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Objectives: An increase in Streptococcus dysgalactiae subsp. equisimilis (SDSE) infections has been documented worldwide. This study aims to analyze invasive disease caused by SDSE (iSDSE) in adults over an 11-year period in Spain., Methods: We conducted a retrospective, laboratory-based study of iSDSE detected at Hospital Universitari de Bellvitge (HUB) from 2012 to 2022 (n = 89) and isolates collected in three Spanish hospitals in 2018 (n = 22). Clinical data from HUB were collected. Isolates were tested for antimicrobial susceptibility (European Committee on Antimicrobial Susceptibility Testing 2023), subjected to whole genome sequencing and analyzed for mobile genetic elements (MGEs). A mouse model was used to analyze virulence., Results: iSDSE episodes at HUB occurred predominantly in older patients with comorbidities (particularly, diabetes, chronic heart disease, and malignancies). Whole genome sequencing revealed a high genetic diversity, with the most common lineages being CC15, CC17, and CC20. Various virulence factors, including the superantigen speG, were identified. Macrolides, lincosamides, and tetracyclines exhibited the highest resistance rates (>27%) and changed over time, linked to multiple MGEs. The mouse model highlighted the virulence of the CC20-stG62647 lineage, but these results were discordant with clinical data., Conclusion: iSDSE incidence is increasing and associated with older patients with comorbidities. Genetically, SDSE is diverse with a high capacity to integrate MGEs carrying resistance determinants. Mouse model studies showed the enhanced virulence of the CC20-stG62647 lineage. These findings underscore the need for ongoing surveillance of this emerging pathogen., Competing Interests: Declarations of competing interest The authors have no competing interests to declare., (Copyright © 2025 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Streptococcus pneumoniae causes invasive pneumococcal disease (IPD) in adults. The introduction of pneumococcal conjugate vaccines (PCVs) has reduced vaccine serotypes but has also led to the rise of non-vaccine serotypes. The aim of this study was to analyse pneumococcal lineages and their association with recent changes in IPD among adults in Spain., Methods: Data from adult IPD cases (≥18 years) were collected from six Spanish hospitals in 2019-2021. Strains were serotyped, tested for antibiotic susceptibility and subjected to whole genome sequencing (WGS). Findings were compared with data from previous periods (2008-2016)., Results: A total of 655 IPD episodes were examined. Pneumonia was the main focus (515/655), and 366 episodes occurred in adults over 64 years. Although IPD incidence decreased during COVID-19 pandemic, the burden of disease caused by PCV13 serotypes was significant. Notably, serotype 3 persisted (GPSC12-ST180 and GPSC83-ST260), and a new serotype 4 lineage emerged (GPSC162-ST13022). Among non-PCV13 serotypes, serotype 8 expanded (GPSC3-ST53) and a new serotype 12F lineage emerged (GPSC55-ST8060). Most serotypes presented a dominant Global Pneumococcal Sequencing Cluster (GPSC) like GPSC16-ST67 of 9N or GPSC19-ST433 of 22F. Nevertheless, some GPSCs were associated with several serotypes, the most numerous were GPSC3 (serotypes 8, 11A, and 33F) and GPSC6 (serotypes 11A and 14). The overall penicillin non-susceptibility rate was 17.0 %, 14.6 % resistance for meningitis and 1.6 % for pneumonia (15.1 % susceptible at increased exposure [SIE]). Serotypes 11A and 14 (GPSC6-ST156/6521) and 19A (GPSC1-ST320) had penicillin MICs above 1 mg/L. Acquired resistance genes associated with macrolide and/or tetracycline resistance were present in 19.4 % of isolates, particularly among serotypes 6C (GPSC47-ST386/4310) and 19A (GPSC1-ST320)., Conclusions: The burden of PCV13 serotypes in adult IPD remains significant, and serotype 3 is the primary contributor. However, the rise of stable lineages associated with non-PCV13 serotypes, particularly 8, 9N, and 22F highlights a shifting epidemiology. The persistence of multidrug-resistant lineages, such as GPSC6-ST156 and GPSC1-ST320, emphasizes the need for continued surveillance. Vaccination of high-risk adults with current and broader coverage PCVs would help to control the burden of pneumonia and IPD among adults., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Sara Calvo-Silveria declares that the Project was partially funded by PFIS predoctoral grant number FI22/00279. José Yuste declares grants or contracts paid to his institution from MSD, Pfizer and Meiji. Support for attending meetings and/or travel from MSD and Pfizer. Participation on a Data Safety Monitoring Board or Advisory Board from GSK, MSD and Pfizer. Carmen Ardanuy declares funding to the institution from Instituto de Salud Carlos III through PI18/0339; PI21/1000 and INT22/0096; CB06/06/0037. Grants or contracts paid to her institution from MSD, Pfizer and Menarini. Payment or honoraria for lectures, or educational events from MSD and Pfizer to her o her institution. Support for attending meetings and/or travel from MSD and Pfizer., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Countries across Europe have faced similar evolutions of SARS-CoV-2 variants of concern, including the Alpha, Delta, and Omicron variants., Materials and Methods: We used data from GISAID and applied a robust, automated mathematical substitution model to study the dynamics of COVID-19 variants in Europe over a period of more than 2 years, from late 2020 to early 2023. This model identifies variant substitution patterns and distinguishes between residual and dominant behavior. We used weekly sequencing data from 19 European countries to estimate the increase in transmissibility  ( Δ β )   between consecutive SARS-CoV-2 variants. In addition, we focused on large countries with separate regional outbreaks and complex scenarios of multiple competing variants., Results: Our model accurately reproduced the observed substitution patterns between the Alpha, Delta, and Omicron major variants. We estimated the daily variant prevalence and calculated Δ β between variants, revealing that: ( i ) Δ β increased progressively from the Alpha to the Omicron variant; ( i i ) Δ β showed a high degree of variability within Omicron variants; ( i i i ) a higher Δ β was associated with a later emergence of the variant within a country; ( i v ) a higher degree of immunization of the population against previous variants was associated with a higher Δ β for the Delta variant; ( v ) larger countries exhibited smaller Δ β ,  suggesting regionally diverse outbreaks within the same country; and finally ( v i ) the model reliably captures the dynamics of competing variants, even in complex scenarios., Conclusion: The use of mathematical models allows for precise and reliable estimation of daily cases of each variant. By quantifying Δ β ,  we have tracked the spread of the different variants across Europe, highlighting a robust increase in transmissibility trend from Alpha to Omicron. Additionally, we have shown that the geographical characteristics of a country, as well as the timing of new variant entrances, can explain some of the observed differences in variant substitution dynamics across countries., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (Copyright © 2024 de Rioja, Perramon-Malavez, Alonso, Andrés, Antón, Bordoy, Càmara, Cardona, Català, López, Martí, Martró, Saludes, Prats and Alvarez-Lacalle.)

