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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".
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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.
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Evolución Molecular , Genoma Viral , Filogenia , Infecciones por Virus Sincitial Respiratorio , Virus Sincitial Respiratorio Humano , Humanos , Virus Sincitial Respiratorio Humano/genética , Virus Sincitial Respiratorio Humano/inmunología , Virus Sincitial Respiratorio Humano/clasificación , Infecciones por Virus Sincitial Respiratorio/epidemiología , Infecciones por Virus Sincitial Respiratorio/virología , Preescolar , Niño , Masculino , Lactante , Femenino , Persona de Mediana Edad , España/epidemiología , Adolescente , Adulto , Variación Genética , Anticuerpos Monoclonales/inmunología , Anciano , Adulto Joven , Mutación , Secuenciación Completa del Genoma , Anticuerpos Antivirales/sangre , Prevalencia , Secuenciación de Nucleótidos de Alto Rendimiento , Recién NacidoRESUMEN
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.
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[This corrects the article DOI: 10.3389/fmicb.2022.918362.].
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Background: Pseudomonas aeruginosa healthcare-associated infections are one of the top antimicrobial resistance threats world-wide. In order to analyze the current trends, we performed a Spanish nation-wide high-resolution analysis of the susceptibility profiles, the genomic epidemiology and the resistome of P. aeruginosa over a five-year time lapse. Methods: A total of 3.180 nonduplicated P. aeruginosa clinical isolates from two Spanish nation-wide surveys performed in October 2017 and 2022 were analyzed. MICs of 13 antipseudomonals were determined by ISO-EUCAST. Multidrug resistance (MDR)/extensively drug resistance (XDR)/difficult to treat resistance (DTR)/pandrug resistance (PDR) profiles were defined following established criteria. All XDR/DTR isolates were subjected to whole genome sequencing (WGS). Findings: A decrease in resistance to all tested antibiotics, including older and newer antimicrobials, was observed in 2022 vs 2017. Likewise, a major reduction of XDR (15.2% vs 5.9%) and DTR (4.2 vs 2.1%) profiles was evidenced, and even more patent among ICU isolates [XDR (26.0% vs 6.0%) and DTR (8.9% vs 2.6%)] (p < 0.001). The prevalence of Extended-spectrum ß-lactamase/carbapenemase production was slightly lower in 2022 (2.1%. vs 3.1%, p = 0.064). However, there was a significant increase in the proportion of carbapenemase production among carbapenem-resistant strains (29.4% vs 18.1%, p = 0.0246). While ST175 was still the most frequent clone among XDR, a slight reduction in its prevalence was noted (35.9% vs 45.5%, p = 0.106) as opposed to ST235 which increased significantly (24.3% vs 12.3%, p = 0.0062). Interpretation: While the generalized decrease in P. aeruginosa resistance, linked to a major reduction in the prevalence of XDR strains, is encouraging, the negative counterpart is the increase in the proportion of XDR strains producing carbapenemases, associated to the significant advance of the concerning world-wide disseminated hypervirulent high-risk clone ST235. Continued high-resolution surveillance, integrating phenotypic and genomic data, is necessary for understanding resistance trends and analyzing the impact of national plans on antimicrobial resistance. Funding: MSD and the Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea-NextGenerationEU.
