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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↗

PubMed2026

Genomic characterization of KPC-2 and NDM coproducing carbapenem-resistant Klebsiella pneumoniae in a hospital: discovery of ST1869 clone and a novel hybrid plasmid.

UNLABELLED: To characterize the plasmid architecture and molecular background of KPC-NDM coproducing carbapenem-resistant Klebsiella pneumoniae (KN-CRKP) in a South China hospital. Five KN-CRKP isolates were collected, including three from one patient. All underwent Illumina sequencing; two (ST11 and ST1869) additionally had Nanopore sequencing. Antimicrobial susceptibility testing strain sequence types, conjugation assays, resistance gene profiling, plasmid typing, genetic structure comparison, core-genome single nucleotide polymorphisms (SNPs) analysis, and plasmid clustering were performed. All isolates exhibited an imipenem minimum inhibitory concentration (MIC) of ≥128 µg/mL and harbored multiple resistance genes. One isolate (1/5) belonged to ST1869 and co-harbored blaKPC-2 and blaNDM-5. The blaNDM-5-carrying plasmid was a novel IncI1/X3 fusion plasmid that also carried blaCMY-42. Unlike several IncX3 plasmids carrying blaNDM in publicly available KN-CRKP genomes from South China, this IncI1/X3 hybrid lacked a complete conjugative transfer system. ST11 was the predominant clone (4/5), co-harboring blaKPC-2 and blaNDM-1. A rare genetic structure, ΔISKpn6-blaKPC-2-ISKpn28, was identified on IncFII plasmids carrying blaKPC-2. Plasmid clustering analysis of 126 comparative KN-CRKP genomes showed diverse sequence types and plasmid backgrounds associated with the KPC/NDM co-production pattern. The observed plasmid diversity and structural variation in KN-CRKP support continued genomic surveillance, with particular attention to the ST1869 clone, the novel IncI1/X3 hybrid plasmid harboring blaNDM-5 and blaCMY-42, and the rare "ΔISKpn6-blaKPC-2-ISKpn28" genetic structure. Expanded genomic data on KN-CRKP are needed to further elucidate its resistance mechanisms and plasmid evolutionary trajectories. IMPORTANCE: The co-production of KPC and NDM carbapenemases in Klebsiella pneumoniae poses a formidable threat to clinical antimicrobial therapy, as these enzymes confer resistance to virtually all β-lactam agents, including carbapenems. Here, we report novel genomic features of KN-CRKP in South China, including the emergence of the ST1869 clone, a unique IncI1/X3 hybrid plasmid harboring blaNDM-5 and blaCMY-42, and the rare ΔISKpn6-blaKPC-2-ISKpn28 genetic structure. These findings substantially expand current understanding of plasmid evolution and resistance gene dissemination in this region. The identification of diverse resistance mechanisms and clonal backgrounds supports enhanced genomic surveillance and infection-control awareness for pan-resistant Enterobacterales.

Plasmids↗

PubMed2026

Genomic Characterization of Antimicrobial Resistance and Virulence in ST11 Carbapenem-Resistant Klebsiella Pneumoniae Colonizing the Intestinal Tract of Elderly Inpatients.

BACKGROUND: This study aimed to elucidate the molecular epidemiology and virulence characteristics of ST11 carbapenem-resistant Klebsiella pneumoniae (CRKP) colonizing the intestinal tract of elderly inpatients in the Chongzhou region, providing a basis for controlling the transmission of such resistant bacteria in high-risk populations. METHODS: CRKP strains isolated from the intestines of elderly inpatients in this region between January 2023 and June 2024 were collected. ST11 strains were identified via multilocus sequence typing (MLST). Whole-genome sequencing, antimicrobial susceptibility testing, and string test, serum killing, biofilm formation, capsular polysaccharide quantification were employed to characterize their resistance genes, virulence genes, and molecular typing profiles. RESULTS: Among 58 CRKP isolates, 17 (29.3%) were ST11. ST11-KL64 was the dominant clone (70.6%). All isolates carried the carbapenemase gene bla KPC-2 and exhibited extensive drug resistance, with tigecycline retaining the highest susceptibility (64.7%). The yersiniabactin system genes (ybtS, fyuA, entB) were universally present, whereas the aerobactin gene cluster (iucABCD-iutA) was detected in only 17.6% of isolates. The virulence regulator rmpA2 was incomplete in all carriers. The hypermucoviscosity phenotype was observed in 35.3% of isolates, which correlated with serum resistance in some strains. Biofilm formation was variable. The mortality rate among colonized patients was 35.3%. CONCLUSION: The ST11-KL64 clone is dominant among CRKP strains colonizing the intestinal tract of elderly patients in this region. This clone universally carries the bla KPC-2 gene conferring carbapenem resistance and exhibits a unique virulence gene profile characterized by a low carriage rate of classical hypervirulence markers and an incomplete rmpA2 regulator gene. This finding clarifies the local epidemic status of this clone and underscores the importance of implementing active surveillance and targeted prevention strategies for high-risk populations.

