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The recommended empiric ceftriaxone dosing regimen for acute bacterial meningitis in adults is 2 g every 12 h. After penicillin-susceptible Streptococcus pneumoniae is isolated as a causative microorganism, the ceftriaxone dose may be continued or reduced to a single dose of 2 g every 24 h, per institutional preference. There is no clear guidance that indicates the superiority of one regimen over the other. The objective of this study was to evaluate the susceptibility of S. pneumoniae in the cerebral spinal fluid (CSF) of patients with meningitis and the relationship between ceftriaxone dose and clinical outcomes. We identified 52 patients with S. pneumoniae meningitis with positive CSF cultures who were treated at the University Hospital, Bern, Switzerland, over a 19-year period. We collected clinical and microbiological data for evaluation. Broth microdilution and Etest methods were performed to test penicillin and ceftriaxone susceptibility. All isolates were susceptible to ceftriaxone. Ceftriaxone was empirically used in 50 patients, with a starting dosing regimen of 2 g every 24 h in 15 patients and 2 g every 12 h in 35 patients. In 32 patients started on a twice-daily regimen (91%), doses were reduced to once daily after a median of 1.5 (95% CI 1–2) days. The overall in-hospital mortality was 15.4% (n = 8), and 45.7% of patients reported at least one sequela of meningitis at the last follow-up (median 375, 95% CI 189–1585 days). We found no statistical difference in outcome between the 2 g every 24 h and the 2 g every 12 h ceftriaxone dosing regimens. A ceftriaxone total daily dose of 2 g may be associated with similar outcomes to a 4 g total daily dose, provided that the causative organism is highly susceptible to ceftriaxone. The persistence of neurological and infection sequelae at the last follow-up underscores the need for optimal treatment of these complex infections.

A large clonal outbreak caused by vancomycin-resistant Enterococcus faecium (VRE) affected the Bern University Hospital group from the end of December 2017 until July 2020. We describe the characteristics of the outbreak and the bundle of infection prevention and control (IPC) measures implemented. The outbreak was first recognised when two concomitant cases of VRE bloodstream infection were identified on the oncology ward. During 32 months, 518 patients in the 1,300-bed hospital group were identified as vanB VRE carriers. Eighteen (3.5%) patients developed an invasive infection, of whom seven had bacteraemia. In 2018, a subset of 328 isolates were analysed by whole genome sequencing, 312 of which were identified as sequence type (ST) 796. The initial IPC measures were implemented with a focus on the affected wards. However, in June 2018, ST796 caused another increase in cases, and the management strategy was intensified and escalated to a hospital-wide level. The clinical impact of this large nosocomial VRE outbreak with the emergent clone ST796 was modest. A hospital-wide approach with a multimodal IPC bundle was successful against this highly transmissible strain.

Background Agrobacterium spp. are infrequent agents of bloodstream infections linked to healthcare-associated outbreaks. However, it is unclear if outbreaks also occur across larger geographic areas. Triggered by two local clusters from putative point sources, our aim was to detect potential additional clusters in Switzerland. Methods We performed a nationwide descriptive study of cases in Switzerland based on a prospective surveillance system (Swiss Centre for Antibiotic Resistance, anresis.ch), from 2008 to 2019. We identified patients with Agrobacterium spp. isolated from blood cultures and used a survey to collect clinical-epidemiological information and susceptibility testing results. We performed whole genome sequencing (WGS) of available clinical isolates and determined their relatedness by single nucleotide polymorphism (SNP) variant calling analysis. Results We identified a total of 36 cases of Agrobacterium spp. from blood samples over 10 years. Beyond previously known local clusters, no new ones were identified. WGS-based typing was performed on 22 available isolates and showed no clonal relationships between newly identified isolates or to those from the known clusters, with all isolates outside these clusters being at least 50 SNPs apart. Conclusion and relevance Agrobacterium spp. bacteraemia is infrequently detected and, given that it may be healthcare-associated and stem from a point source, occurrence of multiple episodes should entail an outbreak investigation. With the help of the national antimicrobial resistance surveillance system we identified multiple clinical cases of this rare pathogen but found no evidence by WGS that suggested a nation-wide outbreak. Graphical abstract

Additional file 1. Survey.

