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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↗
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↗
PubMed2026

Activity of Aztreonam-avibactam and Ceftazidime-Avibactam against Enterobacterales and Pseudomonas aeruginosa causing infections in patients hospitalized in hematology, oncology, and transplant units from United States medical centres (2019-2024).

Immunosuppression increases the risks and severity of infections and is associated with a higher incidence of infection with multidrug-resistant (MDR) pathogens. We evaluated the antimicrobial susceptibility of Enterobacterales and Pseudomonas aeruginosa from patients hospitalized in hospital units where the frequency of immunosuppressed patients is very high. Bacterial isolates were consecutively collected (1/patient) from 75 US medical centres in 2019-2024 and susceptibility tested by broth microdilution. Enterobacterales (n = 2,407) and P. aeruginosa (n = 485) from patients hospitalized in hematology, oncology, and transplant units were evaluated. Carbapenem-resistant Enterobacterales (CRE) were screened for β-lactamases by whole genome sequencing. Enterobacterales were mainly from bloodstream infection (BSI; 53.6%) and urinary tract infection (19.9%) and P. aeruginosa were mainly from BSI (37.9%) and pneumonia (35.0%). Aztreonam-avibactam, ceftazidime-avibactam, and meropenem-vaborbactam were highly active against Enterobacterales (99.9-99.4% susceptible), including MDR isolates (99.6-98.1% susceptible), but only aztreonam-avibactam exhibited good activity against CRE (95.8% susceptible). Ceftolozane-tazobactam showed good activity against Escherichia coli (95.7% S) and Klebsiella pneumoniae (92.8% S), but limited activity against Enterobacter cloacae species complex (75.9% susceptible). All (100.0%) carbapenemase (CBase)-producing CRE isolates were aztreonam-avibactam-susceptible while 77.4% were ceftazidime-avibactam-susceptible and 67.7% were meropenem-vaborbactam-susceptible. The most common CBases were KPC (41.7%), NDM (12.5%), and OXA-48 types (10.4%). Metallo-β-lactamases represented 23.5% of CBases and were identified in 16.7% of CREs. The most active agents against P. aeruginosa were ceftazidime-avibactam (95.7% susceptible), ceftolozane-tazobactam (94.8% susceptible), and tobramycin (91.5% susceptible). Piperacillin-tazobactam and meropenem were active against 81.4% and 82.5% of P. aeruginosa, respectively, and aztreonam-avibactam inhibited 78.6% of P. aeruginosa at ≤8 mg/L.

Humans↗
PubMed2025

Integrated metagenomic, culture-based, and whole genome sequencing analyses of antimicrobial resistance in wastewater and drinking water treatment plants in Barcelona, Spain.

The misuse and overuse of antimicrobials drive the emergence of antimicrobial resistance (AMR), a critical global health concern. While wastewater treatment plants (WWTPs) are essential for removing microorganisms and contaminants, they also serve as hotspots for antibiotic-resistant bacteria (ARB) and antimicrobial resistance genes (ARGs), facilitating their persistence and dissemination. This study investigated AMR in two WWTPs and one drinking water treatment plant (DWTP) in the Baix Llobregat area of Barcelona, Spain. Four sampling campaigns were conducted during winter and summer 2023 across different treatment stages. Due to drought conditions, reclaimed water from the Baix Llobregat WWTP was discharged upstream of the DWTP intake to supplement water resources for indirect potable reuse. A total of 991 cultivable ARB were obtained, enabling phenotypic and genotypic characterisation. The most prevalent included Aeromonas spp. (44.3 %), Enterobacterales (27.9 %), Pseudomonas spp. (19.1 %), Acinetobacter spp. (4.8 %), Shewanella spp. (2.2 %), Stenotrophomonas spp. (1 %), and others (0.7 %). Among these, 57.3 % were multidrug-resistant and 2.7 % were extensively drug-resistant. Furthermore, 34.6 % produced extended-spectrum beta-lactamases, 14.1 % harboured carbapenemase genes, and 2.9 % exhibited colistin resistance. Shotgun metagenomic analysis revealed high taxonomic diversity, without dominant genera across treatment stages. The resistome was dominated by ARGs conferring resistance to beta-lactams, aminoglycosides, and macrolides, alongside genes linked to biocide resistance and heavy metal tolerance. Spearman correlation analysis of selected sequenced strains suggested a weak to moderate co-occurrence between ARGs and biocide or heavy metal tolerance genes. These findings underline WWTPs as AMR hotspots and reinforce the need to monitor DWTP source water within the One Health framework.

Wastewater↗
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

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

Genomic characterization of novel human-associated CTX-M-15-producing Serratia nevei ST625 lineage infecting a vulnerable loggerhead sea turtle.

