SEARCH · Search PubMed

Results for “beta-Lactam Resistance”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

SourceResearch connectionFrom yearThrough year

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources

PubMed2026

The antimicrobial gut resistome of the Wayampi reveals a shared background of antibiotic and metal resistance genes with industrialized populations, underscoring the "robust-yet-fragile" architecture of human gut microbiomes.

BACKGROUND: Metagenomics enables detailed profiling of genes encoding antimicrobial resistance. However, most studies focus exclusively on antibiotic resistance genes (ARGs), excluding those associated with non-antibiotic antimicrobials (metals, biocides), and often rely on methods with low-sensitivity and low-specificity. Furthermore, they rarely examine populations exposed to minimal anthropogenic pollution. We analyzed fecal resistomes of 95 Wayampi individuals, an Indigenous community in remote French Guiana, using a targeted metagenomic capture platform covering 8667 genes, including ARGs, metal resistance genes (MRGs) and biocide resistance genes (BRGs) (PMID: 29335005). Resistome profiles were compared with those of Europeans to assess population-level differences. RESULTS: ARG richness was similar between groups (259 in Wayampi vs. 264 in Europeans, 159 shared), but MRGs + BRGs gene richness was significantly higher in Wayampi (11,930 vs. 7419). Most genes appeared in a minority of individuals (mean 5% for ARGs, 2% for MRGs + BRGs), but several ARGs for tetracyclines [tet(32), tet(40), tet(O), tet(Q), tet(W), tet(X), tetAB(P)], aminoglycosides (ant6'-I, aph3-III), macrolides (ermB, ermF, mefA), and sulfonamides (sul2) were present in all individuals. Tetracycline resistance genes predominated overall, while beta-lactam resistance genes were more common in Wayampi, and genes conferring resistance to aminoglycosides, amphenicols, and folate inhibitors were more frequent in Europeans. Among MRGs, copper and arsenic resistance genes prevailed in both groups, followed by those for zinc, iron, cobalt, and nickel. Up to 76% of Wayampiis carried acquired MRGs for copper (pcoABCDRS and tcrB), silver (silACFPRS), arsenic (ars), and mercury (mer) detoxification. Shannon diversity indices were similar for ARGs, MRGs, and BRGs, but composition and evenness differed significantly. UMAP and ADONIS analyses distinguished cohorts based on ARG profiles (p < 0.001), but not on MRGs or BRGs. Correlation analysis revealed conserved gene-sharing networks and introgression of acquired ARGs and MRGs within both gut microbiomes. CONCLUSIONS: The diverse and balanced Wayampi resistome reflects a less perturbed microbiome compared to industrialized populations, and reveals a background of "core" and "shell" acquired ARGs and MRGs, consistent with the "robust-yet-fragile" architecture of scale-free networks. The patchy yet resilient gene distribution suggests varying levels of conserved gene sharing highways among populations, likely shaped by long-term microbial-human evolution, and supports a broader view on acquired antimicrobial resistance. Video Abstract.

Humans↗

PubMed2026

Draft genome sequence of Vibrio parahaemolyticus GISV1-1 associated with AHPND in Bangladesh.

Vibrio parahaemolyticus GISV1-1 was isolated from diseased shrimp with acute hepatopancreatic necrosis disease in Bangladesh. Its draft genome is 5,078,728 bp with 45% GC content. The genome exhibits several virulence-associated genes and the beta-lactam resistance gene blaCARB-33. It will enhance our understanding of pathogenesis and disease management in shrimp aquaculture.

AHPND↗

PubMed2025

Global genomic and antimicrobial resistance profiling of Neisseria gonorrhoeae: Insights from whole genome sequencing and minimum inhibitory concentration analysis.

