Search Results (328)

Cefepime-enmetazobactam is a novel β-lactam/β-lactamase inhibitor combination showing good activity against multidrug-resistant (MDR) Gram-negative bacteria producing a variety of β-lactamases. In this systematic review, we aimed to evaluate the available data on resistance to this drug. We performed a thorough search of four databases (Embase, PubMed, Scopus, and Web of Science), as well as backward citation searching, to identify studies containing data on resistance to cefepime-enmetazobactam. The data were extracted and analyzed according to the breakpoints established by the European Committee on Antimicrobial Susceptibility Testing (EUCAST) and the Food and Drug Administration (FDA), or the specific breakpoints reported by the authors of the respective studies. Analysis based on the type of lactamases produced by the isolates was also performed. Ten studies reported in vitro susceptibility testing and mechanisms of antimicrobial resistance. The total number of isolates was 15,408. The activity of cefepime-enmetazobactam against β-lactamase-producing isolates was variable. The resistance of the studied extended-spectrum β-lactamase (ESBL)-producing and ampicillin C β-lactamase (AmpC)-producing isolates was low (0–2.8% and 0%, respectively). The resistance was higher among oxacillinase-48 β-lactamase (OXA-48)-producing and Klebsiella pneumoniae carbapenemase (KPC)-producing isolates (3.4–13.2% and 36.7–57.8%, respectively). High resistance was noted among metallo-β-^lactamase (MBL)-producing isolates (reaching 87.5% in one study), especially those producing New Delhi metallo-β-lactamase (NDM) and Verona integron-encoded metallo-β-lactamase (VIM), which had the highest rates of resistance. The high activity of cefepime-enmetazobactam against Enterobacterales and selected lactose non-fermenting Gram-negative pathogens, including ESBL-producing and AmpC-producing isolates, makes it a potential carbapenem-sparing agent. The drug should be used after in vitro antimicrobial susceptibility testing in patients with infections caused by OXA-48, KPC, and MBL-producing isolates. Full article

Introduction: Carbapenem-resistant Klebsiella pneumoniae (CRKP) represents a critical public health threat due to its rapid nosocomial dissemination, limited therapeutic options, and elevated mortality rates. This study aimed to characterize the epidemiology, carbapenemase profiles, and antimicrobial susceptibility patterns of CRKP isolates, as well as the clinical features and outcomes observed in infected or colonized patients. Materials and Methods: We conducted a retrospective analysis of clinical and microbiological data from patients with CRKP infections or colonization admitted between January 2023 and January 2024. Descriptive statistics were used to assess prevalence, resistance patterns, and patient outcomes. Two binary logistic regression models were applied to identify independent predictors of sepsis and in-hospital mortality. Results: Among 89 CRKP isolates, 45 underwent carbapenemase typing. More than half were metallo-β-lactamase (MBL) producers, with 44.4% co-harbouring NDM and OXA-48-like enzymes. Surgical intervention was associated with a significantly lower risk of sepsis (p < 0.01) and in-hospital mortality (p = 0.045), whereas intensive care unit (ICU) stay was a strong predictor of both outcomes. ICU admission conferred a 10-fold higher risk of sepsis (95%Cl 2.4–41.0) and a 40.8-fold higher risk of in-hospital death (95% Cl 3.5–473.3). Limitations: This single-center retrospective study included a limited number of isolates in certain groups. Additionally, cefiderocol (FDC) susceptibility was assessed by disk diffusion rather than by the broth microdilution method. Conclusions: Our study underscores the increasing prevalence of metallo-beta-lactamase-producing CRKP, particularly strains harbouring dual carbapenemases. Timely recognition of high-risk patients, combined with the implementation of targeted infection control measures and the integration of novel therapeutic options, is crucial to optimize clinical management and reduce mortality associated with CRKP. Full article

