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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 β-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-ΔTn2 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 São 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↗
PubMed2026

Genomic Analysis of CTX-M-15-Producing E. coli Colonizing a Rescued Capuchin Monkey.

Illegal wild animal trade and possession represents a threat to One Health due to the pathogens exchange between wild animals and humans. We report the detection and genomic characterization of a multidrug-resistant (MDR) Escherichia coli strain (MP02) colonizing a capuchin monkey (Sapajus sp.) rescued from illegal possession. MP02 exhibited ExPEC-related genes, harbored an IncHI2-ST1 plasmid composed of quinolones, aminoglycosides, and sulfonamides resistance genes, besides the extended-spectrum β-lactamase (ESBL)-encoding gene blaCTX-M-15 located in a conserved Tn3-like transposon. To the author's knowledge, this is the first report and genomic analysis of a MDR bacterium isolated from an illegally traded non-human primate.

antibiotic resistance↗
PubMed2026

Genomic Diversity and Extended-Spectrum β-Lactamase Gene Contexts of Community Resident-Carried Escherichia coli in Ecuador.

Community carriage of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli represents an important reservoir of antimicrobial resistance. However, the genomic diversity and population structure of ESBL-producing E. coli circulating in community settings remain poorly characterized. This study aimed to characterize ESBL-producing E. coli isolated from fecal samples of residents in Ecuador, with an emphasis on the diversity and genomic context of ESBL genes. ESBL-producing E. coli was isolated from fecal samples obtained from 55 residents using MacConkey agar supplemented with cefotaxime. Whole-genome sequencing of the isolates was performed using a hybrid approach combining long- and short-read platforms. Plasmids and β-lactamase genes were identified using DFAST and PlasmidFinder. Bacterial identification and antimicrobial susceptibility testing were conducted by MALDI-TOF MS and the broth microdilution method, respectively. ESBL-producing E. coli were isolated from 35 of 55 fecal samples (63.6%). Complete circular genomes were obtained from 31 isolates. All isolates harbored bla CTX-M genes, predominantly belonging to the bla CTX-M-1 group, whereas 65.7% carried bla TEM, mainly bla TEM-1, and related variants. Although β-lactamase genes were predominantly plasmid-borne, chromosomal integration was detected in 40% of the isolates. Notably, 87.5% of the isolates harbored IncF plasmids with multiple replicons. Conserved IS26-flanked transposons carrying bla CTX-M and bla TEM were frequently identified in the plasmids. Phylogenetic analysis revealed substantial genomic diversity across seven phylogroups, together with closely related isolates detected within and between households. These findings provide high-resolution genomic insights into the ESBL determinants circulating in community residents and reveal region-specific patterns of ESBL genomic diversity.

CTX-M β-lactamases↗
PubMed2026

Aztreonam-avibactam Activity against Enterobacterales from Asia Pacific and Latin American Medical Centres: Summary of 5 years of Surveillance prior to Clinical Use (2020-2024).

OBJECTIVES: To assess the in vitro activity of aztreonam-avibactam against Enterobacterales from the Asia Pacific region (APAC) and Latin America (LATAM) during a 5-year period prior to its approval for clinical use in these regions. METHODS: 12,039 Enterobacterales isolates were consecutively collected in 2020-2024 from 17 medical centres in APAC (n=7,369) and 10 in LATAM (n=4,670) then susceptibility tested by broth microdilution. Carbapenem-resistant Enterobacterales (CRE) and isolates with elevated aztreonam-avibactam MICs (>4 mg/L) were submitted to whole genome sequencing. RESULTS: Aztreonam-avibactam was active against 99.9% of Enterobacterales from APAC and LATAM and exhibited potent activity against CRE isolates (MIC50/90, 0.25/2 mg/L; 97.3% susceptible in APAC and MIC50/90, 0.25/0.5 mg/L; 99.4% susceptible in LATAM). Cefiderocol was active against 91.2% of CREs from APAC and LATAM. Ceftazidime-avibactam, meropenem-vaborbactam, and imipenem-relebactam showed limited activity against CRE isolates from LATAM (53.5% to 64.8% susceptibility) and APAC (27.3% to 38.8% susceptible). The occurrence of carbapenemases varied clearly among the countries evaluated. In general, metallo-β-lactamases (MBLs) prevailed in APAC and KPCs predominated in LATAM, but with great variability among countries within a region. Decreased susceptibility to aztreonam-avibactam was largely due to PBP3 alterations plus the production of CMY and/or CTX-M β-lactamases among Escherichia coli, and decreased membrane permeability associated with KPC production among Klebsiella pneumoniae. CONCLUSIONS: The results of this investigation provide a baseline for monitoring the activity of aztreonam-avibactam in APAC and LATAM and emphasize the importance of surveillance programs to monitor the emergence of resistance markers.