KL64 serotype↗

PubMed2026

A fitness advantage from the pLVPK plasmid fuels the global spread of a carbapenem-resistant hypervirulent Klebsiella pneumoniae high-risk clone: ST11-KL64.

BACKGROUND: The global emergence of carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKP), particularly the ST11-KL64 subclone acquiring pLVPK-like virulence plasmids, represents a critical public health threat. This study investigates the epidemiological dominance and molecular mechanisms underlying ST11-KL64's fitness advantage over KL47 variants. METHODS: We performed comparative genomic analysis on 43,722 K. pneumoniae genomes (2011-2022) from 112 countries, focusing on ST11-CRKP strains. Capsular typing (KL64 vs. KL47), virulence gene profiling (aerobactin, RmpADC), and plasmid stability analysis were conducted using Kleborate, RAST, and PlasmidFinder. Plasmid-chromosome interactions were characterized through hybrid assembly approaches. RESULTS: ST11-KL64 demonstrated rapid expansion post-2016, surpassing KL47 as China's dominant CRKP subtype (40.5% vs. 28.9%), with regional predominance in Zhejiang (62.3%) and Sichuan (58.7%) provinces. Notably, 94.8% of KL64 strains maintained intact pLVPK plasmids with high aerobactin carriage (60.5%), while KL47 exhibited frequent plasmid fusion (58.8% with IncFIB[pNDM-Mar]) or chromosomal integration (41.4%), resulting in lower virulence potential (27.3% aerobactin+). Genomic analysis revealed KL64's superior plasmid stability (71.2% gene retention vs. KL47's 43.6%) and clinical correlation with severe outcomes (OR = 2.34, 95%CI 1.67-3.28). CONCLUSION: The ST11-KL64 subclone's epidemiological success stems from stable pLVPK plasmid maintenance, enabling simultaneous carbapenem resistance and hypervirulence. These findings highlight the urgent need for genomic surveillance targeting plasmid-mediated virulence in CRKP outbreaks, particularly in critical care settings where horizontal gene transfer may accelerate strain evolution.

Klebsiella pneumonia↗

PubMed2025

Microbiome therapeutic PMC101 inhibits the translocation of carbapenem-resistant Klebsiella while enhancing eubiosis in antibiotic-induced dysbiosis mice.

Carbapenem-resistant Enterobacteriaceae (CRE), known for their extensive antibiotic resistance, pose a severe global medical threat. Therefore, developing novel therapeutics beyond conventional antibiotics is urgently needed, and the importance of microbiome therapeutics is increasingly being recognized. This study explores the expanded systemic efficacy of PMC101, a microbiome therapeutic, beyond intestinal CRE infections and investigates its mechanism of action from a microbiome perspective. First, the genetic characteristics of the novel strain were identified through whole-genome analysis, and a scalable cultivation process was established as part of the overall development of this microbiome therapeutic. PMC101 increased the survival rate to 100%, significantly reduced disease severity scores, and prevented weight loss in CRE-infected mice treated with antibiotics. These effects are attributed to the inhibition of CRE growth in stool and the reduced detection of CRE in the lungs and kidneys, indicating suppression of systemic translocation. Metagenomic analysis revealed that PMC101 prevented the reduction in microbial population caused by antibiotics and CRE infection, restored species diversity indices, and mitigated dysbiosis while promoting eubiosis. This CRE translocation suppression was closely associated with increased CRE translocation-microbiome index, defined as the ratio of Bacteroidetes to Proteobacteria. This relationship was further confirmed through simulations using a human intestinal microbial ecosystem model. Additionally, increases in short-chain fatty acids, reductions in excessive inflammatory responses, and decreases in tissue damage were observed, all of which contribute to preventing CRE translocation. Finally, pathogen inhibition effects and safety tests were conducted, confirming the prophylactic potential of PMC101 as a microbiome therapeutic. These findings strongly support PMC101 as a promising candidate for future microbiome-based therapies against CRE infections.

