Person:
García-Cobos, Silvia

First Name

Silvia

Last Name

García-Cobos

Institution

ISCIII

Centrre

ISCIII::Centro Nacional de Microbiología (CNM)

Identifiers

Full item page

Search Results

Now showing 1 - 9 of 9

An increase in erythromycin resistance in methicillin-susceptible Staphylococcus aureus from blood correlates with the use of macrolide/lincosamide/streptogramin antibiotics. EARS-Net Spain (2004–2020)
(Frontiers Media, 2023-09) El Mammery, Achraf; Ramirez de Arellano, Eva; Cañada-Garcia, Javier Enrique; Cercenado, Emilia; Villar-Gómara, Laura; Casquero-García, Verónica; García-Cobos, Silvia; Lepe, José Antonio; Ruiz de Gopegui Bordes, Enrique; Calvo-Montes, Jorge; Larrosa Escartín, Nieves; Cantón, Rafael; Perez-Vazquez, Maria; Aracil, Belen; Oteo-Iglesias, Jesus; Spanish EARS-Net Group; Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas); Centro de Investigación Biomédica en Red - CIBERES (Enfermedades Respiratorias); Instituto de Salud Carlos III; Ministerio de Ciencia e Innovación (España); Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
Objectives: To describe and analyse erythromycin resistance trends in blood isolates of Staphylococcus aureus (EARS-Net Spain, 2004–2020) and the association of these trends with the consumption of macrolide, lincosamide, and streptogramin B (MLSB) antibiotics. To assess molecular changes that could be involved in erythromycin resistance trends by whole genome analysis of representative isolates. Materials and methods: We collected antibiotic susceptibility data for all firstblood S. aureus isolates in patients from 47 Spanish hospitals according to EARS-Net criteria. MLSB antibiotic consumption was obtained from the Spanish Agency for Medicines and Medical Devices (2008–2020). We sequenced 137 representative isolates for core genome multilocus sequence typing, resistome and virulome analysis. Results: For the 36,612 invasive S. aureus isolates, methicillin resistance decreased from 26.4% in 2004 to 22.4% in 2020. Erythromycin resistance in methicillin-susceptible S. aureus (MSSA) increased from 13.6% in 2004 to 28.9% in 2020 (p < 0.001); however, it decreased from 68.7 to 61.8% (p < 0.0001) in methicillin-resistant S. aureus (MRSA). Total consumption of MLSB antibiotics increased from 2.72 defined daily doses per 1,000 inhabitants per day (DID) in 2014 to 3.24 DID in 2016. By WGS, the macrolide resistance genes detected were erm (59.8%), msrA (46%), and mphC (45.2%). The erm genes were more prevalent in MSSA (44/57, 77.2%) than in MRSA (38/80, 47.5%). Most of the erm genes identified in MSSA after 2013 differed from the predominant ermC gene (17/22, 77.3%), largely because ermT was significantly associated with MSSA after 2013 (11/29, 37.9%). All 13 ermT isolates in this study, except one, belonged to ST398 and came from 10 hospitals and six Spanish provinces. Conclusion: The significant increase in erythromycin resistance in blood MSSA correlated with the consumption of the MLSB antibiotics in Spain. These preliminary data seem support the hypothesis that the human ST398 MSSA clade with ermT-mediated resistance to erythromycin may be involved in this trend.
Carbapenemase-Producing Klebsiella pneumoniae in COVID-19 Intensive Care Patients: Identification of IncL-VIM-1 Plasmid in Previously Non-Predominant Sequence Types
(Multidisciplinary Digital Publishing Institute (MDPI), 2023-01-06) Cañada-Garcia, Javier Enrique; Ramirez de Arellano, Eva; Jiménez-Orellana, Miguel; Viedma, Esther; Sánchez, Aida; Alhambra, Almudena; Villa, Jennifer; Delgado-Iribarren, Alberto; Bautista, Veronica; Lara Fuella, Noelia; García-Cobos, Silvia; Aracil, Belen; Cercenado, Emilia; Perez-Vazquez, Maria; Oteo-Iglesias, Jesus; Instituto de Salud Carlos III; Centro de Investigación Biomédica en Red - CIBERINFEC (Enfermedades Infecciosas); Ministerio de Ciencia e Innovación (España); Unión Europea; Plan Nacional de I+D+i (España); RETICS-Investigación en Patología Infecciosa (REIPI-ISCIII) (España); Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
