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PubMed2026

Performance of seven carbapenemase detection assays in Pseudomonas aeruginosa across different epidemiological settings: a multicenter cross-sectional study.

The detection of carbapenemases in Pseudomonas aeruginosa remains challenging due to a great variety of other resistance mechanisms, and most laboratories, therefore, do not test for them. This study aimed to comparatively evaluate seven phenotypic carbapenemase detection assays across three epidemiological settings. A total of 320 P. aeruginosa isolates from three German centers with varying carbapenemase prevalences (5.8%-51.4%), including 113 carbapenemase-producing isolates carrying VIM-2 (n = 58), NDM-1 (n = 19), and GIM-1 (n = 16), underwent whole-genome sequencing as reference to assess seven phenotypic carbapenemase-detection tests: modified- and modified-zinc-supplemented carbapenem inactivation method (mCIM and mzCIM), simplified carbapenem inactivation method (sCIM), Carba NP, imipenem-cloxacillin test (IC-4000), and two imipenem-EDTA disk assays. Of all confirmation assays, mzCIM and sCIM showed the best overall performance for carbapenemase detection (sensitivity/specificity: 100%/94.2% and 99.1%/92.8%), followed by mCIM (93.8%/96.1%). Carba NP achieved the highest specificity (99.0%), but the lowest sensitivity (85.8%). EDTA-based assays and IC-4000 were highly sensitive (96.5%-100%) but less specific (79.7%-87.0%). Negative predictive values were consistently high (≥98%-100%) across all assays and prevalence settings, whereas positive predictive values varied (72.5%-98.0%). Both mzCIM and sCIM exhibited robust performance for carbapenemase detection in P. aeruginosa, representing the most suitable approach across diverse epidemiological settings. Their high negative predictive values indicate that these assays are particularly effective for ruling out carbapenemase production. Furthermore, both assays are cost-effective, simple to perform, and can be readily implemented in any routine microbiology laboratory.IMPORTANCEThis study provides comparative diagnostic accuracy data for seven phenotypic carbapenemase detection assays in Pseudomonas aeruginosa (PA) across different prevalence settings. Modified-zinc-supplemented carbapenem inactivation method (mzCIM) and simplified carbapenem inactivation method (sCIM) are the most robust screening tools and show that local carbapenemase-producing P. aeruginosa (CP-PA) prevalence substantially influences the utility of all evaluated assays.

CIM↗
PubMed2026

Emergence of Acinetobacter soli harboring three carbapenemase-encoding genes (blaNDM-1, blaIMP-14, and blaOXA-58) on a single plasmid in an ICU patient.

Acinetobacter soli is an environmentally adaptable species increasingly recognized as an emerging pathogen in hospital settings, particularly in intensive care units (ICUs). In this study, we report the first A. soli isolate from an ICU patient that co-harbors three carbapenemase-encoding genes (blaNDM-1, blaIMP-14, and blaOXA-58) on a single plasmid. Whole-genome sequencing revealed that multidrug resistance in this strain is mediated by a 294,790 bp plasmid, pSLAB-A, carrying 16 antimicrobial resistance genes, including all three carbapenemases. Comparative plasmid analysis showed a highly conserved backbone but identified a unique ~40 kb multidrug-resistance region containing blaNDM-1, blaIMP-14, and eight additional resistance genes. Genetic context analysis indicated that insertion sequences (ISAba125 and ISAba3) and class 1 integrons contribute to the mobilization and accumulation of carbapenemase-encoding genes. Plasmid stability assays demonstrated that pSLAB-A remained stably maintained for more than 90 generations without antibiotic selection. A global survey of the NCBI database identified 15 A. soli strains carrying carbapenemase-encoding genes, most of which were isolated from China, with clinical specimens representing the predominant source. Seven carbapenemase-encoding genes were detected, with blaNDM-1 being the most prevalent. Among eight isolates with complete genomes, all carried carbapenemase-encoding genes on plasmids. Phylogenetic analysis revealed regional dissemination of a clonal lineage across hospitals in Zhejiang Province and sustained nosocomial transmission within a hospital in Taiwan. These findings suggest that the spread of carbapenem resistance in A. soli is largely driven by multidrug-resistance plasmids, facilitating clonal expansion in hospital environments and posing a growing challenge for antimicrobial therapy and infection control in ICUs.IMPORTANCECarbapenem-resistant A. soli is an emerging clinical concern, capable of causing severe invasive infections, including bacteremia, in intensive care unit settings, and its emergence poses substantial challenges to antimicrobial therapy. In this study, we demonstrate that carbapenem resistance in A. soli is predominantly mediated by the acquisition of multidrug-resistance plasmids carrying carbapenemase-encoding genes. Owing to its strong environmental persistence, A. soli can readily undergo nosocomial clonal dissemination once carbapenem resistance is acquired. Moreover, the spread of multidrug plasmids co-harboring multiple carbapenemase-encoding genes may accelerate the evolutionary trajectory of resistance in A. soli, further exacerbating the threat to clinical management. Given its demonstrated capacity to cause hospital-associated infections and to rapidly acquire multidrug resistance, A. soli warrants heightened vigilance from both clinical and public health perspectives.

beta-Lactamases↗
PubMed2026

Evaluation of carbapenem inactivation method-based phenotypic assays for the detection of GES-type carbapenemases in Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii.

