Genomic evolution of human respiratory syncytial virus during a decade (2013-2023): bridging the path to monoclonal antibody surveillance.

OBJECTIVES: This study investigated the prevalence, genetic diversity, and evolution of human respiratory syncytial virus (HRSV) in Barcelona from 2013 to 2023. METHODS: Respiratory specimens from patients with RTI suspicion at Hospital Universitari Vall d'Hebron were collected from October 2013 to May 2023 for laboratory-confirmation of respiratory viruses. Next-generation sequencing was performed in randomly-selected samples with Illumina technology. Phylogenetic analyses of whole genome sequences were performed with BEAST v1.10.4. Signals of selection and evolutionary pressures were inferred by population dynamics and evolutionary analyses. Mutations in major surface proteins were genetic and structurally characterised, emphasizing those within antigenic epitopes. RESULTS: Analyzing 139,625 samples, 5.3% were HRSV-positive (3008 HRSV-A, 3882 HRSV-B, 56 HRSV-A and -B, and 495 unsubtyped HRSV), with a higher prevalence observed in the paediatric population. Pandemic-related shifts in seasonal patterns returned to normal in 2022-2023. A total of 198 whole-genome sequences were obtained for HRSV-A (6.6% of the HRSV-A positive samples) belonging to GA2.3.5 lineage. For HRSV-B, 167 samples were sequenced (4.3% of the HRSV-B positive samples), belonging to GB5.0.2, GB5.0.4a and GB5.0.5a. HRSV-B exhibited a higher evolution rate. Post-SARS-CoV-2 pandemic, both subtypes showed increased evolutionary rates and decreased effective population size initially, followed by a sharp increase. Analyses indicated negative selective pressure on HRSV. Mutations in antigenic epitopes, including S276N and M274I in palivizumab-targeted site II, and I206M, Q209R, and S211N in nirsevimab-targeted site Ø, were identified. DISCUSSION: Particularly in the context of the large-scale use in 2023-2024 season of nirsevimab, continuous epidemiological and genomic surveillance is crucial.

Clinical, microbiological, and molecular characterization of pediatric invasive infections by Streptococcus pyogenes in Spain in a context of global outbreak.

In December 2022, an alert was published in the UK and other European countries reporting an unusual increase in the incidence of Streptococcus pyogenes infections. Our aim was to describe the clinical, microbiological, and molecular characteristics of group A Streptococcus invasive infections (iGAS) in children prospectively recruited in Spain (September 2022-March 2023), and compare invasive strains with strains causing mild infections. One hundred thirty isolates of S. pyogenes causing infection (102 iGAS and 28 mild infections) were included in the microbiological study: emm typing, antimicrobial susceptibility testing, and sequencing for core genome multilocus sequence typing (cgMLST), resistome, and virulome analysis. Clinical data were available from 93 cases and 21 controls. Pneumonia was the most frequent clinical syndrome (41/93; 44.1%), followed by deep tissue abscesses (23/93; 24.7%), and osteoarticular infections (11/93; 11.8%). Forty-six of 93 cases (49.5%) required admission to the pediatric intensive care unit. iGAS isolates mainly belonged to emm1 and emm12; emm12 predominated in 2022 but was surpassed by emm1 in 2023. Spread of M1UK sublineage (28/64 M1 isolates) was communicated for the first time in Spain, but it did not replace the still predominant sublineage M1global (36/64). Furthermore, a difference in emm types compared with the mild cases was observed with predominance of emm1, but also important representativeness of emm12 and emm89 isolates. Pneumonia, the most frequent and severe iGAS diagnosed, was associated with the speA gene, while the ssa superantigen was associated with milder cases. iGAS isolates were mainly susceptible to antimicrobials. cgMLST showed five major clusters: ST28-ST1357/emm1, ST36-ST425/emm12, ST242/emm12.37, ST39/emm4, and ST101-ST1295/emm89 isolates. IMPORTANCE: Group A Streptococcus (GAS) is a common bacterial pathogen in the pediatric population. In the last months of 2022, an unusual increase in GAS infections was detected in various countries. Certain strains were overrepresented, although the cause of this raise is not clear. In Spain, a significant increase in mild and severe cases was also observed; this study evaluates the clinical characteristics and the strains involved in both scenarios. Our study showed that the increase in incidence did not correlate with an increase in resistance or with an emm types shift. However, there seemed to be a rise in severity, partly related to a greater rate of pneumonia cases. These findings suggest a general increase in iGAS that highlights the need for surveillance. The introduction of whole genome sequencing in the diagnosis and surveillance of iGAS may improve the understanding of antibiotic resistance, virulence, and clones, facilitating its control and personalized treatment.

