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185400.9906Whole genome analysis reveals the distribution and diversity of plasmid reservoirs of NDM and MCR in commercial chicken farms in China. The increase in multidrug-resistant (MDR) Enterobacteriaceae presents a significant challenge to clinical treatment, particularly in infections where carbapenems and colistin serve as the last-resort antimicrobial agents. In this study, we isolated 119 non-repetitive gram-negative bacteria from MacConkey medium supplemented with imipenem and colistin. The isolates were dominated by Klebsiella pneumoniae (58.0%, n = 69) and Escherichia coli (31.1%, n = 37). The predominant sequence types (STs) of E. coli were ST226, ST1286, and ST11738, whereas K. pneumoniae displayed ST152, ST395, and ST709 as major types. Genomic analysis identified mcr-1/3/8/9 in 44 strains and bla(NDM) in 63 strains across various species. IncX3 (n = 57) and IncFII (n = 5) were the most common bla(NDM-5)-carrying plasmid types. Several plasmid replicons were associated with mcr genes, including IncI2, IncX4, and novel plasmids. Remarkably, we discovered four combinations of bla(NDM) and mcr co-occurrence in 28 isolates, including bla(NDM-5)/mcr-1, bla(NDM-5)/mcr-3, bla(NDM-5)/mcr-8, and bla(NDM-5)/mcr-9. Our findings reveal that chicken farms are significant reservoirs for both bla(NDM) and mcr genes, with frequent co-occurrence of these resistance determinants. The presence of these genes alongside other resistance factors, such as blaESBL, highlights a critical public health risk. This study underscores the need for enhanced surveillance and intervention strategies to mitigate the spread of MDR pathogens from agricultural environments to clinical settings.IMPORTANCEThis study reveals that commercial poultry farms in China serve as critical reservoirs for MDR gram-negative bacteria harboring carbapenemase (bla(NDM)) and mobilized colistin resistance (mcr) genes. By analyzing 119 isolates, we uncovered extensive genetic diversity and plasmid-mediated co-occurrence of these resistance determinants, enabling bacteria to evade nearly all available treatments. Alarmingly, the horizontal transfer of resistance genes via highly mobile plasmids facilitates their spread across microbial communities and potentially into clinical settings. These findings underscore the urgent need to address antibiotic overuse in agriculture and strengthen surveillance under the One Health framework. The persistence of MDR pathogens in poultry environments highlights a significant risk for zoonotic transmission, emphasizing the necessity of coordinated interventions to curb the global antimicrobial resistance crisis.202540488461
83910.9905Molecular characterization of carbapenemase-producing Enterobacterales in a tertiary hospital in Lima, Peru. Carbapenemase-producing Enterobacterales (CPE) are a growing threat to global health and the economy. Understanding the interactions between resistance and virulence mechanisms of CPE is crucial for managing difficult-to-treat infections and informing outbreak prevention and control programs. Here, we report the characterization of 21 consecutive, unique clinical isolates of CPE collected in 2018 at a tertiary hospital in Lima, Peru. Isolates were characterized by phenotypic antimicrobial susceptibility testing and whole-genome sequencing to identify resistance determinants and virulence factors. Seven Klebsiella pneumoniae isolates were classified as extensively drug-resistant. The remaining Klebsiella, Enterobacter hormaechei, and Escherichia coli isolates were multidrug-resistant. Eighteen strains carried the metallo-β-lactamase NDM-1, two the serine-carbapenemase KPC-2, and one isolate had both carbapenemases. The bla(NDM-1) gene was located in the truncated ΔISAba125 element, and the bla(KPC-2) gene was in the Tn4401a transposon. ST147 was the most frequent sequence type among K. pneumoniae isolates. Our findings highlight the urgent need to address the emergence of CPE and strengthen control measures and antibiotic stewardship programs in low- and middle-income settings.IMPORTANCEGenomic surveillance of antimicrobial resistance contributes to monitoring the spread of resistance and informs treatment and prevention strategies. We characterized 21 carbapenemase-producing Enterobacterales collected at a Peruvian tertiary hospital in 2018, which exhibited very high levels of resistance and carried numerous resistance genes. We detected the coexistence of carbapenemase-encoding genes (bla(NDM-1) and bla(KPC-2)) in a Klebsiella pneumoniae isolate that also had the PmrB(R256G) mutation associated with colistin resistance. The bla(KPC-2) genes were located in Tn4401a transposons, while the bla(NDM-1) genes were in the genetic structure Tn125 (ΔISAba125). The presence of high-risk clones among Klebsiella pneumoniae (ST11 and ST147) and Escherichia coli (ST410) isolates is also reported. The study reveals the emergence of highly resistant bacteria in a Peruvian hospital, which could compromise the effectiveness of current treatments and control.202438193666
