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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.

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.

Summary: 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.

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. Keywords: Nocardia, Pneumonia, Multicentre study, Nocardia cyriacigeorgica, Spain, Respiratory infection

Summary: Background: Assessing the burden of antimicrobial resistance is essential to determine the magnitude of this problem and to set its priority. We aimed to estimate the burden of disease caused by multidrug-resistant microorganisms (MDRO) in hospitalised patients in Spain. Methods: Three prospective nationwide studies were conducted in 2018, 2019 and 2023. All patients with a new diagnosis of infection with any of 10 selected MDROs plus Clostridioides difficile during the study period (one week in 2018 and 2019 and two weeks in 2023) were included. Patient demographic, and clinical outcomes were analysed, including incidence, crude all-cause 30-day mortality and years of life lost (YLL). These results were used to calculate weighted and seasonally adjusted annual estimates for the whole country. Findings: In total, 82, 133 and 130 centres participated in the study in 2018, 2019 and 2023, respectively, recording a total of 907, 1392 and 2351 MDRO infections, representing a weighted incidence density of 3.54 (95% CI 2.92–4.17), 5.01 (3.95–6.07), and 4.41 (3.55–5.27) cases/1000 stays, respectively. A total of 161, 198 and 352 patients died with an MDRO infection, representing a weighted incidence density of 0.46 (0.16–0.76), 0.43 (0.17–0.69), and 0.62 (0.52–0.72) deaths/1000 stays, respectively. Based on these data, a nationwide occurrence of 155,294 MDRO infections (95% CI 127,928–182,569) with 20,065 deaths (6938–32,958) was estimated for 2018, 210,451 MDRO infections (165,963–254,975) with 17,982 deaths (7071–28,700) for 2019, and 173,653 MDRO infections (139,814–207258) with 24,582 deaths (20,461–28,796) for 2023. Interpretation: The burden of disease caused by MDRO infections among hospitalised patients in Spain is very high and remains stable over the study period. National actions to combat bacterial resistance need to be intensified. Funding: The management costs of this study were funded by the Spanish Society of Infectious Diseases and Clinical Microbiology (SEIMC). Researchers have participated voluntarily and none of the investigators received funding for conducting the study.

Summary: Background: Data on risk factors for carbapenem-resistant Enterobacterales (CRE) with wider applicability are needed to inform preventive measures and efficient design of randomised trials. Methods: An international matched case-control-control study was performed in 50 hospitals with high CRE incidence from March 2016 to November 2018 to investigate different aspects of infections caused by CRE (NCT02709408). Cases were patients with complicated urinary tract infection (cUTI), complicated intraabdominal (cIAI), pneumonia or bacteraemia from other sources (BSI-OS) due to CRE; control groups were patients with infection caused by carbapenem-susceptible Enterobacterales (CSE), and by non-infected patients, respectively. Matching criteria included type of infection for CSE group, ward and duration of hospital admission. Conditional logistic regression was used to identify risk factors. Findings: Overall, 235 CRE case patients, 235 CSE controls and 705 non-infected controls were included. The CRE infections were cUTI (133, 56.7%), pneumonia (44, 18.7%), cIAI and BSI-OS (29, 12.3% each). Carbapenemase genes were found in 228 isolates: OXA-48/like, 112 (47.6%), KPC, 84 (35.7%), and metallo-β-lactamases, 44 (18.7%); 13 produced two. The risk factors for CRE infection in both type of controls were (adjusted OR for CSE controls; 95% CI; p value) previous colonisation/infection by CRE (6.94; 2.74–15.53;

Injection of MPP+ into the substantia nigra causes extensive necrosis and anterograde degeneration of pars compacta dopaminergic neurons. We studied secondary effects in the ipsilateral striatum by examining dopaminergic terminals, signs of neuronal damage, and glial reactivity at 1, 2, 3, and 7 days after injection of MPP+ into the substantia nigra. Dopaminergic terminals and uptake sites were evaluated with [3H]GBR-12935 binding and tyrosine hydroxylase immunoreactivity. Glial reaction was examined with markers of astrocytes and microglia. Stereology was used to evaluate any changes in neuronal density. Tyrosine hydroxylase immunoreactivity and [3H]GBR-12935 binding markedly decreased (74%) from days 2 to 7. Loss of dopaminergic terminals in the ipsilateral striatum was accompanied by an intense astroglial and, to a lesser extent, microglial reaction. However, no signs of cell damage, neuronal loss, or disruption of the blood–brain barrier were found in the striatum. Resident astroglial and microglial cells showed a morphological shift and notable changes in protein expression typical of glial reactivity, yet the presence of macrophage-like cells was not detected. This study shows that injection of MPP+ in the substantia nigra causes a secondary reaction within the ipsilateral striatum involving the transformation of quiescent glia to reactive glia. It is suggested that stimuli derived from damaged dopaminergic terminals within the striatum are able to activate resident glia and that this glial transformation may promote repair and regeneration.