UNLABELLED: Detection of GES-type carbapenemases remains challenging because of their low prevalence and frequently weak hydrolytic activity against carbapenems. Carbapenem inactivation method (CIM)-based assays are widely used as phenotypic screening tools for carbapenemase detection; however, their performance in large collections of GES producers has not been systematically evaluated. We assessed the performance of CIM, modified CIM (mCIM), and CIM-Tris in a diverse collection of GES-producing clinical isolates, including 110 Enterobacterales and 108 Pseudomonas aeruginosa, recovered from Spanish hospitals (2010-2024), and 10 Acinetobacter baumannii isolates, mostly obtained from a hospital in Egypt. Whole-genome sequencing was carried out for species confirmation and resistome analysis. Meropenem MICs were determined by broth microdilution. Overall, 92.1% of isolates were GES-carbapenemase producers (CP), whereas 7.9% expressed GES-type extended-spectrum β-lactamases (ESBLs). In Enterobacterales (predominantly carrying blaGES-6), mCIM improved sensitivity compared with CIM (63.6% vs 40.0%), although many isolates remained undetected due to low meropenem MICs (MIC50, 0.5 µg/mL). In CP-P. aeruginosa (mainly blaGES-5), CIM, mCIM, and CIM-Tris showed sensitivities of 89.1%, 94.6%, and 100%, respectively; however, CIM-Tris yielded false-positive results in 50% of non-CP isolates (mostly blaGES-1 producers). Meropenem MICs in P. aeruginosa were higher (MIC50, >32 µg/mL). In A. baumannii, CIM-Tris improved sensitivity compared with CIM (100% vs 25.0%). These findings indicate that CIM-based methods can detect GES-type carbapenemases, but performance varies according to bacterial species and GES variant, and reduced specificity may occur in isolates producing GES-type ESBLs. Complementary molecular testing may therefore be necessary to ensure accurate detection of GES-type carbapenemases in routine clinical laboratories. IMPORTANCE: GES-type carbapenemases represent an important but underrecognized diagnostic challenge due to their low global prevalence, heterogeneous hydrolytic activity, and the limited performance data available for routine phenotypic detection methods. Although CIM-based assays are widely implemented in clinical microbiology laboratories for carbapenemase screening, their performance against GES-producing organisms has not been comprehensively evaluated across different bacterial genera and GES variants. In this study, we evaluated the performance of CIM, modified CIM (mCIM), and CIM-Tris in a large multicenter collection of well-characterized GES-producing clinical isolates, including Enterobacterales, Pseudomonas aeruginosa, and Acinetobacter baumannii. Our findings demonstrate substantial variability in assay performance according to bacterial species and GES variant. Notably, mCIM improved sensitivity among Enterobacterales with low meropenem MICs, whereas CIM-Tris achieved excellent sensitivity in P. aeruginosa and A. baumannii but at the expense of reduced specificity in isolates producing GES-type ESBLs. To the best of our knowledge, this is the first study directly comparing multiple CIM-based approaches in such a large and taxonomically diverse collection of GES-producing isolates.

beta-Lactamases↗
PubMed2025

Global emergence and transmission dynamics of carbapenemase-producing Citrobacter freundii sequence type 22 high-risk international clone: a retrospective, genomic, epidemiological study.

BACKGROUND: Carbapenemase-producing Citrobacter (CPC) species have recently been recognised as emerging pathogens associated with nosocomial infections in humans. The increased rate of Citrobacter freundii infections is a public health concern and there is a paucity of genomic data regarding its global transmission dynamics. We aimed to characterise the genetic features of CPC species, and their associated carbapenemase-encoding plasmids, obtained from hospitalised patients in China and from publicly available global data, with a particular focus on high-risk clones. METHODS: This was a retrospective, genomic epidemiological study of CPC species obtained from a tertiary hospital in Zhejiang Province, China, from March 5, 2013, to March 5, 2023. We used antimicrobial susceptibility testing, short-read and long-read whole-genome sequencing, phylogenomic analysis, and plasmid structure analysis. A global dataset of complete plasmid sequences encoding blaKPC, blaNDM, and blaIMP was constructed from the National Center for Biotechnology Information (NCBI) RefSeq database to provide insights into their diversity and distribution. All carbapenemase-producing Citrobacter freundii genomes from the NCBI GenBank database were incorporated in the comparative genomic analyses. Bayesian phylogeographical analysis and growth rate assays were carried out to characterise the high-risk C freundii sequence type (ST) 22 clone. FINDINGS: 1724 Citrobacter species isolates were collected from diverse clinical specimens, with 48 identified as CPC species. Citrobacter koseri (22 [46%] of 48) and C freundii (20 [42%]) were the predominant CPC species. Comparative analysis found C freundii carried significantly higher median numbers of plasmid replicons (5&#xb7;0 [IQR 3&#xb7;3-6&#xb7;0] vs 2&#xb7;0 [2&#xb7;0-3&#xb7;0]; p<0&#xb7;0001) and acquired antimicrobial resistance genes (12&#xb7;0 [7&#xb7;3-15&#xb7;8] vs 3&#xb7;0 [3&#xb7;0-5&#xb7;3]; p<0&#xb7;0001) than did C koseri. Molecular characterisation identified Inc-type plasmids, In823::Kl.pn.I3/In1589-like/In837-like integrons, Tn6296/Tn125/Tn5060 transposons, and insertion sequences (eg, IS26, IS3000, IS5, ISAba125, ISCR1), collectively facilitating the dissemination of carbapenemase genes. Global analysis of 3126 carbapenemase-encoding plasmids found epidemic plasmids with broad host ranges and global diversity. Phylogenetic investigation of predominant carbapenemase-encoding plasmids showed their persistence across geographical regions, temporal spans, and Enterobacterales species, exhibiting high genetic similarity to our clinical plasmids. A phylogenetic tree of 726 global carbapenemase-producing C freundii genomes showed that ST22 (227 [31&#xb7;3%]) represents the predominant multidrug-resistant clone across community, health-care, and environmental niches. Transmission across continents contributes to the global predominance of the ST22 clone, which carries a high load of resistance genes (median 15&#xb7;0 [IQR 11&#xb7;0-17&#xb7;0] vs 12&#xb7;0 [3&#xb7;0-16&#xb7;0]; p<0&#xb7;0001) and enhanced plasmid maintenance capacity (median replicons 5&#xb7;0 [IQR 4&#xb7;0-7&#xb7;0] vs 4&#xb7;0 [3&#xb7;0-6&#xb7;0]; p<0&#xb7;0001) relative to non-ST22 clones. INTERPRETATION: Our study provides evidence to suggest that Citrobacter species are emerging carriers of carbapenem-resistance genes. These findings provide insight into the population structure of CPC species and highlight C freundii ST22 as a prominent high-risk international clone. FUNDING: National Natural Science Foundation of China, National Health Commission Scientific Research Fund-Zhejiang Provincial Major Health Science and Technology Plan Project, Zhejiang Province Natural Science Foundation Project, Outstanding Youth Foundation of Jiangsu Province of China, the Priority Academic Program Development of Jiangsu Higher Education Institutions, and Postgraduate Research and Practice Innovation Program of Jiangsu Province.