During the COVID-19 pandemic, intensive care units (ICUs) operated at or above capacity, and the number of ICU patients coinfected by nosocomial microorganisms increased. Here, we characterize the population structure and resistance mechanisms of carbapenemase-producing Klebsiella pneumoniae (CP-Kpn) from COVID-19 ICU patients and compare them to pre-pandemic populations of CP-Kpn. We analyzed 84 CP-Kpn isolates obtained during the pandemic and 74 CP-Kpn isolates obtained during the pre-pandemic period (2019) by whole genome sequencing, core genome multilocus sequence typing, plasmid reconstruction, and antibiotic susceptibility tests. More CP-Kpn COVID-19 isolates produced OXA-48 (60/84, 71.4%) and VIM-1 (18/84, 21.4%) than KPC (8/84, 9.5%). Fewer pre-pandemic CP-Kpn isolates produced VIM-1 (7/74, 9.5%). Cefiderocol (97.3-100%) and plazomicin (97.5-100%) had the highest antibiotic activity against pandemic and pre-pandemic isolates. Sequence type 307 (ST307) was the most widely distributed ST in both groups. VIM-1-producing isolates belonging to ST307, ST17, ST321 and ST485, (STs infrequently associated to VIM-1) were detected during the COVID-19 period. Class 1 integron Int1-blaVIM-1-aac(6')-1b-dfrB1-aadAI-catB2-qacEΔ1/sul1, found on an IncL plasmid of approximately 70,000 bp, carried blaVIM-1 in ST307, ST17, ST485, and ST321 isolates. Thus, CP-Kpn populations from pandemic and pre-pandemic periods have similarities. However, VIM-1 isolates associated with atypical STs increased during the pandemic, which warrants additional monitoring and surveillance.
Spread of Escherichia coli strains with high-level cefotaxime and ceftazidime resistance between the community, long-term care facilities, and hospital institutions
(American Society for Microbiology (ASM), 2006-07) Oteo-Iglesias, Jesus; Navarro Rivas, Carmen; Cercenado, Emilia; Delgado-Iribarren, Alberto; Wilhelmi, Isabel; Orden, Beatriz; Garcia, Carmen; Miguelañez, Silvia; Perez-Vazquez, Maria; García-Cobos, Silvia; Aracil, Belen; Bautista, Veronica; Campos, Jose; Instituto de Salud Carlos III; RETICS-Investigación en Patología Infecciosa (REIPI-ISCIII) (España)
A total of 151 Escherichia coli strains resistant to cefotaxime and ceftazidime were isolated during a prospective surveillance study. These strains were characterized by clinical, microbiological, and molecular analyses and were distributed into four clusters of 103, 11, 6, and 5 isolates, along with 25 unrelated strains. The principal cluster was isolated from urine, wound, blood, and other samples in three hospitals, eight nursing homes, and a community healthcare center. This cluster was associated with both nosocomial (65%) and community-acquired (35%) infections. Most strains were resistant to ciprofloxacin, gentamicin, tobramycin, cefepime, amoxicillin-clavulanic acid, and trimethoprim-sulfamethoxazole but were susceptible to imipenem. All isolates from the four clusters expressed the extended-spectrum beta-lactamase (ESBL) CTX-M-15. This enzyme was also present in 8 (30.8%) of the 26 unrelated isolates. The other ESBLs, CTX-M-14 and CTX-M-32, were detected in five and seven cases, respectively, but they were detected in individual E. coli isolates only. In three clusters, blaCTX-M-15 alleles were linked to an ISEcp1-like element, while in eight strains of cluster II an IS26 element preceded the blaCTX-M-15 allele. An additional pool of resistance genes included tetA, drfA14 or dfrA17, sul1 or sul2, aac(6')Ib, and aac(3)IIb. All except one of the 27 isolates tested for genetic virulence markers harbored the same three virulence genes: iutA and fyuA (siderophores), and traT (serum survival factor). Epidemic or occasional isolates of cefotaxime- and ceftazidime-resistant E. coli can spread between distinct health facilities including hospitals, community health centers, and long-term care centers.