Klebsiella pneumoniae carbapenemases (KPCs) are a group of class A β-lactamases of Gram-negative bacteria leading to difficult-to-treat infections. We evaluated the global epidemiology of KPC-producing Gram-negative clinical isolates. A systematic search of six databases (Cochrane Library, Embase, Google Scholar, PubMed, Scopus, and Web of Science) was conducted. Extracted data were tabulated and evaluated. After screening 1993 articles, 119 were included in the study. The included studies originated from Asia (n = 49), Europe (n = 29), North America (n = 14), South America (n = 11), and Africa (n = 3); 13 studies were multicontinental. The most commonly reported KPC-producing species were Klebsiella pneumoniae (96 studies) and Escherichia coli (52 studies), followed by Enterobacter cloacae (31), Citrobacter spp. (24), Klebsiella oxytoca (23), Serratia spp. (15), Enterobacter spp. (15), Acinetobacter baumannii complex (13), Providencia spp. (11), Morganella spp. (11), Klebsiella aerogenes (9), Pseudomonas aeruginosa (8), Raoultella spp. (8), Proteus spp. (8), and Enterobacter aerogenes (6). Among the studies with specific bla_KPC gene detection, 52/57 (91%) reported the isolation of bla_KPC-2 and 26/57 (46%) reported bla_KPC-3. The antimicrobial resistance of the studied KPC-producing isolates was the lowest for ceftazidime–avibactam (0–4%). Resistance to polymyxins, tigecycline, and trimethoprim–sulfamethoxazole in the evaluated studies was 4–80%, 0–73%, and 5.6–100%, respectively. Conclusions: The findings presented in this work indicate that KPC-producing Gram-negative bacteria have spread globally across all continents. Implementing proper infection control measures, antimicrobial stewardship programs, and enhanced surveillance is crucial. Full article

Grazing is a free-range farming model commonly practiced in low-external-input agricultural systems. The widespread use of veterinary antibiotics in livestock farming has led to significant environmental accumulation of antibiotic residues and antibiotic resistance genes (ARGs), posing global health risks. This study investigated the antibiotic residues, bacterial community, ARG profiles, and mobile genetic elements (MGEs) in cattle feces from three provinces in western China (Ningxia, Xinjiang, and Inner Mongolia) under grazing modes. The HPLC-MS detection showed that the concentration of tetracycline antibiotics was the highest in all three provinces. Correlation analysis revealed a significant negative correlation between antibiotic residues and the diversity and population abundance of intestinal microbiota. However, the abundance of ARGs was directly proportional to antibiotic residues. Then, the Sankey analysis revealed that the ARGs in the cattle fecal samples were concentrated in 15 human pathogenic bacteria (HPB) species, with 9 of these species harboring multiple drug resistance genes. Metagenomic sequencing revealed that carbapenemase-resistant genes (bla_KPC and bla_VIM) were also present in considerable abundance, accounting for about 10% of the total ARGs detected in three provinces. Notably, Klebsiella pneumoniae strains carrying bla_CTX-M-55 were detected, which had a possibility of IncFII plasmids harboring transposons and IS19, indicating the risk of horizontal transfer of ARGs. This study significantly advances the understanding of the impact of antibiotic residues on the fecal microbiota composition and ARG profiles in grazing cattle from northwestern China. Furthermore, it provides critical insights for the development of rational antibiotic usage strategies and comprehensive public health risk assessments. Full article