BACKGROUND: The rising antimicrobial resistance (AMR) of Neisseria gonorrhoeae is a major global health concern that limits treatment options and complicates disease management. Efflux pump systems and resistance genes are key to bacteria's ability to evade antibiotics. This study examined the genetic and phenotypic resistance landscape using a large dataset of whole-genome sequences to identify key resistance mechanisms, assess efflux pump gene prevalence, and analyze regional variations in Minimum Inhibitory Concentration (MIC) values to inform treatment strategies and public health interventions. METHODS: A total of 38,585 whole-genome sequences of N. gonorrhoeae were analyzed to identify AMR determinants. This study focused on the presence and distribution of efflux pump genes (mtrC, farB, norM, and mtrA) and specific resistance genes, including tet(C) (tetracycline resistance) and aph(3')-Ia (aminoglycoside resistance). The MIC values were assessed for multiple antibiotics to evaluate resistance trends and regional variations, including penicillin, spectinomycin, zoliflodacin, gentamicin, and fluoroquinolones. RESULTS: This analysis revealed widespread resistance to multiple antibiotics. Efflux pump genes (mtrC, farB, norM, and mtrA) were found in nearly all isolates, highlighting their essential roles in resistance and adaptation. The presence of tet(C) and aph (3')-Ia varied across different Gene Presence Patterns, suggesting that regional or therapeutic factors may influence tetracycline and aminoglycoside resistance. High MIC values for penicillin were observed, likely because of blaTEM, a beta-lactamase gene responsible for beta-lactam resistance. Resistance to spectinomycin is also widespread, raising concerns about the diminishing efficacy of this antibiotic. In contrast, zoliflodacin, gentamicin, and fluoroquinolones exhibited relatively low MIC values, indicating their sustained effectiveness against N. gonorrhoeae. DISCUSSION: Efflux pump systems are key to N. gonorrhoeae resistance and adaptability. Regional MIC variations indicate that local antibiotic use shapes resistance patterns. The high resistance to penicillin and spectinomycin highlights the need for alternative treatments, whereas zoliflodacin and fluoroquinolones remain effective but require monitoring. This study emphasizes global AMR surveillance, novel therapies, and targeted antimicrobial stewardship to address multidrug-resistant infections.

Neisseria gonorrhoeae↗

PubMed2026

Antibiotic Resistance Genes in Dust from Kindergarten Environments: A Systematic Review of Occurrence, Diversity, Determinants, and Exposure Implications.

Kindergarten environments combine high microbial exposure with increased immunological vulnerability, yet antibiotic resistance genes (ARGs) in kindergarten dust remain poorly characterized. This systematic review synthesized evidence on the occurrence and potential health relevance of ARGs in kindergarten dust. Following PRISMA 2020 guidelines, PubMed, Scopus, and Web of Science were searched. Four studies from China, Hong Kong, and Norway (2018-2024) met the inclusion criteria. ARGs were detected in all kindergarten dust samples, indicating that dust is a consistent reservoir of antibiotic resistance determinants. A consensus resistome (classes detected in ≥2 studies) encompassed sulfonamide, macrolide-lincosamide-streptogramin B (MLSB), tetracycline, beta-lactam, aminoglycoside, and multidrug resistance genes; beta-lactam resistance genes were the only class reported in all four studies. Clinically important ARGs associated with last-resort antibiotics, including mecA, vanA, blaNDM, and mcr-5, were reported in three studies. Class 1 integron-integrase genes (intI1) frequently co-occurred with ARGs, suggesting potential horizontal gene transfer. Limited evidence indicated higher ARG abundance in urban and winter samples. One study reported antibiotic-resistant bacteria carrying resistance markers concordant with those in kindergarten dust in the urine of children attending the same facilities; however, this cross-sectional, single-site evidence is consistent with, but not sufficient to establish, a dust-to-child exposure pathway. The available evidence supports the plausibility that kindergarten dust may contribute to children's exposure to ARGs and ARG-carrying bacteria, but current studies do not establish causal transmission from dust to child colonization or infection. Standardized monitoring and longitudinal studies are needed to assess health risks and guide mitigation strategies in early childhood educational settings.

Dust↗

PubMed2026

Frequency and characteristics of extended-spectrum beta-lactamase-producing Escherichia coli in wastewater in Dakar, Senegal.