BACKGROUND: Serratia nevei is a newly classified and opportunistic bacterial species belonging to the Serratia marcescens complex (SMC). Genomic data from this species is highly relevant for public health and epidemiological tracking. OBJECTIVE: To report the first identification and genomic characterization of extended-spectrum &#x3b2;-lactamase (CTX-M-15)-producing S. nevei sequence type (ST) ST625 lineage infecting a vulnerable loggerhead sea turtle. METHODS: Strain BP02 was recovered from the coelomic cavity of a loggerhead sea turtle (Caretta caretta) admitted to a rehabilitation center in southeastern Brazil. MALDI-TOF MS was initially used for species identification and was further confirmed by whole-genome sequencing on the Illumina HiSeq platform, followed by ANI, dDDH, multilocus sequence typing, resistome, plasmidome, virulome, and SNP-based phylogenomic analyses. RESULTS: Strain BP02 exhibited a multidrug-resistant profile, including resistance to third- and fourth-generation cephalosporins. Genomic analyses identified BP02 as S. nevei ST625 carrying blaCTX-M-15 within the ISEcp1-blaCTX-M-15-wbuC-&#x394;Tn2 genetic environment, in addition to multiple AMR determinants and the IncC plasmid replicon. Phylogenomic analysis demonstrated close relatedness between BP02 and human clinical ST625 strains, previously reported in S&#xe3;o Paulo, Brazil, including a urine-derived strain isolated in 2019, differing by only 27 SNPs. Notably, all publicly available ST625 genomes were associated with human clinical sources and displayed multidrug resistance genotypes. CONCLUSION: This study expands the current knowledge regarding the ecology and genomic features of S. nevei, demonstrating the emergence of a human multidrug-resistant clone in marine wildlife. Our findings reinforce the importance of monitoring clinically relevant SMC members across distinct ecological niches within a One Health perspective.

ESBL↗
PubMed2025

Multidrug resistance and recurrence in urinary bacteraemia among cancer patients.

BACKGROUND: Urinary tract infections (UTI) in oncological patients can lead to bacteraemia (bUTI), increasing morbidity and mortality. This study assessed the characteristics, outcomes and recurrence of bUTI in oncological patients. METHODS: A retrospective cohort study was conducted at Hospital Clinic, Barcelona, from 2008 to 2019. All episodes of bUTI in oncological patients were analysed. Multivariable regression models identified independent risk factors for multidrug-resistant (MDR) Gram-negative bacilli (GNB), recurrent bUTI and related mortality. RESULTS: A total of 561 bUTI episodes were identified in 478 oncological patients. Urinary tract involvement due to neoplasm was present in 62.2%, and 59.4% had urinary tract instrumentation. Prior UTI-related admission without bacteraemia was reported in 63.8%. Following bUTI, oncological treatment was delayed in 47% and stopped in 33.6% of cases. GNB caused 87.3% of episodes, with Escherichia coli and Klebsiella spp. being the most common pathogens. Enterococcus spp. and Pseudomonas aeruginosa were frequent, particularly in patients with urinary instrumentation. MDR-GNB caused 19.6% of episodes, and 23.4% of cases received inappropriate empirical antibiotic therapy (IEAT). Recurrent bUTI occurred in 14.0% of patients. A simple predictive score efficiently identified patients at high risk of recurrence. Thirty-day mortality was 15.3%, and bUTI-related mortality was 10.7%, with absence of fever, septic shock and carbapenemase-producing Enterobacterales linked to higher related mortality. CONCLUSION: bUTI in oncological patients is predominantly caused by GNB, with high rates of MDR isolates and high mortality. IEAT is common, and recurrence is significant, highlighting the need for targeted preventive strategies and optimized empirical therapy.

Humans↗
PubMed2026

Single unscreened carrier triggered ICU outbreak of a KPC-producing Klebsiella pneumoniae which acquired in vivo resistance to ceftazidime-avibactam, and cefiderocol.

