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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

Emergence of ceftazidime-avibactam resistance mediated by KPC variants KPC-71 and KPC-78 in ST463 Pseudomonas aeruginosa.

UNLABELLED: Pseudomonas aeruginosa is a well-recognized opportunistic pathogen and a leading cause of healthcare-associated infections. The shrinking effectiveness of available antimicrobial therapies has intensified the global threat posed by carbapenem-resistant P. aeruginosa (CRPA). Here, we elucidate the mechanisms of ceftazidime-avibactam (CZA) resistance mediated by the rare KPC variants, KPC-71 and KPC-78, identified during the treatment of CRPA infections. Two CZA-resistant P. aeruginosa strains, SY-206885 and HZ-231016032, were isolated from critically ill male patients with severe pneumonia. Whole-genome sequencing assigned both isolates to the high-risk sequence type 463 (ST463). Isolate SY-206885 harbors the blaKPC-71 gene, while HZ-231016032 carries blaKPC-78. Cloning and expression of these genes in P. aeruginosa PAO1 conferred a marked increase in the CZA minimum inhibitory concentration. Notably, expression of KPC-71 or KPC-78 conferred CZA resistance while simultaneously reducing carbapenem hydrolytic activity, a trade-off previously described for some KPC variants but still rarely documented in P. aeruginosa. Structural analysis and kinetic profiling showed that, relative to wild-type KPC-2, both KPC-71 and KPC-78 exhibited reduced catalytic turnover but increased substrate affinity for ceftazidime, together with significantly weakened binding to avibactam. In addition, elevated expression of MexAB-OprM and AmpC-related determinants in the clinical isolates likely further enhanced the high-level CZA resistance phenotype. These findings highlight the capacity of the ST463 CRPA lineage to evolve CZA resistance through KPC structural diversification under antimicrobial pressure and underscore the need for close surveillance during therapy. IMPORTANCE: In this study, we report the detection of the uncommon KPC variants KPC-71 and KPC-78 in clinical sequence type 463 (ST463) carbapenem-resistant Pseudomonas aeruginosa isolates exhibiting resistance to ceftazidime-avibactam (CZA). We demonstrate that CZA resistance is driven by specific structural alterations-a serine insertion between residues 182 and 183 or a D179A substitution within the Ω-loop-that reshape the functional balance of the KPC enzyme. These changes appear to create an evolutionary trade-off by improving ceftazidime recognition while weakening avibactam-mediated inhibition. Given the widespread dissemination of the ST463 lineage in China, the emergence of these variants highlights the urgent need for clinicians to monitor for CZA resistance development during therapy. CLINICAL TRIALS: This study is registered with ClinicalTrials.gov as ChiCTR2500105846.

Ceftazidime↗

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↗

PubMed2026

Genomic epidemiology and ceftazidime-avibactam resistance mechanism of KPC-3-producing Pseudomonas aeruginosa: A decade retrospective study in China.

OBJECTIVES: Carbapenem-resistant Pseudomonas aeruginosa (CRPA), especially KPC-producing P. aeruginosa, is rapidly expanding and posing a serious public health threat. Here, we aim to characterise the epidemiology of KPC-3-producing P. aeruginosa in a tertiary hospital over a 10-year period and elucidate the mechanism of ceftazidime-avibactam (CZA) resistance driven by blaKPC-3 to blaKPC-267 mutations in CRPA, along with conducting a global phylogeographic analysis of KPC-3-producing P. aeruginosa. METHODS: 11 non-duplicate KPC-3-producing CRPA isolates collected over a 10-year period were characterized by antimicrobial susceptibility testing and whole-genome sequencing (WGS). The genetic context and transferability of blaKPC-3/267 and the mechanism of KPC-267-mediated CZA resistance were investigated. Global phylogenomic analysis was performed to characterize the geographic distribution and population structure of blaKPC-3-carrying P. aeruginosa. RESULTS: All 11 KPC-3-producing CRPA strains in this study belonged to ST1076 and exhibited multidrug resistance. The blaKPC-267-positive CZA-resistant strain SRMPA3523 was isolated from patient 1 after blaKPC-3-positive P. aeruginosa SRMPA1139 and SRMPA1630 were treated with CZA. WGS indicated that blaKPC-3/267 was located on the Tn6296 transposon contained in the transferable IncP-2 plasmid. KPC-267 mediates resistance to CZA by reducing the inhibitory effect of avibactam and increasing affinity for ceftazidime. Global analysis indicated that blaKPC-3-carrying P. aeruginosa were predominantly in China, America, and Colombia, with ST1076 and ST111 as dominant clones. CONCLUSIONS: This study characterised the global phylogeography of blaKPC-3-carrying P. aeruginosa and identified KPC-267 as a KPC-3-derived variant associated with CZA resistance. This finding highlighted the risk of developing CZA resistance in KPC-producing P. aeruginosa strains under therapeutic pressure.