250020.9902The crisis of carbapenemase-mediated carbapenem resistance across the human-animal-environmental interface in India. Carbapenems are the decision-making antimicrobials used to combat severe Gram-negative bacterial infections in humans. Carbapenem resistance poses a potential public health emergency, especially in developing countries such as India, accounting for high morbidity, mortality, and healthcare cost. Emergence and transmission of plasmid-mediated "big five" carbapenemase genes including KPC, NDM, IMP, VIM and OXA-48-type among Gram-negative bacteria is spiralling the issue. Carbapenemase-producing carbapenem-resistant organisms (CP-CRO) cause multi- or pan-drug resistance by co-harboring several antibiotic resistance determinants. In addition of human origin, animals and even environmental sites are also the reservoir of CROs. Spillage in food-chains compromises food safety and security and increases the chance of cross-border transmission of these superbugs. Metallo-β-lactamases, mainly NDM-1 producing CROs, are commonly shared between human, animal and environmental interfaces worldwide, including in India. Antimicrobial resistance (AMR) surveillance using the One Health approach has been implemented in Europe, the United-Kingdom and the United-States to mitigate the crisis. This concept is still not implemented in most developing countries, including India, where the burden of antibiotic-resistant bacteria is high. Lack of AMR surveillance in animal and environmental sectors underestimates the cumulative burden of carbapenem resistance resulting in the silent spread of these superbugs. In-depth indiscriminate AMR surveillance focusing on carbapenem resistance is urgently required to develop and deploy effective national policies for preserving the efficacy of carbapenems as last-resort antibiotics in India. Tracking and mapping of international high-risk clones are pivotal for containing the global spread of CP-CRO.202336241158
84230.9902Molecular characterization of antimicrobial resistance genes and plasmid profiles in enterobacterales isolated from urinary tract infections in rural outpatient women in Otavalo, Ecuador. BACKGROUND: The rise of antibiotic-resistant bacteria poses a significant public health threat, particularly in the context of urinary tract infections (UTIs), which rank as the second most common ambulatory illness. UTIs are often caused by Enterobacterales species, such as Escherichia coli and Klebsiella pneumoniae, with increasing resistance to critical antibiotics complicating treatment. Indigenous rural populations, like those in Ecuador, face unique challenges due to cultural, social, and economic barriers that hinder access to healthcare, exacerbating the issue of antibiotic resistance. METHODS: This study analyzed 154 Enterobacterales strains isolated from ambulatory UTI cases in outpatiens from Otavalo, Ecuador, between October 2021 and February 2022. DNA was extracted, and the presence of antibiotic resistance genes (ARGs) was screened using PCR for extended-spectrum beta-lactamases and carbapenemases. Plasmid incompatibility groups were identified through replicon typing, and multi-locus sequence typing (MLST) was performed to characterize strains. RESULTS: The analysis revealed four prevalent ARGs, with bla(TEM) being the most common (87.01% of isolates), followed by bla(CTX-M-1) (44.16%), bla(SHV) (18.83%), and bla(CTX-M-9) (13.64%). No carbapenemases or mcr-1 genes were detected. Among the incompatibility groups, IncFIB, IncF, and IncY were the most prevalent. A diverse array of ARG combinations was observed, indicating significant plasmid-mediated genetic plasticity. MLST identified 33 distinct sequence types among E. coli isolates, with ST10 and ST3944 being the most frequent. For K. pneumoniae, ST15 and ST25 were predominant. CONCLUSIONS: This study reveals significant antibiotic resistance among Enterobacterales from urinary tract infections in rural outpatients in Ecuador. The bla(TEM) gene was found in 87.01% of isolates, with notable clones like E. coli ST10 and ST3944 linked to extraintestinal infections. K. pneumoniae ST15 and ST25 were prevalent, indicating multidrug resistance. The findings highlight the need for ongoing surveillance and targeted public health strategies to combat resistance in these vulnerable communities.202541131447