Citrobacter freundii↗
PubMed2026

Persistent spread of carbapenemase-producing Klebsiella pneumoniae in acute care hospitals in 36 European countries (the CCRE survey): a prospective, multicentre, cross-sectional, epidemiological, microbiological, and genomic surveillance study.

BACKGROUND: Carbapenem-resistant Enterobacterales pose a substantial threat to patients and health-care systems. We conducted a survey of carbapenem-resistant and/or colistin-resistant Enterobacterales (CCRE survey) in 37 European countries to describe their occurrence, geographical distribution, and population dynamics and inform control policies. We report the results of Klebsiella pneumoniae species complex isolates in this study. METHODS: In this cross-sectional, epidemiological, microbiological, and genomic study conducted in all EU, European Economic Area and EU candidate countries as of 2019, hospital microbiology laboratories were selected on the basis of population coverage. Participating laboratories collected, from patient samples, the first ten successive isolates of carbapenem-resistant or carbapenem-susceptible increased exposure (carbapenem-R/I) K pneumoniae species complex or Escherichia coli, and carbapenem-susceptible (carbapenem-S) comparator isolates of the same species, accompanied by patient epidemiological and clinical information. Isolate collection started in 2019, with three possible starting dates-ie, March 1, April 1, or May 1, 2019, and ended after collection of ten carbapenem-R/I and carbapenem-S isolates or a maximum period of 6 months. Isolates were tested for phenotypic susceptibility to 16 antimicrobial agents of relevance to K pneumoniae species complex. Whole-genome sequencing was performed centrally using Illumina technology. Isolates from the CCRE survey were compared with those from the European Survey of Carbapenemase-Producing Enterobacteriaceae (EuSCAPE) study. FINDINGS: 1566 carbapenem-R/I and 1407 carbapenem-S K pneumoniae species complex isolates collected from patients in 302 hospitals in 36 countries (one country did not send isolates) were analysed in this study. The high-risk lineages identified during a previous similar survey in 2013-14 (EuSCAPE) were found to continue to circulate across European hospitals in 2019 (ST11, ST15, ST101, and ST258/512). Moreover, concerning shifts in the pathogen population were observed. First, a higher proportion of carbapenem-R/I isolates was found to carry a carbapenemase gene in the CCRE survey (1398 [89&#xb7;3%] of 1566) than in EuSCAPE (657 [69&#xb7;6%] of 944), mainly related to increased acquisition of carbapenemase genes by high-risk lineages. Of note, among ST307 isolates from all hospitals, the proportion of carbapenem-R/I isolates carrying a carbapenemase gene increased from 14 (60&#xb7;9%) of 23 in EuSCAPE to 164 (91&#xb7;1%) of 180 in the CCRE survey. Second, an expansion of emerging multidrug-resistant lineages (ST147, ST307, and ST39) was also noted: Among 113 hospitals that contributed K pneumoniae species complex isolates to both EuSCAPE and the CCRE survey, the proportion of ST147 increased from 16 (3&#xb7;4%) of 476 in EuSCAPE to 49 (7&#xb7;4%) of 662 carbapenem-R/I isolates in the CCRE survey, that of ST307 increased from 15 (3&#xb7;2%) of 476 to 88 (13&#xb7;3%) of 662, and that of ST39 increased from 3 (0&#xb7;6%) of 476 to 10 (1&#xb7;5%) of 662. Third, there was an increased spread of isolates harbouring acquired virulence loci: isolates with the highest Kleborate virulence score of five increased from 7 (0&#xb7;4%) of 1717 in EuSCAPE to 40 (1&#xb7;3%) of 2973 in the CCRE survey. Notably, the increase was mainly observed in the carbapenem-S-group. INTERPRETATION: The survey findings portray an escalating epidemiological situation and suggest that control measures have not been able to interrupt transmission of high-risk lineages of carbapenemase-producing K pneumoniae in European hospitals. The heterogeneous and evolving situation with regards to circulating lineages and dominant carbapenemase genes requires strengthening and continuous adaptation of diagnostic, treatment, and control measures guided by genomic surveillance. FUNDING: European Centre for Disease Prevention and Control and Centre for Genomic Pathogen Surveillance.

Humans↗
PubMed2026

Coexistence of carbapenemase and hypervirulence-associated genes among Klebsiella pneumoniae high-risk clones in Hungary.