CRPA↗

PubMed2025

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

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

Pseudomonas aeruginosa↗

PubMed2026

Repeated emergence and fitness heterogeneity of KPC-33 in ST11 Klebsiella pneumoniae under ceftazidime-avibactam pressure.

Ceftazidime-avibactam (CZA) is an important therapeutic option for infections caused by Klebsiella pneumoniae carbapenemase (KPC)-producing Klebsiella pneumoniae. However, CZA exposure also selects for emergent KPC variants. Their in vivo evolutionary patterns, fitness consequences, and underlying molecular mechanisms remain unclear. We performed a longitudinal multiomics analysis of 35 clonally related ST11 KPC-producing K. pneumoniae isolates collected from eight hospitalized patients during clinical follow-up, most of whom had received CZA therapy. Whole-genome sequencing, antimicrobial susceptibility testing, in vitro competition assays, enzyme kinetic analysis, and transcriptomic sequencing were used to systematically characterize the within-host evolutionary dynamics of KPC variants and the fitness heterogeneity of KPC-33. Multiple KPC variants were identified during longitudinal follow-up, among which KPC-33 was the most frequently detected. Among the seven patients who received CZA treatment, KPC-33 was detected in longitudinal isolates from four patients. It was also identified in patient P3, who had not received CZA, whereas other variants were only sporadically identified. Biochemical analysis showed that KPC-33 exhibited an altered kinetic profile relative to KPC-2, characterized by reduced catalytic turnover and altered substrate affinity. KPC-33 did not exhibit a uniform and pronounced fitness defect but instead showed marked strain-dependent heterogeneity. Strains with higher competitive fitness generally showed only limited transcriptional changes, whereas those with lower fitness were accompanied by broader transcriptional remodeling. In this longitudinal cohort, KPC-33 was repeatedly detected, predominantly under CZA-associated selective conditions. Its fitness consequences were clearly strain background dependent and may be associated with the extent of transcriptional remodeling. These findings provide new evidence for understanding the in vivo evolution of CZA resistance.

KPC-33↗

PubMed2025

Mechanisms of resistance to ceftazidime/avibactam in mutants derived in vitro from Klebsiella pneumoniae producing OXA-48-like enzymes.

OBJECTIVES: To generate in vitro ceftazidime-avibactam-resistant mutants derived from Klebsiella pneumoniae producing OXA-48 or OXA-48 derivatives OXA-131 and OXA-232 carbapenemases, to define their antimicrobial susceptibility phenotype and to analyse mutations potentially involved in resistance to ceftazidime-avibactam. METHODS: Mutants were obtained by plating overnight bacterial cultures on Mueller-Hinton agar plates containing increasing concentrations of ceftazidime-avibactam (0.5/4-32/4 mg/L). MICs were determined using Sensititre™ DKMNG panels. Whole-genome sequencing of 8 parental strains and 31 mutant derivatives was performed with Illumina. RESULTS: All parental strains were susceptible to ceftazidime-avibactam (MIC ≤ 0.5/4-2/4 mg/L) and either susceptible or resistant to meropenem (MIC 0.5 to >16 mg/L) and imipenem (MIC ≤ 0.5 to >16 mg/L). MICs of ceftazidime-avibactam for the mutants increased up to 4 to >16 mg/L, while MICs of meropenem and imipenem for most mutants either increased up to >16 mg/L or remained unchanged. Whole-genome sequencing of the mutants identified alterations in genes coding for proteins related to AcrAB-TolC (AcrB, AcrR), PBPs (PBP2, PBP3), porins (OmpK36, EnvZ) or the stress or stringent responses (RseB, CpxA, SpoT). No mutations were detected in genes coding for OXA-48-like enzymes or other β-lactamases. CONCLUSIONS: Ceftazidime-avibactam can select in vitro mutants of OXA-48-like carbapenemase-producing K. pneumoniae resistant to this combination and, in some cases, also to carbapenems. No mutations related to ceftazidime-avibactam resistance were found in genes coding OXA-48-like enzymes, but they were detected in genes related to active efflux, PBPs, permeability or proteins of the stress and stringent responses.