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In view of the current increase and spread of antimicrobial resistance (AMR), there is an urgent need to find new strategies to combat it. This study had two aims. First, we synthesized highly monodispersed silver nanoparticles (AgNPs) of approximately 17 nm, and we functionalized them with mercaptopoly(ethylene glycol) carboxylic acid (mPEG-COOH) and amikacin (AK). Second, we evaluated the antibacterial activity of this treatment (AgNPs_mPEG_AK) alone and in combination with hyperthermia against planktonic and biofilm-growing strains. AgNPs, AgNPs_mPEG, and AgNPs_mPEG_AK were characterized using a suite of spectroscopy and microscopy methods. Susceptibility to these treatments and AK was determined after 24 h and over time against 12 clinical multidrug-resistant (MDR)/extensively drug-resistant (XDR) isolates of Acinetobacter baumannii, Escherichia coli, Klebsiella pneumoniae, and Pseudomonas aeruginosa. The efficacy of the treatments alone and in combination with hyperthermia (1, 2, and 3 pulses at 41°C to 42°C for 15 min) was tested against the same planktonic strains using quantitative culture and against one P. aeruginosa strain growing on silicone disks using confocal laser scanning microscopy. The susceptibility studies showed that AgNPs_mPEG_AK was 10-fold more effective than AK alone, and bactericidal efficacy after 4, 8, 24, or 48 h was observed against 100% of the tested strains. The combination of AgNPs_mPEG_AK and hyperthermia eradicated 75% of the planktonic strains and exhibited significant reductions in biofilm formation by P. aeruginosa in comparison with the other treatments tested, except for AgNPs_mPEG_AK without hyperthermia. In conclusion, the combination of AgNPs_mPEG_AK and hyperthermia may be a promising therapy against MDR/XDR and biofilm-producing strains. IMPORTANCE Antimicrobial resistance (AMR) is one of the greatest public health challenges, accounting for 1.27 million deaths worldwide in 2019. Biofilms, a complex microbial community, directly contribute to increased AMR. Therefore, new strategies are urgently required to combat infections caused by AMR and biofilm-producing strains. Silver nanoparticles (AgNPs) exhibit antimicrobial activity and can be functionalized with antibiotics. Although AgNPs are very promising, their effectiveness in complex biological environments still falls below the concentrations at which AgNPs are stable in terms of aggregation. Thus, improving the antibacterial effectiveness of AgNPs by functionalizing them with antibiotics may be a significant change to consolidate AgNPs as an alternative to antibiotics. It has been reported that hyperthermia has a large effect on the growth of planktonic and biofilm-producing strains. Therefore, we propose a new strategy based on AgNPs functionalized with amikacin and combined with hyperthermia (41°C to 42°C) to treat AMR and biofilm-related infections.
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Hipertermia Inducida , Nanopartículas del Metal , Amicacina/farmacología , Plata/farmacología , Plata/química , Nanopartículas del Metal/química , Antibacterianos/farmacología , Antibacterianos/química , BiopelículasRESUMEN
In 2012, The Spanish Societies of Infectious Diseases and Clinical Microbiology (SEIMC), Hospital Pharmacy (SEFH), and Preventive Medicine, Public Health and Healthcare Management (SEMPSGS) lead a consensus document including recommendations for the implementation of antimicrobial stewardship (AMS) programs (AMSP; PROA in Spanish) in acute care hospitals in Spain. While these recommendations were critical for the development of these programs in many centres, there is a need for guidance in the development of AMS activities for specific patient populations, syndromes or other specific aspects which were not included in the previous document or have developed significantly since then. The objective of this expert recommendation guidance document is to review the available information about these activities in these patient populations or circumstances, and to provide guidance recommendations about them. With this objective the SEIMC, SEFH, SEMPSPGS, the Spanish Society of Intensive Care Medicine (SEMICYUC) and the Spanish Pediatric Infectious Disease Society (SEIP) selected a panel of experts who chose the different aspects to include in the document. Because of the lack of high-level evidence in the implementation of the activities, the panel opted to perform a narrative review of the literature for the different topics for which recommendations were agreed by consensus. The document was open to public consultation for the members of these societies for their comments and suggestions, which were reviewed and considered by the panel.
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Programas de Optimización del Uso de los Antimicrobianos , Enfermedades Transmisibles , Niño , Humanos , Hospitales , España , Cuidados CríticosRESUMEN
Infections caused by multidrug resistant Gram-negative bacteria are becoming a worldwide problem due to their increasing incidence and associated high mortality. Carbapenem-resistant bacteria such as Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii are the most important in clinical practice. The objective of these guidelines is to update the recommendations for the diagnosis and treatment of infections caused by these multidrug resistant bacteria. Although 'old' antibiotics such as aminoglycosides, colistin, or tigecycline are frequently used for therapy of these bacteria, the 'new' beta-lactams such as ceftazidime-avibactam, ceftolozane-tazobactam, meropenem-vaborbactam, imipenem-cilastatin-relebactam or cefiderocol are progressively becoming the first-line therapy for most of these microorganisms. The Spanish Society of Infectious Diseases and Clinical Microbiology (Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica) designated a panel of experts in the field to provide evidence-based recommendations in response to common clinical questions. This document is primarily focused on microbiological diagnosis, clinical management, and targeted antimicrobial therapy of these infections, with special attention to defining the role of the new antimicrobials in the treatment of these bacteria.