Applying our workflow adaptations can be helpful for laboratories generating low quality mass spectra. The data acquired in this study suggest that these simple workflow adaptations are not sufficient to reach highest mass spectra quality in all cases, but other factors such as device maintenance may be helpful.

Incidence of invasive pneumococcal disease (IPD) has been low during the peak of the COVID-19 pandemic. In this study, we found that the IPD numbers again increased in Switzerland during the first six months of 2021, and that this coincides with the loosening of COVID 19 measures.Vaccine pneumococcal serotypes have continued to decrease but non-vaccine type serotype 23B has emerged (8% of the isolates in 2021). Worryingly, serotype 23B is associated with reduced susceptibility to penicillin.

Additional file 1: Figure S1. Schematic representation of the workflow of the project. Figure S2. Gene accumulation curves for species of the K. pneumoniae group (A) and the K. oxytoca group (B). Figure S3. Genes associated with AMR detected in Klebsiella spp.Figure S4. Partial least squares discriminant analysis (PLS-DA) score plot containing primary metabolites measured of five Klebsiella spp.Figure S5. Species identity of datasets (a), (b) and (c) included in the statistical analysis.

Additional file 10: Summary data compiled for the statistical analysis of clinical endpoints: Table S11. Summary of outcome variables for the clinical data set. Table S12. Summary of explanatory variables for the clinical data set. Statistical analyses examining differences in clinical outcome between the Klebsiella groups and species: Table S13. Odds ratio estimates from the generalized linear mixed-effects model (GLMM) for all cause death within 30 days from diagnosis. Table S14. Odds ratio estimates from the generalized linear mixed-effects model (GLMM) for ICU admission. Table S15. Hazard ratio estimates from cause-specific hazards Cox proportional hazards model for time to death within hospital after diagnosis with hospital discharge as competing event. Table S16. Estimates of the multiplicative effects from the Poisson generalized linear mixed-effects model (GLMM) for the number of medical disciplines involved. Table S17. Odds ratio estimates from the generalized linear mixed-effects model (GLMM) for the mentioning of the infection in the patient letter.

We have shown that the laboratory procedures imapct spectral quality. based on the data acquired within this study, we have developed protocols, likely able to increase mass spectral quality. This will be assessed in follow-up measurements at all laboratories.

Background In non-pregnant adults, the incidence of invasive Group B Streptococcus (GBS) disease is continuously increasing. Elderly and immunocompromised persons are at increased risk of infection. GBS commonly colonizes the vaginal tract, though data on colonization in the elderly are scarce. It is unknown whether the prevalence of GBS colonization is increasing in parallel to the observed rise of invasive infection. We conducted a three-year (2017–2019) prospective observational cross-sectional study in two teaching hospitals in Switzerland to determine the rate of GBS vaginal colonization in women over 60 years and i) to compare the proportions of known risk factors associated with invasive GBS diseases in colonized versus non-colonized women and ii) to evaluate the presence of GBS clusters with specific phenotypic and genotypic patterns in this population. Methods GBS screening was performed by using vaginal swabs collected during routine examination from women willing to participate in the study and to complete a questionnaire for risk factors. Isolates were characterized for antibiotic resistance profile, serotype and sequence type (ST). Results The GBS positivity rate in the elderly was 17% (44/255 positive samples), and similar to the one previously reported in pregnant women (around 20%). We could not find any association between participants’ characteristics, previously published risk factors and GBS colonization. All strains were susceptible to penicillin, 22% (8/36) were not susceptible to erythromycin, 14% (5/36) were not susceptible to clindamycin and 8% (3/36) showed inducible clindamycin resistance. Both M and L phenotypes were each detected in one isolate. The most prevalent serotypes were III (33%, 12/36) and V (31%, 11/36). ST1 and ST19 accounted for 11% of isolates each (4/36); ST175 for 8% (3/36); and ST23, ST249 and ST297 for 6% each (2/36). Significantly higher rates of resistance to macrolides and clindamycin were associated with the ST1 genetic background of ST1. Conclusions Our findings indicate a similar colonization rate for pregnant and elderly women. Trial registration Current Controlled Trial ISRCTN15468519; 06/01/2017 Supplementary Information The online version contains supplementary material available at 10.1186/s12879-021-06102-x.