Background: Invasive pneumococcal disease due to serotype 3 (S3-IPD) is associated with high mortality rates and long-term adverse effects. The introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) into the Spanish paediatric immunisation programme has not led to a decrease in the adult S3-IPD. We aimed to analyse the incidence, clinical characteristics and genomics of S3-IPD in adults in Spain., Methods: Adult IPD episodes hospitalized in a Southern Barcelona hospital were prospectively collected (1994-2020). For genomic comparison, S3-IPD isolates from six Spanish hospitals (2008-2020) and historical isolates (1989-1993) were analysed by WGS (Illumina and/or MinION)., Findings: From 1994 to 2020, 270 S3-IPD episodes were detected. When comparing pre-PCV (1994-2001) and late-PCV13 (2016-2020) periods, only modest changes in S3-IPD were observed (from 1.58 to 1.28 episodes per 100,000 inhabitants year). In this period, the incidence of the two main lineages shifted from 0.38 to 0.67 (CC180-GPSC12) and from 1.18 to 0.55 (CC260-GPSC83). The overall 30-day mortality remained high (24.1%), though a decrease was observed between the pre-PCV (32.4%; 95.0% CI, 22.0-45.0) and the late-PCV13 period (16.7%; 95.0% CI, 7.5-32.0) (p = 0.06). At the same time, comorbidities increased from 77.3% (95.0% CI, 65.0-86.0) to 85.7% (95.0% CI, 71.0-94.0) (p = 0.69). There were no differences in clinical characteristics or 30-day mortality between the two S3 lineages. Although both lineages were genetically homogeneous, the CC180-GPSC12 lineage presented a higher SNP density, a more open pan-genome, and a major presence of prophages and mobile genetic elements carrying resistance genes., Interpretation: Adult S3-IPD remained stable in our area over the study period despite PCV13 introduction in children. However, a clonal shift was observed. The decrease in mortality rates and the increase in comorbidities suggest a change in clinical management and overall population characteristics. The low genetic variability and absence of clinical differences between lineages highlight the role of the S3 capsule in the disease severity., Funding: This study has been funded by Instituto de Salud Carlos III (ISCIII) "PI18/00339", "PI21/01000", "INT22/00096", "FI22/00279", CIBER "CIBERES-CB06/06/0037", "CIBERINFEC-CB21/13/00009" and MSD grant "IISP 60168"., Competing Interests: C.A. has been a scientific adviser for, and/or has received research funding from, Merck Sharp & Dohme Corp and Pfizer. J.Y. has been a scientific adviser for, and/or has received research funding from, Merck Sharp & Dohme Corp, Pfizer and GSK. All other authors declare that they have no conflicts of interest regarding this research., (© 2024 The Author(s).)