OBJECTIVE: This study aimed to investigate the occurrence, antimicrobial resistance profiles, and genetic characteristics of extended-spectrum beta-lactamase (ESBL)-producing E. coli in wastewater collected in Dakar, Senegal. RESULTS DESCRIPTION: All samples (n = 48) carried ESBL-producing isolates. The concentrations of ESBL-producing E. coli ranged from 1.4 × 10⁴ to 3.3 × 10⁵ CFU/100 mL, whereas the ratio of ESBL-producing E. coli among the total E. coli population varied between 0.2% and 16.3%. All the 107 isolated ESBL-producing E. coli isolates were multidrug resistant (MDR), with 100% resistance to beta-lactams (ampicillin, cefalotin, cefotaxime, ceftazidime, cefepime, aztreonam) and high resistance rates to non-beta-lactam antibiotics, including ciprofloxacin (77.6%). No resistance was observed to imipenem. CTX-M-type genes were present in all isolates, with blaCTX-M-1 group (89.7%) and blaCTX-M-8 group (88.8%) being the most prevalent. The blaCTX-M-15 variant, a subgroup of blaCTX-M- group1, was detected in 96.9% of blaCTX-M-1 positive isolates. Additionally, blaTEM (31.8%) and blaOXA-1 (34.6%) were detected, while blaSHV and blaCTX-M-25 group were absent. Phylogenetic analysis of 107 isolates revealed a diverse distribution across four phylogroups: A (37.4%), D (22.4%), B1 (14.0%), and B2 (5.7%). The predominance of phylogroup A, mainly associated with intestinal commensal carriage, suggests fecal contamination as a primary source.

Senegal↗

PubMed2026

Patterns of antimicrobial resistance genes in pathogens across One Health sectors in Ireland: an in silico approach.

As part of a rapid risk assessment, an in silico approach was used to detect antimicrobial resistance (AMR) in pathogenic isolates from humans, animals, and the environment. A total of 11,670 genomic data sets were retrieved from the NCBI Pathogen Detection system for Ireland, which represented 47 pathogenic species, including Salmonella enterica, Escherichia coli/Shigella spp., Staphylococcus aureus, Klebsiella pneumoniae, and Enterococcus faecium. Identifying the most critical pathogenic strains over time is essential, as these organisms significantly contribute to mortality, morbidity, and hospitalization. The analysis identified 799 antimicrobial resistance genes (ARGs), including their allelic diversity, 117 plasmid replicons, and 274 virulence factors. Several critical ARGs, particularly those conferring resistance to beta-lactams, aminoglycosides, quinolones, and colistin, were common across isolates originating from human, animal, and environmental sources, suggesting shared resistance profiles across One Health sectors. Klebsiella pneumoniae, E. coli/Shigella spp., S. enterica, and S. aureus were the dominant hosts of these ARGs and associated mobile genetic elements. Increasing resistance across major antibiotic classes aligned with trends reported across other European countries. This study provides a national-scale in silico comparison of AMR across pathogens and One Health sectors using publicly available genomic data. The findings help reinforce Ireland's AMR surveillance by showing which resistance genes are present and how they spread across critical pathogens in humans, animals, and the environment. These findings highlight the urgent need for improved antibiotic stewardship and integrated One Health surveillance to limit the emergence and spread of AMR.IMPORTANCEAntimicrobial resistance (AMR) is a growing threat to human, animal, and environmental health. This study used publicly available genomic data to identify antimicrobial resistance genes (ARGs) in key bacterial pathogens circulating in Ireland. By analyzing over 11,000 genomes from humans, animals, and the environment, we found that several dangerous resistance genes, including those against last-resort antibiotics, were widespread across different sources. The study highlights which bacteria and resistance genes are most critical and how they may spread between humans, animals, and the environment. These insights provide a national snapshot of AMR, supporting more effective monitoring and prevention strategies. By revealing patterns of resistance and modes of transmission, our findings underscore the importance of coordinated antibiotic stewardship and One Health approaches to slow the emergence and spread of resistant infections, protecting public health and ensuring antibiotics remain effective.

Humans↗

PubMed2026

Occurrence of blaOXA-72 in a clinical isolate of carbapenem-resistant Acinetobacter pittii ST206 in Japan.