182140.9902Emergence and dissemination of bla(KPC-31) and bla(PAC-2) among different species of Enterobacterales in Colombia: a new challenge for the microbiological laboratories. Ceftazidime/avibactam (CZA) is a promising treatment option for infections caused by carbapenem-resistant Enterobacterales (CRE). However, CZA resistance is increasingly reported worldwide, largely due to the emergence of KPC variants and increase of metallo-β-lactamases (MBL). This study describes the mechanisms associated with CZA resistance in circulating Enterobacterales isolates from Colombia, highlighting the challenge this represents for microbiological identification. Between 2021 and 2024, 68 CZA-resistant Enterobacterales isolates were identified by automated methods in seven Colombian cities. Resistance to CZA was subsequently confirmed by broth microdilution and E-test. Carbapenemase production was evaluated using phenotypic tests, such as the mCIM test, Carba NP, lateral flow assay, and qPCR (bla(KPC), bla(NDM), bla(VIM), bla(IMP), and bla(OXA-48)). Whole-genome sequencing was performed on 15 isolates that tested negative for MBL genes. Whole-genome sequencing of these 15 isolates revealed a variety of resistance determinants: six isolates harbored bla(KPC-31), one bla(KPC-33), one bla(KPC-8), five harbored bla(PAC-2), and two co-harbored bla(PAC-2) and bla(KPC-2). Notably, bla(PAC-2) was located on an IncQ plasmid. However, some of these variants were not detected by phenotypic assays, likely due to their low or undetectable carbapenemase activity. CZA resistance in non-MBL producing Enterobacterales in Colombia is primarily mediated by the presence of bla(KPC-31) and emergence of bla(PAC-2). These resistance mechanisms pose significant diagnostic, therapeutic, and epidemiological challenges, as they frequently go undetected by conventional microbiological methods. In this context, enhanced molecular surveillance and improved diagnostic strategies are urgently needed to enable early detection, guide antimicrobial therapy, and support infection control and stewardship efforts.IMPORTANCEAntibiotic resistance is a serious global health threat. Ceftazidime/avibactam (CZA) is a key treatment option for multidrug-resistant (MDR) Enterobacterales often used when other antibiotics fail. However, bacteria are now developing resistance to this drug as well, making infections increasingly difficult to treat. In this study, we examined CZA-resistant bacteria from multiple cities in Colombia and found uncommon resistance genes across several bacterial species. These genes are frequently missed, as they often do not test positive due to the limitations of most routinely used laboratory tests. Importantly, some of these genes can be transferred between bacteria, increasing the likelihood of indiscriminate dissemination in the hospital setting. Therefore, our findings highlight the urgent need for improved diagnostic tools and molecular surveillance. Early detection will help physicians select effective treatments quickly and prevent the wider dissemination of these MDR-resistant bacteria.202541070989
153150.9901Emergence of Plasmids Co-Harboring Carbapenem Resistance Genes and tmexCD2-toprJ2 in Sequence Type 11 Carbapenem Resistant Klebsiella pneumoniae Strains. OBJECTIVES: To characterize two plasmids co-harboring carbapenem resistance genes and tmexCD2-toprJ2 in carbapenem-resistant Klebsiella pneumoniae (CRKP) strains. METHODS: Two clinical CRKP strains were isolated and characterized by antimicrobial susceptibility testing, conjugation assays, whole-genome sequencing, and bioinformatics analysis. RESULTS: The two CRKP strains NB4 and NB5 were both resistant to imipenem, meropenem and tigecycline. Whole-genome sequencing revealed that two CRKP strains belonged to the ST11 type and carried multiple resistance genes. The tmexCD2-toprJ2 clusters in both strains were located on the IncFIB(Mar)-like/HI1B-like group of hybrid plasmids, which co-harbored the metallo-β-lactamase gene bla(NDM-1). In addition, the co-existence of bla(NDM-1) and bla(KPC-2) and the presence of tmexCD2-toprJ2 in CRKP strain NB5 was observed. CONCLUSIONS: In this study, tmexCD2-toprJ2 gene clusters were identified in two NDM-1-producing CRKP ST11 strains. These gene clusters will likely spread into clinical high-risk CRKP clones and exacerbate the antimicrobial resistance crisis. In addition, we detected the co-occurrence of bla(NDM-1), bla(KPC-2) and tmexCD2-toprJ2 in a single strain, which will undoubtedly accelerate the formation of a "superdrug resistant" bacteria. Hence, effective control measures should be implemented to prevent the further dissemination of such organisms in clinical settings.202235646740
174260.9901Shelter dogs as reservoirs of international clones of Escherichia coli carrying mcr-1.1 and bla(CTX-M) resistance genes in Lima, Peru. Antimicrobial resistance (AMR) poses a critical public health threat worldwide, particularly at the human-animal interface where cross-transmission of critical priority Enterobacterales, such as Escherichia coli, have become increasingly reported. Worryingly, E. coli encoding extended-spectrum β-lactamases (ESBLs) has been documented in companion animals worldwide. Conversely, the presence of mcr genes, which confer resistance to polymyxins, in bacteria from pets remains more infrequent. In this study, we sequenced and reported on the first genomic data of E. coli strains carrying mcr-1 and/or bla(CTX-M) genes isolated from rectal swabs of stray dogs in a shelter in the city of Lima, Peru. Antimicrobial susceptibility revealed that E. coli strains exhibited a multidrug resistance profile. In addition to mcr-1 and bla(CTX-M) genes, other