (median age 72, range 65-87). Older adults (≥65) were more likely to have associated comorbidities (88.0% vs 51.2%; P < .001), primarily chronic pulmonary diseases (46.0% vs 27.3%; P < .001). Lower respiratory tract symptoms and signs such as dyspnea (60.0% vs 45.6%) and wheezing (46.0% vs 27.8%; P = .007) were also more common in these elderly adults, although pulmonary infiltrates were present in just 14 (28.0%) of the older adults, compared with 221 (41.3%) of the younger adults ( P = .06). Multilobar involvement was less frequent in elderly adults with pulmonary infiltrates than younger adults with pulmonary infiltrates (21.4% vs 60.0%; P = .05). Rhinorrhea (4.0% vs 21.9%; P = .003), myalgias (42.0% vs 59.1%; P = .01), and sore throat (14.0% vs 29.2%; P = .02) were more frequent in younger adults. Early antiviral therapy (<48 hours) was similar in the two groups (34.0% vs 37.9%; P = .58). Two older adults (4.0%) died during hospitalization, compared with 11 (2.1%) younger adults ( P = .30). Conclusion Elderly adults with 2009 A(H1N1) influenza had fewer viral-like upper respiratory symptoms than did younger adults. Pneumonia was more frequent in younger adults. No significant differences were observed in hospital mortality. [ABSTRACT FROM AUTHOR]

Purpose: To explore the main factors that make it difficult to empirically monitor tacrolimus (TAC) in the early period post-liver transplantation (LTx), with a specific focus on those aspects related to patient idiosyncrasy and clinical status as well as to the pharmacokinetic (PK) assumptions on which drug individualization in clinical practice is based. Methods: Retrospective monitoring data from 75 de novo liver transplant patients treated with twice daily with TAC and followed for up to 15 days were analyzed. An extensive battery of laboratory measurements were available. Dose adjustment was performed empirically using trough levels (C). The population was separated into two major background groups according to low or high values of aspartate aminotransferase (AST) (Group 1 and 2, respectively) based on AST measurements made during the first 4 days post-LTx. Each of these two major groups was then further subdivided into two subgroups based on elevated (Groups 1A, 2A) or reduced (Groups 1B, 2B) combined albumin (cut-off 2.5 g/dl) and hematocrit (cut-off 28%). Results: The C/Dose ratio [inversely proportional to systemic clearance (CL)] had a variability [coefficient of variation (CV) >80%) that was incongruently higher for the ratio than for C and Dose separately. This was attributed to most patients not being at steady state or physiologically stable in the early post-LTx period. Group 1 patients were more predictable than Group 2 patients, who were responsible for the variability in the ratio. C was lower in the reduced ALB and HCT patient groups when AST conditions were similar (1A vs. 1B and 2A vs. 2B), likely due to increased TAC metabolic clearance (reduced C/Dose). This situation existed for two periods: 0-15 days post-LTx and 4-15 days post-LTx observations. Group 2A patients were the main source of the paradoxical variability in C/Dose (higher ratio of 2.7; CV = 100%), suggesting a lower clearance and difficulty in the recovery of stability. In contrast, Group 2B patients had the lower ratio (1.4; 47%) but required the highest number of dose adjustments as the variability was hard to identify clinically. Group 1A patients were the most predictable empirically. When observations from 15 new patients who entered the clinic in 2007 and 2008 were used for the analysis, the same sub-groups existed in the same proportions in both years. Conclusion: The difficulty in empirical dose adjustment of TAC is associated to the inevitable non-fulfillment of PK assumptions early post-LTx and also to the inherent complexity of the clinical condition, leading to increased uncertainty for the clinician regarding dose selection. Identifying these sub-categories provides a rational means of classifying patients akin to a phenotype. The complexity of the kinetics in LTx and TAC treatment does not invalidate C as a biomarker, but a Bayes algorithm including a full PK structure and these covariates would be optimal. [ABSTRACT FROM AUTHOR]

Objectives: To characterize the population structure and resistance mechanisms of Klebsiella pneumoniae isolates that are highly resistant to third-generation cephalosporins, collected from five Spanish hospitals. [ABSTRACT FROM PUBLISHER]