The development of carbapenem resistance in Acinetobacter spp., which are recognized as significant opportunistic pathogens, is of critical importance as it poses challenges to therapy and the control of healthcare-associated infections in clinical settings. This study investigated the genetic characteristics of a carbapenem-resistant A. pittii clinical isolate from a university hospital using whole-genome sequencing. The A. pittii strain SU8507, which was detected in the abdominal drainage fluid of a patient, exhibited resistance to imipenem (MIC: 128 μg/mL) and meropenem (MIC: 64 μg/mL) and produced positive results by the CIMTris method. A. pittii SU8507, belonging to ST206, harbored the blaOXA-72 and new variants of intrinsic blaOXA-213-like gene blaOXA-1222, which lacks an upstream insertion sequence element, and blaADC-1-like gene blaADC-343. The blaOXA-72 gene, flanked by XerC/XerD-like recombination sites, was located on a plasmid pSU8507, sized at 10,913 bp, carrying 13 predicted protein-coding genes. Complete pSU8507 containing mobA, repB, and the yoeB-yefM toxin-antitoxin genes, showed 98.9% nucleotide sequence identity and 75% coverage with plasmid pA2702 of the A. baylyi strain A2702, but a low BLAST MAX score. SU8507 harbored virulence genes involved in biofilm formation, types II and VI secretion systems, type IV pilus system, and serum resistance. This study describes the first isolation of an OXA-72-producing, carbapenem-resistant A. pittii clinical isolate in Japan. Given that the isolation rate of carbapenem-resistant Acinetobacter spp. Remains low in Japan, it is crucial to expand the scope of rapid, accurate carbapenemase detection to include not only A. baumannii, but also non-baumannii Acinetobacter spp.

Humans↗

PubMed2026

Metagenomics Reveals Microbial Community Shifts Associated With Contrasting Anthropogenic Impacts in Freshwater Sources of A Coastal Protected Area in Southeastern Brazil.

This study aimed to characterize freshwater microbial communities, environmental drivers, and anthropogenic impact patterns across three sites on Marambaia Island (southeastern Brazil) using metagenomics. Samples collected from freshwater sources used for human consumption were processed through concentration, nucleic acid extraction, and sequencing on the Illumina NextSeq 2000 platform. A total of 67.2 million reads were assembled into 89,230 bacterial contigs, mostly attributed to Gammaproteobacteria, Alphaproteobacteria, and Betaproteobacteria. Sites under lower anthropogenic influence exhibited higher microbial diversity, whereas impacted sites showed enrichment of opportunistic and fecal-associated genera. A heterogeneous anthropogenic impact profile was observed across sites, corroborated by the proposed Anthropogenic Impact Index (AII). Fourteen antimicrobial resistance genes conferring resistance to beta-lactams, quinolones, sulfonamides, tetracyclines, and macrolides were detected predominantly in sewage-impacted areas, indicating potential diffuse contamination. Redundancy analysis revealed that environmental variables explained 88.1% of microbial community variation, with conductivity, salinity, and turbidity as key drivers. These findings demonstrate the applicability of metagenomics as a powerful tool for assessing microbial diversity, ecological dynamics, and contamination risks in vulnerable freshwater systems.

Brazil↗

PubMed2025

Characterization of blaOXA-542-mediated carbapenem resistance in Acinetobacter baumannii.

BACKGROUND: Carbapenem-resistant Acinetobacter baumannii (CRAB) causes multiple anatomical site infections, representing a significant public health threat. AIM: This study reports the isolation and characterization of a carbapenem-resistant A. baumannii harbouring blaOXA-542, followed by a comprehensive investigation of its antimicrobial resistance mechanisms and genomic characteristics. METHODS: Firstly, antimicrobial susceptibility testing was performed using the broth microdilution method. Subsequently, whole-genome sequencing was employed to identify and characterize the resistance and virulence determinants. The functional validation of resistance mechanisms was performed by gene knockdown and construction of expression vectors. The fitness cost of β-lactamase expression was identified by a bacterial growth kinetic test. Molecular docking was utilized to predict potential binding sites of β-lactamase and carbapenems. Finally, the genetic characteristics of the isolates were analysed through comparative genomics analyses and phylogenetic tree construction. RESULTS AND CONCLUSIONS: The results demonstrated that blaOXA-542 confers resistance to carbapenem and penicillin in A. baumannii and Escherichia coli while exhibiting no significant impact on cephalosporins. The ability of blaOXA-542 to hydrolyze meropenem was further confirmed by modified carbapenem inactivation assay (mCIM). Expression of blaOXA-542 in E. coli BL21 showed no significant growth rate alteration. Comparative analysis of the blaOXA-542 genetic environment revealed a close association with Acinetobacter pitti. This study reports the emergence of blaOXA-542-mediated carbapenem and penicillin resistance in a novel A. baumannii lineage (ST2795Pas/ST3464Oxf), highlighting the urgent need for rational antibiotic use against specific pathogens.

Acinetobacter baumannii↗

PubMed2026

Variations in carbapenem resistance associated with the VIM-1 metallo-β-lactamase across the Enterobacterales.