clinically relevant resistance determinants were identified, with notably presence of bla(TEM-176) and the novel bla(SCO-2) variant. The association of mcr-1.1 and IncI2 plasmid was confirmed. Several virulence genes were detected, classifying strains as putative extraintestinal pathogenic E. coli. Multilocus sequence typing prediction recognized diverse sequence types (ST), including ST155, ST189, ST657, ST746, ST1140, ST3014, and ST7188. This study represents the first report of mcr-positive E. coli in dogs from Peru, emphasizing the need for continuous surveillance and genomic characterization to better understand the transmission dynamics of these critical resistance genes at the human-animal interface. Furthermore, our results provide evidence that stray, and shelter dogs could be a reservoir for the spread of WHO priority pathogens, and/or polymyxin and β-lactam resistance genes, which is a public health and One Health concern that requires appropriate management strategies.202540339258
84070.9901Outbreak of colistin and carbapenem-resistant Klebsiella pneumoniae ST16 co-producing NDM-1 and OXA-48 isolates in an Iranian hospital. BACKGROUND: Colistin and carbapenem-resistant Klebsiella pneumoniae (Col-CRKP) represent a significant and constantly growing threat to global public health. We report here an outbreak of Col-CRKP infections during the fifth wave of COVID-19 pandemic. METHODS: The outbreak occurred in an intensive care unit with 22 beds at a teaching university hospital, Isfahan, Iran. We collected eight Col-CRKP strains from seven patients and characterized these strains for their antimicrobial susceptibility, determination of hypermucoviscous phenotype, capsular serotyping, molecular detection of virulence and resistance genes. Clonal relatedness of the isolates was performed using MLST. RESULTS: The COVID-19 patients were aged 24-75 years with at least 50% pulmonary involvement and were admitted to the intensive care unit. They all had superinfection caused by Col-CRKP, and poor responses to antibiotic treatment and died. With the exception of one isolate that belonged to the ST11, all seven representative Col-CRKP strains belonged to the ST16. Of these eight isolates, one ST16 isolate carried the iucA and ybtS genes was identified as serotype K20 hypervirulent Col-CRKP. The bla(SHV) and bla(NDM-1) genes were the most prevalent resistance genes, followed by bla(OXA-48) and bla(CTX-M-15) and bla(TEM) genes. Mobilized colistin-resistance genes were not detected in the isolates. CONCLUSIONS: The continual emergence of ST16 Col-CRKP strains is a major threat to public health worldwide due to multidrug-resistant and highly transmissible characteristics. It seems that the potential dissemination of these clones highlights the importance of appropriate monitoring and strict infection control measures to prevent the spread of resistant bacteria in hospitals.202438368365
188080.9900Emergence and Dissemination of mcr-Carrying Clinically Relevant Salmonella Typhimurium Monophasic Clone ST34. Antibiotic resistance in bacteria is one of the urgent threats to both public and global health. The Salmonella Typhimurium monophasic sequence type 34 (ST34) clone, with its rapid dissemination and resistance to numerous critical antimicrobials, has raised global concerns. Here, we present an updated overview on the emerging infections caused by mobile colistin resistance (mcr)-carrying colistin-resistant ST34 isolates, covering their global dissemination and virulence-associated efficacy. The higher rates of mcr-1-positive ST34 in children in China highlights the increasing threat caused by this pathogen. Most of the ST34 isolates carrying the mcr-1 gene were isolated from animals and food products, indicating the role of foodborne transmission of mcr-1. The emergence of multidrug resistance genes along with various virulence factors and many heavy metal resistance genes on the chromosome and plasmid from ST34 isolates will challenge available therapeutic options. The presence of the colistin resistance gene (mcr-1, mcr-3, and mcr-5) with the multidrug-resistant phenotype in ST34 has spread across different countries, and most of the mcr-1 genes in ST34 isolates were detected in plasmid type IncHI2 followed by IncI2, and IncX4. Together, mcr-carrying S. Typhimurium ST34 may become a new pandemic clone. The fast detection and active surveillance in community, hospital, animal herds, food products and environment are urgently warranted.201931466338