Background/Objectives: Cefiderocol is a novel siderophore cephalosporin with potent in vitro activity against a broad spectrum of Gram-negative bacteria, including carbapenemase-producing Enterobacterales (CPE). However, the recent emergence of resistance in clinical settings raises important concerns regarding its long-term effectiveness. This study aims to investigate the genomic determinants associated with cefiderocol resistance in CPE isolates of human origin. Methods: Comparative genomic analyses were conducted between cefiderocol-susceptible and -resistant CPE isolates recovered from human clinical and epidemiological samples at a tertiary care hospital. Whole-genome sequencing, variant annotation, structural modelling, and pangenome analysis were performed to characterize resistance mechanisms. Results: A total of 59 isolates (29 resistant and 30 susceptible) were analyzed, predominantly comprising Klebsiella pneumoniae, Escherichia coli, and Enterobacter cloacae. The most frequent carbapenemase gene among the resistant isolates was bla_NDM, which was also present in a subset of susceptible strains. The resistant isolates exhibited a significantly higher burden of non-synonymous mutations in their siderophore receptor genes, notably within fecR, fecA, fiu, and cirA. Structural modelling predicted deleterious effects for mutations such as fecR:G104S and fecA:A190T. Additionally, porin loss and loop 3 insertions (e.g., GD/TD) in OmpK36, as well as OmpK35 truncations, were more frequent in the resistant isolates, particularly in high-risk clones such as ST395 and ST512. Genes associated with toxin–antitoxin systems (chpB2, pemI) and a hypothetical metalloprotease (group_2577) were uniquely found in the resistant group. Conclusions: Cefiderocol resistance in CPE appears to be multifactorial. NDM-type metallo-β-lactamases and missense mutations in siderophore uptake systems—especially in those encoded by fec, fhu, and cir operons—play a central role. These may be further potentiated by alterations in membrane permeability, such as porin disruption and efflux deregulation. The integration of genomic and structural approaches provides valuable insights into emerging resistance mechanisms and may support the development of diagnostic tools and therapeutic strategies. Full article

Carbapenem-resistant Enterobacteriaceae (CRE) pose an emerging threat, with a high mortality rate among children with cancer. This study aimed to evaluate the impact of routine rectal swab surveillance and rapid PCR-based detection of carbapenemase genes to facilitate the early initiation of appropriate treatment and assess its effects on outcomes. The study compared two groups of pediatric cancer patients with CRE bloodstream infections: a retrospective cohort of 254 patients from 2013 to 2017, and a prospective cohort of 186 patients from 2020 to 2022, following the implementation of these tools. A rapid diagnostic test in the prospective cohort resulted in the early initiation of proper antibiotics in 85% (165/186) of patients, compared to only 58% (147/254) in the retrospective group. This led to a decrease in the need for ICU admission related to sepsis from CRE and a significant reduction in the 30-day mortality rate (16% vs. 30%, p ≤ 0.01). Genotypic profiling revealed that class B carbapenemases were the most prevalent (69%), with the NDM type being identified in 67% of patients. OXA-48 and KPC enzymes were detected in 59% and 4% of patients, respectively. Multivariate analysis revealed that patients having Klebsiella pneumoniae, NDM genotype carbapenemases, presence of pneumonia, and septic shock requiring ICU admission were predictors of poor outcomes. Rapid diagnostics and targeted colonization lead to the appropriate use of targeted antibiotics, resulting in improved patient outcomes. Understanding carbapenemase-producing microorganisms and administering newer antibiotics may further reduce mortality and enhance treatment strategies for high-risk patients. Full article

Klebsiella pneumoniae is a major public health concern due to its role in Gram-negative bacteremia, which leads to high mortality and increased healthcare costs. This study characterizes phenotypic and genomic features of K. pneumoniae isolates from clinical samples in Karachi, Pakistan. Among 507 isolates, 213 (42%) were carbapenem-resistant based on disk diffusion and MIC testing. Urine (29.7%) and blood (28.3%) were the most common sources, with infections predominantly affecting males (64.7%) and individuals aged 50–70 years. Colistin was the only antibiotic showing consistent activity against these isolates. The whole-genome sequencing of 24 carbapenem-resistant K. pneumoniae (CR-KP) isolates revealed bla_NDM-5 (45.8%) as the dominant carbapenemase gene, followed by bla_NDM-1 (12.5%) and bla_OXA-232 (54.2%). Other detected bla_OXA variants included bla_OXA-1, bla_OXA-4, bla_OXA-10, and bla_OXA-18. The predominant beta-lactamase gene was bla_CTX-M-15 (91.6%), followed by bla_CTX-M-163, bla_CTX-M-186, and bla_CTX-M-194. Sequence types ST147, ST231, ST29, and ST11 were associated with resistance. Plasmid profiling revealed IncR (61.5%), IncL (15.4%), and IncC (7.7%) as common plasmid types. Importantly, resistance was driven not only by acquired genes but also by chromosomal mutations. Porin mutations in OmpK36 and OmpK37 (e.g., P170M, I128M, N230G, A217S) reduced drug influx, while acrR and ramR mutations (e.g., P161R, G164A, P157*) led to efflux pump overexpression, enhancing resistance to fluoroquinolones and tigecycline. These findings highlight a complex resistance landscape driven by diverse carbapenemases and ESBLs, underlining the urgent need for robust antimicrobial stewardship and surveillance strategies. Full article