Enterobacterales carrying chromosomal AmpC ß-lactamases in Europe (EuESCPM): Epidemiology and antimicrobial resistance burden from a cohort of 27 hospitals, 2020-2022.

INTRODUCTION: The ESCPM group (Enterobacter species including Klebsiella aerogenes - formerly Enterobacter aerogenes, Serratia species, Citrobacter freundii complex, Providencia species and Morganella morganii) has not yet been incorporated into systematic surveillance programs. METHODS: We conducted a multicentre retrospective observational study analysing all ESCPM strains isolated from blood cultures in 27 European hospitals over a 3-year period (2020-2022). Diagnostic approach, epidemiology, and antimicrobial susceptibility were investigated. RESULTS: Our study comprised 6,774 ESCPM isolates. MALDI-TOF coupled to mass spectrometry was the predominant technique for bacterial identification. Susceptibility to new ß-lactam/ß-lactamase inhibitor combinations and confirmation of AmpC overproduction were routinely tested in 33.3% and 29.6% of the centres, respectively. The most prevalent species were E. cloacae complex (44.8%) and S. marcescens (22.7%). Overall, third-generation cephalosporins (3GC), combined third- and fourth-generation cephalosporins (3GC + 4GC) and carbapenems resistance phenotypes were observed in 15.7%, 4.6%, and 9.5% of the isolates, respectively. AmpC overproduction was the most prevalent resistance mechanism detected (15.8%). Among carbapenemase-producers, carbapenemase type was provided in 44.4% of the isolates, VIM- (22.9%) and OXA-48-enzyme (16%) being the most frequently detected. E. cloacae complex, K. aerogenes and Providencia species exhibited the most notable cumulative antimicrobial resistance profiles, with the former displaying 3GC, combined 3GC + 4GC and carbapenems resistance phenotypes in 15.2%, 7.4%, and 12.8% of the isolates, respectively. K. aerogenes showed the highest rate of both 3GC resistant phenotype (29.8%) and AmpC overproduction (32.1%), while Providencia species those of both carbapenems resistance phenotype (42.7%) and carbapenemase production (29.4%). ESCPM isolates exhibiting both 3GC and combined 3GC + 4GC resistance phenotypes displayed high susceptibility to ceftazidime/avibactam (98.2% and 95.7%, respectively) and colistin (90.3% and 90.7%, respectively). Colistin emerged as the most active drug against ESCPM species (except those intrinsically resistant) displaying both carbapenems resistance phenotype (85.8%) and carbapenemase production (97.8%). CONCLUSIONS: This study presented a current analysis of ESCPM species epidemiology in Europe, providing insights to inform current antibiotic treatments and guide strategies for antimicrobial stewardship and diagnostics.

Catastrophic Streptococcus pyogenes Disease: A Personalized Approach Based on Phenotypes and Treatable Traits.