International journal of molecular sciences 22(9), 4580 (2021). doi:10.3390/ijms22094580 special issue: "Special Issue "Bacterial Carbohydrates: Structures, Applications, and Structure/Activity Relationships" / Special Issue Editor: Prof. Dr. Maria Michela Corsaro, Guest Editor", Published by MDPI, Basel

Additional file 9: Odds ratio estimates comparing Klebsiella groups and species for resistance to different antibiotic classes: Table S7. Penicillins with beta-lactamase Inhibitors. Table S8. 3rd-generation cephalosporins. Table S9. 4th-generation cephalosporins. Table S10. Aminoglycosides.

Additional file 3. Supplementary methods for: Measurement of primary metabolites. Fatty acid analysis. Statistical analysis of clinical outcome data.

Additional file 1.

Background The optimal screening strategy in hospitals to identify secondary cases after contact with a meticillin-resistant Staphylococcus aureus (MRSA) index patient in a low prevalence setting is not well defined. We aimed at identifying factors associated with documented MRSA transmissions. Method Single center, retrospective, nested case-control study. We evaluated the screening strategy in our 950 bed tertiary care hospital from 2008 - 2014. Room and ward contacts of MRSA index patients present at time of MRSA identification were screened. We compared characteristics of Staphylococcus aureus Protein A (spa)-type matched contact patients (cases) to negative or spa-type mismatched contact patients (controls). Results Among 270,000 inpatients from 2008 - 2014, 215 MRSA screenings yielded 3013 contact patients, and 6 (0.2%) spa-type matched pairs. We included 225 controls for the nested case-control study. The contact type for the cases was more frequently "same room" and less frequently "same ward" compared with the controls (P = 0.001). Also, exposure time was longer for cases (median of 6 days [IQR 3-9]) than for controls (1 day [0-3], P=0.016). Conclusion The extensive MRSA screening strategy revealed only few index/contact matches based on spa-typing. Prolonged exposure time and a shared room were significantly associated with MRSA transmission. A targeted screening strategy may be more useful in a low prevalence setting than screening entire wards.

Additional file 1: Table S1. Overview of environmental sampling. Sampling was performed with premoistened (0,9% NaCl) sterile swabs, direct plating of contrast agents (200 μl per sample) and direct wiping of plant material on plates. Plates were incubated at 35 °C in CO2 enriched atmosphere for 6 days. MALDI-TOF MS was used for bacterial identification. Table S2. Overview of eight isolates described in this study. The genome datasets are available in the European Nucleotide Archive repository, under Project number PRJEB34002 [ https://www.ebi.ac.uk/ena/data/view/PRJEB34002 ]. Table S3. Peak list generated from visual examination of MALDI-TOF spectra of the Isolates A-H. Presence (1) or absence (0) of peaks is indicated at the m/z positions. Potentially double-ionized peaks are indicated with an asterisk (*); numbers in bold indicate peaks with a signal-to-noise ratio > 10. Table S4. Results of digital DNA:DNA hybridization for isolates F, H, G and B performed against all known Agrobacterium genomospecies. A dDDH value over 70 ( http://ggdc.dsmz.de/; Formula 2) or ANI value over 95% ( http://enve-omics.ce.gatech.edu/ani/ ) indicates the same species. Table S5. Comparison of MALDI-TOF MS spectra with a database generated on the base of putatively ascribed ribosomal protein masses extracted from genomic data. G = genomospecies. Figure S1. Timeline of clinical, microbiological, environmental, and treatment features of the two Index cases (Cluster I). Figure S2. Representative differentiating mass to charge (m/z) peaks. The m/z peak 7882 (*) is present in isolates C (pink), D (violet), E (light green), F (dark green) and H (orange) – the peak at 7924 m/z (**) is present in isolates A (light blue) and B (dark blue). Both peaks are absent in isolate G (red). Four spectra were recorded for each isolate A-H. Figure S3. (A) Disposable contrast reservoir with the rubber seal (#) in resting position. The potential contaminable zone lies behind the rubber seal (★). (B) The contrast reservoir is filled with contrast media by pushing (1) the rubber-sealed plunger (*) and pulling it (2) back to resting position. (C) The reservoir is inserted in the injector device system and ready to use. Figure S4. Model highlighting the potentially contaminable area of the reservoir behind the rubber seal (★), for visualization a fluorescent solution was used (A: resting position, B: rubber seal pushed in, C: rubber seal back in resting position). Figure S5. Principal component analysis: Four spectra were recorded for each isolate A-H. Two-dimensional plot of the first two principal components indicating the two clusters I (isolates A and B) and II (isolates C, D, E and F) and the “unrelated” isolates G and H. Figure S6. PFGE based typing of isolates A-H. The scale indicates the degree of similarity (%) as calculated by dice correlation analysis.