Introduction: Infections caused by carbapenem-resistant Enterobacterales (CRE) and carbapenem-resistant Pseudomonas aeruginosa , including isolates producing acquired carbapenemases, constitute a prevalent health problem worldwide. The primary objective of this study was to determine the distribution of the different carbapenemases among carbapenemase-producing Enterobacterales (CPE, specifically Escherichia coli , Klebsiella pneumoniae , Enterobacter cloacae complex, and Klebsiella aerogenes ) and carbapenemase-producing P. aeruginosa (CPPA) in Spain from January 2014 to December 2018., Methods: A national, retrospective, cross-sectional multicenter study was performed. The study included the first isolate per patient and year obtained from clinical samples and obtained for diagnosis of infection in hospitalized patients. A structured questionnaire was completed by the participating centers using the REDCap platform, and results were analyzed using IBM SPSS Statistics 29.0.0., Results: A total of 2,704 carbapenemase-producing microorganisms were included, for which the type of carbapenemase was determined in 2692 cases: 2280 CPE (84.7%) and 412 CPPA (15.3%), most often using molecular methods and immunochromatographic assays. Globally, the most frequent types of carbapenemase in Enterobacterales and P. aeruginosa were OXA-48-like, alone or in combination with other enzymes (1,523 cases, 66.8%) and VIM (365 cases, 88.6%), respectively. Among Enterobacterales, carbapenemase-producing K. pneumoniae was reported in 1821 cases (79.9%), followed by E. cloacae complex in 334 cases (14.6%). In Enterobacterales, KPC is mainly present in the South and South-East regions of Spain and OXA-48-like in the rest of the country. Regarding P. aeruginosa , VIM is widely distributed all over the country. Globally, an increasing percentage of OXA-48-like enzymes was observed from 2014 to 2017. KPC enzymes were more frequent in 2017-2018 compared to 2014-2016., Discussion: Data from this study help to understand the situation and evolution of the main species of CPE and CPPA in Spain, with practical implications for control and optimal treatment of infections caused by these multi-drug resistant organisms., Competing Interests: LM-M has been a consultant for MSD, Shionogi and Fastinov, has served as speaker for Merck, Astra-Zeneca, Astellas, and Becton Dickinson and has received research support from MSD, Shionogi, Janssen-Cilag and Pfizer. JD-R is an employee of MSD Spain. RC has participated in educational programs organized by MSD, Pfizer and Shionogi and has received research support form MSD, and Venatrox. NL-E has been a consultant for MSD, Menarini, Shionogi and Fastinov and has served as a speaker for MSD, Pfizer, Menarini, Shionogi, Biomerieux and Accelerate Diagnostics. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Gracia-Ahufinger, López-González, Vasallo, Galar, Siller, Pitart, Bloise, Torrecillas, Gijón-Cordero, Viñado, Castillo-García, Campo, Mulet, Madueño-Alonso, Chamizo-López, Arrastia-Erviti, Galán-Sánchez, Fernández-Quejo, Rodríguez-Díaz, Gutiérrez-Zufiaurre, Rodríguez-Maresca, Ortega-Lafont, Yagüe-Guirao, Chaves-Blanco, Colomina-Rodríguez, Vidal-Acuña, Portillo, Franco-Álvarez de Luna, Centelles-Serrano, Azcona-Gutiérrez, Delgado-Iribarren García Campero, Rey-Cao, Muñoz, Calvo-Montes, Zboromyrska, Grandioso, Càmara, Cantón, Larrosa-Escartín, Díaz-Regañón and Martínez-Martínez.)