The VIM-1 metallo-β-lactamase enzyme, encoded within class 1 integrons, is found in Gram-negative clinical isolates worldwide and has been linked to outbreaks of bacterial pathogens in nosocomial settings. Six vim-1+ clinical isolates, from the genera Escherichia, Klebsiella and Enterobacter, were obtained from Kingston, Ontario, Canada. Whole-genome sequencing revealed that vim-1 was plasmid-borne in all strains and situated as the first gene in In916 or In110 integrons. Analysis of related plasmids suggested that these vim-1-containing plasmids are globally disseminated and have spread via horizontal gene transfer and autochthonous vertical spread within Ontario. Interestingly, the MICs of ertapenem and meropenem, two clinically relevant carbapenem antibiotics, against these six isolates varied more than tenfold, suggesting that the effects of VIM-1 are dependent on the genomic content of the host microbe. Introducing vim-1 into three common Enterobacterales laboratory strains was not sufficient to confer resistance to ertapenem and meropenem. Instead, adaptive laboratory evolution of the vim-1 + laboratory strains revealed that vim-1-mediated carbapenem resistance in these strains was dependent on epistatic interactions with ompC mutations, likely due to decreased outer membrane permeability to these antibiotics. Together, these results provide additional support for the role of gene epistasis in modulating the antimicrobial resistance phenotypes of acquired resistance genes, as well as previous results suggesting that the presence of a β-lactamase gene is insufficient to confer strong resistance to carbapenems without being paired with reduced outer membrane permeability.

beta-Lactamases↗

PubMed2026

Whole Genome Characterization of Klebsiella Strains in European Hedgehogs and Human Nosocomial Settings Identified Shared Sequence Types, Antimicrobial Resistance Genes and Plasmids.

INTRODUCTION: Klebsiella pneumoniae is a pathogen associated with healthcare-acquired infections and antimicrobial resistance (AMR) to beta-lactams and carbapenems. Although wild animals are not typically exposed to antibiotics, they can harbour resistant strains. The European hedgehog (Erinaceus europaeus) is increasingly found in urban areas, where it interacts with humans and livestock. Studies have identified concerning levels of AMR in hedgehogs, including Extended-Spectrum β-Lactam (ESBL) and carbapenems-resistant Klebsiella pneumoniae strains. METHODS: This study focuses on Klebsiella spp. isolated in hedgehogs from urban areas, using whole-genome sequencing (WGS). We compared these isolates with openly available strains isolated from humans in the same region with the objective to have a thorough understanding of ST, AMR gene, and plasmid overlap between human and environmental compartments. RESULTS: High AMR gene levels, including the carbapenemase blaOXA-48, were found in the hedgehog population. Notably, human nosocomial clones, including ST307 and ST392, globally distributed sequence types also found in wildlife, were identified in both hedgehogs and humans. The presence of conjugative plasmids, including IncFIB(K) and IncL1 types, was identified in both hedgehogs and humans, highlighting plasmid dissemination as a significant factor in AMR spread. CONCLUSIONS: Although no direct transmission from wildlife to hospital settings has been conclusively demonstrated, our findings suggest that hedgehogs may play a role in bridging environmental and healthcare environments. The study underscores the need for further investigation into multidrug-resistant Klebsiella spp. and other resistant bacteria in wildlife to better understand their potential role in the dissemination of resistance genes across ecosystems.

Animals↗

PubMed2026

Concurrence of antibiotic resistance genes in plasmid genomes shape environmental resistomes.

Horizontal transfer of plasmid-associated antibiotic resistance genes (ARGs) plays a pivotal role in environmental antibiotic resistance dissemination. Here, we characterized ARG concurrence patterns in plasmid genomes and examined plasmid-associated ARGs across 106 environmental metagenomes. Approximately half of known ARG subtypes (257) occurred in plasmid genomes, and nearly one-quarter of plasmids carried ARGs, including "super plasmids" harboring over 20 ARG subtypes spanning 10 antibiotic categories. Aminoglycoside resistance genes (AmRGs) exhibited the highest concurrence frequency (CF) with other ARGs in plasmid genomes, followed by beta-lactam and sulfonamide resistance genes. Many high-risk ARGs preferentially coexisted with AmRGs (45.6% of total AmRGs CF). Environmental metagenomes revealed distinct plasmid-associated ARG profiles between polluted and relatively pristine environments, with significantly greater diversity and abundance under anthropogenic pollution. Five widespread ARG subtypes occurred across all environmental media, whereas polluted environments contained more unique ARGs. Co-occurrence networks identified AmRGs as "hubs" linking multiple ARG subtypes in environmental resistomes. Plasmid-ARG interaction networks further showed more complex potential plasmid-mediated concurrent dissemination in polluted environments. Collectively, use of aminoglycosides is more likely to cause co-transmission of multiple plasmid-related ARGs than other antibiotics, and CF of ARGs is proposed as an important supplementary factor for evaluating ARG dissemination under anthropogenic antibiotic stress.