Aztreonam-avibactam↗
PubMed2025

Antimicrobial resistance among Gram-negative agents of bacteraemia in the UK and Ireland: trends from 2001 to 2019.

OBJECTIVES: The BSAC Bacteraemia Resistance Surveillance Programme collected isolates from UK and Irish hospitals for central testing. Concurrent UKHSA surveillance collected English hospitals' own susceptibility data. Results were reviewed and compared. METHODS: The BSAC surveillance collected fixed quotas of isolates per site annually from 2001 to 2019. MIC testing was by BSAC agar dilution. Resistance mechanisms were investigated by synergy tests, interpretive reading and PCR. The UKHSA seeks data on all bacteraemia isolates in England. RESULTS: For Escherichia coli, which now causes >30% of all bacteraemias, there were marked early (2002-06) rises in resistance to cephalosporins, fluoroquinolones and gentamicin, followed by small falls, stabilization, then from around 2015, very slow rises, with similar patterns seen for Klebsiella pneumoniae. Most cephalosporin resistance in these two species involved ESBLs, principally CTX-M types. Both species had frequent co-amoxiclav resistance. Cephalosporin resistance-mostly AmpC-mediated-declined in Enterobacter and Serratia spp., as did fluoroquinolone resistance, likely reflecting reduced use and selection pressure. Proteeae showed few changes; increasing dominance of Proteus mirabilis in the BSAC collection was not confirmed by the UKHSA dataset. Resistance in Pseudomonas aeruginosa was uncommon and showed little temporal change in either dataset. Carbapenemases remained extremely rare in all species. Newer and developmental agents covered many resistance types, but none covered all types. CONCLUSIONS: Except for early rises of cephalosporin, fluoroquinolone and gentamicin resistance in E. coli and K. pneumoniae, there was little evidence for rising resistance and some evidence of declining resistance, notably in species where it predominantly involves AmpC derepression.

Humans↗
PubMed2025

Snapshot Genomic Surveillance Reveals Insights into Antimicrobial Resistance and Lineage Diversity of Uropathogens in Older Adults in Queensland.

BACKGROUND: Community-acquired urinary tract infections (UTIs) are a significant health concern in older adults. However, few studies have investigated the epidemiology of uropathogens across diverse settings where older adults reside. METHODS: In this study, we whole-genome sequenced urinary isolates of Escherichia coli, Klebsiella species, and Enterobacter cloacae complex collected from individuals aged 70 and over living in the community and residential aged care facilities (RACFs) in Queensland, Australia. We investigated the prevalence of antimicrobial resistance (AMR), pathogen population structure, and transmission dynamics across the settings. RESULTS: E. coli was most frequently identified (82.2%, 447/544), followed by K. pneumoniae (10.8%, 59/544) and E. hormaechei (2.6%, 14/544). Intraspecies lineages were diverse, and a total of 177 sequence types were identified. The three predominant lineages were E. coli ST73 (10.7%, 54/504), ST95 (8.1%, 41/504), and ST131 (5.4%, 27/504). Transmission events were minimal, being identified in 13 patients (2.5%), mainly from the community. The resistance rate to antibiotics was low, with only a small proportion (9.7%) of multidrug-resistant (MDR) isolates. The predominant MDR lineage was E. coli ST131, which carried extended-spectrum beta-lactamase bla CTX-M genes. CONCLUSIONS: Community-acquired UTIs in older adults are predominantly caused by diverse E. coli lineages, with limited evidence of transmission within aged care facilities. The low rates of AMR in the community, along with the absence of strains adapted to a particular setting, suggest that current empiric therapy guidelines remain appropriate. Our prospective genomic surveillance offers valuable insights for monitoring UTIs in this population. It demonstrates the importance of an unbiased approach to accurately capture the prevalence and diversity of uropathogen lineages.