Abstract: In this study, we investigated the population structure of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli in Spain and determined possible associations between specific multilocus sequence typing (MLST) types and ESBL types. Ninety-two ESBL-producing E. coli isolates from 11 Spanish hospitals were studied. The predominant ESBLs in this collection were CTX-M-14 (45.7%), SHV-12 (21.7%) and CTX-M-9 (20.6%). Phylogenetic groups and MLST types were studied. Thirty-seven isolates (40.2%) belonged to phylogroup A, 26 (28.3%) to group B1, 13 (14.1%) to group B2 and 16 (17.4%) to group D. Fifty-six sequence types (STs) were identified, but ST131 (eight isolates) and ST167 (five isolates) were the most prevalent. The most common ST complexes were ST10 (13 isolates; 14.3%) and ST23 (10 isolates; 11%). Escherichia coli ST131 carried six different ESBLs (CTX-M-1, CTX-M-9, CTX-M-10, CTX-M-14, CTX-M-15 and SHV-12), E. coli ST10 complex carried five ESBLs and E. coli ST23 complex carried four ESBLs. A great diversity of MLST types was observed among Spanish ESBL-producing E. coli isolates. [Copyright &y& Elsevier]

The article presents a study which analyses tick-borne lymphadenopathy complicated by acute myopericarditis in Spain. Topics discussed include development of acute myopericarditis in patient biten by large tick, several cases of rickettsiosis in Europe, and examination of the patient revealing elevated punctiform lesion.

In an attempt to know the potential risk of human disease after exposure to ticks in La Rioja (North of Spain), the objective of our study was to investigate the presence of Rickettsiaspecies in Haemaphysalisticks collected in our area. A total of 177 Haemaphysalisspp. belonging to three species (H. punctata, H. sulcata, and H. inermis) were subjected to DNA extraction and tested by polymerase chain reaction (PCR) targeting three rickettsial genes gltA, ompB, and ompA. Six (3 H. inermis, 2 H. punctata, and 1 H. sulcata) of the 177 specimens were found to be infected (3.4). The rickettsiae in H. inermisticks (n 3) were identified as Rickettsia aeschlimanniiby sequencing of the genes coding for gltA, ompB, and ompA. Nucleotide sequences from H. punctataand H. sulcatasamples that yielded PCR products (n 3), showed >99 similarity with sequences of Rickettsiaendosymbiont of H. sulcataand ‘Candidatus Rickettsia hoogstraalii’ for gltAand ompBgenes, respectively. Attempts to amplify ompAfrom these two H. punctataand one H. sulcatafailed. This study suggests that H. inermiscould be a vector for tick-borne spotted fever caused by R. aeschlimanniiin the north of Spain. Further studies on characterization and culture of rickettsial endosymbionts found in Haemaphysalisspp. should be performed. [ABSTRACT FROM AUTHOR]

To determine the evolution and trends of amoxicillin --clavulanic acid resistance among Escherichia coli isolates in Spain, we tested 9,090 blood isolates from 42 Spanish hospitals and compared resistance with trends in outpatient consumption. These isolates were collected by Spanish hospitals that participated in the European Antimicrobial Resistance Surveillance System network from April 2003 through December 2006. [ABSTRACT FROM AUTHOR]