Antibiotic resistance genes (ARGs)↗

PubMed2026

Complicated urinary tract infections: evolving definitions, clinical burden, and treatment landscape amid antimicrobial resistance.

INTRODUCTION: Complicated urinary tract infection (cUTI) is a common and heterogeneous infection associated with substantial morbidity, high healthcare utilization, and increasing antimicrobial resistance. Evolving definitions, increasing device use, and changing patient populations have altered its epidemiology and management. Marked variability in diagnostic criteria, clinical trial endpoints within and outside registrational settings, and treatment strategies complicates clinical decision-making and interpretation of therapeutic advances. AREAS COVERED: This review examines contemporary cUTI epidemiology, classification frameworks, and drivers of disease burden. It evaluates resistance trends and their therapeutic implications, alongside stewardship-based management strategies, including empiric antibiotic selection, intravenous-to-oral transition, treatment duration, and source control. Challenges in catheter-associated infection, recurrence, and regulatory endpoint design are discussed, together with the emerging role of novel agents targeting resistant Gram-negative pathogens. EXPERT OPINION: Rising multidrug resistance and limited oral options are reshaping cUTI management, necessitating individualized, stewardship-aligned therapy guided by illness severity and local epidemiology. Current regulatory endpoints inadequately reflect patient-centered outcomes, particularly in the context of asymptomatic bacteriuria. Expanding availability of effective oral agents may enable earlier discharge and outpatient care. Integration of rapid diagnostics and risk stratification will be essential to optimize therapy, limit resistance, and improve outcomes.

Humans↗

PubMed2026

Genome sequence of Raoultella ornithinolytica from urine isolates.

Raoultella ornithinolytica was isolated from a patient's urine. This strain was misidentified as Klebsiella oxytoca by matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF), but whole-genome sequencing identified it as Raoultella ornithinolytica and detected Raoultella-specific hdc gene. This isolate showed beta-lactams, fluoroquinolones, and tetracycline resistance. Here, we report the genome and antimicrobial susceptibility of this strain.

MALDI-TOF↗

PubMed2026

A descriptive analysis of Streptococcus suis-associated disease in Irish pigs from 2010 to 2024: serotypes, pathology, and antimicrobial resistance.

BACKGROUND: Streptococcus suis is a major cause of respiratory and systemic diseases in post-weaned pigs, leading to significant production losses and animal welfare concerns. This study provides the first long-term national level analysis of Streptococcus suis-associated disease (SSAD) in the Republic of Ireland. We examined the pig diagnostic submissions, characterised serotype distribution, antimicrobial susceptibility, and co-infection patterns from 2010 to 2024. RESULTS: The findings confirm that serotypes 9 and 2 or 1/2 were most frequently associated with disease. We observed a significant shift in recent years where serotype 9 has surpassed serotype 2 or 1/2 in number of occurrences. S. suis was frequently co-detected with viral pathogens including porcine reproductive and respiratory syndrome virus (PRRSV), porcine circovirus type 2, and swine influenza virus (SIV), as well as bacterial pathogens such as Actinobacillus pleuropneumonia and Pasteurella multocida, typically from pneumonic lungs. While resistance to tetracycline and erythromycin was high (44.4% to 65.8%), isolates remained susceptible to first-line beta-lactam antibiotics such as penicillin (7.9% resistance), ampicillin (5.5% resistance) and amoxycillin/clavulanate (0% resistance). CONCLUSION: The observed heterogeneity between and within herds challenges successful implementation of vaccination and highlights the need for ongoing disease monitoring. These findings provide the first in-depth assessment of SSAD in Ireland's pig population which will offer valuable insights for future surveillance efforts, including genomic studies and supporting evidence-based strategies and vaccine selection for controlling S. suis in Irish pig sector.