Animals↗

PubMed2026

Limited efficacy of plazomicin against carbapenem resistant Enterobacterales in a tertiary care centre in Eastern India.

The global escalation of carbapenem resistant Enterobacterales (CRE) represents a critical threat to public health, necessitating the investigation of alternative therapeutic agents. Plazomicin, a newer aminoglycoside, was engineered to evade common aminoglycoside-modifying enzymes. This study evaluated the susceptibility of plazomicin among 100 CRE isolates. The findings reveal a strikingly low plazomicin susceptibility rate of only 15/100 (15%). Whole-genome sequencing identified a high prevalence of 16S rRNA methyltransferase (RMTase) genes, such as armA and rmtB1, which confer high-level resistance to plazomicin. These results suggest that plazomicin may have limited utility against CRE in regions where RMTase-mediated resistance is prevalent.

Sisomicin↗

PubMed2026

Post-infection colonization and recurrent infections by ST11-KL64 carbapenem-resistant Klebsiella pneumoniae: a study of within-host evolution.

Bacteria pose a serious threat to hosts through adaptive mutations that confer stress resistance and promote persistent colonization. Here, we describe an adaptive evolution event involving eight highly similar ST11-KL64 carbapenem-resistant Klebsiella pneumoniae (CRKP) strains, isolated from a non-infected inpatient who acquired two distinct CRKP strains, CRKP-F1 and CRKP-S2 during the first hospitalization, recovered, and was discharged after receiving antimicrobial therapy but subsequently experienced two additional recurrent febrile episodes and re-admission. The strain CRKP-S2 showed significantly enhanced resistance to oxidative stress, survival within macrophages, and internalization ability, and carried an additional ~72 kb fragment containing oxidative stress response factors (including NAD(P)-dependent oxidoreductases), and a ~ 19kb plasmid fragment harboring catA2, sul2, umuC/D genes, compared to the initial strain CRKP-F1. All four strains, CRKP-B3, CRKP-U4, CRKP-F5 and CRKP-S6, from the second hospitalization exhibited higher genetic similarity to CRKP-S2 than each other, and each of these strains has its own unique mutations compared to CRKP-S2. The third-hospitalization strain CRKP-U7 displayed the highest average nucleotide identity (ANI) with CRKP-S2, and possessed unique mutations in cecR, rlmA1, and selB, distinct from second-hospitalization strains. However, the last strain, CRKP-B8, carries a new gene mutation based on CRKP-U7 and exhibits greater host adaptability than all other isolates. While these findings are suggestive, whether the ~72-kb and ~19-kb fragments and mutations in CRKP-S2 drove enhanced colonization, and whether subsequent mutations contributed to subclones linked to recurrent febrile, or merely coincided, remains unclear. The possibility of mixed colonization by co-circulating subclones cannot be excluded, and functional validation is needed.

Klebsiella pneumoniae↗

PubMed2026

Cefiderocol susceptibility rates in carbapenem-resistant Gram-negative bacteria in a comparative, multicenter surveillance study in China.