INTRODUCTION: Strains of Klebsiella pneumoniae carrying hypervirulence and carbapenemase genes represent a rapidly emerging global public health threat. Our study aimed to comprehensively characterise the genomics of hypervirulence-associated and carbapenemase genes carrying K. pneumoniae (hv(a)CpKp) isolates in Hungary. MATERIALS AND METHODS: Between January 2022 and April 2024, 89 aerobactin (iucA-D/iutA)-positive non-duplicate carbapenemase-producing K. pneumoniae isolates from 15 Hungarian healthcare institutes underwent short-read (Illumina, MiSeq, NextSeq) whole-genome sequencing, followed by detailed plasmid analysis using long-read sequencing (Nanopore, MinION) in a representative subset of 32 strains. RESULTS: Most isolates (79/89) belonged to the high-risk clone ST147. Hypervirulence-associated (hva) genes-including rmpA/rmpA2, peg344, shiF, iucA-D, and iutA-were universally present, and 59 isolates possessed chromosomally integrated yersiniabactin loci. Most isolates (87/89) carried the bla NDM-1 carbapenemase gene. Hypervirulence-associated genes were most frequently (29/32) associated with IncHI1B/IncFIB(Mar) plasmids. Notably, we identified plasmids carrying both hva and carbapenemase genes-designated as hybrid plasmids-in 13 of 32 strains. The bla NDM-1 was linked to the IS26 transposase and was present in conserved, identical cassettes on all bla NDM-1-carrying plasmids. DISCUSSION/CONCLUSION: Our study identified hv(a)CpKp strains, particularly the ST147 clone, circulating in Hungary. Our findings highlight the need for routine virulence gene monitoring and continuous genomic and plasmid-based surveillance to mitigate the clinical and epidemiological impact of emerging hv(a)CpKp lineages.

Klebsiella pneumoniae↗
PubMed2026

Emergence and persistence of ESBL- and carbapenemase-producing Klebsiella pneumoniae-related species in Barcelona wastewater treatment plants.

The World Health Organization classifies extended-spectrum beta-lactamase (ESBL) and carbapenemase-producing Klebsiella pneumoniae as critical-priority pathogens due to their high incidence, mortality, transmissibility, rapid resistance acquisition, and limited treatment options. Beyond clinical settings, their detection in wastewater treatment plants (WWTPs) provides an opportunity to assess their prevalence, persistence, and circulation within wastewater systems. This study characterized 37 antibiotic-resistant K. pneumoniae-related species strains isolated from two WWTPs in the metropolitan area of Barcelona, analyzing their antimicrobial resistance (AMR) profiles, antimicrobial resistance genes (ARGs), biocide and heavy metal tolerance genes (HMTGs), virulence factor genes (VFGs), biofilm-forming capacity, and conjugation ability. Among them, 70.3% were multidrug-resistant (MDR), and 16.2% were extensively drug-resistant. Whole-genome sequencing revealed diverse ARGs; all strains carried &#x3b2;-lactam resistance genes (14 ESBL and 12 carbapenemase producers), nearly all (96.9%) carried biocide or HMTGs, 64.9% harbored integrases, and all carried VFGs. Core-genome SNP analysis identified closely related strains across sampling periods and treatment stages, suggesting long-term persistence within the wastewater treatment system, despite biological and chemical processes in secondary treatment. Most strains (67.6%) displayed biofilm-forming capacity, and conjugation assays confirmed horizontal gene transfer in five of the seven ESBL-producing strains tested. High-risk clones were predominantly detected in the IFAS secondary treatment stage of the Gav&#xe0;-Viladecans WWTP. The three strains recovered from the reclaimed water of the Baix Llobregat WWTP were ESBL or carbapenemase producers. Altogether, these results provide genomic and phenotypic evidence of the persistence and circulation of antibiotic-resistant K. pneumoniae-related species within wastewater treatment systems.IMPORTANCEWWTPs are essential for urban sanitation and environmental protection. Understanding how clinically relevant pathogens, such as ESBL and carbapenemase-producing K. pneumoniae-related species strains, behave in these settings may inform public health considerations. Investigating the presence and persistence of high-risk MDR pathogens in WWTPs helps identify circulation of AMR, assess the risk of gene transfer, and evaluate the potential for co-selection with other contaminants. This knowledge supports efforts to improve wastewater treatments, strengthen environmental surveillance, and develop integrated One Health strategies to limit the spread of AMR across human, animal, and environmental sectors.

Wastewater↗
PubMed2026

Global epidemiology, genomic evolution, and clinical implications of dual- and multiple-carbapenemase-producing Klebsiella pneumoniae: A systematic qualitative review.

BACKGROUND: The global emergence of dual- and multiple-carbapenemase-producing Klebsiella pneumoniae, particularly isolates co-harbouring blaNDM and blaOXA-48/OXA-48-like determinants, represents a critical threat to global health because of limited therapeutic options and expanding genomic complexity. METHODS: This systematic qualitative review synthesized evidence from 44 English-language peer-reviewed studies published between 2017 and 2026 and indexed in Scopus, with a focus on genomic evolution and spatiotemporal distribution. RESULTS: High-risk clones ST147, ST101, and ST11 were identified as major drivers of dissemination. Genomic analysis revealed key adaptive mechanisms, including stable IncL 96-kb fusion plasmids and IS10-mediated truncation of blaNDM-1, potentially reducing fitness costs while preserving resistance. Convergence events were also documented in which dual-carbapenemase-producing isolates acquired additional colistin resistance determinants (mcr-1 or mgrB alterations) and virulence-associated markers such as iuc1. Importantly, related resistance determinants were identified beyond hospital settings, including community, environmental, and food-associated reservoirs. CONCLUSION: The shift from single to dual and multiple carbapenemase production in K. pneumoniae underscores the need for integrated genomic surveillance, improved antimicrobial stewardship, and broader reservoir monitoring to address this evolving public health threat.

Klebsiella pneumoniae↗
PubMed2026

Emergence of carbapenemase-producing Escherichia coli in acute care hospitals in 32 European countries (the CCRE survey): a prospective, multicentre, cross-sectional, epidemiological, microbiological, and genomic surveillance study.