Ireland↗

PubMed2026

Dual β-lactam therapy against high-risk Pseudomonas aeruginosa isolates: a dynamic in-vitro infection model study integrating population genomics with quantitative systems pharmacology modelling and simulations.

BACKGROUND: Pseudomonas aeruginosa has an extraordinary capacity for resistance emergence during treatment, even with newer antipseudomonals. There is a gap in understanding how resistance mechanisms affect the time-course of bacterial response to these newer agents. Traditional approaches for predicting pathogen response to an antibiotic do not apply to combination therapy. We aimed to develop a modelling framework to predict treatment response based on resistome information, using isolates of the worldwide-disseminated high-risk clone sequence type (ST) 235 and β-lactam antibiotics as the example. METHODS: In this hollow-fibre in-vitro infection study, we used three extensively drug-resistant ST235 clinical isolates from the national collection of the Clinical Microbiology Department of the Hospital Son Espases (Palma de Mallorca, Spain) that were hospital-acquired, were isolated following routine microbiological procedures from different patients between 2017 and 2022, were susceptible to ceftolozane-tazobactam, and had different levels of meropenem resistance. The selected isolates (ST235-05, ST235-09, and ST235-10) showed classical β-lactam resistance mechanisms pre-treatment. The isolates were investigated in 240-h dynamic hollow-fibre in-vitro infection models (HFIMs). The studies exposed the isolates to pharmacokinetic profiles of ceftolozane-tazobactam (simulating 1 g of ceftolozane and 0·5 g of tazobactam as a 3-h infusion every 8 h) and meropenem (simulating 6 g per day continuous infusion) as observed in hospitalised patients, as monotherapy and in combination. Treatment response was assessed through the quantification of the time-courses of viable total and resistant bacteria. Whole-genome sequencing identified the mechanisms of emerging resistance. A quantitative systems pharmacology (QSP) approach was used to model total and resistant bacterial counts and corresponding pharmacokinetic data from the HFIM. Monte Carlo simulations were used to predict treatment responses in 1000 virtual infected patients treated with ceftolozane-tazobactam and meropenem as monotherapies or in combination over 10 days. FINDINGS: In the HFIMs, each antibiotic alone amplified resistance by approximately 48 h for all isolates; that is, monotherapies resulted in a higher concentration of resistant bacteria compared with the control treatment at the respective time, except ceftolozane-tazobactam against ST235-10. Combination of ceftolozane-tazobactam and meropenem was synergistic (bacterial counts ≥2 log10 colony forming units [CFU] per mL lower than the best performing monotherapy and initial inoculum) against all isolates and suppressed resistance. Against ST235-10, ceftolozane-tazobactam monotherapy reduced counts to less than 1 log10 CFU per mL from 192 h onwards, whereas the combination reached less than 1 log10 CFU per mL by 24 h. Across strains, population genomics confirmed monotherapy failures were associated with emerging resistance mechanisms (ceftolozane-tazobactam: ampC Ω-loop mutations; meropenem: ftsl mutation). The developed QSP model incorporated baseline resistance mechanisms and those emerging in resistant mutant subpopulations. The model explained and predicted the monotherapy failures involving amplification of these subpopulations, and synergistic killing and resistance suppression by the combination. Simulations using the model predicted bacterial regrowth above the initial inoculum for more than 90% of patients after 0 to approximately 3 days for meropenem monotherapy across all strains and for ceftolozane-tazobactam monotherapy against ST235-05 and ST235-09. For ceftolozane-tazobactam monotherapy against ST235-10, regrowth was predicted for approximately 30% of patients. In contrast, the simulations predicted sustained bacterial killing of at least 2 log10 CFU per mL compared with the initial inoculum by the combination for more than 89% of patients across all strains. INTERPRETATION: To our knowledge, this model is the first to characterise and predict the time-course of responses of clinical isolates to antibiotics only by the resistance mechanisms present and their complex interplay, representing a step towards pathogen-specific, personalised medicine. FUNDING: Australian National Health and Medical Research Council.

Pseudomonas aeruginosa↗

PubMed2025

Comparative in vitro activity of ceftazidime-avibactam plus aztreonam and the fixed combination aztreonam/avibactam against multidrug-resistant Pseudomonas aeruginosa.