Staphylococcus aureus populations from the gut and the blood are not distinguished by virulence traits-a critical role of host barrier integrity
(BioMed Central (BMC), 2022-12-26) Raineri, Elisa J M; Maaß, Sandra; Wang, Min; Brushett, Siobhan; Palma Medina, Laura M; Sampol Escandell, Neus; Altulea, Dania; Raangs, Erwin; de Jong, Anne; Vera Murguia, Elias; Feil, Edward J; Friedrich, Alex W; Buist, Girbe; Becher, Dörte; García-Cobos, Silvia; Couto, Natacha; van Dijl, Jan Maarten; China Scholarship Council; Dutch Research Council (Holanda); Unión Europea. Comisión Europea; Ministry of Health Welfare and Sport (Países Bajos); Saxony
Background: The opportunistic pathogen Staphylococcus aureus is an asymptomatically carried member of the microbiome of about one third of the human population at any given point in time. Body sites known to harbor S. aureus are the skin, nasopharynx, and gut. In particular, the mechanisms allowing S. aureus to pass the gut epithelial barrier and to invade the bloodstream were so far poorly understood. Therefore, the objective of our present study was to investigate the extent to which genetic differences between enteric S. aureus isolates and isolates that caused serious bloodstream infections contribute to the likelihood of invasive disease. Results: Here, we present genome-wide association studies (GWAS) that compare the genome sequences of 69 S. aureus isolates from enteric carriage by healthy volunteers and 95 isolates from bloodstream infections. We complement our GWAS results with a detailed characterization of the cellular and extracellular proteomes of the representative gut and bloodstream isolates, and by assaying the virulence of these isolates with infection models based on human gut epithelial cells, human blood cells, and a small animal infection model. Intriguingly, our results show that enteric and bloodstream isolates with the same sequence type (ST1 or ST5) are very similar to each other at the genomic and proteomic levels. Nonetheless, bloodstream isolates are not necessarily associated with an invasive profile. Furthermore, we show that the main decisive factor preventing infection of gut epithelial cells in vitro is the presence of a tight barrier. Conclusions: Our data show that virulence is a highly variable trait, even within a single clone. Importantly, however, there is no evidence that blood stream isolates possess a higher virulence potential than those from the enteric carriage. In fact, some gut isolates from healthy carriers were more virulent than bloodstream isolates. Based on our present observations, we propose that the integrity of the gut epithelial layer, rather than the pathogenic potential of the investigated enteric S. aureus isolates, determines whether staphylococci from the gut microbiome will become invasive pathogens.
Phenotypic and molecular characterization of IMP-producing Enterobacterales in Spain: Predominance of IMP-8 in Klebsiella pneumoniae and IMP-22 in Enterobacter roggenkampii
(Frontiers Media, 2022-09-28) Cañada-Garcia, Javier Enrique; Grippo, Natalin; Ramirez de Arellano, Eva; Bautista, Veronica; Lara Fuella, Noelia; Navarro, Ana; Cabezas, Teresa; Martínez-Ramírez, Nora Mariela; García-Cobos, Silvia; Calvo, Jorge; Cercenado, Emilia; Aracil, Belen; Perez-Vazquez, Maria; Oteo-Iglesias, Jesus; Spanish IMP Study Group; Instituto de Salud Carlos III; Centro de Investigación Biomedica en Red - CIBER; Ministerio de Ciencia e Innovación (España); Unión Europea; Plan Nacional de I+D+i (España); Ministerio de Economía, Industria y Competitividad (España); RETICS-Investigación en Patología Infecciosa (REIPI-ISCIII) (España); Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF)