Background: The combination of aztreonam (ATM) and avibactam (AVI) presents an important therapeutic option for carbapenem-resistant Enterobacterales, particularly the NDM-producing Enterobacterales. In 2024, both the CLSI and EUCAST published their methods in antimicrobial susceptibility testing for this combination of agents. Materials and Methods: Forty carbapenem-resistant Enterobacterales isolates, including Escherichia coli (n = 35), Enterobacter cloacae complex (n = 2), Klebsiella pneumoniae complex (n = 2), and Citrobacter freundii complex (n = 1) were included in this study. All isolates harbored the NDM carbapenemase except one, which had no known detected carbapenemases. Four antimicrobial susceptibility testing methods of the combination of ATM and AVI were evaluated on these isolates, including the CLSI broth disk elution (BDE) method, the disk diffusion (DD) method of aztreonam–avibactam (AZA) following the EUCAST breakpoints, the MIC test strip (MTS) method of AZA following the EUCAST breakpoints, and the gradient strip stacking (SS) method. BDE was used as the standard of comparison. Results: Using BDE as the standard of comparison, the AZA DD, AZA MTS, and SS methods had 100% categorical agreement (CA), 0% very major error (VME), and 0% major error (ME). The essential agreement (EA) between the AZA MTS and SS method was 57.5%. Conclusions: The AZA DD, AZA MTS, and the SS methods showed complete concordance with the BDE method. However, the MICs obtained from the AZA MTS and SS were not comparable. Full article

Background/Objectives: Antibiotic resistance is a significant and escalating challenge that limits available therapeutic options. This issue is further exacerbated by the decreasing number of new antibiotics being developed. Our study aims to describe the epidemiology and pattern of antibiotic resistance in Gram-negative infections isolated from a cohort of hospitalized patients and to analyze the distribution of infections within the hospital setting. Methods: A retrospective study was conducted on all patients admitted to Vito Fazzi Hospital in Lecce, Italy, who required an infectious disease consultation due to the isolation of Gram-negative bacteria from 1 January 2018 to 31 December 2022. Results: During the study period, 402 isolates obtained from 382 patients (240 men and 142 women) with infections caused by Gram-negative bacteria were identified. Among these isolated, 226 exhibited multidrug resistance, defined as resistance to at least one antimicrobial agent from three or more different classes. In 2018, the percentage of multidrug-resistant isolates peaked at 87.6%, before decreasing to the lowest level (66.2%) in 2021. Overall, of the 402 isolates, 154 (38.3%) displayed resistance to carbapenems, while 73 (18.1%) were resistant to extended-spectrum beta-lactamases (ESBLs). Among the resistant microorganisms, Klebsiella pneumoniae showed the highest resistance to carbapenems, accounting for 85.2% of all resistant strains. Escherichia coli exhibited the greatest resistance to ESBLs, with a rate of 86.7%. Among carbapenem-resistant K. pneumoniae isolates, the following resistance rates were observed: KPC-1 at 98.2%, IMP-1 at 0.9%, VIM-1 at 0.9%, and NDM-1 at 0.9%. Conclusions: Patients with infections caused by multidrug-resistant bacteria have limited treatment options and are therefore at an increased risk of death, complications, and longer hospital stays. Rapid diagnostic techniques and antimicrobial stewardship programs—especially for ESBLs and carbapenemases—can significantly shorten the time needed to identify the infection and initiate appropriate antimicrobial therapy compared to traditional methods. Additionally, enhancing surveillance of antimicrobial resistance within populations is crucial to address this emerging public health challenge. Full article

