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The dramatic increase in the prevalence and clinical impact of infections caused by bacteria producing carbapenemases is a global health concern. Carbapenemase production is especially problematic when encountered in members of the family Enterobacteriaceae. Due to their ability to readily spread and colonize patients in healthcare environments, preventing the transmission of these organisms is a major public health initiative and coordinated international effort are needed. Central to the treatment and control of carbapenemase-producing organisms (CPOs) are phenotypic (growth-/biochemical-dependent) and nucleic acid-based carbapenemase detection tests that identify carbapenemase activity directly or their associated molecular determinants. Importantly, bacterial isolates harboring carbapenemases are often resistant to multiple antibiotic classes, resulting in limited therapy options. Emerging agents, novel antibiotic combinations and treatment regimens offer promise for management of these infections. This review highlights our current understanding of CPOs with emphasis on their epidemiology, detection, treatment, and control.

To elucidate the zoonotic potential of carbapenemase-producing carbapenem-resistant Enterobacterales (CP-CRE) in US companion animals (i.e., dogs and cats), we queried the National Center for Biotechnology Pathogen Detection database to identify One Health clusters containing CP-CRE isolates from companion animals and humans. The 11 One Health clusters we found included most (69% [169/246]) publicly available CP-CRE sequences from US companion animals and were from 8 internationally disseminated, high-risk sequence types from 3 bacterial species (Escherichia coli, Klebsiella pneumoniae, and Enterobacter cloacae). All clustered isolates had New Delhi metallo-β-lactamase-family carbapenemases, and most (92%) carried the bla allele. The One Health clusters included several closely related subclusters with geographically linked isolates from both humans and companion animals. Those results suggest that CP-CRE is an emerging One Health issue and that direct or indirect transmission of CP-CRE is occurring between humans and companion animals in the United States.

Background Antimicrobial resistance (AMR) represents a pressing global health challenge, influencing human, animal, and environmental health within the interconnected One Health framework. ESBL- and carbapenemase-producing Enterobacteriaceae constitute a major global public health threat. In Lebanon, their presence is particularly concerning, as they are detected across diverse environments, including hospitals, surface water, wastewater, poultry, and livestock. Despite close contact between pets and their owners, the role of companion animals, particularly cats, in spreading AMR determinants has been overlooked. Based on the One Health approach, the study addresses this gap by presenting the first Whole Genome Sequencing (WGS)-based report of multidrug-resistant (MDR) Enterobacteriaceae isolated from cats in Lebanon. Results A total of 13 ESBL-producing Enterobacteriaceae, including 11 Escherichia coli and two Enterobacter hormaechei , were isolated from fecal samples of domestic and stray cats. The isolates were among those classified as World Health Organization (WHO) Critical Priority Pathogens, highlighting their public health importance. Whole-genome characterization and antimicrobial susceptibility testing revealed alarmingly high resistance rates to multiple antibiotics, including carbapenems and tigecycline. In silico resistome analysis identified over 37 diverse resistance determinants, including bla CTX-M-15 , bla TEM-1B , bla OXA-1 , and bla NDM-5. Plasmid analysis uncovered 17 distinct Inc groups, markedly IncU, IncFII, and IncFIB. Phylogenetic analysis demonstrated high genetic similarity among isolates of the same sequence type (ST), irrespective of their isolation source or geographical location. E. coli ST167, a high-risk clone, carried the bla NDM-5 gene, associated with carbapenem resistance, on an IS 26 -flanked composite transposon. It’s noteworthy that bla CTX-M-15 was chromosomally encoded in one E. coli isolate within a rare genetic cassette, co-localized with qnrS1 , Tn 2 , IS Ecp1 , and IS Kpn19 . Conclusions This study provides the first whole-genome sequencing-based evidence of multidrug-resistant ESBL- and carbapenemase-producing Enterobacteriaceae in cats in Lebanon, highlighting their overlooked role as reservoirs of antimicrobial resistance. The detection of high-risk clones, along with a diverse resistome and mobilome linked to multidrug resistance, reinforces the urgent need for integrated national AMR surveillance within a One Health framework.