BACKGROUND: Cefiderocol is a siderophore cephalosporin with potent, broad spectrum of activity against carbapenem-resistant (CR) Gram-negative bacteria. The objective of this surveillance study was to assess cefiderocol susceptibility in molecularly characterized CR Gram-negative pathogens collected from hospitalized patients across China. METHODS: Susceptibility testing was performed by the broth microdilution method according to Clinical and Laboratory Standards Institute guidelines, using pre-prepared frozen 96-well microtiter Thermo Fisher plates. Susceptibilities to cefiderocol and most comparators were determined by Clinical and Laboratory Standards Institute breakpoints, to tigecycline by US Food and Drug Administration breakpoints, and to colistin by European Committee on Antimicrobial Susceptibility Testing criteria. Carbapenemases were identified by whole-genome sequencing and polymerase chain reaction. RESULTS: Of 149 CR Klebsiella pneumoniae, 95.3% were susceptible to cefiderocol (OXA-48-positive 100% [n = 15]; IMP-positive 100% [n = 9]; KPC-positive 95.4% [n = 108]; NDM-positive 88.2% [n = 17]) and against 103 NDM-positive CR Escherichia coli, cefiderocol susceptibility was 45.6%. Among comparator antibiotics, ceftazidime-avibactam was only active against K. pneumoniae carbapenemase-positive and OXA-48-positive K. pneumoniae isolates. Susceptibilities to tigecycline and colistin were between 22.2% and 97.1% and between 88.2% and 100% across CR Enterobacterales with different carbapenemases, respectively. High cefiderocol susceptibility rates were found for CR Pseudomonas aeruginosa (98.4%), CR Acinetobacter baumannii (99.6%), and Stenotrophomonas maltophilia (99.6%). Among comparator antibiotics, only colistin showed high activity against CR P. aeruginosa (99.2%) and CR A. baumannii (99.2%). CONCLUSIONS: Cefiderocol susceptibility rates were ≥88% against a collection of carbapenemase-positive CR Gram-negative isolates, except for lower susceptibility in NDM-positive CR E. coli isolates. Continuous monitoring of cefiderocol susceptibility is warranted.

Cefiderocol↗

PubMed2026

Contribution of the Arg-33-His replacement in the histidine kinase CpxA to carbapenem and cefiderocol resistance in Serratia marcescens.

OBJECTIVE: The Serratia marcescens ROT_R clinical isolate, which was resistant to almost all β-lactams, including cefiderocol (4 mg/L), was recovered from a neonate 2 months after the isolation of the S. marcescens ROT_S strain that was susceptible to extended-spectrum cephalosporins (ESCs). In this study, we attempted to decipher the mechanism of resistance displayed by the ROT_R isolate. METHODS: The genomes of ROT_S and ROT_R were sequenced using the Illumina and the Oxford Nanopore Technologies. Long and short reads were assembled together, giving rise to a circularized hybrid genome. RESULTS: Genomic comparison between ROT_S and ROT_R disclosed only one mutation (G98A) in the cpxA gene of ROT_R, which led to the Arg-33-His substitution in the histidine kinase of the two-component system CpxA/CpxR. The cpxA alleles of ROT_S and ROT_R were amplified and cloned, thus giving rise to the pCpxA_WT and pCpxA_R33H recombinant plasmids, respectively, which were subsequently introduced into the S. marcescens HatR recipient strain, which lacks functional CpxA. The S. marcescens HatR (pCpxA_R33H) recombinant clone, which produced the altered CpxA_R33H variant, differed from the S. marcescens HatR (pCpxA_WT) recombinant clone, which produced the wild-type CpxA, by enhanced MICs of carbapenems and ESCs, including cefiderocol (1 mg/L). CONCLUSIONS: This study demonstrates that CpxA alteration, such as Arg-33-His substitution, can contribute to cefiderocol resistance. Although it increases slightly the MIC of cefiderocol without resulting per se in clinical resistance, it can contribute, in combination with other additional mechanisms, to achieve a high level of resistance to this siderophore cephalosporin.

Cefiderocol↗

PubMed2026

Multidimensional prophage profiling of carbapenem-resistant Enterobacteriaceae in Thailand: a nationwide, multicentre, genomic study.