BACKGROUND: The emergence of carbapenem resistance in Escherichia coli is of major concern due to the high propensity of spread of this species and scarce treatment options. Herein, we examined the occurrence and spread of carbapenem-resistant E coli based on the carbapenem-resistant and/or colistin-resistant Enterobacterales (CCRE) survey performed across European countries in 2019. METHODS: We analysed epidemiological, microbiological, and whole-genome sequencing data of 548 E coli isolates from individual patients from 156 hospitals in 32 European countries over 6 months in 2019. These hospitals collected the first ten successive isolates of carbapenem-resistant or carbapenem-susceptible increased exposure (carbapenem-R/I) Klebsiella pneumoniae species complex or E coli, and carbapenem-susceptible (carbapenem-S) comparator isolates of the same species. Antimicrobial susceptibility testing was performed for 19 antimicrobial agents. Whole-genome sequencing was performed centrally using Illumina technology. Isolates from the CCRE survey were compared with those from the European Survey of Carbapenemase-Producing Enterobacteriaceae (EuSCAPE) study. FINDINGS: Of the 548 E coli isolates, 211 (38&#xb7;5%) were carbapenem-resistant or susceptible, increased exposure (carbapenem-R/I), and 337 (61&#xb7;5%) were carbapenem-susceptible (carbapenem-S). Five sequence types (STs) accounted for 96 (45&#xb7;5%) of 211 carbapenem-R/I isolates: ST131 (27), ST410 (20), ST38 (19), ST167 (16), and ST648 (14). Carbapenemase genes were identified in 182 (86&#xb7;3%) carbapenem-R/I isolates, a pronounced increase from the 2013-14 EuSCAPE study (36 of 99, 36&#xb7;4%). The most common genes were blaNDM-5 (62 of 182, 34&#xb7;1%) and blaOXA-48 (40 of 182, 22&#xb7;0%). blaNDM-5 carriage increased substantially compared with that in EuSCAPE (two of 99, 2&#xb7;02%). Phylogenetic analysis showed substantial clonal spread of globally disseminated blaNDM-5-harbouring lineages, with numerous introductions into Europe but minimal onward transmission. INTERPRETATION: High-risk STs of E coli carrying carbapenemase genes are rapidly spreading globally, although our results indicate that, in 2019, most cases in Europe were sporadic. We urge vigilant monitoring, including genomic surveillance, and strengthening of control efforts, to reduce mortality and morbidity associated with the impending rise in carbapenem-R/I E coli cases. FUNDING: European Centre for Disease Prevention and Control and the Centre for Genomic Pathogen Surveillance.

Humans↗
PubMed2025

Molecular insights into carbapenemase-producing Enterobacterales from Senegal.

BACKGROUND: Carbapenemase-producing Enterobacterales (CPE) are an urgent global health threat, especially in resource-limited countries. Here we determined the prevalence and the molecular characteristics of CPE isolated from infections in Dakar, Senegal. METHOD: From January 2019 to December 2020, Enterobacterales with reduced susceptibility to ertapenem (diameter < 25&#x2005;mm) from infections were collected at the Pasteur Institute of Dakar. Carbapenemases were detected using biochemical and immunochromatographical assays. WGS was used to determine resistome, MLST, plasmids, virulence genes and genetic relatedness. RESULTS: Of the 1045 Enterobacterales collected during the study period, 86 had a diameter around ertapenem of <25&#x2005;mm (8%) and 19 were confirmed as CPE (2%). These included Escherichia coli (n&#x200a;=&#x200a;6) [ST410 (n&#x200a;=&#x200a;3), ST405 (n&#x200a;=&#x200a;2) and ST2083], Enterobacter spp. (n&#x200a;=&#x200a;6) [ST231 (n&#x200a;=&#x200a;3), ST245, ST760 and ST960] and Klebsiella spp. (n&#x200a;=&#x200a;5) (ST22, ST25, ST231, ST1535, ST4843), Citrobacter freundii ST22 (n&#x200a;=&#x200a;1) and Citrobacter koseri with unknown ST (n&#x200a;=&#x200a;1). blaOXA-48 (n&#x200a;=&#x200a;7; 35%), blaOXA-181 (n&#x200a;=&#x200a;7; 35%) and blaNDM-5 (n&#x200a;=&#x200a;6; 30%) genes were identified. C. freundii ST22 harboured blaNDM-5, blaOXA-48 and blaCTX-M-15 genes. Some E. coli isolates belonging to the high-risk clone ST410 were closely related (<20 SNPs) to isolates recovered in France from patients returning from Senegal, suggesting transnational spread. In addition, 5/6 carbapenemase-producing E. coli isolates possessed a four amino acid insertion in PBP3, conferring reduced susceptibility to aztreonam/avibactam and cefiderocol. CONCLUSIONS: This study highlights the spread of NDM-5 and OXA-181 in Senegal, and reports the first co-occurrence of NDM-5 and OXA-48 in sub-Saharan Africa. The spread of CPE, especially in high-risk clones, underscores the urgent need for continued surveillance and targeted interventions.

Senegal↗
PubMed2026

Temporal shifts in K-locus composition and expansion of dual-carbapenemase-producing ST11-KL62 Klebsiella pneumoniae: a retrospective genomic surveillance study.

OBJECTIVES: To characterize longitudinal changes in carbapenem-resistant Klebsiella pneumoniae (CRKP) and investigate the recent increase in dual-carbapenemase-producing ST11-KL62 isolates. METHODS: We retrospectively analysed 1,239 non-duplicate CRKP isolates recovered at a tertiary hospital in China during 2018-2025. Antimicrobial susceptibility testing, whole-genome sequencing, K-locus and resistance/virulence gene profiling, core-genome single-nucleotide polymorphism analysis, reference-guided plasmid comparison, conjugation and stability assays, and a murine lethality model were used. RESULTS: ST11 accounted for 936/1,239 isolates (75.5%). KL47 declined from 39/151 (25.8%) in 2018-2019 to 45/755 (6.0%) in 2024-2025, whereas KL62 increased from 3/151 (2.0%) to 147/755 (19.5%). Among 148 ST11-KL62 isolates, 13/148 (8.8%) co-harboured blaKPC-2 and blaNDM-1, of which 12/13 (92.3%) met the study's molecular definition of hypervirulent CRKP. Pairwise single-nucleotide polymorphism distances among local ST11-KL62 isolates ranged from 0 to 43 (median, 14), suggesting that clonal expansion may have contributed to their increase. Complete genome analysis of ZD872 located blaKPC-2, blaNDM-1, and major virulence-associated genes on distinct plasmids; related plasmid backbones were predicted in other isolates using short-read comparisons. ZD872 exhibited a hypervirulent phenotype in the murine model. CONCLUSIONS: The ST11 CRKP population underwent temporal shifts in K-locus composition, including expansion of a closely related ST11-KL62 subset carrying dual carbapenemases and hypervirulence-associated markers. These findings support integrating longitudinal genomic surveillance with local transmission analysis.