Ceftazidime↗

PubMed2026

Efficacy of the NMIC-150 system in identifying extended-spectrum beta-lactamases in clinical isolates.

Extended-spectrum beta-lactamases (ESBLs) are significant contributors to the growing global crisis of antimicrobial resistance. This study evaluated the performance of the NMIC-150 System for susceptibility testing of third-generation cephalosporins (3GCs) and assessed whether ceftazidime-avibactam and aztreonam-avibactam could identify ESBL-producing carbapenem-resistant Enterobacterales (CREs). A total of 278 non-duplicate clinical isolates (Klebsiella pneumoniae, E. coli, and Proteus mirabilis) were analyzed. Antimicrobial susceptibility was determined using reference broth microdilution (BMD) and the NMIC-150 System. ESBL production was defined as an ≥eight-fold reduction in the minimum inhibitory concentration (MIC) of 3GCs in the presence of clavulanic acid, according to CLSI criteria. Whole-genome sequencing was performed to characterize ESBL and carbapenemase genes among 3GC-resistant isolates. A Random Forest model was used to predict ESBL-producing isolates based on MIC values. The NMIC-150 System demonstrated over 90% categorical and essential agreement with BMD for ceftazidime and ceftriaxone, along with robust predictive performance via Random Forest analysis. These findings suggest that the NMIC-150 System is a reliable platform for 3GC susceptibility testing and that an ≥eight-fold MIC reduction with ceftazidime-avibactam or aztreonam-avibactam may serve as a phenotypic indicator of ESBL production in CRE isolates. In conclusion, the NMIC-150 System shows potential for routine antimicrobial resistance surveillance and may facilitate the rapid identification of ESBL-producing CREs in clinical settings.

Microbial Sensitivity Tests↗

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

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↗

PubMed2026

Detection and antimicrobial susceptibility patterns of Salmonella enterica subsp. arizonae and Proteus spp. associated with gastrointestinal disease in rescued hedgehogs (Erinaceus europaeus).

Western European hedgehogs (Erinaceus europaeus) are frequently admitted to wildlife rehabilitation centres, where infectious diseases may affect recovery and raise One Health concerns. This study aimed to identify bacterial isolates recovered from hedgehog samples submitted for suspected gastrointestinal infection and to characterise their antimicrobial susceptibility profiles. Five bacterial isolates were analysed using the MicroScan WalkAway Plus® system with the Neg-Urine-Combo 98 panel, and the results were interpreted in accordance with EUCAST guidelines. The identified bacteria included one isolate of Salmonella enterica subsp. arizonae, three isolates of Proteus mirabilis and one isolate of Proteus penneri. The Salmonella enterica subsp. arizonae isolate was susceptible to all antimicrobials for which a valid result was obtained. Proteus spp. isolates were susceptible to cefotaxime, nalidixic acid, ciprofloxacin, levofloxacin, norfloxacin, amikacin, gentamicin, tobramycin, aztreonam, cefoxitin, ceftazidime and fosfomycin. However, resistance was observed to amoxicillin-clavulanic acid, ampicillin, ertapenem, meropenem, trimethoprim-sulfamethoxazole, cefuroxime, piperacillin-tazobactam, colistin and nitrofurantoin, with the latter two showing resistance in all Proteus spp. The Proteus penneri isolate displayed the broadest resistance profile, including resistance to several β-lactams, carbapenems. As expected, all Proteus spp. showed intrinsic non-susceptibility to colistin and nitrofurantoin. Although the Salmonella enterica subsp. arizonae isolate was susceptible to the tested agents, Proteus spp. from hedgehog samples may display relevant antimicrobial resistance (AMR) patterns. Therefore, continuous bacteriological monitoring and antimicrobial susceptibility testing are important in wildlife rehabilitation settings to guide treatment decisions and support One Health surveillance.