Enterobacteriaceae↗
PubMed2025

Chromosomal resistance mutations facilitate acquisition of multidrug-resistant plasmids in Escherichia coli.

Bacteria can gain multiple resistance mechanisms in a single step by the acquisition of multidrug-resistant (MDR) plasmids, but it is unclear how antibiotic selection during the acquisition of MDR plasmids affects the evolution of additional resistance mechanisms. Through conjugating separate extended-spectrum β-lactamase (ESBL)- and carbapenemase-producing MDR plasmids into plasmid-naive Escherichia coli hosts, we examine the effects of acquisition of a single plasmid or co-acquisition of multiple plasmids upon fitness costs, resistance and subsequent genomic adaptation. We show that acquisition of pOXA-48, encoding OXA-48 carbapenemase, is associated with highly variable fitness costs and levels of resistance to ertapenem in transconjugants independent of the presence of pLL35. This phenomenon was not observed during the acquisition of ESBL CTX-M-15-encoding pLL35 alone. Within a single growth cycle, transconjugants receiving pOXA-48 rapidly gained parallel mutations affecting the membrane porin OmpF, or its regulators OmpR or EnvZ. These chromosomal mutations were not compensatory for the fitness costs imposed by the plasmid, nor did they provide significant increases in resistance to carbapenems in the absence of the pOXA-48. Rather, they acted synergistically with the plasmid-encoded carbapenemase, which alone only provided marginal resistance, together providing high-level resistance to ertapenem. Such rapid evolutionary processes may play an important role in plasmid dynamics within environments with strong antibiotic selection for plasmid-encoded antimicrobial resistance genes (ARGs), particularly when these ARGs provide only marginal resistance.

Escherichia coli↗
PubMed2025

Whole-Genome Sequencing Uncovers Chromosomal and Plasmid-Borne Multidrug Resistance and Virulence Genes in Poultry-Associated Escherichia coli from Nigeria.

BACKGROUND: Broad and unregulated antibiotic use in livestock production, particularly poultry farming, has increased the development and persistence of multidrug-resistant (MDR) bacterial strains in animals. These resistant pathogens and their antibiotic resistance genes (ARGs) can spread to humans through environmental exposure and the food chain, posing serious public health risks. Whole-genome sequencing (WGS), alongside phenotypic antimicrobial susceptibility testing (AST), enables a comprehensive understanding of resistance mechanisms and informs antimicrobial stewardship strategies, particularly in resource-limited settings. AIM: This study aimed to characterize the phenotypic and genotypic antimicrobial resistance profiles, plasmid content, and virulence factors of an MDR E. coli strain (S3) isolated from a poultry farm in Enugu State, Nigeria, to elucidate potential risks to public health and the role of poultry as a reservoir for resistance determinants. METHODS: E. coli strain S3 was isolated from chicken droppings using standard microbiological methods and confirmed by MALDI-TOF mass spectrometry. AST was assessed using disc diffusion and broth microdilution to determine minimum inhibitory concentrations (MICs) for ten antibiotics across multiple classes. WGS was performed with a hybrid approach combining Illumina and Nanopore platforms, followed by genome assembly and annotation. ARGs, plasmid replicons, and virulence factors were identified in silico using AMRFinderPlus, starAMR, RGI/CARD, PlasmidFinder, MOB-suite, and the Virulence Factor Database (VFDB). RESULTS: Phenotypic testing revealed extensive resistance, with complete resistance to six of seven tested antibiotics (cefotaxime, ampicillin, erythromycin, gentamicin, ciprofloxacin, and doxycycline). MICs exceeded clinical breakpoints for multiple classes, confirming an MDR phenotype. Genome analysis indicated a 5.33 Mb genome distributed across five contigs, including one chromosome and four plasmid-associated contigs. The strain harboured numerous ARGs, including bla CTX-M-15, bla OXA-1, bla TEM-1, aac(6')-Ib-cr, aadA5, aph(3")-Ib, sul1/sul2, tet(A), dfrA17, and mph(A), co-localized on plasmids indicative of horizontal gene transfer (HGT) potential. Plasmid types included Col156, IncF, and two rep clusters. Virulence profiling revealed genes associated with adhesion (pap cluster, ECP), iron acquisition (enterobactin, yersiniabactin, aerobactin, heme uptake), and toxins (sat, senB), highlighting the isolate's potential for urinary tract and intestinal infections. CONCLUSION: This study highlights the significant role of poultry-associated bacteria as reservoirs of AMR genes, particularly those harboured on mobile plasmids with potential for HGT. E. coli strain S3 exhibits extensive multidrug resistance and carries a complex plasmid repertoire facilitating horizontal transfer of ARGs. Coupled with a rich virulence gene profile, this strain underscores the public health risk posed by poultry-associated E. coli in Nigeria. These findings demonstrate the urgent need for stringent antimicrobial stewardship, regulatory oversight, and genomic surveillance in poultry production milieus to mitigate the dissemination of MDR pathogens.