Streptococcal toxic shock syndrome (STTS) is a critical medical emergency marked by high morbidity and mortality, necessitating swift awareness, targeted treatment, and early source control due to its rapid symptom manifestation. This report focuses on a cohort of 13 patients admitted to Vall d'Hebron University Hospital Intensive Care Unit, Barcelona, from November 2022 to March 2023, exhibiting invasive Streptococcus pyogenes infections and meeting institutional sepsis code activation criteria. The primary infections were community-acquired pneumonia (61.5%) and skin/soft tissue infection (30.8%). All patients received prompt antibiotic treatment, with clinical source control through thoracic drainage (30.8%) or surgical means (23.1%). Organ support involved invasive mechanical ventilation, vasopressors, and continuous renal replacement therapy as per guidelines. Of note, 76.9% of patients experienced septic cardiomyopathy, and 53.8% required extracorporeal membrane oxygenation (ECMO). The study identified three distinct phenotypic profiles-hyperinflammatory, low perfusion, and hypogammaglobulinemic-which could guide personalized therapeutic approaches. STTS, with a mean SOFA score of 17 (5.7) and a 53.8% requiring ECMO, underscores the need for precision medicine-based rescue therapies and sepsis phenotype identification. Integrating these strategies with prompt antibiotics and efficient source control offers a potential avenue to mitigate organ failure, enhancing patient survival and recovery in the face of this severe clinical condition.

Corrigendum: CARB-ES-19 multicenter study of carbapenemase-producing Klebsiella pneumoniae and Escherichia coli from all Spanish provinces reveals interregional spread of high-risk clones such as ST307/OXA-48 and ST512/KPC-3.

[This corrects the article DOI: 10.3389/fmicb.2022.918362.].

The prognostic impact of SIGLEC5-induced impairment of CD8+ T cell activation in sepsis.

BACKGROUND: Sepsis is associated with T-cell exhaustion, which significantly reduces patient outcomes. Therefore, targeting of immune checkpoints (ICs) is deemed necessary for effective sepsis management. Here, we evaluated the role of SIGLEC5 as an IC ligand and explored its potential as a biomarker for sepsis. METHODS: In vitro and in vivo assays were conducted to both analyse SIGLEC5's role as an IC ligand, as well as assess its impact on survival in sepsis. A multicentre prospective cohort study was conducted to evaluate the plasmatic soluble SIGLEC5 (sSIGLEC5) as a mortality predictor in the first 60 days after admission in sepsis patients. Recruitment included sepsis patients (n = 346), controls with systemic inflammatory response syndrome (n = 80), aneurism (n = 11), stroke (n = 16), and healthy volunteers (HVs, n = 100). FINDINGS: SIGLEC5 expression on monocytes was increased by HIF1α and was higher in septic patients than in healthy volunteers after ex vivo LPS challenge. Furthermore, SIGLEC5-PSGL1 interaction inhibited CD8+ T-cell proliferation. Administration of sSIGLEC5r (0.8 mg/kg) had adverse effects in mouse endotoxemia models. Additionally, plasma sSIGLEC5 levels of septic patients were higher than HVs and ROC analysis revealed it as a mortality marker with an AUC of 0.713 (95% CI, 0.656-0.769; p < 0.0001). Kaplan-Meier survival curve showed a significant decrease in survival above the calculated cut-off (HR of 3.418, 95% CI, 2.380-4.907, p < 0.0001 by log-rank test) estimated by Youden Index (523.6 ng/mL). INTERPRETATION: SIGLEC5 displays the hallmarks of an IC ligand, and plasma levels of sSIGLEC5 have been linked with increased mortality in septic patients. FUNDING: Instituto de Salud Carlos III (ISCIII) and "Fondos FEDER" to ELC (PIE15/00065, PI18/00148, PI14/01234, PI21/00869), CDF (PI21/01178), RLR (FI19/00334) and JAO (CD21/00059).

Use of Biomarkers to Improve 28-Day Mortality Stratification in Patients with Sepsis and SOFA ≤ 6.