Background Infections caused by carbapenemase-producing Enterobacteriaceae (CPE) have continually grown as a global public health threat, with significant mortality rates observed across the world. We examined the clinical data from patients with CPE infections and their outcomes, concentrating on Klebsiella pneumoniae isolates. We analysed the clinical information, performed antimicrobial susceptibility testing, and conducted molecular epidemiological and genomic analyses on the isolates to identify patterns in the data. Methods The clinical characteristics of 33 hospitalised patients with confirmed CPE, including patient-related factors associated with the development of CPE infections, were examined. Patients were divided according to whether they were “colonised” or “infected” with CPE and by the timing and frequency of their rectal swab collections, from which 45 swabs were randomly selected for analysis. CPE isolates were purified, and antimicrobial susceptibility tests performed. Whole genome sequences of these isolates were determined and analysed to compute bacterial multilocus sequence types and plasmid replicon types, infer phylogenetic relationships, and identify antimicrobial resistance and virulence genes. Results Altogether, 88.9% (40/45) of the CPE isolates were K. pneumoniae . The most abundant carbapenemase gene family in the K. pneumoniae isolates (33/39) was bla OXA-232 , with bla NDM-1 additionally identified in 19 of them. All CPE isolates carrying either bla OXA-232 or bla NDM-1 were resistant to meropenem, but only 40 from 45 were susceptible to colistin. Among the CPE-infected patients ( n  = 18) and CPE-colonised patients who developed CPE infections during the study ( n  = 3), all but one received standard colistin-based combination therapy. Phylogenetic analysis revealed the polyclonal spread of carbapenemase-producing K. pneumoniae (CPKP) within the patient population, with the following two major subclades identified: ST16 ( n  = 15) and ST231 ( n  = 14). CPKP-ST231 had the highest virulence score of 4 and was associated with primary bacteraemia. The siderophores yersiniabactin and aerobactin, considered to be important virulence factors, were only identified in the CPKP-ST231 genomes. Conclusions This study has revealed the genomic features of colonising CPE isolates, focusing on antimicrobial resistance and virulence determinants. This type of multi-layered analysis can be further exploited in Thailand and elsewhere to modify the regimes used for empirical antibiotic treatment and improve the management strategies for CPE infections in hospitalised patients.

We conducted surveillance for carbapenem-resistant Enterobacterales (CRE) during 2016–2020 at 10 US sites and extended-spectrum β-lactamase–producing Enterobacterales (ESBL-E) during 2019–2020 at 6 US sites. Among 159 CRE cases in children (median age 5 years), CRE was isolated from urine for 131 (82.4%) and blood from 20 (12.6%). Annual CRE incidence rate (cases/100,000 population) was 0.47–0.87. Among 207 ESBL-E cases in children (median age 6 years), ESBL-E was isolated from urine of 196 (94.7%) and blood of 8 (3.9%). Annual ESBL-E incidence rate was 26.5 in 2019 and 19.63 in 2020. CRE and ESBL-E rates were >2-fold higher among infants than other age groups. Most CRE and ESBL-E cases were healthcare-associated community-onset (68 [43.0%] for CRE vs. 40 [23.7%] for ESBL-E) or community-associated (43 [27.2%] for CRE vs. 109 [64.5%] for ESBL-E). Programs to detect, prevent, and treat multidrug-resistant infections must include pediatric populations (particularly the youngest) and outpatient settings.

Plasmid-mediated transmission can account for half of carbapenem-producing Enterobacterales (CPE) dissemination, underscoring the need to identify genetic determinants of plasmid persistence in the hospital setting. From 1,088 CPE isolates detected through nationwide surveillance in Singapore over five years, 1,115 closed carbapenemase-producing plasmids were identified and clustered, of which 92.5% ( n  = 1031) were grouped into 48 plasmid clusters (PCs). The most common plasmid genotypes were PC1 and PC2. Of 389 isolates carrying bla KPC-2 -positive PC1 plasmids and 283 isolates carrying bla NDM-1 -positive PC2 plasmids, 236 (60.7%) and 168 (59.4%) putatively acquired the carbapenemase gene via plasmid-mediated horizontal transmission, whereas 153 (39.3%) and 115 (40.6%) putatively acquired the carbapenemase gene via clonal lineage-dependent vertical transmission, respectively. Less abundant plasmids showed distinct inserted genomic regions encoding genes related to heavy metal and formaldehyde detoxification not found in predominant plasmids. Our data suggest that PC1 and PC2 genotypes are better adapted for stable propagation of bla KPC-2 and bla NDM-1 , respectively, during inter-patient clonal spread and across multiple species (and sequence types) compared to other genetic settings. We propose that a crucial factor enabling evolutionarily successful carbapenemase plasmid genotypes to achieve hyperendemicity in the population is the maintenance of conserved genomes, thus minimizing fitness costs to their hosts. Plasmid-mediated transmission plays a significant role in the spread of carbapenem-resistant Enterobacterales. Here, analyzing 1,115 carbapenemase-producing plasmids from Singapore, the authors suggest that maintenance of conserved genomes adapted for stable propagation across multiple species, enables evolutionarily successful carbapenemase plasmid genotypes to achieve hyperendemicity in the population.

