Publications by authors named "Belen Aracil"

Xeruborbactam is a broad-spectrum boronate-type β-lactamase inhibitor. We aimed to evaluate its activity in combination with meropenem and compare it with other β-lactam/β-lactamase inhibitor combinations against Enterobacterales. The following isolates were screened: (i) an isogenic collection of 94 isolates producing β-lactamases under wild-type and low-permeability conditions, (ii) 300 genetically diverse clinical Enterobacterales isolates producing the three main carbapenemase types (KPC-like, OXA-48-like, and metallo-β-lactamases), and (iii) two collections of isolates producing mechanisms of resistance to β-lactam/β-lactamase inhibitor combinations, such as KPC variants or PBP3 insertions combined with metallo-β-lactamases (MBLs).

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The global emergence of carbapenem-resistant (CRAB) represents a significant public health threat. In the summer of 2022, a polyclonal CRAB outbreak occurred in our hospital, marking the first detection of an NDM-1 plus OXA-23 co-producing strain in Spain. The aim of this study was to phenotypically and genotypically characterize the clonal spread of NDM-1 and OXA-23 co-producing isolates and to describe the infection control measures implemented to contain the outbreak.

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Introduction: Antimicrobial resistance (AMR) is a major public health threat, driving the need for alternative treatments such as phage therapy. However, bacterial defense mechanisms, often regulated by the quorum sensing (QS) network and encoded in genomic islands (GIs), can generate phage-resistant mutants. Understanding these resistance mechanisms is essential for optimizing phage therapy.

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Article Synopsis
  • The study investigated the efficacy and resistance mechanisms of cefiderocol and new β-lactam/β-lactamase inhibitor combinations against strains of Enterobacterales producing multiple carbapenemases, specifically focusing on clinical samples from Spanish hospitals collected between 2017 and 2022.
  • The analysis involved 57 isolates, where minimum inhibitory concentration (MIC) values were determined for various antibiotics, and whole-genome sequencing was utilized to identify genetic resistance factors.
  • Ceftazidime/avibactam, imipenem/relebactam, and meropenem/vaborbactam showed the least activity, while combinations like aztreonam/avibactam and cefepime/zidebactam were
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The combination of several therapeutic strategies is often seen as a good way to decrease resistance rates, since bacteria can more easily overcome single-drug treatments than multi-drug ones. This strategy is especially attractive when several targets and subpopulations are affected, as it is the case of persister cells, a subpopulation of bacteria able to transiently survive antibiotic exposures. This work aims to evaluate the potential of a repurposed anticancer drug, mitomycin C, combined with the lytic phage vB_KpnM-VAC13 in vitro and its safety in an in vivo murine model against two clinical isolates of this pathogen, one of them exhibiting an imipenem-persister phenotype.

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  • CP-Eco isolates are a type of bacteria that can spread antibiotic resistance genes quickly and lead to infections that are hard to treat. This study aimed to analyze these isolates from Spain to learn more about their resistance and genetic makeup.
  • A total of 90 isolates from various hospitals in Spain were examined for their antibiotic susceptibility and genetic characteristics. Notably, a common strain (ST131) was identified, with many isolates demonstrating resistance to multiple antibiotic groups.
  • The research found that a significant number of isolates had complex genetic traits that contribute to their resistance, with some exhibiting virulence genes. The study underscores the concern of CP-Eco's ability to spread antibiotic resistance in both community and hospital settings.
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  • The study investigates the effectiveness of various antibiotics against E. coli strains that express clinically relevant β-lactamases, particularly focusing on the antibiotics cefiderocol and different β-lactam combinations.
  • Researchers created 82 E. coli strains with different levels of outer membrane permeability and β-lactamase production to test antibiotic susceptibility using broth microdilution methods.
  • Results showed that cefiderocol and certain β-lactam/β-lactamase inhibitor combinations were highly effective against most strains, even those with low permeability or multiple β-lactamases, while double-carbapenemase strains demonstrated significantly reduced antibiotic activity.
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Mucins are important glycoproteins that form a protective layer throughout the gastrointestinal and respiratory tracts. There is scientific evidence of increase in phage-resistance in the presence of mucin for some bacterial pathogens. Manipulation in mucin composition may ultimately influence the effectiveness of phage therapy.