Methicillin-resistant Staphylococcus aureus bloodstream infections (MRSA-BSI) are a significant cause of mortality. We analysed the evolution of the molecular and clinical epidemiology of MRSA-BSI (n = 784) in adult patients (Barcelona, 1990−2019). Isolates were tested for antimicrobial susceptibility and genotyped (PFGE), and a selection was sequenced (WGS) to characterise the pangenome and mechanisms underlying antimicrobial resistance. Increases in patient age (60 to 71 years), comorbidities (Charlson’s index > 2, 10% to 94%), community-onset healthcare-associated acquisition (9% to 60%), and 30-day mortality (28% to 36%) were observed during the 1990−1995 and 2014−2019 periods. The proportion of catheter-related BSIs fell from 57% to 20%. Current MRSA-BSIs are caused by CC5-IV and an upward trend of CC8-IV and CC22-IV clones. CC5 and CC8 had the lowest core genome proportions. Antimicrobial resistance rates fell, and only ciprofloxacin, tobramycin, and erythromycin remained high (>50%) due to GyrA/GrlA changes, the presence of aminoglycoside-modifying enzymes (AAC(6′)-Ie-APH(2″)-Ia and ANT(4′)-Ia), and mph(C)/msr(A) or erm (C) genes. Two CC22-IV strains showed daptomycin resistance (MprF substitutions). MRSA-BSI has become healthcare-associated, affecting elderly patients with comorbidities and causing high mortality rates. Clonal replacement with CC5-IV and CC8-IV clones resulted in lower antimicrobial resistance rates. The increased frequency of the successful CC22-IV, associated with daptomycin resistance, should be monitored.

Background: During early stages of COVID-19 pandemic, antimicrobials were commonly prescribed., Aim: To describe clinical, microbiological and antimicrobial use changes in bloodstream infections (BSI) of ICU patients during the first wave of COVID-19 pandemic compared to pre-COVID-19 era., Methods: Observational cohort study of patients admitted to ICU of Bellvitge University Hospital was conducted during the COVID-19 pandemic (March-June 2020) and before COVID-19 pandemic (March-June 2019). Differences in clinical characteristics, antimicrobial consumption and incidence and aetiology of BSI were measured., Findings: COVID-19 patients had significantly less comorbidities with obesity the only risk factor that increased in frequency. COVID-19 patients more frequently required invasive supportive care measures, had longer median ICU stay and higher mortality rates. The incidence of BSIs was higher in COVID-19 period (RR 3.2 [95%CI 2.2-4.7]), occurred in patients who showed prolonged median ICU stay (21days) and was associated with high mortality rate (47%). The highest increases in the aetiological agents were observed for AmpC-producing bacteria (RR 11.1 [95%CI 2.6-47.9]) and non-fermenting rods (RR 7.0 [95%CI 1.5-31.4]). The emergence of bacteraemia caused by Gram-negative rods resistant to amoxicillin-clavulanate, which was used as empirical therapy during early stages of the pandemic, led to an escalation towards broader-spectrum antimicrobials such as meropenem and colistin which was also associated with the emergence of resistant isolates., Conclusions: The epidemiological shift towards resistant phenotypes in critically ill COVID-19 patients was associated with the selective use of antimicrobials. Our study provides evidence of the impact of empirical therapy on the selection of bacteria and their consequences on BSI over the subsequent months., (© 2022 The Authors.)