Early diagnosis and appropriate treatments are crucial to reducing mortality risk in septic patients. Low SOFA scores and current biomarkers may not adequately discern patients that could develop severe organ dysfunction or have an elevated mortality risk. The aim of this prospective observational study was to evaluate the predictive value of the biomarkers mid-regional pro-adrenomedullin (MR-proADM), procalcitonin (PCT), C-reactive protein (CRP), and lactate for 28-day mortality in patients with sepsis, and patients with a SOFA score ≤6. 284 were included, with a 28-day all-cause mortality of 8.45% (n = 24). Non-survivors were older (p = 0.003), required mechanical ventilation (p = 0.04), were ventilated for longer (p = 0.02), and had higher APACHE II (p = 0.015) and SOFA (p = 0.027) scores. Lactate showed the highest predictive ability for all-cause 28-day mortality, with an area under the receiver-operating characteristic curve (AUROC) of 0.67 (0.55-0.79). The AUROC for all-cause 28-day mortality in patients with community-acquired infection was 0.69 (0.57-0.84) for SOFA and 0.70 (0.58-0.82) for MR-proADM. A 2.1 nmol/L cut-off point for this biomarker in this subgroup of patients discerned, with 100% sensibility, survivors from non-survivors at 28 days. In patients with community-acquired sepsis and initial SOFA score ≤ 6, MR-proADM could help identify patients at risk of 28-day mortality.

Increasing trend of antimicrobial resistance in Shigella associated with MSM transmission in Barcelona, 2020-21: outbreak of XRD Shigella sonnei and dissemination of ESBL-producing Shigella flexneri.

BACKGROUND: Several countries have recently reported the detection of ESBL-producing Shigella sonnei associated with transmission among MSM. In a previous study by our group, 2.8% of Shigella spp. obtained from MSM in Barcelona between 2015 and 2019 were ESBL producers. OBJECTIVES: To describe and characterize the emerging ESBL-producing Shigella spp. associated with sexual transmission among MSM detected from 2020 to 2021 in Barcelona, elucidating their connectivity with contemporaneous ESBL-producing Shigella spp. from other countries. RESULTS: From 2020 to 2021, we identified that among MSM, 68% of S. sonnei were XDR harbouring blaCTX-M-27 and 14% of Shigella flexneri were MDR harbouring blaCTX-M-27. WGS analysis showed that the ESBL-producing S. sonnei were part of a monophyletic cluster, which included isolates responsible for the prolonged outbreak occurring in the UK. Our data also reveal the first emergence and clonal dissemination of ESBL-producing and fluoroquinolone-resistant S. flexneri 2a among MSM. CONCLUSIONS: We report an increasing trend of antimicrobial resistance in Shigella spp. among MSM in Barcelona since 2021, mainly as a consequence of the dissemination of XDR ESBL-producing S. sonnei, previously reported in the UK. These results highlight the importance of international collaborative surveillance of MDR/XDR S. sonnei and S. flexneri for rapid identification of their emergence and the prevention of the transmission of these pathogens.

Ceftazidime-Avibactam plus Aztreonam for the Treatment of Infections by VIM-Type-Producing Gram-Negative Bacteria.

This is a retrospective single-center study of 24 patients who received ceftazidime-avibactam plus aztreonam (CZA/ATM) for the treatment of VIM-type-producing Gram-negative bacillus (GNB) infections. The bacteria isolated were Enterobacterales in 22 patients and Pseudomonas aeruginosa in 2. Sixteen out of 19 isolates showed synergistic activity. Two patients presented clinical failure at day 14, and the 30-day mortality was 17% (4/24). CZA/ATM could be considered an alternative therapy for VIM-type-producing GNB infections.

CARB-ES-19 Multicenter Study of Carbapenemase-Producing Klebsiella pneumoniae and Escherichia coli From All Spanish Provinces Reveals Interregional Spread of High-Risk Clones Such as ST307/OXA-48 and ST512/KPC-3.