Carbapenem-resistant Enterobacterales are disseminated worldwide and associated with infections with high rates of morbidity and mortality. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a useful tool for identification of pathogens directly from blood cultures in clinical microbiology laboratories. Furthermore, it has been applied for the detection of carbapenemase production, by evaluating carbapenem hydrolysis. To determine meropenem hydrolysis to detect carbapenemase production directly from positive blood cultures, using logRQ to establish a quantitative measure of hydrolysis. We evaluated 100 Enterobacterales from positive blood cultures, with 81 carrying a carbapenemase gene (blaKPC, blaGES, blaNDM-1, blaIMP, blaVIM, and blaOXA-48-like), as determined by real-time multiplex polymerase chain reaction with high-resolution melting (HRM-qPCR). Bacterial proteins extracted from positive blood culture bottles were incubated in a meropenem solution (2-4 hours) followed by centrifugation for MALDI-TOF MS analysis. The intensity of peaks of the hydrolyzed and nonhydrolyzed forms were used to calculate the logRQ value. Overall, sensitivity was 86.8% and specificity, 89.5%. Of note, sensitivity varied depending on enzyme type. For blaKPC-positive isolates, sensitivity was 97.9%, while it reduced significantly for blaNDM-1 and blaOXA-48-like isolates: 62.5% (10 of 16) and 66.7% (6 of 9), respectively. Indeed, logRQ was higher in blaKPC-positive isolates (0.37-1.97) than in blaNDM-1 (-1.37 to 0.83) and blaOXA-48-like isolates (-1.08 to 1.79). This is an inexpensive and rapid test to identify carbapenemase activity directly from blood culture bottles, which contributes to early adequate antimicrobial therapy and implementation of infection control measures.

Background Infections resulting from multidrug-resistant Enterobacterales (MDR-E) pose a growing global threat, presenting challenges in treatment and contributing significantly to morbidity and mortality rates. The main objective of this study was to characterize phenotypically and genetically extended-spectrum β-lactamase- and carbapenemase- producing Enterobacterales (ESBLE and CPE respectively) isolated from clinical samples in the West Bank, Palestine. Methods A cross sectional study was conducted in October 2023 on clinical bacterial isolates collected from five governmental hospitals in the West Bank, Palestine. The isolates obtained from the microbiology laboratories of the participating hospitals, underwent identification and antibiotic susceptibility testing (AST) using the VITEK ® 2 Compact system. ESBL production was determined by the Vitek2 Compact system. A modified carbapenem inactivation method (mCIM) was employed to identify carbapenemase-producing Enterobacterales (CPE). Resistance genes were detected by real-time PCR. Results Out of the total 1380 collected isolates, we randomly selected 600 isolates for analysis. Our analysis indicated that 287 (47.83%) were extended-spectrum beta-lactamase producers (ESBLE), and 102 (17%) as carbapenem-resistant Enterobacterales (CRE) isolates. A total of 424 isolates (70.67%) were identified as multidrug-resistant Enterobacterales (MDRE). The most prevalent ESBL species were K. pneumoniae ( n  = 124; 43.2%), E. coli ( n  = 119; 41.5%) and E. cloacae ( n  = 31; 10.8%). Among the CRE isolates, 85 (83.33%) were carbapenemase-producing Enterobacterales (CPE). The most frequent CRE species were K. pneumoniae ( n  = 63; 61.7%), E. coli ( n  = 25; 24.5%) and E. cloacae ( n  = 13; 12.8%). Additionally, 47 (7.83%) isolates exhibited resistance to colistin (CT), with 38 (37.62%) being CT-resistant CRE and 9 (3.14%) being CT-resistant ESBLE while sensitive to carbapenems. We noticed that 11 isolates (6 Klebsiella pneumoniae and 5 Enterobacter cloacae complex) demonstrated sensitivity to carbapenems by phenotype but carried silent CPE genes (1 bla OXA48, and 6 bla NDM, 4 bla OXA48, bla NDM). ESBL-producing Enterobacterales strains exhibited varied resistance patterns across different antibiotic classes. E. coli isolates showed notable 48% resistance to trimethoprim/sulfamethoxazole. K. pneumoniae isolates displayed a significant resistance to trimethoprim/sulfamethoxazole, nitrofurantoin, and fosfomycin (54%, 90%, and 70% respectively). E. cloacae isolates showed complete resistance to nitrofurantoin and fosfomycin. P. mirabilis isolates exhibited high resistance against fluoroquinolones (83%), and complete resistance to trimethoprim/sulfamethoxazole, nitrofurantoin and fosfomycin. Conclusion This study showed the high burden of the ESBLE and CRE among the samples collected from the participating hospitals. The most common species were K. pneumoniae and E. coli . There was a high prevalence of bla CTXm. Adopting both conventional and molecular techniques is essential for better surveillance of the emergence and spread of antimicrobial-resistant Enterobacterales infections in Palestine.