Streptococcal infections are usually treated with beta-lactam antibiotics, but, in case of allergic patients or reduced antibiotic susceptibility, macrolides and fluoroquinolones are the main alternatives. This work focuses on studying macrolide resistance rates, genetic associated determinants and antibiotic consumption data in Spain, Europe and also on a global scale. Macrolide resistance (MR) determinants, such as ribosomal methylases ( erm (B), erm (TR), erm (T)) or active antibiotic efflux pumps and ribosomal protectors ( mef (A/E)- mrs (D)), are differently distributed worldwide and associated with different clonal lineages and mobile genetic elements. MR rates vary together depending on clonal dynamics and on antibiotic consumption applying selective pressure. Among Streptococcus , higher MR rates are found in the viridans group, Streptococcus pneumoniae and Streptococcus agalactiae , and lower MR rates are described in Streptococcus pyogenes . When considering different geographic areas, higher resistance rates are usually found in East-Asian countries and milder or lower in the US and Europe. Unfortunately, the availability of data varies also between countries; it is scarce in low- and middle- income countries from Africa and South America. Thus, surveillance studies of macrolide resistance rates and the resistance determinants involved should be promoted to complete global knowledge among macrolide resistance dynamics.

We compared hospital-acquired catheter-related bacteremia (CRB) episodes diagnosed at acute care hospitals in Catalonia, Spain, during the COVID-19 pandemic in 2020 with those detected during 2007-2019. We compared the annual observed and predicted CRB rates by using the negative binomial regression model and calculated stratified annual root mean squared errors. A total of 10,030 episodes were diagnosed during 2007-2020. During 2020, the observed CRB incidence rate was 0.29/10 3 patient-days, whereas the predicted CRB rate was 0.14/10 3 patient-days. The root mean squared error was 0.153. Thus, a substantial increase in hospital-acquired CRB cases was observed during the COVID-19 pandemic in 2020 compared with the rate predicted from 2007-2019. The incidence rate was expected to increase by 1.07 (95% CI 1-1.15) for every 1,000 COVID-19-related hospital admissions. We recommend maintaining all CRB prevention efforts regardless of the coexistence of other challenges, such as the COVID-19 pandemic.

Methicillin-resistant Staphylococcus aureus (MRSA) may persist for long periods due to biofilm formation. The objective of this study was to describe biofilm formation in association with the presence of S. aureus surface protein G (sasG) and its allelic variants in MRSA bacteraemia isolates from endemic (CC5, CC8, CC22) and sporadic clones in Spain (2008-2015). Crystal violet staining was used to assess biofilm formation; DNA microarray, RT-qPCR, and long-read whole genome sequencing were applied to determine the presence, expression and structure of sasG, respectively. The endemic CC5 and CC8 clones produced more biofilm than the sporadic clones; these endemic clones carried sasG allelic variant 1. Otherwise, sporadic clones, with less biofilm formation, showed either an absence of sasG (65%) or the presence of allelic variant 2 (35%). Variants 1 and 2 differed in the expression of sasG (1.56 ± 1.20 and 0.37 ± 0.32, respectively). The analysis of a large cohort of closed S. aureus genomes available on the NCBI database confirmed the distribution of the two allelic variants with low amino acid identity (68.1%) among endemic and sporadic clones. SasG variant 1 present in the major CC5 and CC8 clones was correlated with increased biofilm formation and may represent an important virulence determinant., Competing Interests: Declaration of competing interest The authors declare that there is no conflict of interest regarding the publication of this article., (Copyright © 2022 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.)

Introduction: Streptococcus suis (S. suis) is a human zoonotic pathogen of occupational origin, with infection acquired through contact with live pigs or pig meat. Pig farming is one of Catalonia's biggest industries and as a result this region of Spain has one of the highest density pig populations per km 2 . The aim of our study was to describe the infections caused by S. suis occurring in that area over a 9-year period. Materials and Methods: A retrospective, multi-center study was carried out by searching records from 15 hospitals in Catalonia for the period between 2010 and 2019. Results: Over the study period altogether nine cases of S. suis infection were identified in five hospitals, with five of these cases occurring in the 2018-2019 period. The mean age of patients was 48 ± 8.9 years and all of them were males. Five patients (55.6%) worked in pig farms. The most frequent manifestation of infection was meningitis (5 cases; 55.6%) followed by septic arthritis (3 cases; 33.3%). None of the patients died at 30 days; nonetheless, 4 developed hearing loss as a long-term complication. Conclusion: The most commonly identified S. suis infection was meningitis. Over 50% of the episodes occurred in the last 2 years and have affected pig farm workers. Further surveillance is needed in order to know its prevalence., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Díez de los Ríos, Reynaga, García-Gonzàlez, Càmara, Ardanuy, Cuquet, Quesada, Navarro, Vilamala, Párraga-Niño, Quero, Romero, Benítez, Altimiras and Pedro-Botet.)