Antimicrobial resistance↗

PubMed2026

Treatment strategies for imipenemase-producing Gram-negative infections: lessons from Japan.

Carbapenems remain essential for treating serious infections caused by drug-resistant Gram-negative bacteria because of their broad-spectrum activities and favourable safety profiles. However, the emergence of carbapenemase-producing Enterobacterales, which produce enzymes that efficiently hydrolyse β-lactams including carbapenems, continues to undermine their clinical utility. Although new antibiotics such as ceftazidime-avibactam, imipenem-relebactam, meropenem-vaborbactam, aztreonam-avibactam, and cefiderocol have expanded therapeutic options, their effectiveness varies substantially across different carbapenemase families. Carbapenemases produced by Enterobacterales include serine β-lactamases (Ambler classes A and D) and metallo-β-lactamases (MBLs; Ambler class B), each with distinct substrate and inhibitor profiles. Clinically relevant MBLs-including imipenemase (IMP), New Delhi MBL (NDM), and Verona integron-encoded MBL (VIM) variants-show markedly different biochemical properties and inhibitor susceptibilities. Despite their clinical relevance, optimal treatment strategies for infections caused by IMP-producing Enterobacterales remain poorly defined. The unique reactivity of IMP-type MBLs to inhibitors differs from that of other MBLs such as NDMs or VIMs, underscoring the need for tailored therapeutic approaches. In this Personal View, we summarise current evidence and, drawing on Japan's experience as an endemic setting for IMP producers, outline key scientific, clinical, and public health challenges that should be addressed globally to develop effective, evidence-based treatment strategies for IMP-producing Enterobacterales infections.

Humans↗

PubMed2026

Genomic diversity, antimicrobial resistance, and virulence-associated characteristics of Escherichia coli recovered from poultry hatchery-box material.

Hatcheries are early points of exposure of newly hatched chicks to Escherichia coli from eggshell debris, dust, meconium, and the hatchery environment. This study used descriptive genomic surveillance to characterize population structure, antimicrobial resistance, virulence-associated genes, plasmid replicons, and genetic relatedness in a purposively selected collection of E. coli recovered from hatchery-box material in a Czech commercial poultry hatchery. From 83 samples collected between 2019 and 2023, 409 isolates were recovered. Following within-sample reduction based on antimicrobial susceptibility profiles and PCR screening for selected APEC-associated virulence genes, 91 isolates enriched for cefotaxime-medium recovery or APEC-associated gene profiles were selected for Illumina whole-genome sequencing. The sequenced collection comprised 35 sequence types across nine phylogenetic groups or clades; phylogroup B1 (59/91) and ST162 (28/91) predominated. ColV-associated markers were detected in 88 isolates, acquired resistance genes in 61, and a multidrug-resistant phenotype in 31. Seventeen isolates were resistant to ceftazidime; eight carried ESBL or plasmid-mediated AmpC determinants, while eight additional isolates had the chromosomal ampC promoter substitution C-42T as the only identified determinant associated with this phenotype. Closely related isolates, including ST131, ST162, and ST675, were recovered from different samples or parent-farm groups within restricted sampling periods. These findings document genomically diverse, resistance- and virulence-associated E. coli in hatchery-box material and identify genetically related isolates that warrant investigation through structured longitudinal sampling. Because sampling was unequal and isolates were purposively selected, the findings do not provide prevalence estimates or demonstrate source, transmission, persistence, or pathogenicity.

APEC-associated virulence genes↗

PubMed2026

Molecular characterization and antimicrobial resistance profiles of Shigella flexneri isolates from pediatric clinical cases in Ahvaz, Iran.