Objectives: Little is known about IMP-producing Enterobacterales (IMP-Ent) in Europe. We analyzed at genomic and phenotypic level IMP-Ent isolates circulating in Spain in a 9-year period. Materials and methods: IMP-Ent isolates submitted to our reference laboratory were included. Antibiotic susceptibility was performed using microdilution method (EUCAST), and IMP-carbapenemase activity was measured with carbapenemase inhibitors, the β-CARBA method, the modified Hodge test (MHT), and the modified carbapenemase inhibition method (mCIM). All isolates collected were sequenced for high-resolution single-nucleotide polymorphism (SNP) typing, core genome multilocus sequence typing (cgMLST), and resistome analysis. Results: Fifty IMP-Ent isolates, collected from 19 hospitals in 13 Spanish provinces, were detected: Klebsiella pneumoniae (IMP-Kpn) (24; 48%), Enterobacter roggenkampii (13; 26%), Enterobacter hormaechei (8, 16%), Klebsiella oxytoca (two; 4%), Enterobacter asburiae (one, 2%), Serratia marcescens (one; 2%) and Escherichia coli (one; 2%). All isolates were positive by the MHT and β-CARBA tests; 48 (96%) were mCIM positive; 12 (24%) and 26 (52%) displayed positive inhibition with dipicolinic (meropenem) and EDTA (ertapenem), respectively. Five IMP-carbapenemase types were identified: IMP-8 (22; 44%), IMP-22 (17; 34%), IMP-13 (7; 14%), IMP-28 (two; 4%), and IMP-15 (two; 4%), predominating IMP-8 in K. pneumoniae and IMP-22 in E. roggenkampii. IMP-28 was exclusively identified in K. oxytoca and IMP-15 in E. hormaechei. Predominant STs were ST405 (29.2%), ST15 (25%) and ST464 (20.8%) in IMP-Kpn; ST96 (100%) in E. roggenkampii and ST182 (62.5%) in E. hormachei. Colistin and amikacin were the most active non-carbapenem antibiotics against IMP-Ent. Conclusion: IMP-Ent isolates remain infrequent in Spain, although in recent years have been circulating causing nosocomial outbreaks, being IMP-8-producing K. pneumoniae and IMP-22-producing E. roggenkampii the most frequently detected in this study. Inhibition with EDTA or dipicolinic acid presented false negative results in some IMP-producing strains. Active microbiological and molecular surveillance is essential for a better comprehension and control of IMP-Ent dissemination.
Widespread Detection of Yersiniabactin Gene Cluster and Its Encoding Integrative Conjugative Elements (ICEKp) among Nonoutbreak OXA-48-Producing Klebsiella pneumoniae Clinical Isolates from Spain and the Netherlands
(American Society for Microbiology (ASM), 2023-08-17) Jati, Afif P; Sola-Campoy, Pedro Juan; Bosch, Thijs; Schouls, Leo M; Hendrickx, Antoni P A; Bautista, Veronica; Lara Fuella, Noelia; Raangs, Erwin; Aracil, Belen; Rossen, John W A; Friedrich, Alex W; Navarro, Ana; Cañada-Garcia, Javier Enrique; Ramirez de Arellano, Eva; Oteo-Iglesias, Jesus; Perez-Vazquez, Maria; García-Cobos, Silvia; The Dutch and Spanish Collaborative Working Groups on Surveillance on Carbapenemase-Producing Enterobacterales; Plan Nacional de I+D+i (España); Instituto de Salud Carlos III; Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); Ministerio de Economía y Competitividad (España); RETICS-Investigación en Patología Infecciosa (REIPI-ISCIII) (España); Ministry of Health Welfare and Sport (Países Bajos)