BACKGROUND: Carbapenemase-producing Enterobacterales are a major cause of healthcare-associated outbreaks in intensive care units (ICUs), where unrecognized carriers can drive silent transmission. We report an ICU outbreak caused by KPC-producing Klebsiella pneumoniae and the within-host emergence of resistance to ceftazidime-avibactam and cefiderocol in the index case. METHODS: Four ICU patients with five K. pneumoniae isolates identified between July and August 2023 were investigated. Phenotypic, genomic and functional analyses were performed to determine the clonal relatedness of the isolates and elucidate the mechanisms underlying resistance evolution. RESULTS: All isolates belonged to ST512, confirming dissemination of a single high-risk clone. The first isolate recovered from the index patient was susceptible to ceftazidime-avibactam and cefiderocol, but a later isolate obtained during ceftazidime-avibactam therapy acquired resistance to both agents. Genomic analysis revealed a novel KPC variant (KPC-270) carrying a 19-amino-acid duplication. When expressed in Escherichia coli, KPC-270 conferred ceftazidime-avibactam resistance, but it did not fully reproduce the meropenem or cefiderocol phenotype. Efflux inhibition substantially reduced meropenem and cefiderocol MICs in the resistant isolate, and avibactam partially restored cefiderocol activity, supporting multifactorial mechanism. CONCLUSION: This outbreak illustrates how unrecognized multidrug-resistant carriage in the index patient facilitated the nosocomial dissemination of a high-risk ST512 K. pneumoniae clone, followed by rapid resistance evolution during ceftazidime-avibactam therapy. Resistance was multifactorial, involving the novel KPC-270 variant and efflux activity contributing to ceftazidime-avibactam, meropenem and cefiderocol resistance.

Cefiderocol↗
PubMed2026

Transferable IncX3-blaKPC-2 plasmid and chromosomal blaCTX-M-27 in a commensal Escherichia coli ST7854 isolated from a healthy companion dog.

OBJECTIVES: Carbapenemase-producing Enterobacterales have disseminated globally, largely via highly transmissible plasmids. Their emergence in companion animals is of particular concern, indicating that clinically important carbapenem-resistance determinants have spread beyond healthcare settings. This study characterized a multidrug-resistant Escherichia coli isolate from a healthy dog in South Korea. METHODS: Antimicrobial susceptibility was determined by standardized reference methods. Hybrid whole-genome assembly resolved chromosomal and plasmid architectures, and plasmid transferability was assessed by conjugation assays. Comparative genomic analysis based on nucleotide identity and alignment coverage evaluated relatedness to publicly available blaKPC-carrying IncX3 plasmids. RESULTS: The E. coli ST7854 isolate was resistant to carbapenems (imipenem MIC = 8 &#xb5;g/mL), third-generation cephalosporins, fluoroquinolones, tetracycline, gentamicin, phenicols, and trimethoprim-sulfamethoxazole, but susceptible to amikacin and colistin. Assembly resolved a 4.77 Mb circular chromosome and seven plasmids. The ESBL gene blaCTX-M-27 was chromosomally integrated, whereas carbapenem resistance was conferred by blaKPC-2 on a 54,805 bp IncX3 plasmid. This IncX3-blaKPC-2 plasmid was transferred to E. coli J53 at a frequency of 5.91 &#xd7; 10&#x207b;&#x2074;, whereas the large IncFIB multidrug resistance plasmid was not co-transferred. Comparative analysis revealed extensive structural similarity with Korean clinical IncX3 plasmids, whereas most representative international plasmids shared only the conserved IncX3 backbone. CONCLUSIONS: A commensal E. coli ST7854 isolate from a healthy companion dog carried a conjugative IncX3-blaKPC-2 plasmid and chromosomally integrated blaCTX-M-27. Similarity to Korean clinical plasmids suggests potential human-animal dissemination, and this asymptomatic carriage of mobile carbapenem-resistance determinants supports continued genomic surveillance of antimicrobial resistance in companion animals within a One Health framework.

Bla(CTX-M-27)↗
PubMed2026

Genomic insights into the first blaKPC-2-carrying Klebsiella pneumoniae isolate reported in Chile: limited local dissemination of the globally distributed ST101 lineage.

OBJECTIVE: To genomically characterize Kpn-KPC-1, the first blaKPC-2-carrying Klebsiella pneumoniae isolate reported in Chile, and contextualize it within the global ST101 lineage. METHODS: Kpn-KPC-1 was analyzed by whole-genome sequencing. Its resistome, virulome, plasmid content, and blaKPC-2 genetic context were characterized, and 537 publicly available ST101 genomes were used for comparative phylogenomics. RESULTS: Kpn-KPC-1 belonged to ST101 and carried blaKPC-2 within the conventional Tn4401a transposon on a mosaic plasmid encoding multiple replication initiators and conjugation-associated genes. The isolate also harbored an OmpK36 porin alteration and accessory resistance- and virulence-associated determinants, including ICEKp3/ybt-9, K17, and O1&#x3b1;&#x3b2;,2&#x3b1;. Phylogenomic analysis placed Kpn-KPC-1 within a predominantly European clade, closest to Italian isolates recovered between 2012 and 2018. The absence of additional Chilean ST101 isolates related to Kpn-KPC-1 supports limited local dissemination of this lineage. Globally, ST101 was enriched in carbapenemase genes, particularly blaOXA-48-like and blaKPC variants. CONCLUSIONS: Kpn-KPC-1 represents a transient introduction of a carbapenemase-prone, high-risk ST101 lineage rather than the founder of a locally disseminated clone in Chile. Genome-level analysis resolved the blaKPC-2 context in this historical isolate, linking the carbapenemase gene to Tn4401a on a mosaic multidrug-resistance plasmid within an imported ST101 background. These findings underscore the value of retrospective genomics for reconstructing early antimicrobial-resistance introduction events.