Shigella is a highly invasive pathogen that causes dysentery and is associated with significant morbidity and mortality in children under five years of age. This agent is a major public health problem in developing countries. Multiple-locus variable-number tandem repeat (VNTR) analysis (MLVA) is a reliable, cost-effective typing method with high discriminatory power and reproducible results. The rise of drug resistance in Shigella strains is a growing global health threat. Despite the significance of Shigella in Iran, there is limited knowledge about genetic diversity and drug resistance profiles of local strains. Therefore, the purpose of this study was to characterize the genetic diversity and drug resistance profiles of Shigella strains isolated in Ahvaz, Iran. A total of 49 Shigella flexneri isolates were recovered from 500 stool samples of pediatric patients. Routine biochemical tests were used to identify all isolates. Antimicrobial susceptibility testing was performed, and resistance genes were detected by polymerase chain reaction (PCR). Extended-spectrum β-lactamases (ESBL), carbapenemase, and Metallo-β-lactamase (MBL) production were detected phenotypically using combination disk assays and confirmed by the CLSI-recommended modified Carbapenem inactivation method (mCIM) and EDTA-modified carbapenem inactivation method (eCIM). MLVA based on seven VNTR loci was performed to characterize the genetic diversity of the isolates. All 49 isolates were resistant to ceftazidime, trimethoprim/sulfamethoxazole, ampicillin, and ceftriaxone (100% each). High resistance rates were also observed for imipenem 36/49 (73.5%), meropenem 36/49 (73.5%), azithromycin 21/49 (42.9%), and ciprofloxacin 16/49 (32.7%). Furthermore, phenotypic testing revealed ESBL production in 46/49 (93.9%) isolates and carbapenemase activity in 36/49 (73.5%), of which 22/49 (44.9%) were MBL. PCR analysis identified blaCTX-M 38/49 (77.6%) and blaSHV 35/49 (71.4%) as the most prevalent ESBL genes, whereas blaNDM 14/49 (28.6%), and blaOXA-48 14/49 (28.6%) were the most common carbapenemase genes. MLVA typing divided the isolates into 22 different MLVA types, including 10 clusters and 12 singletons, and locus ms21 showed the highest discriminatory power. The isolates exhibited high genetic diversity with a non-clonal distribution of resistance, which indicates dissemination through horizontal gene transfer. Our results demonstrated that mCIM/eCIM and MLVA are viable methods for investigating Shigella species as they are cost-effective, provide quick results, and allow for easy sharing of numerical data between laboratories.

Humans↗

PubMed2026

Four-year surveillance of major Gram-negative pathogens in a Saudi tertiary hospital: clinical distribution, comorbidity profiles, and antimicrobial resistance.

PURPOSE: To describe four-year diagnostic-distribution, burden, and antimicrobial-resistances of major Enterobacterales and Pseudomonas aeruginosa in a tertiary-care surveillance framework. PATIENTS AND METHODS: We retrospectively studied first non-duplicate-isolate per/patient/organism between 2022-2025 at a Saudi tertiary-care. Diagnostics used automated-platforms with GeneXpert-Carba-R employed parallel to cultures. Susceptibility interpretations used CLSI-breakpoints relevant to test-year. Annual-trends were assessed with grouped-binomial logistic-regression, and Benjamini-Hochberg false-discovery-rate correction was applied within prespecified analysis. RESULTS: Among 1,857 isolates, Klebsiella pneumoniae was most frequent (36.2%), followed by P. aeruginosa (33.4%), Escherichia coli (17.9%), and Enterobacter cloacae (12.3%). Mean patient age was 64.8 years, 51.3% isolates were from intensive-care, 37.4% from urine, and 80.8% records had comorbidity. K. pneumoniae showed overall ESBL (76.6%), CRE (59.9%), MDR (69.3%), panel-defined XDR (64.7%), and panel-defined PDR (15.2%) frequencies. Enterobacterales ESBL-positivity increased (58.1% to 76.8%;q <0.001), whereas meropenem non-susceptibility decreased (52.6% to 33.2%;q <0.001). In P. aeruginosa, ceftazidime non-susceptibility increased (55.2% to 78.6%;q <0.001), meropenem decreased (46.8% to 32.9%;q = 0.031), and tobramycin increased (22.2% to 45.7%;q = 0.030). Crude-comorbidity differences remained insignificant after false-discovery-rate correction. CONCLUSION: We show a persistent species-specific Gram-negative resistance burden, led by K. pneumoniae and accompanied by substantial P. aeruginosa non-susceptibility. This supports organism-specific detections, antibiograms and continued multicenter-surveillance linked to antimicrobial exposure, genomic-data, and patient outcomes.