153890.9899KPC-2 allelic variants in Klebsiella pneumoniae isolates resistant to ceftazidime-avibactam from Argentina: bla(KPC-80), bla(KPC-81), bla(KPC-96) and bla(KPC-97). Ceftazidime-avibactam (CZA) therapy has significantly improved survival rates for patients infected by carbapenem-resistant bacteria, including KPC producers. However, resistance to CZA is a growing concern, attributed to multiple mechanisms. In this study, we characterized four clinical CZA-resistant Klebsiella pneumoniae isolates obtained between July 2019 and December 2020. These isolates expressed novel allelic variants of bla(KPC-2) resulting from changes in hotspots of the mature protein, particularly in loops surrounding the active site of KPC. Notably, KPC-80 had an K269_D270insPNK mutation near the Lys270-loop, KPC-81 had a del_I173 mutation within the Ω-loop, KPC-96 showed a Y241N substitution within the Val240-loop and KPC-97 had an V277_I278insNSEAV mutation within the Lys270-loop. Three of the four isolates exhibited low-level resistance to imipenem (4 µg/mL), while all remained susceptible to meropenem. Avibactam and relebactam effectively restored carbapenem susceptibility in resistant isolates. Cloning mutant bla(KPC) genes into pMBLe increased imipenem MICs in recipient Escherichia coli TOP10 for bla(KPC-80), bla(KPC-96), and bla(KPC-97) by two dilutions; again, these MICs were restored by avibactam and relebactam. Frameshift mutations disrupted ompK35 in three isolates. Additional resistance genes, including bla(TEM-1), bla(OXA-18) and bla(OXA-1), were also identified. Interestingly, three isolates belonged to clonal complex 11 (ST258 and ST11) and one to ST629. This study highlights the emergence of CZA resistance including unique allelic variants of bla(KPC-2) and impermeability. Comprehensive epidemiological surveillance and in-depth molecular studies are imperative for understanding and monitoring these complex resistance mechanisms, crucial for effective antimicrobial treatment strategies. IMPORTANCE: The emergence of ceftazidime-avibactam (CZA) resistance poses a significant threat to the efficacy of this life-saving therapy against carbapenem-resistant bacteria, particularly Klebsiella pneumoniae-producing KPC enzymes. This study investigates four clinical isolates exhibiting resistance to CZA, revealing novel allelic variants of the key resistance gene, bla(KPC-2). The mutations identified in hotspots surrounding the active site of KPC, such as K269_D270insPNK, del_I173, Y241N and V277_I278insNSEAV, prove the adaptability of these pathogens. Intriguingly, low-level resistance to imipenem and disruptions in porin genes were observed, emphasizing the complexity of the resistance mechanisms. Interestingly, three of four isolates belonged to clonal complex 11. This research not only sheds light on the clinical significance of CZA resistance but also shows the urgency for comprehensive surveillance and molecular studies to inform effective antimicrobial treatment strategies in the face of evolving bacterial resistance.202438319084
1853100.9899Dissemination dynamics of colistin resistance genes mcr-9 and mcr-10 across diverse Inc plasmid backbones. BACKGROUND: The polymyxin antibiotic colistin is used as a final line of treatment for life threatening infections caused by multidrug resistant and carbapenem-resistant Gram-negative bacteria. Mobile colistin resistance genes mcr-9 and mcr-10 are increasingly detected in Enterobacteriaceae but their epidemiology is poorly understood. METHODS: The genetic characteristics of mcr-9 and mcr-10, being the only mobile colistin resistance genes detected in a local population of Enterobacter species isolated from bloodstream infections in Dartmouth Hitchcock Medical Center, USA, were elucidated and contextualized against a global dataset of mcr-9/10-bearing plasmids using genomic and phylogenetic tools. RESULTS: Seven out of 59 Enterobacter isolates carry either an mcr-9 or mcr-10 on a plasmid with distinct single and multiple replicon configurations, including IncFIB(pECLA), IncFIB(K), IncFIA(HI1)-IncFIB(K), IncFIB(pECLA)--IncFII(pECLA) and IncFIB(K)--IncFII(pECLA), whereas two genomes harbor mcr-9 on their chromosome. Global contextualization reveals that allelic variants of mcr-9 and mcr-10 are widely disseminated across diverse Inc-type plasmids, transcending geographic and taxonomic boundaries. Plasmid-borne genes conferring resistance to other antimicrobial agents, such as aminoglycoside, tetracycline and trimethoprim, tend to co-occur with mcr-9.1 and mcr-9.2 alleles. CONCLUSIONS: Findings from this study enhance our understanding of the plasmid backgrounds of mcr-9 and mcr-10, their associated antimicrobial resistance gene carriage and co-occurrence. This knowledge may be critical to inform scalable and effective public health interventions aimed at preserving the efficacy of colistin.202540999001