BACKGROUND: Prophages influence bacterial fitness, resistance, and evolution, yet their epidemiology remains poorly understood in carbapenem-resistant Enterobacteriaceae (CRE). In this nationwide study in Thailand, we aimed to describe prophage repertoires in clinical CRE isolates and to explore their potential relevance for molecular epidemiology. METHODS: We performed a nationwide, retrospective, genomic analysis of all CRE clinical isolates collected through our previous national surveillance study involving 11 hospitals in 11 provinces in Thailand between March 25, 2012, and Jul 21, 2017. Whole-genome sequencing data from 747 CRE isolates were analysed. Intact prophages were identified using PHAge Search Tool Enhanced Release (PHASTER) and clustered by nucleotide sequence similarity. Prophage profiles were compared across multilocus sequence types, carbapenemase genotypes, specimens, geography, and patient demographics (age and sex). FINDINGS: Of the included 747 CRE isolates, 170 (23%) were Escherichia coli and 577 (77%) were Klebsiella pneumoniae. 220 (29%) of 747 strains had been isolated from female patients and 264 (35%) from male patients; metadata on patient sex were missing for 263 (35%) isolates. The median patient age was 63 years (IQR 50-72). 71 (10%) of isolates were from blood, 283 (38%) from sputum, 284 (38%) from urine, and 109 (15%) from other specimens. 374 distinct prophage clusters were identified, with significantly more prophages per genome in K pneumoniae (mean 3·01 [SD 1·55]) than in E coli (1·64 [1·46]; p<0·0001). Prophage repertoires largely mirrored bacterial multilocus sequence types. However, even within the highly clonal K pneumoniae sequence type 16 lineage, discrete prophage variation was identified, with common profiles observed in geographically dispersed patients. Respiratory K pneumoniae frequently carried a mosaic prophage with environmental signatures and a type VI secretion system, whereas blood-derived E coli harboured a prophage with immune-modulating genes. Distinct prophage clusters were observed across clinical specimens, age groups, carbapenemase genotype, and geographical region. Strains coharbouring blaNDM-1 plus blaOXA-232 (114 [15%] of 747) had the highest prophage loads. INTERPRETATION: The prophage content was shaped by the bacterial lineage, ecological niche, and temporal dynamics, providing an additional layer of epidemiological resolution beyond conventional genome typing. Integrating prophage profiling into molecular surveillance frameworks could help to identify transmission events, improve infectious source attribution, and enhance infection control strategies. FUNDING: Japan Agency for Medical Research and Development.

Female↗

PubMed2026

Enhanced invasiveness promotes the dominance of a widely-distributed carbapenem-resistant virulence-plasmid-carrying Klebsiella pneumoniae sublineage.

Carbapenem-resistant Klebsiella pneumoniae (CRKP), a WHO's critical priority pathogen, continuously evolves to generate health-threatening high-risk (sub)lineages. Here, we conducted a 10-year surveillance of nosocomial CRKP infections, collecting and whole-genome sequencing 1513 clinical isolates, accompanied by clinical data. We applied fine-scale genome analysis for 60,724 non-local public-available K. pneumoniae genomes. We identified a predominant ST11-KL64 sublineage widely-disseminated across China and internationally-distributed. Isolates of this sublineage were more frequently recovered during seasonal influenza peaks and harbored plasmids encoding 'hypervirulence' factors but caused no increase in patient mortality. Instead, they exhibited enhanced invasiveness and translocation capacity. Mechanistically, this suggested highly invasive CRKP (hiCRKP) sublineage showed elevated resistance to macrophage-mediated phagocytosis, partly due to the virulence-encoding plasmid and the loss of two chromosomal fimD gene copies. Additionally, hiCRKP isolates carried more antimicrobial resistance genes, resulting in enhanced resistance to clinically important quinolones and tetracyclines. To address the hiCRKP-imposed challenge, we constituted a phage cocktail, which significantly improved survival in a murine infection model. Our findings unveil a clinically-relevant high-risk sublineage resulted from the ongoing evolutionary diversification of CRKP. Importantly, the 'hypervirulent' CRKP is more potent to cause diseases rather than the thought-to-be more deaths, explaining its rapid emergence in healthcare settings.

Klebsiella pneumoniae↗

PubMed2025

Rapid replacement of blaKPC variant in ST11 carbapenem-resistant and hypervirulent Klebsiella pneumoniae contributed to ceftazidime/avibactam resistance during severe in vivo infection.

OBJECTIVES: Hypervirulent ceftazidime/avibactam (CAZ/AVI)-resistant Klebsiella pneumoniae (Kp) has emerged; however, its dynamic within-host evolution and competitive features are uncharacterized. This study aimed to clarify the systematic microevolution characteristics of the rapid transformation of blaKPC variants during long-term infection. METHODS: Thirty-nine Kp strains were isolated from a single patient with severe recurrent osteomyelitis during a 2-year period. Whole-genome sequencing and in vitro evolution assay was performed. Microbiological characteristics were examined through antimicrobial susceptibility testing, plasmid stability, growth curve, in vitro competition and Galleria mellonella larvae lethality assays. RESULTS: Among all the clinical Kp isolates, 37 were carbapenem-resistant Kp (CRKP), including 25 CAZ-/AVI-resistant Kp. All isolates belonged to the ST11-K47. During in vivo evolution, the blaKPC variant and its amplification emerged. Twenty-four isolates (24/39, 61.5%) harboured a novel blaKPC variant, blaKPC-144. All five Kp isolates carried blaKPC-2 in 2021. Surprisingly, 24 blaKPC-144-harbouring isolates (70.6%, 24/34) and 10 blaKPC-2-harboring isolates were identified in 2023, indicating rapid changing of blaKPC. Kp4 carried two copies of blaKPC-2, and Kp10-1 exhibited a 1.94-fold increase in the blaKPC-144 copy number. Similarly, in vitro, the blaKPC copy number increased upon exposure to low CAZ/AVI concentrations. However, at higher concentrations (4/1 mg/L), the blaKPC copy number increased significantly, and blaKPC mutations emerged simultaneously. The competition assay indicated that the blaKPC-144-harboring isolates exhibited a superior competitive capacity. CONCLUSIONS: The blaKPC amplification and mutation emerged simultaneously or sequentially during in vivo and in vitro evolution. Kp isolates harbouring blaKPC-144, conferring resistance to CAZ/AVI, exhibited a competitive advantage, promoting the rapid replacement of blaKPC-2.