Carbapenem-resistant enterobacterales↗
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

Dissemination of blaKPC-3-harbouring Klebsiella pneumoniae across ST48 and ST628 in multiple healthcare facilities in the Republic of Korea.

Klebsiella pneumoniae carbapenemase-3 (KPC-3) remains rare in South Korea, where KPC-2 is the dominant carbapenemase, making the repeated detection of a concentrated blaKPC-3 signal over five years notable. We performed genomic analyses of blaKPC-3-harbouring K. pneumoniae from a regional healthcare network. Two chromosomally distinct lineages with concordant capsule loci (ST628/KL15 and ST48/KL62) presented multidrug-resistant phenotypes, and the virulence-associated loci were confined to ST48. Single-nucleotide polymorphism (SNP) analyses revealed near-clonal relatedness within lineages, with 0-38 pairwise SNPs among ST628 isolates and 8 SNPs between the two ST48 isolates. Core-genome multilocus sequence typing (cgMLST) supported this structure, as ST628 isolates were assigned to complex type 19149 with 0-7 allelic differences, and ST48 isolates were assigned to complex type 19150 with 5 allelic differences. These patterns support vertical spread via clonal expansion across multiple facilities. Despite substantial chromosomal separation, most isolates carried the same IncFII(K) plasmid backbone and blaKPC-3, and they were nearly indistinguishable from a plasmid previously reported in South Korea. One isolate carried blaKPC-3 on a distinct multireplicon IncFIB(K)/IncFII(K) plasmid, indicating that the signal was not confined to a single plasmid backbone. In both plasmids, blaKPC-3 was embedded within Tn4401b. These findings indicate that a rare blaKPC-3 genotype can persist regionally through sustained clonal dissemination and that cross-lineage linkage is compatible with past horizontal transfer involving a conserved plasmid. These findings underscore the need for subtype-resolved, regionally coordinated genomic surveillance in connected healthcare networks to detect uncommon carbapenemase variants early.

Klebsiella pneumoniae↗
PubMed2026

Genomic Insights Into Multidrug-Resistant Foodborne Serratia liquefaciens Strains Carrying mcr-9 and Comparative Genomic Analysis of Novel Biosynthetic Gene Clusters.

Serratia liquefaciens is an opportunistic nosocomial pathogen with a wide range of antibiotic resistance patterns. This study reports the characterization of the first mcr-9-positive S. liquefaciens strains, 35E-19E1 and CST-066, isolated from meat products in Japan. The strains were screened for the presence of &#x3b2;-lactamases, plasmid-mediated mobile colistin resistance (mcr) genes, and carbapenemase-encoding genes using PCR. Antimicrobial susceptibility was tested using the broth microdilution method. The strains exhibited multidrug resistance (MDR) phenotypes to third-generation cephalosporins, cephamycin, fosfomycin, and other clinically important antimicrobials. Genomic DNA sequencing showed that the genome sizes of CST-066 and 35E-19E1 are 5,529,704 and 5,261,506&#x2009;bps, respectively. mcr-9 was identified on a chromosome within a genetic environment that included the two-component system qseBC, which plays a key role in the signaling network that triggers colistin resistance in Enterobacterales. Downstream genome analysis revealed a 1695-bp eptB-like kdo2-lipid phosphoethanolamine transferase, which is involved in intrinsic polymyxin resistance mechanisms in Serratia spp. The strain 35E-19E1 carries five CRISPR-Cas enzymes that are essential for adaptive immunity in bacteria, allowing defense against invading elements. Functional analysis using subsystem technology revealed that both strains possess subsystem features responsible for invasion and adhesion within the host biomes. Genome mining using antiSMASH and BAGL4 revealed various biosynthetic gene clusters, responsible for secondary metabolite synthesis. Notably, we identified novel gene clusters, mainly nonribosomal peptide synthetases, in both the strains, indicating their potential to produce bioactive compounds. Although the presence of mcr-9 in Serratia may not be of clinical significance because of natural resistance of the strain to polymyxins, we shed light on the genomic characteristics of this MDR pathogen and the potential spread of mcr-9 among other bacterial species. The emergence of mcr-9 in drug-resistant S. liquefaciens provides significant insights, underscoring the need for increased surveillance of this pathogen.

biosynthetic gene cluster↗