This study provides an update on invasive Haemophilus influenzae disease in Bellvitge University Hospital (2014-2019), reporting its evolution from a previous period (2008-2013) and analysing the non-typeable H. influenzae (NTHi) population structure using a clade-related classification. Clinical data, antimicrobial susceptibility and serotyping were studied and compared with those of the previous period. Population structure was assessed by multilocus sequence typing (MLST), SNP-based phylogenetic analysis and clade-related classification. The incidence of invasive H. influenzae disease remained constant between the two periods (average 2.07 cases per 100 000 population), while the 30 day mortality rate decreased (20.7-14.7 %, respectively). Immunosuppressive therapy (40 %) and malignancy (36 %) were the most frequent comorbidities. Ampicillin and fluoroquinolone resistance rates had increased between the two periods (10-17.6 % and 0-4.4 %, respectively). NTHi was the main cause of invasive disease in both periods (84.3 and 85.3 %), followed by serotype f (12.9 and 8.8 %). NTHi displayed high genetic diversity. However, two clusters of 13 ( n =20) and 5 sequence types (STs) ( n =10) associated with clade V included NTHi strains of the most prevalent STs (ST3 and ST103), many of which showed increased frequency over time. Moreover, ST103 and ST160 from clade V were associated with β-lactam resistance. Invasive H. influenzae disease is uncommon, but can be severe, especially in the elderly with comorbidities. NTHi remains the main cause of invasive disease, with ST103 and ST160 (clade V) responsible for increasing β-lactam resistance over time.

We studied changes in serotype distribution and antimicrobial susceptibility in adult pneumococcal pneumonia in Spain (2011-2019). Among 895 pneumococci collected (433 bacteremic [BPP] and 462 non-bacteremic [non-BPP]), serotypes 3 (17%), 19A (10%), 8 (6.7%) and 11A (6.7%) were the most frequent. Serotypes 16F, 19A and 24F were associated with old people (≥65) and serotypes 4, 7F, 8, 12F and 19F to young adults. Serotypes 12F, 24F and 1 were significantly more frequent in BPP and serotypes 11A, 23A and 19F in non-BPP. Amoxicillin resistance was higher in non-BPP (17% vs. 11%) while penicillin non-susceptibility (37% vs. 24%) and macrolide resistance (29% vs. 14%) were higher in older adults. In the period 2017-2019, the vaccine coverages were: 32% (PCV13), 39% (PCV15), 65% (PCV20) and 69% (PPV23). Differences were found in serotype composition and antimicrobial resistance by age and type of infection. The maintenance of serotype 3 as a leading cause of adult pneumococcal pneumonia and the increase in highly invasive (serotype 8) or antimicrobial-resistant (serotype 11A) serotypes is worrisome. Further studies will be required to analyse the impact of the upcoming broader conjugate vaccines.

Background: Surgical site infections after craniotomy (SSI-CRAN) significantly impact patient outcomes and healthcare costs by increasing length of stay and readmission and reoperation rates. However, to our knowledge, no study has yet analysed the economic impact of a surgical care bundle for preventing SSI-CRAN. The aim is to analyse the hospital cost saving after implementation of a care bundle for the prevention of SSI-CRAN., Methods: A retrospective cost-analysis was performed, considering two periods: pre-care bundle (2013-2015) and care bundle (2016-2017). A bottom-up approach was used to calculate the costs associated with infection in patients who developed a SSI-CRAN in comparison to those who did not, in both periods and on a patient-by-patient basis. The derived cost of SSI-CRAN was calculated considering: (1) cost of the antibiotic treatment, (2) cost of length of stay in the neurosurgery ward within the 1-year follow up period, (3) cost of the re-intervention, and (4) cost of the implant for cranial reconstruction, when necessary., Results: A total of 595 patients were included in the pre-care bundle period and 422 in the care bundle period. Mean cost of a craniotomy procedure was approximately €8000, rising to €24,000 in the case of SSI-CRAN. Mean yearly hospital costs fell by €502,857 in the care bundle period (€714,886 vs. €212,029). Extra costs between periods were mainly due to increased length of hospital stay (€573,555.3 vs. €183,958.9; difference: €389,596.4), followed by the cost of implant for cranial reconstruction (€69,803.4 vs. €9,936; difference: €59,867.4). Overall, implementation of the care bundle saved the hospital €500,844.3/year., Conclusion: The implementation of a care bundle for SSI-CRAN had a significant economic impact. Hospitals should consider the deployment of this multimodal preventive strategy to reduce their SSI-CRAN rates, and also their costs., (© 2021. The Author(s).)