Klebsiella pneumoniae↗

PubMed2025

Clinical carbapenem-resistant Enterobacterales in a University Hospital in Dakar, Senegal: genomic insights into Enterobacter hormaechei ST182 strains carrying blaNDM-5 and blaOXA-48 genes .

Senegal has witnessed the emergence and spread of carbapenem-resistant Enterobacterales (CRE), which often cause deadly infections. Accordingly, this study aimed to determine the antimicrobial susceptibility and prevalence of carbapenemases, as well as to perform a whole-genome sequence analysis of clinical CRE isolates from a university hospital in Dakar, Senegal. MALDI-TOF MS and VITEK2 systems were used for bacterial identification and antimicrobial susceptibility testing (AST). Carbapenemase- and cephalosporinase-encoding genes were screened using simplex end-point polymerase chain reaction. Whole-genome sequencing (WGS) was performed using the Illumina MiSeq platform. The CRE isolates were resistant to almost all the 34 antimicrobials tested. Nevertheless, colistin and amikacin remained active, with susceptibility rates of 96% and 71%, respectively. Only the carbapenemase genes blaOXA-48 (53.8%; 15/28) and blaNDM (35.7%; 10/28) and the cephalosporinase gene blaCMY-1 (25%; 7/28) were identified. In this context, two extensively drug-resistant Enterobacter hormaechei isolates were subjected to WGS analysis. These isolates were assigned as sequence type (ST) 182 and carried several genes related to antimicrobial resistance (AMR), metal tolerance, and virulence. An IncL/M plasmid with 61,054 bp in length was identified as carrying the blaOXA-48 gene, whereas an IncFIB(pECLA)/IncFII(pECLA)/IncX3 mutireplicon plasmid with 217,745 bp in length was detected as harboring the blaNDM-5 gene and other genes related to AMR and metal tolerance. Our study presents the first landscape of clinical CRE circulating in Senegal, along with additional genomic analysis of E. hormaechei ST182 strains, which could be useful for mitigating the burden associated with CRE in this country.IMPORTANCEThe investigation of global critical priority CRE isolates has become crucial to reduce morbidity and mortality associated with AMR. This study revealed that colistin and amikacin can be considered good alternatives for treating CRE-associated infections in Dakar. In addition, the genomic approach revealed that the CRE isolates carried both a wide resistome and virulome. Moreover, the abundance of horizontal gene transfer regions in the genomes suggests the great implications of mobile genetic elements in the spread of AMR in Dakar. Furthermore, this study reported the complete sequences of chromosomes and blaOXA-48 and blaNDM-5-carrying plasmids. Our findings are of great importance because complete genome sequences are still rarely characterized in the West African region. Finally, this study highlights the importance of strengthening genomic surveillance of CRE in sub-Saharan African countries to mitigate the burden associated with these pathogens.

Senegal↗

PubMed2026

Air contamination and cross-room transmission of carbapenem resistant Acinetobacter baumannii in ICU.

Air contamination of carbapenem-resistant Acinetobacter baumannii (CRAB) was investigated in an ICU with genome sequencing. CRAB was recovered from air samples (n=13) and patients (n=9) and belonged to ST2 (n=16) or ST164 (n=6). Four of the 9 ST2 clones were associated with transmission through the air within rooms or cross-room. All ST164 isolates belonged to a common clone and were found in two rooms. CRAB air dispersal may cause cross-room transmission at a long distance.