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Enfermedades Transmisibles , Infecciones por Bacterias Gramnegativas , Humanos , Carbapenémicos/farmacología , Carbapenémicos/uso terapéutico , Consenso , Infecciones por Bacterias Gramnegativas/diagnóstico , Infecciones por Bacterias Gramnegativas/tratamiento farmacológico , Infecciones por Bacterias Gramnegativas/microbiología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Bacterias GramnegativasRESUMEN
There is currently an urgent need to find new strategies to tackle antimicrobial resistance and biofilm-related infections. This study has two aims. First, we evaluated the in vitro efficacy of hyperthermia in preventing biofilm formation on the surfaces of polyvinyl chloride discs. Second, we assessed the in vivo efficacy of hyperthermia in preventing biofilm formation in endotracheal tubes (ETTs) of a rabbit model. For the in vitro studies, nine clinical extensively drug-resistant/multidrug-resistant Gram-negative isolates of Acinetobacter baumannii, Klebsiella pneumoniae, and Pseudomonas aeruginosa and three clinical methicillin-resistant Staphylococcus aureus strains were studied. For biofilm formation, an adhesion step of 30 or 90 min followed by a growth step of 24 h were performed with application of one, two, and three pulses at 42°C for 15 min each pulse after the adhesion step. For the in vivo studies, New Zealand rabbits were intubated with ETTs previously colonized with K. pneumoniae or P. aeruginosa strains, and three pulses at 42°C for 15 min were applied after the adhesion step. The application of three pulses at 42°C for 15 min each pulse was needed to achieve the prevention of the in vitro biofilm formation of 100% of the tested strains. The application of heat pulses in a rabbit intubation model led to biofilm prevention of 85% against two K. pneumoniae strains and 80% against two P. aeruginosa strains compared to the control group. Hyperthermia application through pulses at 42°C could be a new nonantibiotic strategy to prevent biofilm formation in ETTs. IMPORTANCE Biofilm-producing microorganisms are considered medically crucial since they cause 80% of the infections that occur in the human body. Medical devices such as endotracheal tubes (ETTs) can act as a reservoir for pathogens providing the surface to which microorganisms can adhere and cause biofilm-associated infections in critically ill patients. This biofilm has been related with the development of ventilator-associated pneumonia (VAP), with an incidence of 8 to 28%, a mortality rate up to 17% and its associated high extra costs. Although some VAP-preventive measures have been reported, they have not demonstrated a significant reduction of VAP incidence. Therefore, we present a new nonantibiotic strategy based on hyperthermia application to prevent biofilm formation inside ETTs. This technology could reduce VAP incidence, intubation duration, hospital and intensive care unit (ICU) length stays, and mortality rates. Consequently, this could decrease the antibiotics administered and influence the impact of antibiotic resistance in the ICU.
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Hipertermia Inducida , Staphylococcus aureus Resistente a Meticilina , Neumonía Asociada al Ventilador , Humanos , Animales , Conejos , Intubación Intratraqueal/efectos adversos , Antibacterianos , Neumonía Asociada al Ventilador/etiología , Neumonía Asociada al Ventilador/prevención & control , Biopelículas , Pseudomonas aeruginosa , Hipertermia Inducida/efectos adversosRESUMEN
INTRODUCTION: The search for new biomarkers that allow an early diagnosis in sepsis and predict its evolution has become a necessity in medicine. The objective of this study is to identify, through omics techniques, potential protein biomarkers that are expressed in patients with sepsis and their relationship with organ dysfunction and mortality. METHODS: Prospective, observational and single-center study that included adult patients (≥ 18 years) who were admitted to a tertiary hospital and who met the criteria for sepsis. A mass spectrometry-based approach was used to analyze the plasma proteins in the enrolled subjects. Subsequently, using recursive feature elimination classification and cross-validation with a vector classifier, an association of these proteins with mortality and organ dysfunction was established. The protein-protein interaction network was analyzed with String software. RESULTS: 141 patients were enrolled in this study. Mass spectrometry identified 177 proteins. Of all of them, and by recursive feature elimination, nine proteins (GPX3, APOB, ORM1, SERPINF1, LYZ, C8A, CD14, APOC3 and C1QC) were associated with organ dysfunction (SOFA > 6) with an accuracy of 0.82 ± 0.06, precision of 0.85 ± 0.093, sensitivity 0.81 ± 0.10, specificity 0.84 ± 0.10 and AUC 0.82 ± 0.06. Twenty-two proteins (CLU, LUM, APOL1, SAA1, CLEBC3B, C8A, ITIH4, KNG1, AGT, C7, SAA2, APOH, HRG, AFM, APOE, APOC1, C1S, SERPINC1, IGFALS, KLKB1, CFB and BTD) were associated with mortality with an accuracy of 0.86 ± 0.05, a precision of 0.91 ± 0.05, a sensitivity of 0.91 ± 0.05, a specificity of 0.72 ± 0.17, and an area under the curve (AUC) of 0.81 ± 0.08 with a confidence interval of 95%. CONCLUSION: In sepsis there are proteomic patterns associated with organ dysfunction and mortality.