In this study, we determined the presence of virulence factors in nonoutbreak, high-risk clones and other isolates belonging to less common sequence types associated with the spread of OXA-48-producing Klebsiella pneumoniae clinical isolates from The Netherlands (n = 61) and Spain (n = 53). Most isolates shared a chromosomally encoded core of virulence factors, including the enterobactin gene cluster, fimbrial fim and mrk gene clusters, and urea metabolism genes (ureAD). We observed a high diversity of K-Locus and K/O loci combinations, KL17 and KL24 (both 16%), and the O1/O2v1 locus (51%) being the most prevalent in our study. The most prevalent accessory virulence factor was the yersiniabactin gene cluster (66.7%). We found seven yersiniabactin lineages-ybt 9, ybt 10, ybt 13, ybt 14, ybt 16, ybt 17, and ybt 27-which were chromosomally embedded in seven integrative conjugative elements (ICEKp): ICEKp3, ICEKp4, ICEKp2, ICEKp5, ICEKp12, ICEKp10, and ICEKp22, respectively. Multidrug-resistant lineages-ST11, ST101, and ST405-were associated with ybt 10/ICEKp4, ybt 9/ICEKp3, and ybt 27/ICEKp22, respectively. The fimbrial adhesin kpi operon (kpiABCDEFG) was predominant among ST14, ST15, and ST405 isolates, as well as the ferric uptake system kfuABC, which was also predominant among ST101 isolates. No convergence of hypervirulence and resistance was observed in this collection of OXA-48-producing K. pneumoniae clinical isolates. Nevertheless, two isolates, ST133 and ST792, were positive for the genotoxin colibactin gene cluster (ICEKp10). In this study, the integrative conjugative element, ICEKp, was the major vehicle for yersiniabactin and colibactin gene clusters spreading. IMPORTANCE; Convergence of multidrug resistance and hypervirulence in Klebsiella pneumoniae isolates has been reported mostly related to sporadic cases or small outbreaks. Nevertheless, little is known about the real prevalence of carbapenem-resistant hypervirulent K. pneumoniae since these two phenomena are often separately studied. In this study, we gathered information on the virulent content of nonoutbreak, high-risk clones (i.e., ST11, ST15, and ST405) and other less common STs associated with the spread of OXA-48-producing K. pneumoniae clinical isolates. The study of virulence content in nonoutbreak isolates can help us to expand information on the genomic landscape of virulence factors in K. pneumoniae population by identifying virulence markers and their mechanisms of spread. Surveillance should focus not only on antimicrobial resistance but also on virulence characteristics to avoid the spread of multidrug and (hyper)virulent K. pneumoniae that may cause untreatable and more severe infections.
Revealing the Virulence Potential of Clinical and Environmental Aspergillus fumigatus Isolates Using Whole-Genome Sequencing
(Frontiers Media, 2019) Puértolas-Balint, Fabiola; Rossen, John W A; Oliveira Dos Santos, Claudy; Chlebowicz, Monika M A; Raangs, Erwin C; van Putten, Maarten L; Sola-Campoy, Pedro Juan; Han, Li; Schmidt, Martina; García-Cobos, Silvia; Unión Europea. Comisión Europea
Aspergillus fumigatus is considered a common causative agent of human fungal infections. A restricted number of virulence factors have been described, and none of them lead to a differentiation in the virulence level among different strains. Variations in the virulence phenotype depending on the isolate origin, measured as survival percentage in animal infection models, have been previously reported. In this study, we analyzed the whole-genome sequence of A. fumigatus isolates from clinical and environmental origins to determine their virulence genetic content. The sample included four isolates sequenced at the University Medical Center Groningen (UMCG), three clinical (two of them isolated from the same patient) and the experimental strain B5233, and the draft genomes of one reference strain, two environmental and two clinical isolates obtained from a public database. The fungal genomes were screened for the presence of virulence-related genes (VRGs) using an in-house database of 244 genes related to thermotolerance, resistance to immune responses, cell wall formation, nutrient uptake, signaling and regulation, and production of toxins and secondary metabolites and allergens. In addition, we performed a variant calling analysis to compare the isolates sequenced at the UMCG and