(1) Background: CRISPR-Cas systems provide adaptive immunity against mobile genetic elements (MGEs) carrying antimicrobial resistance (AMR) genes. Carbapenem-resistant (CR) Klebsiella pneumoniae is a major public health concern, and the role of CRISPR-Cas in its resistance is understudied. This study explored CRISPR-Cas associations with multidrug resistance in clinical K. pneumoniae. (2) Methods: 400 K. pneumoniae isolates (200 CR and 200 carbapenem susceptible (CS)) were analyzed. Carbapenemase genes (bla_OXA-48, bla_NDM-1, bla_KPC-2), cas1, rpoB, and CRISPR1-3 loci were identified by PCR, while only CRISPR loci were sequenced. Genetic relatedness was assessed via PFGE, MLST, and spacer analysis. Statistical analysis utilized chi-squared and Fisher’s exact tests. (3) Results: CRISPR-Cas was present in 15.8% of isolates, mainly subtypes I-E and I-E* (93.3%), with CRISPR3 loci showing the greatest spacer diversity. Clonal complexes ST14/15/101 (CR) and ST35 (CS) were identified. bla_OXA-48 was linked to CRISPR-Cas-negative strains, while bla_NDM-1 and bla_KPC-2 were more frequent in CRISPR-Cas-positive strains (p < 0.0001). Imipenem/relebactam resistance was higher in CRISPR-Cas-negative isolates. (4) Conclusions: K. pneumoniae CRISPR-Cas systems correlate with specific carbapenemase profiles, suggesting pressure against bla_OXA-48 acquisition. The coexistence of I-E and I-E* subtypes highlight synergies in targeting MGEs. CRISPR loci could be tools for subtyping organisms following MLST. Full article

Background/Objectives: Antimicrobial resistance is a major global health threat. Among the most problematic pathogens are carbapenem-resistant Acinetobacter baumannii and Klebsiella pneumoniae, which are significant causes of mortality in humans, particularly in the context of nosocomial infections. In companion animals, these bacteria have been reported mainly as colonizers of healthy animals or, less frequently, in community-acquired infections. However, no confirmed cases of healthcare-associated infections caused by these species have been documented in this population. This study reports the first confirmed fatal cases of infection with carbapenem-resistant A. baumannii and KPC-producing K. pneumoniae in dogs. Methods: Three hospitalized dogs developed infections associated with distinct anatomical devices, including a venous catheter, an endotracheal tube, and a Penrose drain. Bacterial isolation followed by antimicrobial susceptibility testing identified carbapenem-resistant A. baumannii and K. pneumoniae. The isolates were subsequently subjected to additional antimicrobial resistance tests and whole-genome sequencing (WGS). Results: WGS confirmed the presence of the OXA-23 carbapenemase gene in both A. baumannii isolates and the KPC-2 carbapenemase gene was detected in the K. pneumoniae strain. All three strains exhibited resistance to multiple antimicrobial classes, including β-lactams (amoxicillin-clavulanic acid, ampicillin, cephalotin, piperacillin-tazobactam, cefoxitin, ceftiofur, cefotaxime, ertapenem, imipenem and meropenem), aminoglycosides (gentamicin, neomycin), tetracyclines (doxycycline, tetracycline and oxytetracycline), fluoroquinolones (ciprofloxacin, enrofloxacin), and folate pathway antagonists (trimethoprim-sulfamethoxazole). Multilocus sequence typing identified two high-risk clones: K. pneumoniae ST340 (CC258) and A. baumannii ST15 (CC15). Single nucleotide polymorphism analysis confirmed a high degree of genetic similarity between these isolates and strains previously associated with human infections in Brazil. Conclusions: These findings provide the first evidence of fatal, healthcare-associated infections caused by these multidrug-resistant pathogens in dogs and underscore the need to strengthen surveillance and infection control practices in veterinary hospitals. Furthermore, the results raise concerns about the potential of companion animals to act as reservoirs for multidrug-resistant organisms of public health relevance. Full article