Objectives: CARB-ES-19 is a comprehensive, multicenter, nationwide study integrating whole-genome sequencing (WGS) in the surveillance of carbapenemase-producing K. pneumoniae (CP-Kpn) and E. coli (CP-Eco) to determine their incidence, geographical distribution, phylogeny, and resistance mechanisms in Spain. Methods: In total, 71 hospitals, representing all 50 Spanish provinces, collected the first 10 isolates per hospital (February to May 2019); CPE isolates were first identified according to EUCAST (meropenem MIC > 0.12 mg/L with immunochromatography, colorimetric tests, carbapenem inactivation, or carbapenem hydrolysis with MALDI-TOF). Prevalence and incidence were calculated according to population denominators. Antibiotic susceptibility testing was performed using the microdilution method (EUCAST). All 403 isolates collected were sequenced for high-resolution single-nucleotide polymorphism (SNP) typing, core genome multilocus sequence typing (cgMLST), and resistome analysis. Results: In total, 377 (93.5%) CP-Kpn and 26 (6.5%) CP-Eco isolates were collected from 62 (87.3%) hospitals in 46 (92%) provinces. CP-Kpn was more prevalent in the blood (5.8%, 50/853) than in the urine (1.4%, 201/14,464). The cumulative incidence for both CP-Kpn and CP-Eco was 0.05 per 100 admitted patients. The main carbapenemase genes identified in CP-Kpn were bla OXA-48 (263/377), bla KPC-3 (62/377), bla VIM-1 (28/377), and bla NDM-1 (12/377). All isolates were susceptible to at least two antibiotics. Interregional dissemination of eight high-risk CP-Kpn clones was detected, mainly ST307/OXA-48 (16.4%), ST11/OXA-48 (16.4%), and ST512-ST258/KPC (13.8%). ST512/KPC and ST15/OXA-48 were the most frequent bacteremia-causative clones. The average number of acquired resistance genes was higher in CP-Kpn (7.9) than in CP-Eco (5.5). Conclusion: This study serves as a first step toward WGS integration in the surveillance of carbapenemase-producing Enterobacterales in Spain. We detected important epidemiological changes, including increased CP-Kpn and CP-Eco prevalence and incidence compared to previous studies, wide interregional dissemination, and increased dissemination of high-risk clones, such as ST307/OXA-48 and ST512/KPC-3.

A side-by-side comparison of the performance and time-and-motion data of VITEK MS.

Matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF) mass spectrometry systems are designed for rapid and reliable microbial identification. VITEK MS PRIME is the bioMérieux's new generation instrument equipped with a continuous load-and-go sample loading system, urgent slide prioritization for critical patient samples and new internal components for faster identification. The aim of this study was to assess the performance of VITEK MS PRIME and to compare it to that of the VITEK MS system. In addition, at two sites, we performed a time-and-motion study to evaluate the efficiency of sample analysis from colony picking to slide removal from the instrument. We analyzed by VITEK MS and VITEK MS PRIME a total of 1413 isolates (1320 bacterial and 76 yeast) deriving from routine diagnostic samples that came into four laboratories in Canada, France, Italy, and Spain. VITEK MS PRIME and VITEK MS were concordant to the species and genus level for 1354/1413 (95.8%) and to the species level for 1341/1413 (94.9%). The identification and concordance rates in individual centers were largely homogenous. Overall, VITEK MS PRIME identified 1370/1413 (97.0%) of isolates compared to 1367/1413 (96.7%) identified by VITEK MS. Identification rates were consistently high for all microorganism categories. A time-and-motion study showed that the use of VITEK MS PRIME was associated with significant time saving. VITEK MS PRIME performs as well as VITEK MS and reduces the time necessary for pathogen identification. To fully optimize the laboratory process and obtain maximum efficiency, VITEK MS PRIME must be integrated into the laboratory workflow.

Epidemiology, prevention and control of pertussis in Spain: New vaccination strategies for lifelong protection.

Pertussis is a highly contagious, vaccine-preventable respiratory tract infection, with high morbidity and mortality and a particularly severe effect on newborns and infants under 2 months. The first pertussis vaccines were introduced in the 1940s. Since 1980, however, the incidence of cases has risen despite the extensive vaccination programmes and antibiotic adjuvant treatments available. Transition from the use of whole-cell vaccines to acellular vaccines and the antigenic modifications of Bordetella pertussis have contributed, among other factors, to a reduction in vaccine-acquired immunity and reemergence of the disease. Today, there are still unmet needs not covered by conventional prevention measures and existing antibiotic treatments. This review aims to update the available data, and to discuss which vaccine strategies might contribute to better disease control and prevention.