investigated their genetic relatedness using the TRESP (Tandem Repeats located within Exons of Surface Protein coding genes) genotyping method. We neither observed a difference in the virulence genetic content between the clinical isolates causing an invasive infection and a colonizing clinical isolate nor between isolates from the clinical and environmental origin. The four novel A. fumigatus sequences had a different TRESP genotype and a total number of genetic variants ranging from 48,590 to 68,352. In addition, a comparative genomics analysis showed the presence of single nucleotide polymorphisms in VRGs and repetitive genetic elements located next to VRG groups, which could influence the regulation of these genes. In conclusion, our genomic analysis revealed a high genetic diversity between environmental and clinical A. fumigatus isolates, as well as between clinical isolates from the same patient, indicating an infection with a mixed-population in the latter case. However, all isolates had a similar virulence genetic content, demonstrating their pathogenic potential at least at the genomic level.
Increased amoxicillin-clavulanic acid resistance in Escherichia coli blood isolates, Spain
(Centers for Disease Control and Prevention (CDC), 2008-08) Oteo-Iglesias, Jesus; Campos, Jose; Lázaro, Edurne; Cuevas, Oscar; García-Cobos, Silvia; Perez-Vazquez, Maria; Abajo Iglesias, Francisco J de; Unión Europea. Comisión Europea; Ministerio de Sanidad y Consumo (España); Instituto de Salud Carlos III; RETICS-Investigación en Patología Infecciosa (REIPI-ISCIII) (España)
To determine the evolution and trends of amoxicillin-clavulanic acid resistance among Escherichia coli isolates in Spain, we tested 9,090 blood isolates from 42 Spanish hospitals and compared resistance with trends in outpatient consumption. These isolates were collected by Spanish hospitals that participated in the European Antimicrobial Resistance Surveillance System network from April 2003 through December 2006.
Effects of Clinical Wastewater on the Bacterial Community Structure from Sewage to the Environment
(Multidisciplinary Digital Publishing Institute (MDPI), 2021-03-31) Verburg, Ilse; van Veelen, H Pieter J; Waar, Karola; Rossen, John WA; Friedrich, Alex W; Hernández Leal, Lucia; García-Cobos, Silvia; Schmitt, Heike; Dutch Ministry of Economic Affairs; Unión Europea. Fondo Europeo de Desarrollo Regional (FEDER/ERDF); INTERREG VA; Dutch Ministry of Infrastructure and Environment
This study pertains to measure differences in bacterial communities along the wastewater pathway, from sewage sources through the environment. Our main focus was on taxa which include pathogenic genera, and genera harboring antibiotic resistance (henceforth referred to as "target taxa"). Our objective was to measure the relative abundance of these taxa in clinical wastewaters compared to non-clinical wastewaters, and to investigate what changes can be detected along the wastewater pathway. The study entailed a monthly sampling campaign along a wastewater pathway, and taxa identification through 16S rRNA amplicon sequencing. Results indicated that clinical and non-clinical wastewaters differed in their overall bacterial composition, but that target taxa were not enriched in clinical wastewater. This suggests that treatment of clinical wastewater before release into the wastewater system would only remove a minor part of the potential total pathogen load in wastewater treatment plants. Additional findings were that the relative abundance of most target taxa was decreased after wastewater treatment, yet all investigated taxa were detected in 68% of the treated effluent samples-meaning that these bacteria are continuously released into the receiving surface water. Temporal variation was only observed for specific taxa in surface water, but not in wastewater samples.