Escherichia coli↗
PubMed2026

Dynamics and virulence of Enterobacteriaceae reservoirs harboring blaCTX-M group 1 in community wastewater.

UNLABELLED: Extended-spectrum beta-lactamase (ESBL)-producing bacteria are ubiquitous and can cause serious infections. Here, we examined untreated community wastewater influent as a reservoir for blaCTX-M group 1 organisms and their virulence potential. Raw influent samples (n = 268) were collected from four wastewater treatment plants (WWTPs) representing dense urban populations. We observed that blaCTX-M group 1 levels were high at all WWTPs and only ~1-2 log10 lower and not correlated to common human-specific microbiome fecal markers, Lachno3 and HF183, indicating a lack of connection to human fecal inputs. Concentrations of blaCTX-M group 1 genes and markers for presumptive host organisms Escherichia coli and Klebsiella pneumoniae were influenced by travel time and season. Amplicon sequencing revealed high diversity of blaCTX-M group 1-9 genes, with 63% belonging to group 1. Selective culture and 16S rRNA gene sequencing showed blaCTX-M group 1 isolates were 26% E. coli, 26% K. pneumoniae, 40% other Enterobacteriaceae, and 8% Aeromonas. Overall, E. coli averaged 3.6E7 cells/L, with 3% of all E. coli found to contain blaCTX-M group 1. Whole-genome sequencing of blaCTX-M group 1 E. coli from wastewater revealed resistance and virulence gene profiles similar to clinical isolates and distinct from other wastewater ESBL-resistant and non-resistant E. coli. Interpretation of wastewater data needs to consider both the existence of environmental reservoirs that contain potentially pathogenic organisms and the strong influence the dynamics of the conveyance system can have on final concentrations measured at the WWTP. IMPORTANCE: The CTX-M enzyme family is highly abundant in nosocomial, community, and environmental settings and is leading to treatment of infections with carbapenem antibiotics, a last-line therapeutic option. The progressive increase of the clinically relevant blaCTX-M group 1 resistance genes in the human population warrants investigation, particularly to understand the establishment and dynamics of environmental reservoirs. This study utilized molecular and culture methods to gain insight into the possible origin, abundance, and dynamics of blaCTX-M group 1 genes in untreated wastewater influent samples. We found extremely high levels of these genes, with Escherichia coli as a major host organism that closely resembled clinical strains, suggesting they are seeded and propagate in sewer pipe systems. The significance of our research is in developing approaches to monitor antimicrobial resistance reservoirs in community wastewater, which could shed light on global burdens and potential transmission cycles and indicate increasing inputs of clinically relevant strains originating from human populations.

E. coli↗
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

Outbreak of aztreonam-avibactam-resistant NDM-5-producing Escherichia coli isolates in a hospital of Paris.