INTRODUCCIÓN. El carcinoma de célula pequeña o microcítico es un tumor neuroendocrino muy agresivo, siendo el tumor con mayor mortalidad. El tratamiento de este tumor apenas ha variado, presentando muy buena respuesta quimioterápica al inicio, pero haciéndose resistente al poco tiempo. Al diagnóstico, la mayor parte de los pacientes tiene la enfermedad diseminada. En otros tumores pulmonares los avances en el campo de la biología molecular han dado lugar a efectivas terapias como la inmunoterapia, que están empezando a ser aplicadas a este tumor en diversos estudios. OBJETIVO. El objetivo principal es obtener una revisión actualizada de este tumor, incluyendo los nuevos campos como la inmunoterapia y una revisión de la biología molecular, buscando nuevas posibles terapias y diferenciando la evolución respecto al carcinoma de célula no pequeña en los últimos avances. MATERIAL Y MÉTODOS. Se realizaron 3 búsquedas principales; la primera en diciembre del 2017 en cuatro bases de datos diferentes con un resultado total de 730 artículos. La segunda se realizó para acotar datos y añadir información, en febrero del 2018 con un total de 66 resultados. En abril de 2018 se realizó la última búsqueda para buscar novedades respecto al tema en cuestión y se obtuvieron un total de 241 artículos. Finalmente, se seleccionaron 33, 6 y 14 artículos de las respectivas búsquedas. RESULTADOS. Diversos ensayos están aún en progresión para analizar si realmente la inmunoterapia es una vía factible en este tumor. El tratamiento actual sigue siendo la quimioterapia. La biopsia líquida ofrece una alternativa a la convencional, siendo las células tumorales circulantes una buena vía para ampliar la información que tenemos de este tumor mediante el estudio de la biología molecular de estas células. CONCLUSIONES. A pesar del gran avance en la información que otorga la biología molecular, no se puede decir que actualmente este avance se aprecie en los campos de la terapéutica. A diferencia con otros tumores, en el CPCP la biología molecular y la inmunoterapia, de momento, no han avanzado lo suficiente como para obtener resultados respecto a la mortalidad, lo cual no implica que en un futuro no se puedan obtener nuevas dianas terapéuticas desde estos campos de investigación.