Background/Objectives. Carbapenemase production is the most diffused carbapenem-resistance mechanism among Enterobacterales, with Klebsiella pneumoniae carbapenemase (KPC), Verona-imipenemase (VIM), New-Delhi metallo-β-lactamase (NDM), imipenemase (IMP), and oxacillinase (OXA-48) being reported as the main types within Europe. Particularly, Southern Italy holds a concerningly high percentage of carbapenemases-producing Enterobacterales diffused among different hospital settings. These strains may colonize critical patients’ gastrointestinal tracts, often causing disseminations and severe complications. Scientific data recently reported carbapenemase variants’ worldwide diffusion and several double-carbapenemases reports. The diagnostic routine needs devices whose detection rates are extended to similar epidemiological conditions, avoiding a lack of specificity and potential negative results. Methods. We planned a retrospective study including carbapenem- and/or ceftazidime/avibactam-resistant Enterobacterales (62) which were tested with the KPC/IMP/NDM/VIM/OXA-48 Combo Test Kit (KINVO, Medomics Medical Technology, Nanjing, Jiangsu, China) based on the lateral flow assay (LFA) method. Results. We compared its results to the phenotypic antimicrobial susceptibility testing (AST) MIC results, obtaining a 100% agreement rate. The LFA kit reported carbapenemases in all the tested strains, also identifying cases of KPC variants and double-carbapenemases production. Conclusions. Our data demonstrated how LFAs may represent a reliable alternative requiring minimum economic and personnel resources along with simple result interpretations. Future studies will be necessary to further investigate the system effectiveness on a larger isolates’ number and a broad carbapenemase variant spectrum. Full article

Background: Antimicrobial resistance (AMR) is a global threat in the public healthcare sector. The emergence of carbapenem-resistant Enterobacterales (CRE) has become a serious public health threat in South Africa. The spread of CRE has led to the use of colistin for treating severe infections. Colistin is a cationic, lipopeptide antibacterial agent that is effective against most Gram-negative bacteria through its disruption of the bacterial cell membrane. This study aims to determine the colistin resistance (MIC) and mobile colistin resistance (mcr-1) gene in clinical isolates from healthcare facilities in Mthatha and its surrounding areas. Methods: Fifty-three CRE isolates were collected from health facilities between January 2019 and June 2021 and stored in skim milk 10% and 5% inositol broth. The carbapenemase confirmatory test involved a RESIST-4 O.K.N.V assay (Coris BioConcept, Gembloux, Belgium), which was conducted following manufacturer protocol. Broth microdilution was performed according to the ISO standard method (20776-1) using A ComAspTM colistin 0.25–16 μg/mL MIC Broth. Conventional polymerase reaction (PCR) was performed for the detection of mcr-1. Results: N = 53 (100%) isolates were used. A total of 53% were defined as Klebsiella pneumoniae, Escherichia coli constituted 8%, Enterobacter cloacae 8%, Serratia marcescens 8%, Serratia fonticola 2%, Enterobacter aerogenes 2%, Klebsiella oxytoca 2%, Citrobacter koseri 2%, and Citrobacter freundii 2%. The specimens were from the following wards: Pediatric and Neonatal 38%, Medical 30%, Gynecology, Labour, and Maternity 11%, OPD and A&E 11%, ENT 4%, and Others—Male TB ward, Trauma, and adult ICU 6%. In total, 13% of the isolates were resistant and 86% were sensitive to colistin. The common CRE genes detected were OXA-48 at 47%, NDM at 13%, VIM at 1%, and a combination of OXA-48 and NDM at 5%. Of the isolates, 66% were positive for the production of carbapenamase. In this study, we found that all N = 53 (100%) isolates did not have the mobile colistin resistance gene (mcr-1). Conclusions: Antimicrobial resistance is associated with the emergence of carbapenemases genes. Increasing resistance to colistin in clinical settings can lead to difficulties in treating CRE infections, which may lead to clinical failure. In our study, 13% of isolates were phenotypically resistant to colistin. Full article