1875110.9899Mobile Colistin Resistance (mcr) Gene-Containing Organisms in Poultry Sector in Low- and Middle-Income Countries: Epidemiology, Characteristics, and One Health Control Strategies. Mobile colistin resistance (mcr) genes (mcr-1 to mcr-10) are plasmid-encoded genes that threaten the clinical utility of colistin (COL), one of the highest-priority critically important antibiotics (HP-CIAs) used to treat infections caused by multidrug-resistant and extensively drug-resistant bacteria in humans and animals. For more than six decades, COL has been used largely unregulated in the poultry sector in low- and middle-income countries (LMICs), and this has led to the development/spread of mcr gene-containing bacteria (MGCB). The prevalence rates of mcr-positive organisms from the poultry sector in LMICs between January 1970 and May 2023 range between 0.51% and 58.8%. Through horizontal gene transfer, conjugative plasmids possessing insertion sequences (ISs) (especially ISApl1), transposons (predominantly Tn6330), and integrons have enhanced the spread of mcr-1, mcr-2, mcr-3, mcr-4, mcr-5, mcr-7, mcr-8, mcr-9, and mcr-10 in the poultry sector in LMICs. These genes are harboured by Escherichia, Klebsiella, Proteus, Salmonella, Cronobacter, Citrobacter, Enterobacter, Shigella, Providencia, Aeromonas, Raoultella, Pseudomonas, and Acinetobacter species, belonging to diverse clones. The mcr-1, mcr-3, and mcr-10 genes have also been integrated into the chromosomes of these bacteria and are mobilizable by ISs and integrative conjugative elements. These bacteria often coexpress mcr with virulence genes and other genes conferring resistance to HP-CIAs, such as extended-spectrum cephalosporins, carbapenems, fosfomycin, fluoroquinolone, and tigecycline. The transmission routes and dynamics of MGCB from the poultry sector in LMICs within the One Health triad include contact with poultry birds, feed/drinking water, manure, poultry farmers and their farm workwear, farming equipment, the consumption and sale of contaminated poultry meat/egg and associated products, etc. The use of pre/probiotics and other non-antimicrobial alternatives in the raising of birds, the judicious use of non-critically important antibiotics for therapy, the banning of nontherapeutic COL use, improved vaccination, biosecurity, hand hygiene and sanitization, the development of rapid diagnostic test kits, and the intensified surveillance of mcr genes, among others, could effectively control the spread of MGCB from the poultry sector in LMICs.202337508213
950120.9899Incidence of Extended Spectrum β-Lactamase Genes (ESBLs) among community and health care infection in Mansoura University Hospital, Egypt. BACKGROUND: Multidrug-resistant (MDR) Gram-negative bacteria pose a significant challenge due to their limited treatment options. The production of extended-spectrum β-lactamases (ESBLs) is an important mechanism of resistance. This study aimed to identify the incidence and characteristics of ESBL-encoding genes (bla(CTX-M), bla(TEM), bla(SHV), and bla(OXA)) in MDR isolates. MATERIALS AND METHODS: A cross-sectional study was conducted from September 2022 to May 2023. ESBL-producing isolates (n = 105) out of 412 were recovered from hospitalized and outpatient settings and analyzed. Standard microbiological methods were used for isolates identification, susceptibility testing, and phenotypic ESBL detection. Additionally, bla(CTX-M), bla(TEM), bla(SHV), and bla(OXA) genes were identified using conventional PCR. RESULTS: Molecular profiling of β-lactamase determinants was conducted via PCR targeting bla(CTX-M), bla(TEM), bla(SHV), and bla(OXA) genes. Among phenotypically confirmed (100%) ESBL producers, 98% harbored one or more target genes, with bla(CTX-M) predominant (81%), followed by bla(SHV) (70.4%), bla(TEM) (62%), and bla(OXA) (30.4%). Carbapenem resistance was higher in ESBL-producing strains compared to non-ESBL strains. Extensively drug-resistant (XDR) isolates were the most common across hospital departments and outpatients. DISCUSSION: This study highlights the significant prevalence of ESBL genes and multidrug resistance among Gram-negative bacteria. The dominance of bla(CTX-M) and the existence of multiple resistance genes raise concerns about limited treatment options. The findings emphasize the need for stricter antibiotic stewardship and infection control measures to curb the spread of MDR pathogens. CONCLUSION: This study provides valuable insights into the alarming incidence of ESBL genes and MDR in Mansoura, Egypt. Continuous surveillance and implementation of effective control strategies are crucial to combat this growing public health threat.202540405086
1874130.9898Potential sources and characteristic occurrence of mobile colistin resistance (mcr) gene-harbouring bacteria recovered from the poultry sector: a literature synthesis specific to high-income countries. Understanding the sources, prevalence, phenotypic and genotypic characteristics of mcr gene-harbouring bacteria (MGHB) in the poultry sector is crucial to supplement existing information. Through this, the plasmid-mediated colistin resistance (PMCR) could be tackled to improve food safety and reduce public health risks. Therefore, we conducted a literature synthesis of potential sources and characteristic occurrence of MGHB recovered from the poultry sector specific to the high-income countries (HICs). Colistin (COL) is a last-resort antibiotic used for treating deadly infections. For more than 60 years, COL has been used in the poultry sector globally, including the HICs. The emergence and rapid spread of mobile COL resistance (mcr) genes threaten the clinical use of COL. Currently, ten mcr genes (mcr-1 to mcr-10) have been described. By horizontal and vertical transfer, the