El cáncer de pulmón constituye la principal causa de muerte por cáncer en todo el mundo. La resección quirúrgica con intención curativa es el tratamiento de elección hoy en día, sin embargo, la mayoría de casos se diagnostican en estadíos avanzados, por lo que el pronóstico es sombrío. Dentro del tratamiento no quirúrgico del cáncer de pulmón, que se basa fundamentalmente en quimioterapia y radioterapia, las técnicas de inmunoterapia están ganando protagonismo en los últimos años. Los inhibidores del complejo PD-1/PD-L1, son unos fármacos recientes, tipo anticuerpos monoclonales humanizados, con resultados prometedores, cuyo mecanismo de acción se basa en inhibir dicho complejo, en especial el receptor PD-1, que es utilizado por las células tumorales para escapar del ataque del sistema inmune y así evitar ser eliminadas. Para que estos fármacos sean eficaces frente al tumor, las células tumorales deben expresar la proteína PD-1 en su membrana en un porcentaje suficiente, ya que si esto no sucede así los fármacos carecen de diana y el tumor escapa a los controles del organismo por otras vías, aún desconocidas. El papel del anatomopatólogo es fundamental para determinar si las células tumorales de la muestra expresan o no dicha proteína y en qué porcentaje (Score de expresión del receptor: alta y baja expresión), constituyendo así el pilar fundamental para el inicio del tratamiento con este tipo de fármacos, que han demostrado un aumento de la supervivencia global, de la tasa de respuesta objetiva y de la supervivencia libre de progresión, en comparación con las terapias convencionales hasta la fecha.

Los melanomas de mucosa sinonasal (SNMM) son entidades agresivas e infrecuentes, originadas en melanocitos presentes en el epitelio y estroma de la mucosa respiratoria. El diagnóstico es complicado debido a su morfología, distintos patrones arquitecturales/citológicos y ocasional ausencia de pigmento melánico. La mutación KIT, identificada en melanomas en 2004, esta descrita en aproximadamente 15-30% de los melanomas acrales y mucosos. Su estudio, plantea aprovechar el potencial terapéutico de fármacos inhibidores de la tirosinquinasa. Se revisaron los casos de SNMM, en los servicios de anatomía patológica de los Hospitales Clínico Universitario “Lozano Blesa” de Zaragoza y Complejo Hospitalario de Navarra en Pamplona, entre enero 1990 y junio 2016. Se estudiaron histológico e Inmunohistoquímicamente, incluyendo la técnica CKIT/CD117. Se recopilaron seis casos, cuatro epitelioides, un fusocelular y un plasmocitoide, todos ellos diagnosticados en adultos/ancianos, con características acordes a las descritas en la literatura. La expresión del CKIT (CD117) fue positiva en todos los casos. El tratamiento de elección fue la cirugía en todos los pacientes, algunos con posterior radioterapia. La sobrevida no fue mayor a tres años. Se plantea la utilidad de la tinción inmunohistoquímica como posible complemento al panel diagnóstico, el estudio mediante FISH para confirmar la presencia de la mutación y considerar una probable connotación terapéutica con inhibidores de la tirosinquinasa.

Background The intracellular protozoan parasite Theileria parva transforms bovine lymphocytes inducing uncontrolled proliferation. Proteins released from the parasite are assumed to contribute to phenotypic changes of the host cell and parasite persistence. With 85 members, genes encoding subtelomeric variable secreted proteins (SVSPs) form the largest gene family in T. parva. The majority of SVSPs contain predicted signal peptides, suggesting secretion into the host cell cytoplasm. Methodology/Principal Findings We analysed SVSP expression in T. parva-transformed cell lines established in vitro by infection of T or B lymphocytes with cloned T. parva parasites. Microarray and quantitative real-time PCR analysis revealed mRNA expression for a wide range of SVSP genes. The pattern of mRNA expression was largely defined by the parasite genotype and not by host background or cell type, and found to be relatively stable in vitro over a period of two months. Interestingly, immunofluorescence analysis carried out on cell lines established from a cloned parasite showed that expression of a single SVSP encoded by TP03_0882 is limited to only a small percentage of parasites. Epitope-tagged TP03_0882 expressed in mammalian cells was found to translocate into the nucleus, a process that could be attributed to two different nuclear localisation signals. Conclusions Our analysis reveals a complex pattern of Theileria SVSP mRNA expression, which depends on the parasite genotype. Whereas in cell lines established from a cloned parasite transcripts can be found corresponding to a wide range of SVSP genes, only a minority of parasites appear to express a particular SVSP protein. The fact that a number of SVSPs contain functional nuclear localisation signals suggests that proteins released from the parasite could contribute to phenotypic changes of the host cell. This initial characterisation will facilitate future studies on the regulation of SVSP gene expression and the potential biological role of these enigmatic proteins.