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Objectives: To describe and analyse erythromycin resistance trends in blood isolates of (EARS-Net Spain, 2004-2020) and the association of these trends with the consumption of macrolide, lincosamide, and streptogramin B (MLS) 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 first-blood isolates in patients from 47 Spanish hospitals according to EARS-Net criteria.

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Carbapenem-resistant pathogens have been recognized as a health concern as they are both difficult to treat and detect in clinical microbiology laboratories. Researchers are making great efforts to develop highly specific, sensitive, accurate, and rapid diagnostic techniques, required to prevent the spread of these microorganisms and improve the prognosis of patients. In this context, CRISPR-Cas systems are proposed as promising tools for the development of diagnostic methods due to their high specificity; the Cas13a endonuclease can discriminate single nucleotide changes and displays collateral cleavage activity against single-stranded RNA molecules when activated.

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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 ( = 61) and Spain ( = 53). Most isolates shared a chromosomally encoded core of virulence factors, including the enterobactin gene cluster, fimbrial and gene clusters, and urea metabolism genes (). 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.

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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 (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.

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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.

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Objectives: CARB-ES-19 is a comprehensive, multicenter, nationwide study integrating whole-genome sequencing (WGS) in the surveillance of carbapenemase-producing (CP-Kpn) and (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).

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Carbapenemase-producing (CP) Pseudomonas aeruginosa is rare compared with mutation-driven carbapenem-resistance, but this situation may be changing. A collection of CP P. aeruginosa isolates was characterized in this study.

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The emergence of linezolid-resistant Enterococcus spp. (LRE) due to transferable resistance determinants is a matter of concern. To understand the contribution of the plasmid-encoded optrA and poxtA genes to the emergence of LRE, clinical isolates from different Spanish hospitals submitted to the Spanish Reference Laboratory from 2015-2018 were analysed.

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Objectives: NDM carbapenemases have spread worldwide. However, little information exists about the impact of NDM-producing Enterobacteriaceae in Spain. By WGS, we sought to elucidate the population structure of NDM-like-producing Klebsiella pneumoniae and Escherichia coli in Spain and to determine the plasmids harbouring blaNDM-like genes.

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Article Synopsis
  • The study investigated carbapenemase-producing (CP) isolates from Spanish hospitals between January 2016 and October 2017, identifying a total of 139 nonduplicate isolates, with 80 analyzed in detail.
  • Genetic testing revealed that 60% of the isolates produced the VIM-1 enzyme, while others produced OXA-48, KPC-2, KPC-3, and NDM-1, with some producing two types of carbapenemases.
  • Pulsed-field gel electrophoresis found 69 distinct genetic patterns among the isolates, with a significant clustering of VIM-1 producers and notable plasmid types associated with the spread of these resistance genes.
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  • The study investigates carbapenemase-producing Citrobacter spp. isolates in Spain from 2013-2015, focusing on their molecular epidemiology and microbiological characteristics.
  • Of the 119 isolates analyzed, over half produced carbapenemases, with various types identified, including VIM-1 and OXA-48, along with a presence of extended-spectrum beta-lactamases (ESBLs).
  • Findings indicated that there is both clonal and polyclonal spread of CP Citrobacter spp. across different regions, and some isolates were still susceptible to carbapenems, raising important clinical considerations.
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  • The study examined the population structure of 90 carbapenemase-producing and 88 carbapenemase-susceptible bacterial isolates from 20 hospitals in Spain as part of the EuSCAPE project.
  • Fourteen different multilocus sequence types (MLSTs) were found in the carbapenemase-producing isolates, whereas 50 were detected in the carbapenemase-susceptible ones.
  • Specific clones (ST11 and ST15) were significantly more prevalent in the carbapenemase-producing group compared to the susceptible group, and the cefotaxime-resistant subgroup exhibited distinct population characteristics when compared to both the wild-type strains and the carbapenemase producers.
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  • The study analyzed KPC-producing Enterobacteriaceae in Spain from 2012-2014, finding that 4.5% of identified isolates produced KPC, predominantly Klebsiella pneumoniae.
  • Three major clones of K. pneumoniae were identified: ST11/KPC-2, ST101/KPC-2, and ST512/KPC-3, with significant differences in their genetic makeup and resistance genes.
  • Overall, KPC-producing Enterobacteriaceae are on the rise in Spain, especially ST101/KPC-2, which has the most virulence genes and is linked to recent outbreaks in Italy.
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