Aim: To investigate the subgingival microbiota of distinct periodontitis patient populations, in Chile, Colombia and Spain, using identical clinical and bacteriological methods. Material and Methods: In this multicentre study, 114 chronic periodontitis patients were selected. Patients were examined using an identical clinical protocol and pooled subgingival samples were obtained from each patient. Samples were processed in the three laboratories by means of culturing under identical clinical and microbiological protocols. Total anaerobic counts and frequency of detection and proportions of nine periodontal pathogens were calculated. Variables were analysed by means ofanova, χ2, Kruskal–Wallis and Dunn's multiple comparison tests. Results: The Colombian population demonstrated greater severity of periodontitis, with significantly deeper mean probing pocket depth, and had a significantly lower percentage of current smokers. When comparing samples from the three patient populations, the total counts were significantly higher in the Colombian patients. The numbers of putative pathogens differed among groups. Tannerella forsythia was found less frequently in Chilean samples, while Parvimonas micra and enteric rods differed significantly among the three population groups. Conclusion: Significant differences among Chile, Colombia and Spain existed regarding the frequency and proportions of specific periodontal pathogens in the subgingival microbiota of periodontitis patients. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To study if progression to AIDS and death, as well as clinical and virological response to highly active antiretroviral therapy (HAART), differs between men and women. METHODS: We studied a multicenter, hospital-based cohort of HIV-infected patients attending 10 hospitals in Spain from January 1997 to December 2003. Kaplan-Meier and Cox regression were used to assess the effect of sex on time to AIDS, survival from AIDS, onset of a new AIDS event or death, and viral suppression from HAART. RESULTS: Of 4643 patients, 27% were women. Women had statistically significant lower viral loads (VL) of 3.9 vs. 4.1 log10/mL (p = 0.02) and higher median CD4 counts of 339 vs. 288 cells/mm3 (p < 0.001) at entry and were more likely to be AIDS free at entry. In univariate analysis, women seemed to show a nonsignificant lower progression to AIDS (HR 0.88) (95 CI% 0.73-1.07), which disappeared in multivariate analyses (HR 1.03) (95% CI 0.82-1.29). Survival from AIDS seemed to be higher in women (HR 0.65) (95% CI 0.40-1.05), but differences became clearly nonsignificant after adjustments (HR 0.71) (95% CI 0.42-1.23). No differences were seen in time to new AIDS condition or death after HAART (HR 1.08) (95% CI 0.80-1.46) in multivariate analyses. No differences were seen for time to VL suppression after initiation of HAART (HR 1.07) (95% CI 0.92-1.24). CONCLUSIONS: We have found no differences in HIV progression and response to HAART attributable to gender among patients accessing the Spanish hospital network. [ABSTRACT FROM AUTHOR]

Chiggers, the larvae of trombiculid mites, parasitize a wide variety of terrestrial vertebrates worldwide. Their bites cause seasonal trombiculiasis in humans and animals. Affected canines can have a variety of digestive and systemic clinical signs. We describe a case of canine trombiculiasis in a dog exhibiting severe neurologic symptoms. [ABSTRACT FROM AUTHOR]

This study describes the epidemiological, clinical, and microbiological characteristics of a new tick-borne disease in Spain— Dermacentor-borne necrosis erythema lymphadenopathy (DEBONEL). The clinical presentations include an eschar at the site of the tick bite, surrounded by an erythema and painful regional lymphadenopathy. The disease appears during the colder months and its vector is Dermacentor marginatus (D. marginatus). From January 1990 to December 2004, 54 patients presented at Hospital of La Rioja with these clinical and epidemiological data. The ratio of females to males was 32/22. The average age was 37 years. In all cases tick bites were located on the upper body (90% on the scalp). The median incubation period was 4.7 days. Signs and symptoms were mild in all cases. Only a small number of patients presented mild and nonspecific abnormalities in a complete blood cell count and mild elevation of erythrocyte sedimentation rates and C-protein reactive and liver enzyme levels. Serological evidence of acute rickettsiosis was observed in 19 patients (61%). In 29% sera tested by polymerase chain reactions (PCRs) were positive. The sequence obtained from a PCR product revealed 98% identity with Rickettsia sp. strains RpA4, DnS14, and DnS28. All ticks removed from patients were PCR-positive. Sequencing showed 8 of them identified as R. slovaca and 2 as Rickettsia sp. strains RpA4, DnS14, and DnS28. [ABSTRACT FROM AUTHOR]

Our objective was to learn the prevalence of spotted fever group (SFG) Rickettsia detected in ticks in La Rioja, in the north of Spain. From 2001 to 2005, 496 ticks representing 7 tick species were analysed at the Hospital de La Rioja. Ticks were removed from humans with or without rickettsial syndrome ( n= 59) or collected from mammals ( n= 371) or from vegetation by dragging ( n= 66). The presence of SFG Rickettsia in these ticks was investigated by semi-nested PCR ( ompA gene) and sequencing. A phylogenetic tree using Clustal method (neighbor-joining) was constructed with these data. Only 3 of 170 Hyalomma marginatum ticks carried SFG Rickettsia. Sequencing analysis demonstrated the presence of Rickettsia aeschlimannii (1.8%). Furthermore, Rickettsia massiliae and BAR29 were found in 3 of 120 Rhipicephalus sanguineus specimens (2.5%). In contrast, 81 of 83 tested Dermacentor marginatus ticks were PCR-positive (97%). Rickettsia slovaca (40.6%) and Rickettsia sp. strains RpA4, DnS14, DnS28 and JL-02 (59.3%) were found within this tick species. No SFG Rickettsia was detected using ompA primers when Ixodes ricinus, Rhipicephalus bursa, Rhipicephalus turanicus, Rhipicephalus eversti eversti, Hyalomma detritum scupense and Rhipicephalus sp. were analyzed. We detected 17.5% of ticks associated with different SFG Rickettsia: R. aeschlimannii, R. massiliae, BAR29, R. slovaca and Rickettsia sp. strains RpA4, DnS14, DnS28 and JL-02. Their presence has to be taken into account since most of them have been recognized as human pathogens. [ABSTRACT FROM AUTHOR]