Carbapenem-resistant Klebsiella pneumoniae↗
PubMed2026

Wildlife as a reservoir of OXA-48-like carbapenemase-producing Enterobacterales.

Carbapenemase-producing Enterobacterales (CPEs) have globally emerged and spread beyond human compartments. However, data in wild animals, especially from low- and middle-income countries, such as Algeria, are still very scarce. Here, we investigated CPEs recovered from feces samples collected between October 2021 and June 2023 from wild terrestrial and aquatic mammals, wild migratory/nesters/sedentary birds, and zoo animals, including their environment (water, food, and fecal samples of animal care workers) distributed over six Algerian provinces. Carbapenem-resistant Enterobacterales were characterized using MALDI-TOF-MS, Carba NP, immunochromatographic assay NG-Test CARBA 5, antimicrobial susceptibility testing, and whole-genome sequencing. Thirty CPEs were identified out of the 1,899 samples collected (1.6%). The carriage rate was higher in captive animals (3.2%) than in wild animals (1.2%). Twenty-six produced OXA-48, three OXA-244, and one OXA-181, along with CTX-M-15 ESBL. Clonal expansion of Enterobacter hormaechei hoffmannii ST145 and Klebsiella pneumoniae ST13 was evidenced. Plasmid analysis confirmed that 24/30 isolates harbored a transferable 62 kb IncL pOXA-48 plasmid. Five/six E. coli isolates belonged to high-risk clones with chromosome-mediated blaOXA-244 gene in three isolates, blaOXA-48 in two isolates, and blaOXA-181 gene encoded on an IncFII-ColKP3 hybrid plasmid in one isolate. This study showed widespread dissemination of OXA-48-like producing Enterobacterales in free and captive wild animals, largely driven by epidemic plasmids and clones. It underscores the role of wild animals as a reservoir of CPEs, particularly species living close to humans, such as gulls and pigeons, and occasionally food-producing animals, increasing the risk of bidirectional dissemination between animal, environmental, and human sectors.IMPORTANCEThe global rise of carbapenemase-producing Enterobacterales (CPEs) harboring blaOXA-48-like has been increasingly documented in clinical settings. However, their emergence and transmission in wild and captive animals are less documented. This study provides a high-resolution genomic characterization of CPEs isolated from the feces of wild animals, especially migratory birds, and from captive wild animals, to evaluate the potential risk of dissemination through these animals. Whole-genome sequencing data, genetic investigations, and antimicrobial susceptibility results highlighted the spread of multidrug-resistant CPEs in both animals and humans. The widespread detection of blaOXA-48 across multiple niches suggests sustained circulation beyond hospital settings in Algeria. Human-associated lineages, such as E. coli ST131, ST38, and ST540, were identified with a clear link with humans. This study demonstrates carriage of CPEs in multiple bird species living in areas commonly inhabited by humans and provides further evidence for an effective dissemination of resistance in wildlife, facilitated by feeding habits.

Animals↗
PubMed2026

Carbapenemase-producing Acinetobacter baumannii from Spanish hospitals, 2016-2020: Interregional spread of ST2PAS isolates co-harbouring blaOXA-23, blaOXA-66 and armA genes.

INTRODUCTION AND AIMS: Carbapenem-resistant Acinetobacter baumannii (CRAB) poses a serious global threat, prioritized by the World Health Organization for new antibiotic development. The European Centre for Disease Prevention and Control proposed the integration of genomic sequencing into surveillance. This study characterizes phenotypic and genotypic features of nationwide-collected CRAB isolates from Spanish hospitals (2016-2020). MATERIALS AND METHODS: A total of 822 CRAB isolates sent to the Spanish reference laboratory were analysed, and 108 representative isolates were selected from 48 hospitals in 25 Spanish provinces. Antibiotic susceptibility was determined according to European Committee on Antimicrobial Susceptibility Testing guidelines, and WGS was performed by Illumina. Resistome, virulome, phylogeny (core-genome Multi-Locus Sequence-Typing; 2390 genes), insertion sequences and plasmids were analysed. RESULTS: Of the 108 representative isolates, 68.5% produced OXA-23, 10.2% OXA-24, 7.4% OXA-58, 1.9% NDM-1 and 2.7% others. 3.7% co-produced two acquired carbapenemases, and six that did not have them showed the ISAba1 upstream of the blaOXA-51 like. The predominant sequence types were ST2pas (82.4%) and ST218Oxf (61.1%). blaOXA-66 chromosomal carbapenemase allele was present in 75% of the 108 isolates, armA 16 s rRNA methyltransferase gene in 61.1%, and the kL-7/OCL-18 was present in 59.3% of the isolates. The most active antibiotic was colistin. Overall, 65.4% of invasive cases were caused by isolates harbouring all 38 virulence genes tested. In 64.8% of isolates a plasmid type was detected, mainly pS32-1-like (54.6%). CONCLUSIONS: In Spain, CRAB dissemination is driven by interregional spread of isolates belonging to the ST218Oxf/ST2Pas clones, characterized by the blaOXA-23/blaOXA-66 genotype, the presence of armA, the KL7/OCL18 capsular profile and the presence of pS32-1 plasmid.