The emergence and spread of mobilized colistin resistance ( mcr ) genes have triggered extensive concerns worldwide. Here, we characterized the global distribution of mcr-9 , a newly-identified variant of mcr , by assembling the data set of mcr-9 -positive isolates from GenBank database and the literature available. Genetic features of all the mcr-9 -harboring plasmids were determined by bioinformatic analysis. We showed that mcr-9 is globally distributed in 21 countries across six continents, with a wide dissemination among various species of Enterobacteriaceae strains from human, animal, food and environment. IncHI2-ST1 plasmids were found to be the predominant replicon type carrying mcr-9 . Comparative genomics highlighted that IncHI2-type plasmids may also serve as a critical reservoir of mcr-9 , from which different types of circulating plasmids acquired the mcr-9 . Results revealed that the rcnR-rcnA-pcoE-pcoS-IS 903 -mcr-9 - wbuC structure was consistent in most mcr-9 cassettes, suggesting a relatively unitary model involved in the mobilization of mcr-9 . It is most likely that the spread of mcr-9 was mainly attributed to the conjugation and recombination events of mcr-9 -carrying plasmids. In summary, our results provide a comprehensive picture of the distribution and genetic environment of mcr-9 , and demonstrate the central roles played by IncHI2 plasmids in the worldwide dissemination of mcr-9 .

Introduction: Antimicrobial resistance is a major and growing concern worldwide. The study aimed to describe the occurrence and characterize the antimicrobial resistance profile of carbapenemase-producing Enterobacterales (CPE) isolated from clinical specimens at a private healthcare center in Lima, Peru, between January 2018 and December 2019. Methodology: A total of 59 bacterial isolates were identified as CPE using the modified carbapenem inactivation method. Bacterial identification and antimicrobial susceptibility testing were performed using the Vitek 2 system, and colistin susceptibility was determined using the compact antimicrobial susceptibility panel. Five carbapenemase encoding genes, including blaNDM, blaIMP, blaVIM, blaOXA-48, and blaKPC, were screened using PCR and lateral flow assay. Also, carbapenemases were screened using the boronic acid- and EDTA-based disk synergy methods. The dynamics of CPE were described every month. Results: Carbapenemase-producing Klebsiella pneumoniae was the most prevalent agent (83.1%), followed by Providencia spp. (6.8%), Escherichia coli (5.1%), Enterobacter cloacae (3.4%), and Citrobacter freundii (1.6%). The isolation of blaNDM-carrying CPE was frequent and increased during the second half of 2019, while blaKPC carriers were detected in the second half of 2018. One CPE carrying blaOXA-48 was detected in June 2019. No other carbapenemase-encoding genes were detected. Conclusions: This report is among the first to document CPE in private health care institutions in Lima, Peru. Results suggest that the emergence and spread of carbapenemases are becoming a latent and growing threat in private healthcare settings.