Our aim was to determine the presence of Rickettsia spp. and Bartonella spp. in Ctenocephalides felis and Ctenocephalides canis from La Rioja (Spain). A total of 88 specimens were tested by polymerase chain reaction (PCR) using gltA and ompB genes as targets for Rickettsia spp., and 16S rRNA and ribC genes for Bartonella spp. Rickettsia felis-like (28.4%), Bartonella clarridgeiae (6.8%), and Bartonella henselae (3.4%) were detected in Ctenocephalides spp. Other Bartonella sp. different from B. clarridgeiae and B. henselae could also be present in fleas from La Rioja. [ABSTRACT FROM AUTHOR]

Our aim was to identify variants of Anaplasma phagocytophilum 16S rRNA gene sequences among products amplified from Ixodes ricinus collected in La Rioja, Spain. A. phagocytophilum AP-variant 1, reported as nonpathogenic, was detected in 12 samples (two adults and ten nymphs). This finding could justify the low incidence of human anaplasmosis in our area, despite the high prevalence of A. phagocytophilum in ticks. [ABSTRACT FROM AUTHOR]

van Winkelhoff AJ, Herrera D, Oteo A, Sanz M. Antimicrobial profiles of periodontal pathogens isolated from periodontitis patients in the Netherlands and Spain. J Clin Periodontol 2005; 32: 893–898. doi: 10.1111/j.1600-051X.2005.00782.x. © Blackwell Munksgaard, 2005. Antimicrobial resistance of periodontal pathogens towards currently used antibiotics in periodontics has been investigated in a previous study. Microbial resistance in the periodontal microflora was more frequently observed in Spanish patients in comparison with Dutch patients. The aim of the present study was to compare antimicrobial susceptibility profiles of five periodontal bacteria isolated from periodontitis patients in Spain and in the Netherlands. Subgingival plaque samples from adult patients with periodontitis were collected and cultured on selective and non-selective plates. Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Prevotella intermedia, Fusobacterium nucleatum and Micromonas micros were isolated and used for minimal inhibitory concentration tests using the Epsilometer (E-test) technique. Eight different antibiotics were tested on all bacterial isolates. MIC50 and MIC90 values for each antibiotic and each species were determined and the percentage of resistant strains was calculated. Significantly higher MIC values were noted in Spanish strains of F. nucleatum for penicillin, ciprofloxacin, of P. intermedia for penicillin, amoxicillin and tetracycline, of M. micros for tetracycline, amoxicillin and azithromycin, and of P. gingivalis for tetracycline and ciprofloxacin. Based on breakpoint concentrations, a higher number of resistant strains in Spain were found in F. nucleatum for penicillin, amoxicillin and metronidazole, in Prevotella intermedia for tetracycline and amoxicillin, and in A. actinomycetemcomitans for amoxicillin and azithromycin. Resistance of P. gingivalis strains was not observed for any of the antibiotics tested both in Spain and the Netherlands. Differences exist in the susceptibility profiles of periodontal pathogens isolated from periodontitis patients in Spain and in the Netherlands. This implicates that antibiotic susceptibility testing is necessary to determine efficacy of antimicrobial agents. Also, clinical studies with antibiotics should take these differences into account. The information from the present study indicates that it may not be possible to develop uniform protocols for usage of antibiotics in the treatment of severe periodontitis in the European Union. [ABSTRACT FROM AUTHOR]

This paper describes the epidemiological and clinical features of a tick-borne disease differing somewhat from other tick-borne diseases found previously in Spain. All patients were bitten by Dermacentor marginatus or a large tick. The clinical features include a crustaceous or necrotic lesion at the site of the tick's attachment, surrounded by an erythema (erythema migrans-like) and painful regional lymphadenopathies. The probable aetiological agent is Rickettsia slovaca. Similar cases have been reported in other European countries. [ABSTRACT FROM AUTHOR]