ESBL↗

PubMed2026

Meropenem-Colistin Combination Mitigates Porin-Associated Carbapenem Resistance Development in Ertapenem-Mono-Resistant Enterobacterales.

BACKGROUND: Non-carbapenemase-producing Enterobacterales with isolated ertapenem resistance (ETP-mono-R) may represent an early stage in the evolution toward broader carbapenem resistance, but whether further resistance induction occurs and its underlying mechanisms remain poorly understood. METHODS: Resistance induction was assessed in three Escherichia coli, four Klebsiella pneumoniae, and two Enterobacter cloacae isolates through serial exposure to subinhibitory concentrations of meropenem (MEM), imipenem, ceftazidime-avibactam, or colistin (COL), with antibiotic-free passaging for reversion. Resistance induction under MEM+COL was evaluated separately. Whole-genome sequencing (WGS), targeted porin-gene Sanger sequencing, and transcriptional analysis were used to characterize resistance mechanisms across induction stages. RESULTS: Subinhibitory MEM exposure rapidly selected for carbapenem resistance through porin-associated alterations in a species-specific manner. E. coli accumulated loop-region mutations in ompC, while K. pneumoniae predominantly developed disruptive mutations in ompK36, both accompanied by marked transcriptional downregulation. In contrast, E. cloacae retained wild-type porins but showed increased MEM MICs, suggesting a non-porin-mediated mechanism. Subinhibitory exposure to COL alone rapidly induced colistin resistance but was associated with decreased carbapenem MICs. Co-exposure to MEM and COL significantly delayed resistance development and reduced MIC increases (all P < 0.05). Targeted sequencing of 26 non-carbapenemase-producing K. pneumoniae isolates resistant to all carbapenems revealed widespread disruptive ompK36 alterations, including the S337P substitution identified experimentally, consistent with a shared permeability-loss pathway. CONCLUSIONS: In ETP-mono-R Enterobacterales, subinhibitory carbapenem exposure promotes carbapenem resistance, with porin-associated mechanisms predominating in E. coli and K. pneumoniae. Co-exposure to COL attenuates this process, suggesting a potential strategy to delay the emergence of carbapenem resistance.

Enterobacterales↗

PubMed2026

Molecular determinants of antimicrobial resistance in Klebsiella pneumoniae isolates among geriatric patients in Chattogram, Bangladesh: a cross-sectional study.

Klebsiella pneumoniae (KPN) infections pose heightened risks in the geriatric population due to weakened immunity, prevalent comorbidities, potential exposure in long-term care settings, and increased likelihood of antibiotic resistance (ABR). The study focused on the prevalence and antibiotic resistance of KPN infections, the presence of ABR genes in KPN, and the genomic characterization of KPN obtained from geriatric patients in Chattogram. A total of 543 specimens were collected from four hospitals in Chattogram, along with demographic data from hospital records. Genomic DNA was extracted from multi-drug-resistant (MDR) KPN, and the presence of ABR genes, blaTEM-1, sul-1, aadB, blaNDM-1, blaSHV-11, and phoE was identified. To characterize the KPN genomes, two MDR KPN isolates were subjected to whole-genome sequencing (WGS), and the data were analyzed using bioinformatics tools to identify genomic determinants of ABR. KPN exhibited high resistance to ceftazidime (96%), cefuroxime (92%), and cefixime (83%), but sensitivity to colistin (79%) and amikacin (75%). MDR KPN was mostly detected in sputum (36%) and urine (27%) specimens, where the prevalence of ABR genes, blaTEM-1, sul1, aadB, blaNDM-1, and blaSHV-11 were 28.2%, 17%, 6.17%, 56%, and 48% of these strains, respectively. These genomes exhibited distinct profiles for sequence types, ST420 and ST277 in Kpn007 and Kpn016, respectively, and ABR genes (qnrS1, blaCTX-M-15, and blaSHV-27), virulence factors (ybt, iuc1, iro1), and contained both K (K20, K46) and O antigens (O1, O3b). MDR KPN in the geriatric population poses a serious health concern due to their increased vulnerability to infections and limited treatment options, requiring careful management.IMPORTANCEMultidrug resistance (MDR) and the hypervirulence nature of Klebsiella pneumoniae (KPN) in geriatric patients pose a critical health concern in nosocomial infections worldwide and result in high clinical complexity and mortality. The study investigated the factors for KPN infections and analyzed antimicrobial resistance profiles. More than 60% of Klebsiella pneumoniae isolates from geriatric patients were resistant to third- and fourth-generation cephalosporins, and most isolates carried blaNDM-1 and blaSHV-11 genes. Analyzing whole genomes of two KPNs, Kpn007 (ST277) was identified as a hypervirulent strain with aerobactin and yersinia siderophores, contributing to virulence, and Kpn016 (ST420) carried fluoroquinolone (qnrS1), ESBL (blaCTX-M-15 and blaSHV-27) resistance. Both genomes contained K antigens (K20 and K46) and O antigens (O1 and O3b).