Global spatial dynamics and vaccine-induced fitness changes of Bordetella pertussis.

As with other pathogens, competitive interactions between Bordetella pertussis strains drive infection risk. Vaccines are thought to perturb strain diversity through shifts in immune pressures; however, this has rarely been measured because of inadequate data and analytical tools. We used 3344 sequences from 23 countries to show that, on average, there are 28.1 transmission chains circulating within a subnational region, with the number of chains strongly associated with host population size. It took 5 to 10 years for B. pertussis to be homogeneously distributed throughout Europe, with the same time frame required for the United States. Increased fitness of pertactin-deficient strains after implementation of acellular vaccines, but reduced fitness otherwise, can explain long-term genotype dynamics. These findings highlight the role of vaccine policy in shifting local diversity of a pathogen that is responsible for 160,000 deaths annually.

Pertactin-Deficient Bordetella pertussis with Unusual Mechanism of Pertactin Disruption, Spain, 1986-2018.

Bordetella pertussis not expressing pertactin has increased in countries using acellular pertussis vaccines (ACV). The deficiency is mostly caused by pertactin gene disruption by IS481. To assess the effect of the transition from whole-cell vaccine to ACV on the emergence of B. pertussis not expressing pertactin in Spain, we studied 342 isolates collected during 1986-2018. We identified 93 pertactin-deficient isolates. All were detected after introduction of ACV and represented 38% of isolates collected during the ACV period; 58.1% belonged to a genetic cluster of isolates carrying the unusual prn::del(-292, 1340) mutation. Pertactin inactivation by IS481 insertion was identified in 23.7% of pertactin-deficient isolates, arising independently multiple times and in different phylogenetic branches. Our findings support the emergence and dissemination of a cluster of B. pertussis with an infrequent mechanism of pertactin disruption in Spain, probably resulting from introduction of ACV.

Primer brote documentado de artritis séptica por Kingella kingae en una guardería de España / First documented outbreak of arthritis caused by Kingella kingae in a Spanish childcare center

IntroducciónRecientemente, Kingella kingae (K. kingae) se ha descrito como el principal agente causal de infecciones osteoarticulares entre los 6 meses y 2 años de vida. Más excepcional es su presentación en forma de clúster de infección invasiva por K. kingae. Se describe la investigación del primer brote de 3casos de artritis séptica causada por K. kingae documentado en España en una guardería de Roses, Girona.Pacientes y métodosEn diciembre del 2015, se realizó frotis faríngeo a todos los niños de la misma clase de la guardería. La muestra estaba compuesta por 9 lactantes (rango de edad: 16-23 meses), que incluía los 3casos índice. El estudio microbiológico se realizó mediante cultivo y RT-PCR específicos a K. kingae. Se administró amoxicilina y rifampicina profilácticas a todos los que presentaron colonización por K. kingae. Después de finalizar la profilaxis, se tomó un nuevo frotis faríngeo para confirmar la erradicación.ResultadosSe detectó K. kingae por RT-PCR en los 3casos índices y 5/6 compañeros de clase. Los cultivos fueron negativos en todos los casos. Después de recibir profilaxis, 3lactantes aún presentaban positividad a K. kingae en RT-PCR.ConclusionesK. kingae puede causar brotes de enfermedad invasiva en comunidades cerradas. Para una adecuada investigación, se requiere un mayor conocimiento de su existencia, así como una mejoría de la sensibilidad de las pruebas diagnósticas. En nuestra experiencia, la administración de profilaxis antibiótica puede erradicar parcialmente la colonización orofaríngea por K. kingae. Después de la profilaxis no se detectaron nuevos casos.