Background Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis, which are typically transmitted via respiratory droplets, are leading causes of invasive diseases, including bacteraemic pneumonia and meningitis, and of secondary infections subsequent to post-viral respiratory disease. The aim of this study was to investigate the incidence of invasive disease due to these pathogens during the early months of the COVID-19 pandemic. Methods In this prospective analysis of surveillance data, laboratories in 26 countries and territories across six continents submitted data on cases of invasive disease due to S pneumoniae, H influenzae, and N meningitidis from Jan 1, 2018, to May, 31, 2020, as part of the Invasive Respiratory Infection Surveillance (IRIS) Initiative. Numbers of weekly cases in 2020 were compared with corresponding data for 2018 and 2019. Data for invasive disease due to Streptococcus agalactiae, a non-respiratory pathogen, were collected from nine laboratories for comparison. The stringency of COVID-19 containment measures was quantified using the Oxford COVID-19 Government Response Tracker. Changes in population movements were assessed using Google COVID-19 Community Mobility Reports. Interrupted time-series modelling quantified changes in the incidence of invasive disease due to S pneumoniae, H influenzae, and N meningitidis in 2020 relative to when containment measures were imposed. Findings 27 laboratories from 26 countries and territories submitted data to the IRIS Initiative for S pneumoniae (62���434 total cases), 24 laboratories from 24 countries submitted data for H influenzae (7796 total cases), and 21 laboratories from 21 countries submitted data for N meningitidis (5877 total cases). All countries and territories had experienced a significant and sustained reduction in invasive diseases due to S pneumoniae, H influenzae, and N meningitidis in early 2020 (Jan 1 to May 31, 2020), coinciding with the introduction of COVID-19 containment measures in each country. By contrast, no significant changes in the incidence of invasive S agalactiae infections were observed. Similar trends were observed across most countries and territories despite differing stringency in COVID-19 control policies. The incidence of reported S pneumoniae infections decreased by 68% at 4 weeks (incidence rate ratio 0��32 [95% CI 0��27���0��37]) and 82% at 8 weeks (0��18 [0��14���0��23]) following the week in which significant changes in population movements were recorded. Interpretation The introduction of COVID-19 containment policies and public information campaigns likely reduced transmission of S pneumoniae, H influenzae, and N meningitidis, leading to a significant reduction in life-threatening invasive diseases in many countries worldwide.

BACKGROUND In a 2015 point prevalence study, Clostridioides difficile 027, a hypervirulent ribotype, was absent from healthcare institutions in Switzerland. In late 2016, we detected an outbreak of C. difficile infection (CDI) with ribotype 027 occurring across several hospitals in the same hospital network. METHODS The first cases of CDI due to ribotype 027 triggered an outbreak investigation, including whole genome sequencing (WGS) to identify outbreak strains. FINDINGS We identified 28 patients with CDI caused by ribotype 027 between December 2016 and December 2017, out of which twenty were caused by a single clone. Commonalities among these patients were hospitalization in the same room or on the same ward, receiving care from the same healthcare workers, and shared toilet areas. In addition to the epidemiological links suggesting possible transmission pathways between cases, WGS confirmed the clonality of this C. difficile 027 outbreak. The outbreak was contained by isolation precautions, raising awareness among healthcare workers, harmonizing diagnostic algorithms, and switching to a sporicidal agent for environmental disinfection. Of note, neither default gowning and gloving nor handwashing with water and soap were implemented. CONCLUSIONS This C. difficile 027 outbreak was recognized belatedly due to lack of screening for this ribotype in some hospitals, and was contained by a swift response with simple infection prevention measures and adapting the laboratory approach. In order to have a better understanding of C. difficile epidemiology, diagnostic approaches should be standardized, CDI declared notifiable, and longitudinal data on prevalent ribotypes collected in countries where this is not established.