Humans↗

PubMed2026

Evaluation of Oxford nanopore sequencing for antimicrobial resistance surveillance in Salmonella: comparison with phenotypic antimicrobial susceptibility in a large-scale study.

UNLABELLED: Salmonella is a major zoonotic foodborne pathogen, and antimicrobial resistance (AMR) in Salmonella presents a significant public health challenge. Compared with conventional antimicrobial susceptibility testing (AST), whole-genome sequencing (WGS) provides a more rapid and comprehensive approach to AMR characterization, thereby informing antimicrobial selection and supporting public health surveillance. In this study, Oxford Nanopore Technology (ONT)-based WGS was performed on 1,490 Salmonella isolates collected through nationwide surveillance in Taiwan in 2025. Genotypic resistance inferred from WGS data was compared with phenotypic AST results to assess the performance of ONT-WGS. Overall, WGS-inferred resistance showed high concordance with phenotypic resistance for most antimicrobials. However, major genotype-phenotype discordance was observed, attributed to four categories: (i) breakpoint-dependent classification, (ii) reduced or absent phenotypic expression of resistance genes, (iii) minimum inhibitory concentration (MIC) modulation by ramAp, and (iv) absence of known AMR determinants. Notable discrepancies included tigecycline resistance without known genetic determinants, nalidixic acid resistance linked to ramAp-mediated MIC elevation, and a high prevalence of colistin resistance (35.7%) in S. Enteritidis, with most resistant isolates lacking identifiable AMR determinants. Additionally, a significant proportion of ESBL- and AmpC-producing isolates were classified as susceptible or intermediate to cefotaxime and ceftazidime under CLSI criteria, highlighting the potential for misclassification and treatment failure. These findings demonstrate that ONT-WGS enables accurate and comprehensive AMR characterization by directly identifying resistance determinants and avoiding potential misclassification associated with breakpoint-based AST interpretations. When interpreted appropriately, WGS can support better antimicrobial selection and serve as a valuable alternative to conventional susceptibility testing. IMPORTANCE: Accurate prediction of antimicrobial resistance is essential for appropriate therapy and effective surveillance of Salmonella. However, discordance between genotype-based predictions and phenotypic antimicrobial susceptibility testing (AST) can complicate clinical interpretation. In this nationwide study of 1,490 Salmonella isolates, we show that Oxford Nanopore Technology-based whole-genome sequencing (ONT-WGS) provides rapid and comprehensive detection of antimicrobial resistance determinants with high concordance to phenotypic AST. We further identify four major mechanisms underlying genotype-phenotype discordance, including breakpoint-dependent classification, reduced or absent phenotypic expression of resistance genes, minimum inhibitory concentration (MIC) modulation by ramAp, and the absence of known AMR determinants. These findings demonstrate how WGS can complement conventional AST, improve interpretation of challenging susceptibility results, and strengthen genomic surveillance of emerging antimicrobial-resistant Salmonella.

Microbial Sensitivity Tests↗