BackgroundRecently, Kingella kingae (K. kingae) has been described as the most common agent of skeletal system infections in children 6 months-2 years of age. More exceptional is the clinical presentation in clusters of invasive K. kingae infections. We describe the investigation of the first outbreak of 3cases of arthritis caused by K. kingae documented in Spain detected in a daycare center in Roses, Girona.Patients and methodsIn December of 2015 surveillance throat swabs obtained from all attendees from the same class of the index daycare center were assessed to study the prevalence of K. kingae colonization. The sample was composed of 9 toddlers (range: 16-23 months of age). Investigation was performed by culture and K. kingae-specific RT-PCR. Combined amoxicillin-rifampicin prophylaxis was offered to all attendees who were colonized by K. kingae. Following antimicrobial prophylaxis, a new throat swab was taken to confirm bacterial eradication.ResultsK. kingae was detected by RT-PCR throat swabs in the 3index cases and 5of the 6daycare attendees. Cultures were negative in all cases. After administration of prophylactic antibiotics, 3toddlers were still positive for K. kingae-specific RT-PCR.ConclusionsClusters of invasive K. kingae infections can occur in daycare facilities and closed communities. Increased awareness and use of sensitive detection methods are needed to identify and adequately investigate outbreaks of K. kingae disease. In our experience, the administration of prophylactic antibiotics could result in partial eradication of colonization. No further cases of disease were detected after prophylaxis.

Epidemiology, prevention and control of pertussis in Spain: New vaccination strategies for lifelong protection / Epidemiología, prevención y control de la tosferina en España: nuevas estrategias de vacunación para la protección a lo largo de la vida

La tosferina es una infección respiratoria inmunoprevenible altamente contagiosa, con alta morbilidad y mortalidad, y que afecta con especial gravedad a recién nacidos y lactantes menores de 2 meses. Las primeras vacunas comenzaron a emplearse en la década de los 40. Sin embargo, desde 1980 la incidencia de casos ha aumentado a pesar de los amplios programas de vacunación y tratamientos antibióticos adyuvantes disponibles. El cambio del uso de vacunas celulares a vacunas acelulares, y las modificaciones antigénicas de B. pertussis han podido contribuir entre otros factores a la disminución de la inmunidad adquirida tras la vacunación y a la reemergencia de la enfermedad. En la actualidad, todavía existen necesidades no cubiertas por las medidas convencionales de prevención y los tratamientos antibióticos existentes. Esta revisión pretende actualizar los datos disponibles y plantear qué estrategias vacunales pueden contribuir a un mejor control y prevención global de la enfermedad.

Pertussis is a highly contagious, vaccine-preventable respiratory tract infection, with high morbidity and mortality and a particularly severe effect on newborns and infants under 2 months. The first pertussis vaccines were introduced in the 1940s. Since 1980, however, the incidence of cases has risen despite the extensive vaccination programmes and antibiotic adjuvant treatments available. Transition from the use of whole-cell vaccines to acellular vaccines and the antigenic modifications of Bordetella pertussis have contributed, among other factors, to a reduction in vaccine-acquired immunity and reemergence of the disease. Today, there are still unmet needs not covered by conventional prevention measures and existing antibiotic treatments. This review aims to update the available data, and to discuss which vaccine strategies might contribute to better disease control and prevention.

First documented outbreak of arthritis caused by Kingella kingae in a Spanish childcare center.

BACKGROUND: Recently, Kingella kingae (K. kingae) has been described as the most common agent of skeletal system infections in children 6 months-2 years of age. More exceptional is the clinical presentation in clusters of invasive K. kingae infections. We describe the investigation of the first outbreak of 3 cases of arthritis caused by K. kingae documented in Spain detected in a daycare center in Roses, Girona. PATIENTS AND METHODS: In December of 2015 surveillance throat swabs obtained from all attendees from the same class of the index daycare center were assessed to study the prevalence of K. kingae colonization. The sample was composed of 9 toddlers (range: 16-23 months of age). Investigation was performed by culture and K. kingae-specific RT-PCR. Combined amoxicillin-rifampicin prophylaxis was offered to all attendees who were colonized by K. kingae. Following antimicrobial prophylaxis, a new throat swab was taken to confirm bacterial eradication. RESULTS: K. kingae was detected by RT-PCR throat swabs in the 3 index cases and 5 of the 6 daycare attendees. Cultures were negative in all cases. After administration of prophylactic antibiotics, 3 toddlers were still positive for K. kingae-specific RT-PCR. CONCLUSIONS: Clusters of invasive K. kingae infections can occur in daycare facilities and closed communities. Increased awareness and use of sensitive detection methods are needed to identify and adequately investigate outbreaks of K. kingae disease. In our experience, the administration of prophylactic antibiotics could result in partial eradication of colonization. No further cases of disease were detected after prophylaxis.