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Sepsis , Choque Séptico , Adulto , Humanos , Proteómica , Insuficiencia Multiorgánica , Estudios Prospectivos , Apolipoproteína L1RESUMEN
The aims of this study were as follows. First, we determined the antimicrobial efficacy of hypochlorous acid (HClO) against bacterial, fungal, and yeast strains growing planktonically and growing in biofilms. Second, we sought to compare the activity of the combination of daptomycin and HClO versus those of the antimicrobial agents alone for the treatment of experimental catheter-related Staphylococcus epidermidis infection (CRI) using the antibiotic lock technique (ALT) in a rabbit model. HClO was generated through direct electric current (DC) shots at determined amperages and times. For planktonic susceptibility studies, 1 to 3 DC shots of 2, 5, and 10 mA from 0 to 300 s were applied. A DC shot of 20 mA from 0 to 20 min was applied to biofilm-producing strains. Central venous catheters were inserted into New Zealand White rabbits, inoculated with an S. epidermidis strain, and treated with saline solution or ALT using daptomycin (50 mg/mL), HClO (20 mA for 45 min), or daptomycin plus HClO. One hundred percent of the planktonic bacterial, fungal, and yeast strains were killed by applying one DC shot of 2, 5, and 10 mA, respectively. One DC shot of 20 mA for 20 min was sufficient to eradicate 100% of the tested biofilm-producing strains. Daptomycin plus HClO lock therapy showed the highest activity for experimental CRI with S. epidermidis. HClO could be an effective strategy for treating infections caused by extensively drug-resistant or multidrug-resistant and biofilm-producing strains in medical devices and chronic wounds. The results of the ALT using daptomycin plus HClO may be promising. IMPORTANCE Currently, drug-resistant infections are increasing and there are fewer antibiotics available to treat them. Therefore, there is an urgent need to find new antibiotics and nonantimicrobial strategies to treat these infections. We present a new nonantibiotic strategy based on hypochlorous acid generation to treat long-term catheter-related and chronic wounds infections.
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Antiinfecciosos , Infecciones Relacionadas con Catéteres , Daptomicina , Conejos , Animales , Daptomicina/farmacología , Vancomicina/farmacología , Ácido Hipocloroso/farmacología , Solución Salina/farmacología , Saccharomyces cerevisiae , Biopelículas , Staphylococcus epidermidis , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Infecciones Relacionadas con Catéteres/tratamiento farmacológico , Infecciones Relacionadas con Catéteres/microbiología , Antiinfecciosos/farmacología , Pruebas de Sensibilidad MicrobianaRESUMEN
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.
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Aztreonam , beta-Lactamasas , Humanos , Aztreonam/uso terapéutico , Estudios Retrospectivos , Pruebas de Sensibilidad Microbiana , Antibacterianos/uso terapéutico , Compuestos de Azabiciclo/uso terapéutico , Ceftazidima/uso terapéutico , Bacterias Gramnegativas , Combinación de MedicamentosRESUMEN
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.