mcr-1, mcr-2, mcr-3, mcr-4, mcr-5, and mcr-9 genes have disseminated in the poultry sector in HICs, thus posing a grave danger to animal and human health, as harboured by Escherichia coli, Klebsiella pneumoniae, Salmonella species, and Aeromonas isolates. Conjugative and non-conjugative plasmids are the major backbones for mcr in poultry isolates from HICs. The mcr-1, mcr-3 and mcr-9 have been integrated into the chromosome, making them persist among the clones. Transposons, insertion sequences (IS), especially ISApl1 located downstream and upstream of mcr, and integrons also drive the COL resistance in isolates recovered from the poultry sector in HICs. Genes coding multi-and extensive-drug resistance and virulence factors are often co-carried with mcr on chromosome and plasmids in poultry isolates. Transmission of mcr to/among poultry strains in HICs is clonally unrestricted. Additionally, the contact with poultry birds, manure, meat/egg, farmer's wears/farm equipment, consumption of contaminated poultry meat/egg and associated products, and trade of poultry-related products continue to serve as transmission routes of MGHB in HICs. Indeed, the policymakers, especially those involved in antimicrobial resistance and agricultural and poultry sector stakeholders-clinical microbiologists, farmers, veterinarians, occupational health clinicians and related specialists, consumers, and the general public will find this current literature synthesis very useful.202134707919
1842140.9898Emergence of mcr-9.1 in Extended-Spectrum-β-Lactamase-Producing Clinical Enterobacteriaceae in Pretoria, South Africa: Global Evolutionary Phylogenomics, Resistome, and Mobilome. Extended-spectrum-β-lactamase (ESBL)-producing Enterobacteriaceae are critical-priority pathogens that cause substantial fatalities. With the emergence of mobile mcr genes mediating resistance to colistin in Enterobacteriaceae, clinicians are now left with few therapeutic options. Eleven clinical Enterobacteriaceae strains with resistance to cephems and/or colistin were genomically analyzed to determine their resistomes, mobilomes, and evolutionary relationships to global strains. The global phylogenomics of mcr genes and mcr-9.1-bearing genomes were further analyzed. Ten isolates were ESBL positive. The isolates were multidrug resistant and phylogenetically related to global clones but distant from local strains. Multiple resistance genes, including bla (CTX-M-15) bla (TEM-1), and mcr-9.1, were found in single isolates; ISEc9, IS19, and Tn3 transposons bracketed bla (CTX-M-15) and bla (TEM-1) Common plasmid types included IncF, IncH, and ColRNAI. mcr-9 was of close sequence identity to mcr-3, mcr-5, mcr-7, mcr-8, and mcr-10. Genomes bearing mcr-9.1 clustered into six main phyletic groups (A to F), with those of this study belonging to clade B. Enterobacter species and Salmonella species are the main hosts of mcr-9.1 globally, although diverse promiscuous plasmids disseminate mcr-9.1 across different bacterial species. Emergence of mcr-9.1 in ESBL-producing Enterobacteriaceae in South Africa is worrying, due to the restricted therapeutic options. Intensive One Health molecular surveillance might discover other mcr alleles and inform infection management and antibiotic choices.IMPORTANCE Colistin is currently the last-resort antibiotic for difficult-to-treat bacterial infections. However, colistin resistance genes that can move from bacteria to bacteria have emerged, threatening the safe treatment of many bacterial infections. One of these genes, mcr-9.1, has emerged in South Africa in bacteria that are multidrug resistant, further limiting treatment options for clinicians. In this work, we show that this new gene is disseminating worldwide through Enterobacter and Salmonella species through multiple plasmids. This worrying observation requires urgent action to prevent further escalation of this gene in South Africa and Africa.202032430406
1740150.9897MDR Escherichia coli carrying CTX-M-24 (IncF[F-:A1:B32]) and KPC-2 (IncX3/IncU) plasmids isolated from community-acquired urinary trainfection in Brazil. Acquired antibiotic resistance in bacteria has become an important worldwide challenge. Currently, several bacteria, including Escherichia coli, have multidrug resistance profiles. Genes such as bla CTX-M-24 and bla KPC-2 (carbapenemase) are widespread. This research letter reports about a genomic surveillance study where multidrug-resistant E. coli containing CTX-M-24(IncF [F-:A1:B32]) and KPC-2(IncX3/IncU) plasmids were obtained from community- acquired urinary tract infection in Brazil.202236228665