BACKGROUND AND OBJECTIVES: MDR Pseudomonas aeruginosa is difficult to treat, despite some new beta-lactam/beta-lactamase inhibitors. A combination of ceftazidime-avibactam and aztreonam (CAZ/AVI + AZT) is frequently used to treat Gram-negative bacteria expressing metallo-beta-lactamases. A fixed combination of aztreonam/avibactam was recently licenced for use in Europe, but it remains unknown whether there are differences between both options for use against P. aeruginosa. This study evaluates the comparative in vitro efficacy of the fixed combination aztreonam/avibactam compared to the three antibiotics CAZ/AVI + AZT against clinical MDR P. aeruginosa isolates. METHODS: MICs for aztreonam/avibactam and CAZ/AVI + AZT were determined in 38 MDR P. aeruginosa isolates recovered from routine diagnostics using broth microdilution with checkerboard assays in triplicates as the reference method. Fractional inhibitory concentration (FIC) indices were calculated. Whole-genome sequencing was performed on all isolates. RESULTS: At a fixed ceftazidime concentration of 8 mg/L (EUCAST breakpoint), 25 isolates exhibited lower MICs for CAZ/AVI + AZT compared to aztreonam/avibactam alone in microdilution assays. On FIC analysis, additive and synergistic effects were seen in 28 and 2 cases, respectively. Verona integron-encoded metallo-beta-lactamase (VIM) was the most prevalent carbapenemase (21/38 isolates), followed by Imipenemase (IMP, 4/38) and New Delhi metallo-beta-lactamase (NDM, 2/38). Lower MICs were observed for the combination CAZ/AVI + AZT in isolates carrying VIM-2 as compared to VIM-1. CONCLUSIONS: In vitro testing of CAZ/AVI + AZT revealed increased in vitro susceptibility among MDR P. aeruginosa isolates in comparison to the fixed combination of aztreonam/avibactam.

Pseudomonas aeruginosa↗

PubMed2026

Resistome and microbiome-immune interactions in an Eastern European population with high antibiotic use.

The gut microbiome influences host health, affecting gastrointestinal, metabolic, immune, cardiovascular, and neurological functions. A balanced microbiome is associated with favorable health outcomes. However, excessive antibiotic use and dietary habits can disrupt this ecosystem, leading to dysbiosis and affecting body homeostasis. This first comprehensive metagenomic analysis of the gut microbiome in a healthy Romanian cohort, a population underrepresented in microbiome studies and characterized by high antibiotic consumption, addresses a gap in current microbiome research. We report an enrichment of Enterobacteriaceae although overall composition is more comparable to other European than non-European cohorts. Community configurations align with established enterotype patterns, and our analysis provides insight into their relationship with within-phylum diversity. The analysis of antimicrobial resistance provides insight into the prevalence of resistance genes within this reservoir. We specifically report the presence of cfr(E), a Clostridioides difficile gene, and tet(X5), a variant from the ubiquitous tet family, genes not previously reported in healthy European populations. Integration with data from the European Centre for Disease Prevention and Control links the overall prevalence of resistance genes in this reservoir to antibiotic classes with higher community consumption in this population, notably beta-lactams and quinolones, highlighting potential targets for antibiotic stewardship programs. Finally, we investigate the relationship between the microbial profile and the systemic immune responses, inferred from correlations with in vitro cytokine production. Notably, we identify potential immune-priming roles for Collinsella, Flavonifractor, and Bifidobacterium species.IMPORTANCEThis first comprehensive study of the healthy gut microbiome in a Romanian cohort addresses a gap in current microbiome research, dominated by data sets from a limited number of regions. It sets a baseline for the microbiome and resistome composition of this population, and, while definitions of "healthy" microbiomes, or baseline resistomes, remain lacking, such study helps contextualize future studies and support the monitoring of dynamics. The Enterobacteriaceae abundance suggests a microbiome composition potentially influenced by antimicrobial consumption, a relevant pattern in a region with a high burden of nosocomial infections. In addition, the prevalence of antimicrobial resistance genes and the concordance with commonly used antibiotics in the community reinforce the need to address antibiotic use in public health strategies. Although gut microbiome-immunity relationships remain incompletely understood, our findings support a role for microbiome composition in immune-related traits and provide a valuable resource for future studies.

Humans↗