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BACKGROUND: Although pneumococcal conjugate vaccines (PCVs) effectively prevent invasive pneumococcal disease (IPD), serotype replacement has occurred. OBJECTIVES: We studied the pangenome, antibiotic resistance mechanisms and presence of mobile elements in predominant non-PCV13 serotypes causing adult IPD after PCV13 vaccine introduction in Spain. METHODS: We conducted a multicentre study comparing three periods in six Spanish hospitals and analysed through whole genome sequencing representative strains collected in the pre-PCV13, early-PCV13 and late-PCV13 periods. RESULTS: Among 2197 cases of adult IPD identified, 110 pneumococci expressing non-PCV13 capsules were sequenced. Seven predominant serotypes accounted for 42.6% of IPD episodes in the late-PCV13 period: serotypes 8 (14.4%), 12F (7.5%), 9N (5.2%), 11A (4.1%), 22F (3.9%), 24F (3.9%) and 16F (3.6%). All predominant non-PCV13 serotypes were highly clonal, comprising one or two clonal complexes (CC). In general, CC538, CC4048, CC3016F, CC43322F and CC669N, related to predominant non-PCV13 serotypes, were antibiotic susceptible. CC15611A was associated with resistance to co-trimoxazole, penicillin and amoxicillin. CC23024F was non-susceptible to penicillin and resistant to erythromycin, clindamycin, and tetracycline. Six composite transposon structures of the Tn5252-family were found in CC23024F, CC98912F and CC3016F carrying different combinations of erm(B), tet(M), and cat. Pangenome analysis revealed differences in accessory genomes among the different CC, with most variety in CC3016F (23.9%) and more conservation in CC15611A (8.5%). CONCLUSIONS: We identified highly clonal predominant serotypes responsible for IPD in adults. The detection of not only conjugative elements carrying resistance determinants but also clones previously associated with vaccine serotypes (CC15611A and CC23024F) highlights the importance of the accessory genome.
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Infecciones Neumocócicas , Antibacterianos/farmacología , Genómica , Humanos , Penicilinas , Infecciones Neumocócicas/epidemiología , Infecciones Neumocócicas/prevención & control , Vacunas Neumococicas , Serogrupo , España/epidemiologíaRESUMEN
Sepsis is a heterogeneous disease with variable clinical course and several clinical phenotypes. As it is associated with an increased risk of death, patients with this condition are candidates for receipt of a very well-structured and protocolized treatment. All patients should receive the fundamental pillars of sepsis management, which are infection control, initial resuscitation, and multiorgan support. However, specific subgroups of patients may benefit from a personalized approach with interventions targeted towards specific pathophysiological mechanisms. Herein, we will review the framework for identifying subpopulations of patients with sepsis, septic shock, and multiorgan dysfunction who may benefit from specific therapies. Some of these approaches are still in the early stages of research, while others are already in routine use in clinical practice, but together will help in the effective generation and safe implementation of precision medicine in sepsis.
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The mortality of septic shock remains high [Ann Intensive Care. 2017;7:19], so apart from usual therapy based on source control and antibiotics, some patients may need rescue therapies. Blood purification systems may play a role by facilitating the nonspecific removal of inflammatory mediators and microbiological toxins. There are different hemoadsorption systems, we describe in this case report the sequential use of Polymyxin B (PMX) endotoxin-adsorbing column (Toraymixin PMX-20R; Toray, Tokyo, Japan) and Cytosorb® (Cytosorbents Corp., New Jersey, USA).
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Hemoperfusión , Choque Séptico , Antibacterianos/uso terapéutico , Citocinas , Endotoxinas , Humanos , Insuficiencia Multiorgánica/terapia , Polimixina B/uso terapéuticoRESUMEN
IntroductionIncreasing rates of antimicrobial resistance in Neisseria gonorrhoeae cause problems for treating gonorrhoea.AimThis observational study aimed to describe isolates from all patients found infected with N. gonorrhoeae, in Barcelona, Spain, between 2013 and 2017, and with available antimicrobial susceptibility data.MethodsMinimum inhibitory concentrations (MICs) of penicillin (PEN), cefixime (CFM), ceftriaxone (CRO), azithromycin (AZM), ciprofloxacin (CIP), spectinomycin (SPT), fosfomycin (FOF) and gentamicin (GEN) were determined by E-test. Susceptibility was assessed using clinical breakpoints from the European Committee on Antimicrobial Susceptibility Testing. Time trends for PEN, CFM, AZM and CIP were investigated using logistic regression.ResultsOf 1,979 patients with infection (2,036 isolates), 1,888 (95.4%) were men. Patient median age was 32 years. The proportions of isolates resistant to extended-spectrum cephalosporins were low, with 0.3% (5/1,982) resistant to CRO and 4.9% (98/1,985) to CFM. AZM resistance prevalence was 2.7% (52/1,981), including 16 isolates detected in 2016 and 2017, with high-level resistance. For CIP, 51.3% (1,018/1,986) of isolates were resistant, and for PEN, 20.1% (399/1,985). All isolates were susceptible to SPT. MIC50 and MIC90 values of GEN were 4 and 6 mg/L and of FOF 12 and 24 mg/L, respectively. Between 2013 and 2017, PEN and CFM resistance rates each decreased from 28.1% (92/327) to 12.2% (70/572) and from 8.3% (27/327) to 4.4% (25/572) (p ≤ 0.0073). In contrast, AZM resistance prevalence appeared to increase from 1.5% in 2014 (5/340) to 3.0% (17/572) in 2017. No trend was identified for CIP.ConclusionAntimicrobial susceptibility surveillance is important to timely detect new phenotypes and trends.