Label-Free Plasmonic Biosensor for Rapid, Quantitative, and Highly Sensitive COVID-19 Serology: Implementation and Clinical Validation.

Serological tests are essential for the control and management of COVID-19 pandemic (diagnostics and surveillance, and epidemiological and immunity studies). We introduce a direct serological biosensor assay employing proprietary technology based on plasmonics, which offers rapid (<15 min) identification and quantification of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibodies in clinical samples, without signal amplification. The portable plasmonic device employs a custom-designed multiantigen (RBD peptide and N protein) sensor biochip and reaches detection limits in the low ng mL-1 range employing polyclonal antibodies. It has also been implemented employing the WHO-approved anti-SARS-CoV-2 immunoglobulin standard. A clinical validation with COVID-19 positive and negative samples (n = 120) demonstrates its excellent diagnostic sensitivity (99%) and specificity (100%). This positions our biosensor as an accurate and easy-to-use diagnostics tool for rapid and reliable COVID-19 serology to be employed both at laboratory and decentralized settings for the disease management and for the evaluation of immunological status during vaccination or treatment.

Mycotic Aneurysm of Internal Carotid Artery Secondary to Livestock-associated Methicillin-resistant Staphylococcus Aureus Clonal Complex CC398.

The aim of this article is to present a case of mycotic aneurysm of internal carotid artery secondary to livestock-associated methicillin-resistant Staphylococcus aureus (LA-MRSA) treated with resection and common-to-internal carotid artery bypass with autologous vein graft in a male pig farmer. A 69-year-old man, pig farmer, with recent dental extraction was admitted with a right cervical pulsatile mass, dysphonia, pain, leukocytosis and elevated C-reactive protein (CRP). Ultrasonography (US) and computed tomography angiography (CTA) showed a 3.9 × 4.5 cm mycotic aneurysm of right internal carotid artery with hypermetabolic uptake in positron emission tomography (PET) scan. Resection of the mycotic aneurysm and a common-to-internal carotid artery bypass with major saphenous vein graft were performed. LA-MRSA clonal complex (CC) 398 was detected in intraoperative samples and antibiotic therapy was changed according to antibiogram. Patient was discharged at the seventh postoperative day and received antibiotic therapy for 6 weeks. US 12 months later showed patency of the bypass without collections. Mycotic aneurysms of internal carotid artery are very infrequent. MRSA isolation is rare, and to the best of our knowledge this is the first case caused by multi-drug resistant LA-MRSA CC398. The treatment includes mycotic aneurysm resection and reconstruction with venous graft bypass plus intensive antibiotic therapy.

Rationally Modified Antimicrobial Peptides from the N-Terminal Domain of Human RNase 3 Show Exceptional Serum Stability.

Multidrug resistance against conventional antibiotics poses an important threat to human health. In this context, antimicrobial peptides (AMPs) have been extensively studied for their antibacterial activity and promising results have been shown so far. However, AMPs tend to be rather vulnerable to protease degradation, which offsets their therapeutic appeal. Here, we demonstrate how replacing functional residues in the antimicrobial region of human RNase 3-also named eosinophil cationic protein-by non-natural amino acids increases stability in human serum. These changes were also shown to reduce the hemolytic effect of the peptides in general terms, whereas the antimicrobial activity was reasonably preserved. Digestion profiles enabled us to design new peptides with superior stability and lower toxicity that could become relevant candidates to reach clinical stages.