Background: Acute cardiac events (ACEs) are increasingly being recognized as a major complication in pneumococcal community-acquired pneumonia (CAP). Information regarding host- and pathogen-related factors for ACEs, including pneumococcal serotypes and clonal complexes, is scarce., Methods: A retrospective study was conducted of a prospective cohort of patients hospitalized for CAP between 1996 and 2019. Logistic regression and funnel plot analyses were performed to determine host- and pathogen-related factors for ACEs., Results: Of 1739 episodes of pneumococcal CAP, 1 or more ACEs occurred in 304 (17.5%) patients, the most frequent being arrhythmia (n = 207), heart failure (n = 135), and myocardial infarction (n = 23). The majority of ACEs (73.4%) occurred within 48 hours of admission. Factors independently associated with ACEs were older age, preexisting heart conditions, pneumococcal bacteremia, septic shock at admission, and high-risk pneumonia. Among 983 pneumococcal isolates, 872 (88.7%) were serotyped and 742 (75.5%) genotyped. The funnel plot analyses did not find any statistically significant association between serotypes or clonal complexes with ACEs. Nevertheless, there was a trend toward an association between CC230 and these complications. ACEs were independently associated with 30-day mortality (adjusted odds ratio, 1.88; 95% CI, 1.11-3.13)., Conclusions: ACEs are frequent in pneumococcal pneumonia and are associated with increased mortality. The risk factors defined in this study may help identify patients who must undergo close follow-up, including heart rhythm monitoring, and special care to avoid fluid overload, particularly during the first 48 hours of admission. These high-risk patients should be the target for preventive intervention strategies., (© The Author(s) 2020. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

BackgroundThe successful pneumococcal clone Spain9V-ST156 (PMEN3) is usually associated with vaccine serotypes 9V and 14.AimOur objective was to analyse the increase of a serotype 11A variant of PMEN3 as cause of invasive pneumococcal disease (IPD) in Spain and its spread in south-western Europe.MethodsWe conducted a prospective multicentre study of adult IPD in Spain (2008-16). Furthermore, a subset of 61 penicillin-resistant serotype 11A isolates from France, Italy, Portugal and Spain were subjected to whole genome sequencing (WGS) and compared with 238 genomes from the European Nucleotide Archive (ENA).ResultsAlthough the incidence of serotype 11A in IPD was stable, a clonal shift was detected from CC62 (penicillin-susceptible) to CC156 (penicillin-resistant). By WGS, three major 11A-CC156 lineages were identified, linked to ST156 (n = 5 isolates; France, Italy and Portugal), ST166 (n = 4 isolates; France and Portugal) and ST838/6521 (n = 52 isolates; France, Portugal and Spain). Acquisition of the 11A capsule allowed to escape vaccine effect. AP200 (11A-ST62) was the donor for ST156 and ST838/6521 but not for ST166. In-depth analysis of ST838/6521 lineage showed two multi-fragment recombination events including four and seven fragments from an 11A-ST62 and an NT-ST344 representative, respectively.ConclusionThe increase in penicillin-resistant serotype 11A IPD in Spain was linked to the spread of a vaccine escape PMEN3 recombinant clone. Several recombination events were observed in PMEN3 acquiring an 11A capsule. The most successful 11A-PMEN3 lineage spreading in south-western Europe appeared after two multi-fragment recombination events with representatives of two major pneumococcal clones (11A-ST62 and NT-ST344).