Acinetobacter baumannii↗

PubMed2026

Emergence of cefiderocol resistance in carbapenem-resistant Escherichia coli ST167 prior to clinical use: A multifactored resistance landscape.

OBJECTIVES: Cefiderocol is a novel siderophore cephalosporin with potent activity against multidrug-resistant Gram-negative bacteria. Here, we reported the prevalence and mechanisms of cefiderocol resistance in carbapenem-resistant Escherichia coli (CREC) in China before its clinical use. METHODS: A total of 443 non-duplicate CREC isolates collected from 67 hospitals in China (2013-2021) underwent antimicrobial susceptibility testing according to CLSI guidelines. Whole-genome sequencing, transcriptomic analysis, siderophore quantification, and targeted genetic manipulation were performed to investigate the underlying resistance mechanisms. RESULTS: Among the 443 CREC isolates, 102 (23.0%) were resistant to cefiderocol, and 34 (7.6%) showed intermediate susceptibility. Multivariable logistic regression identified ST167 lineage (OR, 3.05; 95% CI, 1.12-8.29; P = 0.028), blaNDM-5 carriage (OR, 9.04; 95% CI, 2.96-27.57; P < 0.001), and cirA truncation (OR, 49.56; 95% CI, 20.33-120.79; P < 0.001) as independent factors associated with cefiderocol resistance. Among ST167 isolates, cefiderocol-resistant isolates showed increased yersiniabactin carriage and siderophore production but comparable TonB-dependent transporter expression profiles. Phylogenetic analysis revealed that cefiderocol-resistant ST167 isolates clustered into a distinct subclade enriched with resistance-associated determinants, including a recurrent FhuA P50S substitution detected in 59/64 (92.2%) resistant isolates. Functional assays showed that the P50S substitution increased cefiderocol minimum inhibitory concentration (0.032-0.125 µg/mL), particularly in an NDM-5-producing background (0.032-0.5 µg/mL). CONCLUSIONS: Cefiderocol resistance is highly prevalent among high-risk ST167 CREC isolates before the clinical introduction of cefiderocol in China, highlighting the need for continued surveillance of this epidemic lineage. Cefiderocol resistance is mediated by multiple resistance determinants, and we identify the recurrent FhuA P50S substitution as a novel contributor to reduced cefiderocol susceptibility.

Antimicrobial resistance↗

PubMed2026

Characterisation of Carbapenem-Resistant Raoultella planticola and Structural Analysis of NDM Composite Plasmids.

OBJECTIVE: This study aimed to investigate the molecular characteristics, resistant plasmid structures and phylogeny of a carbapenem-resistant Raoultella planticola (CRRP) strain from a patient with pneumonia to inform antimicrobial resistance control strategies. METHODS: We performed strain identification using MALDI-TOF MS, the BD Phoenix 100 system and whole-genome sequencing (WGS). We assessed antimicrobial susceptibility and resistance gene transfer using PCR, conjugation and stability assays, plasmid structure using a bioinformatics tool and phylogeny using a core-genome phylogenetic tree. RESULTS: WGS confirmed the isolate as R. planticola (average nucleotide identity (ANI) > 98.9% with reference type strains), co-harbouring blaKPC-2 and blaNDM-1. It was resistant to 19 antimicrobial agents and susceptible to only polymyxin, amikacin and chloramphenicol. Resistance genes were present on two conjugative plasmids: pzwx_KPC (IncFIA) and pzwx_NDM (a novel repFIB/repHI5B hybrid assembled via non-homologous end joining). Both plasmids demonstrated efficient transfer and stable inheritance over 12 passages. pzwx_KPC was highly homologous to plasmids from Klebsiella pneumoniae. Phylogenetic analysis revealed the closest relationship with German R. planticola strains. CONCLUSION: CRRP carries highly transmissible and stable resistance plasmids. Strengthened monitoring in immunocompromised patients and improved environmental disinfection are recommended. The risk of misidentification by automated systems underscores the importance of WGS for accurate pathogen identification.

Carbapenem resistance↗

PubMed2025

Enhanced barrier precautions to prevent transmission of Staphylococcus aureus and Carbapenem-resistant organisms in nursing home chronic ventilator units.