K Locus↗
PubMed2026

Triple carbapenemase-producing Klebsiella pneumoniae ST6668 resistant to novel &#x3b2;-lactam/&#x3b2;-lactamase inhibitor combinations and cefiderocol, Northern Italy, 2025.

OBJECTIVE: Klebsiella pneumoniae ST6668 has recently emerged in Northern Italy, but data on its resistance architecture remain limited. METHODS: We identified a K. pneumoniae ST6668 (KNVO1) strain co-producing NDM-1, VIM-1, and OXA-48 carbapenemases via multiple megaplasmids from an elderly hospitalized patient who experienced clinical deterioration during a prolonged period of health care exposure. RESULTS: KNVO1 showed resistance to all tested &#x3b2;-lactams, including novel &#x3b2;-lactam/&#x3b2;-lactamase inhibitor combinations and cefiderocol, with susceptibility retained only to colistin, gentamycin and aztreonam/avibactam. Whole-genome sequencing confirmed the ST6668. The plasmidome included two megaplasmids (pKPC-CAV1321 and IncFIB:IncHI) carrying blaVIM-1 and blaNDM-1, respectively, and an IncL plasmid harbouring blaOXA-48. SNPs-based phylogeny demonstrated genomic distance to other ST6668 strains circulating locally, suggesting an independent introduction event. CONCLUSION: The convergence of three major carbapenemase families within ST6668 highlights the capacity of this clone to accumulate complex resistance determinants via megaplasmids, posing a serious threat to infection control and antimicrobial stewardship in health care settings.

Klebsiella pneumoniae↗
PubMed2026

Genomic characterization of carbapenemase-producing Enterobacterales from wastewater reveals the convergence of KPC-2 and GES-16 in Brazil.

Carbapenemase-producing Enterobacterales (CPE) pose a significant public health concern due to the limited therapeutic options and increasing dissemination outside clinical settings. Wastewater treatment plants (WWTPs) have been proposed as relevant environmental reservoirs for antimicrobial-resistant bacteria and mobile genetic elements. In this study, we performed genomic characterization of CPE strains recovered from raw wastewater samples from the influents of different WWTPs. Antimicrobial susceptibility testing revealed multidrug resistance, including coresistance to carbapenems and polymyxins, among Klebsiella pneumoniae, Enterobacter asburiae, and Enterobacter kobei strains. Whole-genome sequencing identified the convergence of the blaKPC-2 and blaGES-16 genes, as well as the presence of blaGES-5 in E. kobei sequence type (ST) 540 strains. Moreover, the blaKPC-2 gene was detected in K. pneumoniae strains belonging to high-risk clones ST11 (capsular types KL64 and KL15) and ST307 (capsular type KL102), and E. asburiae ST384. The blaGES-5 and blaGES-16 genes were associated with class 1 integrons, while the blaKPC-2 gene was embedded within transposons (Tn4401a, Tn4401i, and Tn3-like) and insertion sequences (ISKpn27 and ISKpn6). Notably, genomic analyses and literature review demonstrated that the blaGES-16 gene remains unique to Brazil. The putative pathogenic potential of carbapenem-resistant K. pneumoniae ST11 was also assessed. These findings support the environmental circulation of clinically relevant Enterobacterales genotypes and emphasize the potential role of WWTPs as conduits for CPE dissemination, if not adequately operated. Therefore, genomic surveillance in extra-hospital settings may contribute to a better understanding of antimicrobial resistance ecology and inform One Health mitigation strategies.

Brazil↗
PubMed2024

Investigation of in vitro susceptibility and resistance mechanisms to amikacin among diverse carbapenemase-producing Enterobacteriaceae.

OBJECTIVE: This study aims to assess the in vitro drug susceptibility of various Carbapenemase-Producing Enterobacteriaceae (CPE) genotypes and elucidate the underlying mechanisms of amikacin resistance. METHODS: A total of 72 unique CPE strains were collected from the Second Hospital of Jiaxing between 2019 and 2022, including 51 strains of Klebsiella pneumoniae, 11 strains of Escherichia coli, 6 strains of Enterobacter cloacae, 2 strains of Klebsiella aerogenes, 1 strain of Citrobacter freundii, and 1strain of Citrobacter werkmanii. Among these strains, 24 carried blaKPC gene, 20 carried blaNDM gene, 23 carried blaOXA-48-like gene, and 5 carried both blaKPC and blaNDM. We measured the in vitro activity of amikacin and other common antibiotics. Strains carrying blaOXA-48-like gene were selected for whole genome sequencing (WGS) via next-generation sequencing to identify genes related to antimicrobial resistance (AMR) and virulence factor (VF). RESULTS: Out of the 72 CPE strains tested, 41.7% exhibited resistance to amikacin. The drug resistance rates for K. pneumoniae, E. coli, and Enterobacter spp. were 51.0%, 27.3%, and 10.0%, respectively. The majority of the CPE strains (>&#x2009;90%) displayed resistance to cephalosporins and carbapenems, while most of them were sensitive to polymyxin B and tigecycline (97.2% and 94.4%). The amikacin resistance rate was 100% for strains carrying blaOXA-48, 20.8% for those with blaKPC, 5.0% for those with blaNDM, and 20.0% for those with both blaKPC and blaNDM. These differences were statistically significant (P&#x2009;<&#x2009;0.05). Through sequencing, we detected aminoglycoside resistance genes rmtF and aac(6')-Ib, VF genes iucABCD and rmpA2 in OXA-48-producing multidrug resistance and highly virulent strains. These genes were located on a IncFIB- and IncHI1B-type plasmid, respectively. Both plasmids were highly homologous to the plasmid from OXA-232 strains in Zhejiang province and Shanghai province. Integration of these resistance genes into the IncFIB plasmid, facilitated by the IS6 and/or Tn3 transposons, resulted in OXA232-producing K. pneumoniae with amikacin resistance. CONCLUSION: This study identified significant amikacin resistance in CPE strains, particularly in those carrying the blaOXA-48 gene. Resistance genes rmtF and aac(6')-Ib were identified on plasmids. These results highlight the need for careful monitoring of amikacin resistance.