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Antibacterianos/farmacología , Farmacorresistencia Bacteriana , Gonorrea/tratamiento farmacológico , Gonorrea/microbiología , Neisseria gonorrhoeae/efectos de los fármacos , Adulto , Anciano , Antibacterianos/uso terapéutico , Azitromicina/farmacología , Cefixima/farmacología , Ceftriaxona/farmacología , Cefalosporinas/farmacología , Ciprofloxacina/farmacología , Femenino , Gonorrea/diagnóstico , Gonorrea/epidemiología , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Neisseria gonorrhoeae/aislamiento & purificación , Penicilinas/farmacología , España/epidemiología , Espectinomicina/farmacología , Tetraciclina/farmacologíaRESUMEN
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).
Asunto(s)
Infecciones Neumocócicas/prevención & control , Streptococcus pneumoniae/efectos de los fármacos , beta-Lactamas/farmacología , Adolescente , Adulto , Células Clonales , Farmacorresistencia Bacteriana/genética , Humanos , Persona de Mediana Edad , Tipificación de Secuencias Multilocus , Resistencia a las Penicilinas , Infecciones Neumocócicas/microbiología , Vacunas Neumococicas/administración & dosificación , Vacunas Neumococicas/inmunología , Estudios Prospectivos , Serotipificación , España , Streptococcus pneumoniae/clasificación , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/aislamiento & purificación , Secuenciación Completa del GenomaRESUMEN
BACKGROUND: Few validated biomarker or clinical score combinations exist which can discriminate between cases of infection and other non-infectious conditions following activation of an in-hospital sepsis code, as well as provide an accurate severity assessment of the corresponding host response. This study aimed to identify suitable blood biomarker (MR-proADM, PCT, CRP and lactate) or clinical score (SOFA and APACHE II) combinations to address this unmet clinical need. METHODS: A prospective, observational study of patients activating the Vall d'Hebron University Hospital sepsis code (ISC) within the emergency department (ED), hospital wards and intensive care unit (ICU). Area under the receiver operating characteristic (AUROC) curves, logistic and Cox regression analysis were used to assess performance. RESULTS: 148 patients fulfilled the Vall d'Hebron ISC criteria, of which 130 (87.8%) were retrospectively found to have a confirmed diagnosis of infection. Both PCT and MR-proADM had a moderate-to-high performance in discriminating between infected and non-infected patients following ISC activation, although the optimal PCT cut-off varied significantly across departments. Similarly, MR-proADM and SOFA performed well in predicting 28- and 90-day mortality within the total infected patient population, as well as within patients presenting with a community-acquired infection or following a medical emergency or prior surgical procedure. Importantly, MR-proADM also showed a high association with the requirement for ICU admission after ED presentation [OR (95% CI) 8.18 (1.75-28.33)] or during treatment on the ward [OR (95% CI) 3.64 (1.43-9.29)], although the predictive performance of all biomarkers and clinical scores diminished between both settings. CONCLUSIONS: Results suggest that the individual use of PCT and MR-proADM might help to accurately identify patients with infection and assess the overall severity of the host response, respectively. In addition, the use of MR-proADM could accurately identify patients requiring admission onto the ICU, irrespective of whether patients presented to the ED or were undergoing treatment on the ward. Initial measurement of both biomarkers might therefore facilitate early treatment strategies following activation of an in-hospital sepsis code.