OBJECTIVE: Assess the feasibility and effect of Enhanced Barrier Precautions (EBP) on the transmission of Staphylococcus aureus (SA) and carbapenem-resistant organisms (CRO) among residents in nursing home chronic ventilator units (NH-CVU). DESIGN: Pre-post interventional study. SETTING: Two community-based nursing homes with CVUs in Maryland. A total of 56 residents were enrolled in the baseline period and 64 residents were enrolled in the intervention period. METHODS: During a 3-month baseline and intervention period, residents were swabbed monthly to estimate SA and CRO acquisition. During a 2-month training period, EBP was implemented for residents with chronic wounds, medical devices, or history of multidrug-resistant organism (MDRO) colonization. During the subsequent 3-month intervention period, healthcare personnel (HCP) wore gowns and gloves for high-contact care activities when residents were on EBP. Whole genome sequencing assessed resident-to-resident transmission. RESULTS: At baseline, NH-CVU1 used gowns and gloves for all direct contact, while NH-CVU2 used EBP only for residents with a history of MDRO colonization. After training, the proportion of NH-CVU2 residents on EBP increased from 65% in the baseline period to 87% in the intervention period. Glove use was high (93-98%) in both NH-CVUs. Gown use increased from 39% to 77% in NH-CVU1 and from 26% to 72% in NH-CVU2. Resident-to-resident transmission of SA or CRO decreased by 25% in NH-CVU1 (p = 0.60) and by 67% in NH-CVU2 (p = 0.05). CRO transmission decreased by 33% in NH-CVU1 (p = 0.54) and by 83% in NH-CVU2 (p = 0.02). CONCLUSIONS: EBP is feasible and potentially decreases overall and CRO transmission in nursing home CVUs.

Humans↗

PubMed2026

Genomic and functional characterization of ST11-KL64 hypervirulence-associated carbapenem-resistant Klebsiella pneumoniae co-harboring bla KPC-2 and bla NDM-13.

BACKGROUND: Hypervirulence-associated carbapenem-resistant Klebsiella pneumoniae (hv-CRKP) is a major clinical and public health threat. However, ST11-KL64 hv-CRKP co-harboring bla KPC-2 and bla NDM-13 remains poorly characterized, particularly regarding genomic relatedness, plasmid dynamics, and attenuated virulence-associated phenotypes. METHODS: We retrospectively investigated clinical K. pneumoniae isolates collected at a tertiary hospital in Chengdu, China, between January and December 2024. Hypervirulence-associated markers were screened by PCR, followed by antimicrobial susceptibility testing and carbapenemase inhibitor enhancement assay to identify genotype-defined hv-CRKP. All isolates were subjected to molecular typing. ST11-KL64 isolates co-harboring bla KPC-2 and bla NDM-13 were subjected to Illumina sequencing, with the representative isolate K3 undergoing hybrid whole-genome sequencing and functional characterization. RESULTS: Among the 46 hvKP isolates recovered from 43 patients, 35 were identified as hv-CRKP, predominantly ST11-KL64. Three ST11-KL64 hv-CRKP isolates co-harbored bla KPC-2/bla NDM-13, and Illumina sequencing coupled with core-genome SNP (cgSNP) typing revealed minimal genetic variation. The expanded cgSNP analysis supported close relatedness between K3 and Beijing isolate K56649. K3 carried a pLVPK-like virulence plasmid, a bla KPC-2-bearing IncFII/IncR plasmid, and a bla NDM-13-bearing IncI1 plasmid. Relative to pK2044, K3 exhibited an rmpA-proximal ISKpn26-associated insertion and a complex alteration of the 5'-terminal coding region of rmpA. The bla NDM-13 plasmid was conjugatively transferred to Escherichia coli C600 with a mean conjugation frequency of 5.213 × 10-3 transconjugants per recipient cell and bla NDM-13 maintained high stability following approximately 100 generations of antibiotic-free passage, whereas bla KPC-2 was not detected under the tested conditions. Phenotypically, K3 showed a negative string test, low mucoviscosity, and attenuated virulence-associated phenotypes. CONCLUSION: Our results reveal that the three isolates formed a closely related local genomic cluster, among which K3 was closely related to the K56649 clone. In addition, K3 exhibited conjugative transfer capacity of the bla NDM-13-bearing IncI1 plasmid, and alterations at the rmpA locus accompanied by reduced rmpA transcript abundance were associated with low mucoviscosity.

IncI1 plasmid↗