Objective: To analyse all cases of Nocardia pneumonia occurring between 2010 and 2016 in five Spanish hospitals., Methods: This was a retrospective observational analysis of clinical and microbiological data collected from 55 cases of Nocardia pneumonia., Results: There were one to 20 cases per hospital and six to nine cases per year. Chronic obstructive pulmonary disease, bronchiectasis, and asthma were the main predisposing underlying respiratory conditions. Thirty-four patients were receiving systemic and/or inhaled corticosteroids prior to infection, eight had neoplasia, and six had haematological malignancies. Clinical and radiological findings were common to pneumonia of other infectious aetiologies, except for the frequent presence of nodules and cavitation. Overall, the 1-year mortality was high (38.2%), and mortality was directly related to the pulmonary disease in 15 patients (27.3%). The most frequently identified species were N. cyriacigeorgica (n=21), N. abscessus (n=8), and N. farcinica (n=5). All Nocardia isolates were susceptible to linezolid and all but two were susceptible to amikacin and trimethoprim-sulfamethoxazole., Conclusions: Nocardia pneumonia-associated mortality remains high, probably because of the debilitated status of patients in whom this pathogen is able to cause pulmonary infection., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

The human commensal Haemophilus parainfluenzae is emerging as an opportunistic multidrug-resistant pathogen. The objectives of this work were to characterise a new capsular operon of extensively drug-resistant (XDR) H. parainfluenzae clinical isolates and study their resistance mechanisms using whole-genome sequencing. All strains were resistant to: ß-lactams, via amino acid changes in PBP3 (S385T, I442F, V511A, N526K and V562I); quinolones, by alterations in GyrA (S84F and D88Y) and ParC (S84F and S138T); chloramphenicol, through the presence of catS; macrolides, via the presence of mel and mef(E)-carrying MEGA element; and tetracycline, through the presence of tet(M) and/or tet(B). Phylogenetic analysis revealed high genomic diversity when compared to the H. parainfluenzae genomes available on the NCBI, the isolates from this study being closely related to the Swiss XDR AE-2096513. A full capsular operon showing homology to that of H. influenzae was identified, in accordance with the observation of a capsular structure by TEM. This study describes for the first time a capsular operon in H. parainfluenzae, a major determinant of pathogenicity that may contribute to increased virulence in XDR clinical isolates. Moreover, phylogenetic analysis suggests the possible spread of an XDR-encapsulated strain in Europe.

Urban wild boars (Sus scrofa) from Barcelona, Spain, harbor great diversity of Streptococcus suis strains, including strains with the cps2 gene and with the same molecular profile as local human cases. The increasing trend of potential effective contacts for S. suis transmission is of public health concern.

A prospective laboratory-based multicenter study that collected all adult invasive pneumococcal disease (IPD) episodes from 6 Spanish hospitals before (2008-2009) and after (2012-2013). The 13-valent pneumococcal conjugate vaccine (PCV13) licensure was conducted in order to analyze the impact of PCV13 introduction for children on adult IPD. A total of 1558 IPD episodes were detected. The incidence of IPD decreased significantly in the second period by -33.9% (95% CI, -40.3% to -26.8%). IPD due to PCV7 serotypes (-52.7%; 95% CI, -64.2% to -37.5%) and to PCV13 additional serotypes (-55.0% 95% CI, -62.0% to -46.7%) significantly decreased whereas IPD due to non-PCV13 serotypes remained stable (1.0% 95% CI, -12.9% to 17.2%). IPD due to all PCV13 additional serotypes significantly declined with the exception of serotype 3 (-11.3%; 95%CI -35.0% to 21.1%). IPD due to two non-PCV13 serotypes varied: serotype 6C that rose (301.6%; 95%CI, 92.7% to 733.3%, p<0.001), related to the expansion of ST3866C, and serotype 8 that decreased (-34.9%, 95%CI, -57.1 to -1.2, p = 0.049), related to a decline of the ST638. The recombinant clone ST652111A (variant of ST1569V) increased in frequency. The decrease of serotype 19A IPD was linked to a fall in those antibiotic susceptible clones. In the last period, rates of penicillin- and cefotaxime-resistance remained under 10% and 4%, respectively. Adult IPD decreased after the PCV13 introduction in Spain due to herd protection. The spread of multidrug resistant clones (ST3866C, ST652111A) related to non-PCV13 serotypes needs further surveillance.