1553160.9897Current epidemiology, genetic evolution and clinical impact of extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae. The worldwide spread of extended-spectrum β-lactamase (ESBL)-producing bacteria, particularly Escherichia coli and Klebsiella pneumoniae, is a critical concern for the development of therapies against multidrug-resistant bacteria. Since the 2000s, detection rates of CTX-M types ESBL-producing E. coli in the community have been high, possibly contributing to their nosocomial detection. Various factors, such as environmental sources, food animals, and international travel, accelerate the global ESBL spread in the community. The dramatic dissemination of ESBLs in the community is associated with the relatively recent emergence of CTX-M-15-producing ST131 E. coli clones, which often carry many other antibiotic resistance genes (including quinolone). The usefulness of β-lactam/β-lactamase inhibitor, particularly, piperacillin/tazobactam, has been considered as a carbapenem-sparing regimen for ESBL infections, although the global trend of AmpC β-lactamase-producing bacteria should be monitored carefully. Careful therapeutic selection and continued surveillance for the detection of multidrug-resistant bacteria are required.201829626676
841170.9897blaOXA-48 carrying clonal colistin resistant-carbapenem resistant Klebsiella pneumoniae in neonate intensive care unit, India. Bacteria resistant to colistin, a last resort antibiotic reflect the pre-antibiotic era. In this study, colistin resistance carbapenem-resistant K. pneumoniae (COL(R)- CRKP) strains from neonate's intensive care unit were evaluated. Molecular analysis showed that all the four colistin resistant K. pneumoniae isolates were clonally related with strong biofilm formation ability and harbored bla(SHV-34) and bla(OXA-48) genes. Our result suggested the need of proper surveillance and adequate infection control to limiting the spread of these organisms.201627622347
1882180.9897Genomic Characterization of Multidrug-Resistant Pathogenic Enteric Bacteria from Healthy Children in Osun State, Nigeria. Antimicrobial resistance (AMR) is responsible for the spread and persistence of bacterial infections. Surveillance of AMR in healthy individuals is usually not considered, though these individuals serve as reservoirs for continuous disease transmission. Therefore, it is essential to conduct epidemiological surveillance of AMR in healthy individuals to fully understand the dynamics of AMR transmission in Nigeria. Thirteen multidrug-resistant Citrobacter spp., Enterobacter spp., Klebsiella pneumoniae, and Escherichia coli isolated from stool samples of healthy children were subjected to whole genome sequencing (WGS) using Illumina and Oxford nanopore sequencing platforms. A bioinformatics analysis revealed antimicrobial resistance genes such as the pmrB_Y358N gene responsible for colistin resistance detected in E. coli ST219, virulence genes such as senB, and ybtP&Q, and plasmids in the isolates sequenced. All isolates harbored more than three plasmid replicons of either the Col and/or Inc type. Plasmid reconstruction revealed an integrated tetA gene, a toxin production caa gene in two E. coli isolates, and a cusC gene in K. quasivariicola ST3879, which induces neonatal meningitis. The global spread of AMR pathogenic enteric bacteria is of concern, and surveillance should be extended to healthy individuals, especially children. WGS for epidemiological surveillance will improve the detection of AMR pathogens for management and control.202438543556
1526190.9896Carbapenem resistance determinants and their transmissibility among clinically isolated Enterobacterales in Lebanon. BACKGROUND: The occurrence of carbapenem-resistant bacterial infections has increased significantly over the years with Gram-negative bacteria exhibiting the broadest resistance range. In this study we aimed to investigate the genomic characteristics of clinical carbapenem-resistant Enterobacterales (CRE). METHODS: Seventeen representative multi-drug resistant (MDR) isolates from a hospital setting showing high level of resistance to carbapenems (ertapenem, meropenem and imipenem) were chosen for further characterization through whole-genome sequencing. Resistance mechanisms and transferability of plasmids carrying carbapenemase-encoding genes were also determined in silico and through conjugative mating assays. RESULTS: We detected 18 different β-lactamases, including four carbapenemases (bla(NDM-1), bla(NDM-5), bla(NDM-7), bla(OXA-48)) on plasmids with different Inc groups. The combined results from PBRT and in silico replicon typing revealed 20 different replicons linked to plasmids ranging in size between 80 and 200 kb. The most prevalent Inc groups were IncFIB(K) and IncM. OXA-48, detected on 76-kb IncM1 conjugable plasmid, was the most common carbapenemase. We also detected other conjugative plasmids with different carbapenemases confirming the role of horizontal gene transfer in the dissemination of antimicrobial resistance genes. CONCLUSION: Our findings verified the continuing spread of carbapenemases in Enterobacterales and revealed the types of mobile elements circulating in a hospital setting and contributing to the spread of resistance determinants. The occurrence and transmission of plasmids carrying carbapenemase-encoding genes call for strengthening active surveillance and prevention efforts to control antimicrobial resistance dissemination in healthcare settings.202337871361