Background: High-risk Escherichia coli clones, such as sequence type (ST)131 and ST1193, along with multidrug-resistant (MDR) Klebsiella pneumoniae, are globally recognized for their significant role in urinary tract infections (UTIs). This study aimed to provide an overview of the virulence factors, clonal diversity, and antibiotic resistance profiles of extended-spectrum cephalosporin (ESC)-E. coli and K. pneumoniae causing UTIs in humans in the Tebessa region of Algeria. Methods: Forty E. coli and 17 K. pneumoniae isolates exhibiting ESC-resistance were recovered (July 2022–January 2024) from urine samples of patients at three healthcare facilities to be phenotypically and genotypically characterized. Whole genome sequencing (WGS) was performed on the ST1193 clone. Results: Among K. pneumoniae isolates, all except one harbored CTX-M-15, with a single isolate carrying bla_CTX-M-194. Additionally, two K. pneumoniae isolates co-harboring bla_CTX-M-15 and bla_NDM exhibited phenotypic and genotypic hypervirulence traits. Fluoroquinolone resistance (FQR) was detected in 94.1% of K. pneumoniae isolates. The E. coli isolates carried diverse ESC-resistance genes, including CTX-M-15 (87.5%), CTX-M-27 (5%), CTX-M-1, CMY-59, and CMY-166 (2.5% each). Co-carriage of bla_ESC and bla_OXA-48 was identified in three E. coli isolates, while 62.5% exhibited FQR. Phylogenetic analysis revealed that 52.5% of E. coli belonged to phylogroup B2, including the high-risk clonal complex (CC)131 CH40-30 (17 isolates) and ST1193 (one isolate). In silico analysis of the ST1193 genome determined O75:H5-B2 (CH14-64), and the carriage of IncI1-I(Alpha) and IncF [F-:A1:B10] plasmids. Notably, core genome single-nucleotide polymorphism (SNP) analysis demonstrated high similarity between the Algerian ST1193 isolate and a previously annotated genome from a hospital in Northwest Spain. Conclusions: This study highlights the spread and genetic diversity of E. coli CC131 CH40-30 and hypervirulent K. pneumoniae clones in Algeria. It represents the first report of a CTX-M-15-carrying E. coli ST1193 in the region. The findings emphasize the urgent need for antibiotic optimization programs and enhanced surveillance to curb the dissemination of high-risk clones that pose an increasing public health threat in Algeria. A simplified method based on virulence traits for E. coli and K. pneumoniae is proposed here for antimicrobial resistance (AMR) monitoring. Full article

Despite the increased reporting of Carbapenem-resistant hypervirulent Klebsiella pneumoniae (CR-hvKp) in Egypt, there is a paucity of information regarding the molecular characteristics of such strains. Herein, we present the genome sequence of two CR-hvKp strains, K22 and K45, which were isolated from VAP (ventilator-associated-pneumonia) patients admitted to pediatric ICU at Assiut University Children’s Hospital, Egypt. K22 and K45 isolates were subjected to antimicrobial susceptibility testing and whole-genome sequencing. Genomic analysis was performed to characterize each strain, determining their plasmids, antimicrobial resistance (AMR) genes, and virulence determinants. K22 possessed an extensive drug resistance phenotype (XDR), whilst K45 exhibited a multidrug resistance phenotype (MDR), with genome sequencing revealing the presence of a diverse array of AMR genes. Both strains were resistant to the carbapenem antibiotic imipenem, carrying the OXA-48 carbapenemase, with K22 additionally possessing an NDM-1 carbapenemase. Each strain was considered high-risk, with K22 and K45 respectively belonging to sequence types ST383 and ST14 and possessing virulence genes implicated in hypervirulence (e.g., iucABCD-iutA and rmpA). Importantly, both strains carried multiple plasmid replicons, including an AMR/virulence IncHI1B/FIB hybrid plasmid and MDR IncL/M plasmids. This report highlights the critical role of plasmids in the evolution of virulent K. pneumoniae strains and suggests the circulation of an IncHI1B/FIB hybrid plasmid, simultaneously disseminating AMR and hypervirulence, amongst K. pneumoniae strains within Assiut University Children’s Hospital. Full article