The emergence of aztreonam-avibactam resistance among NDM-producing Escherichia coli represents a major therapeutic and infection control concern. Four cases of aztreonam-avibactam-resistant (AZAR) NDM-producing E. coli, recovered from three blood cultures and one rectal surveillance culture in a hospital of Paris, prompted an investigation based on whole-genome sequencing. The three isolates responsible for bloodstream infection, which were clonally related, belonged to the ST405 and produced NDM-5, DHA-1, CTX-M-15, and TEM-1 β-lactamases. They also had a penicillin-binding protein 3 (PBP3) modified by the insertion of four amino acids (YRIK). On the other hand, the isolate recovered from the rectal swab belonged to another sequence type (ST2083). It produced NDM-5, CMY-42, and TEM-1 β-lactamases and had an altered PBP3 by the insertion of four other residues (YRIN). Epidemiological investigation identified endoscopic retrograde cholangiopancreatography as a potential risk factor, leading to the detection of three additional patients infected with the ST405 clone after exposure to the same duodenoscope. The outcome of the bloodstream infections was favorable except for one patient. In total, seven patients infected or colonized by AZAR NDM-5-producing E. coli were identified over a 5-month period in 2025, six with duodenoscope exposure.IMPORTANCEThis study underlines the emergence of aztreonam-avibactam resistance among NDM-producing Escherichia coli isolates in France. To our knowledge, this report describes the first clonal outbreak due to aztreonam-avibactam-resistant NDM-producing E. coli.

Humans↗
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 µg/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 × 10⁻⁴, 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

Escalation of CTX-M-producing extensively drug-resistant Shigella spp. in Kolkata, India, following the COVID-19 pandemic.

Shigella spp. is recognized by the World Health Organization as a high-priority pathogen due to its global prevalence, unique pathogenic mechanisms, and growing antimicrobial resistance (AMR). Nearly half of all Shigella strains worldwide are now multidrug-resistant (MDR), and the emergence of extensively drug-resistant (XDR) variants-resistant to ciprofloxacin, ceftriaxone, and azithromycin-has severely limited effective treatment options. The present study is based on prospective laboratory surveillance involving 323 Shigella isolates collected during 2021-2023, with pre-COVID-19 pandemic data included from a previously published study solely for historical comparison. The presence of antibiotic resistance genes (ARGs) was investigated, and whole-genome sequencing (WGS) was performed on representative isolates to assess phylogenetic relatedness with global isolates. Approximately 10% of isolates exhibited resistance to third-generation cephalosporins. While only 3% of Shigella isolates carried the blaCTX-M-15 gene from 2013 to 2019, its prevalence increased to 26% by 2022-2023. Among 38 ceftriaxone-resistant S. sonnei isolates, 33 were also resistant to azithromycin, categorizing them as XDR. These isolates showed 48% clonal similarity and high phylogenetic resemblance to the isolates reported from England. Hybrid genome assembly revealed a plasmid harboring both the blaCTX-M-15 and mphA ARGs. Conjugation experiments and plasmid profiling confirmed the plasmid's transferability. We report a rising trend in third-generation cephalosporin resistance among Shigella spp., primarily driven by the spread of extended-spectrum β-lactamase-producing S. flexneri and the emergence of XDR S. sonnei. These findings underscore the urgent need for strengthened national AMR containment strategies and enhanced international surveillance of cephalosporin-resistant Shigella to mitigate this growing public health threat.IMPORTANCEShigella is a leading cause of diarrheal disease globally and has been prioritized by the World Health Organization due to its rapid acquisition of antimicrobial resistance. Our prospective surveillance in Kolkata, India, reveals a worrisome escalation of third-generation cephalosporin resistance over the past decade, primarily associated with the spread of blaCTX-M-15 and the emergence of extensively drug-resistant (XDR) S. sonnei. The detection of plasmids carrying both blaCTX-M-15 and mphA, coupled with evidence of their transferability, highlights the potential for accelerated dissemination of multidrug resistance. When compared with a global data set of international genomes, the Kolkata XDR isolates were found to cluster closely with isolates reported from England. By linking local surveillance with global genomic context, our findings provide critical insights for treatment guidelines, antimicrobial stewardship, and the design of international containment strategies aimed at curbing the rise of cephalosporin- and azithromycin-resistant Shigella.

India↗