Amikacin↗
PubMed2026

In vitro susceptibility testing of aztreonam-avibactam against predominantly NDM-producing Enterobacterales in Peru.

Metallo-&#x3b2;-lactamase-producing Enterobacterales are distributed worldwide, but some Latin American countries show a higher prevalence. Aztreonam-avibactam (ATM-AVI) may be an option for treating these infections. To evaluate in vitro susceptibility to aztreonam (ATM) alone and ATM-AVI in carbapenem-non-susceptible Enterobacterales isolates, based on the type of carbapenemase production, we prospectively collected carbapenem-non-susceptible Enterobacterales isolates from Peruvian hospitals during 2023-2024. Identification and susceptibility testing were performed by commercial panels and disk diffusion. Carbapenemases were detected by immunochromatography. ATM and ATM-AVI MICs were determined using broth microdilution panels with avibactam fixed at 4 &#xb5;g/mL. The non-susceptible isolates to ATM-AVI and those with double production of carbapenemases underwent whole-genome sequencing. A total of 438 Enterobacterales isolates were analyzed; carbapenemase production was detected in 422 (96.3%) and NDM was the most frequent (61.9%). Coproduction of NDM + KPC in K. pneumoniae and NDM + OXA-48-like in Escherichia coli was observed. Overall, 99.3% were susceptible to ATM-AVI; MIC50 and MIC90 were 0.12 and 2 &#xb5;g/mL, respectively. Overall, K. pneumoniae isolates had lower MIC50 and MIC90 values to ATM-AVI (0.12 and 0.5 &#xb5;g/mL) compared to E. coli (0.5 and 4 &#xb5;g/mL). Three E. coli isolates were resistant to ATM-AVI (MIC &#x2265; 8 &#xb5;g/mL), they belonged to ST410, ST167, and ST10 and harbored a YRIN insertion in PBP3 along with CYM-type, PER-type, and CTX-M-type beta-lactamase genes. ATM-AVI demonstrated potent activity against carbapenem-non-susceptible Enterobacterales, including those producing NDM, which is the carbapenemase most frequently detected in Peruvian hospitals.IMPORTANCEEnterobacterales isolates cause common illnesses in humans. Carbapenems are the antibiotics used to treat several of these infections, and increasingly, isolates resistant to these antibiotics are found. The most important mechanism of resistance to carbapenem among Enterobacterales is the production of enzymes called carbapenemases. Our results allowed us to recognize that NDM is the most frequent type of carbapenemase detected. Most of the antimicrobials available do not cover the Enterobacterales carrying NDM carbapenemase. In this scenario, we found that the new combination of drugs, aztreonam-avibactam, has high in vitro efficacy against most of the carbapenem-resistant isolates and against those isolates carrying NDM carbapenemase.

Aztreonam↗
PubMed2024

Spatiotemporal and genomic analysis of carbapenem resistance elements in Enterobacterales from hospital inpatients and natural water ecosystems of an Irish city.

Carbapenemase-producing Enterobacterales (CPE) is a diverse group of often multidrug-resistant organisms. Surveillance and control of infections are complicated due to the inter-species spread of carbapenemase-encoding genes (CEGs) on mobile genetic elements (MGEs), including plasmids and transposons. Due to wastewater discharges, urban water ecosystems represent a known reservoir of CPE. However, the dynamics of carbapenemase-bearing MGE dissemination between Enterobacterales in humans and environmental waters are poorly understood. We carried out whole-genome sequencing, combining short- and long-sequencing reads to enable complete characterization of CPE isolated from patients, wastewaters, and natural waters between 2018 and 2020 in Galway, Ireland. Isolates were selected based on their carriage of Class A blaKPC-2 (n = 6), Class B blaNDM-5 (n = 12), and Class D blaOXA-48 (n = 21) CEGs. CEGs were plasmid-borne in all but two isolates. OXA-48 dissemination was associated with a 64 kb IncL plasmid (62%), in a broad range of Enterobacterales isolates from both niches. Conversely, blaKPC-2 and blaNDM-5 genes were usually carried on larger and more variable multireplicon IncF plasmids in Klebsiella pneumoniae and Escherichia coli, respectively. In every isolate, each CEG was surrounded by a gene-specific common genetic environment which constituted part, or all, of a transposable element that was present in both plasmids and the bacterial chromosome. Transposons Tn1999 and Tn4401 were associated with blaOXA-48 and blaKPC-2, respectively, while blaNDM-5 was associated with variable IS26 bound composite transposons, usually containing a class 1 integron.IMPORTANCESince 2018, the Irish National Carbapenemase-Producing Enterobacterales (CPE) Reference Laboratory Service at University Hospital Galway has performed whole-genome sequencing on suspected and confirmed CPE from clinical specimens as well as patient and environmental screening isolates. Understanding the dynamics of CPE and carbapenemase-encoding gene encoding mobile genetic element (MGE) flux between human and environmental reservoirs is important for One Health surveillance of these priority organisms. We employed hybrid assembly approaches for improved resolution of CPE genomic surveillance, typing, and plasmid characterization. We analyzed a diverse collection of human (n = 17) and environmental isolates (n = 22) and found common MGE across multiple species and in different ecological niches. The conjugation ability and frequency of a subset of these plasmids were demonstrated to be affected by the presence or absence of necessary conjugation genes and by plasmid size. We characterize several MGE at play in the local dissemination of carbapenemase genes. This may facilitate their future detection in the clinical laboratory.

Humans↗