One Health Spread of 16S Ribosomal RNA Methyltransferase-Harboring Gram-Negative Bacterial Genomes: An Overview of the Americas. - Related Documents




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185001.0000One Health Spread of 16S Ribosomal RNA Methyltransferase-Harboring Gram-Negative Bacterial Genomes: An Overview of the Americas. Aminoglycoside antimicrobials remain valuable therapeutic options, but their effectiveness has been threatened by the production of bacterial 16S ribosomal RNA methyltransferases (16S-RMTases). In this study, we evaluated the genomic epidemiology of 16S-RMTase genes among Gram-negative bacteria circulating in the American continent. A total of 4877 16S-RMTase sequences were identified mainly in Enterobacterales and nonfermenting Gram-negative bacilli isolated from humans, animals, foods, and the environment during 1931-2023. Most of the sequences identified were found in the United States, Brazil, Canada, and Mexico, and the prevalence of 16S-RMTase genes have increased in the last five years (2018-2022). The three species most frequently carrying 16S-RMTase genes were Acinetobacter baummannii, Klebsiella pneumoniae, and Escherichia coli. The armA gene was the most prevalent, but other 16S-RMTase genes (e.g., rmtB, rmtE, and rmtF) could be emerging backstage. More than 90% of 16S-RMTase sequences in the Americas were found in North American countries, and although the 16S-RMTase genes were less prevalent in Central and South American countries, these findings may be underestimations due to limited genomic data. Therefore, whole-genome sequence-based studies focusing on aminoglycoside resistance using a One Health approach in low- and middle-income countries should be encouraged.202337764972
184510.9996Plasmid-mediated colistin resistance in Latin America and Caribbean: A systematic review. A systematic review was performed in order to integrate and synthesize available information on mcr genes dissemination in Latin America. Four databases were searched for articles reporting plasmid-mediated colistin resistance between bacteria isolated from countries of Latin America and the Caribbean. Abstract books of scientific events realized in each region were also examined. After search and selection, 48 studies that included 18,705 isolates recovered between 2000 and 2018 were evaluated. The overall frequency of mcr genes in Latin America was 2.9% (550/18,705), with IncX4 plasmids shown to be the key vectors responsible for the dissemination of genes within the continent. Brazil, Bolivia and Argentina were the countries with the highest number of mcr-positive isolates, and only Colombia (mcr-5) and Brazil (mcr-3) presented mcr genes other than type 1. Escherichia coli, Klebsiella pneumoniae, and Salmonella enterica serovar Typhimurium were mainly found to carry the gene within the continent and these microorganisms showed high susceptibility to ertapenem, meropenem, piperacillin/tazobactam, fosfomycin and tigecycline. This review showed that the mcr gene is circulating in several countries of Latin America. Thus, it is important to encourage microbiological and molecular surveillance programs to avoid the spread of these genes within and outside the continent.201931336179
207920.9996Prevalence of 16S rRNA methylases in Gram-negative bacteria derived from companion animals and livestock in Japan. The emergence and spread of aminoglycoside-resistant bacteria are a public health concern. The acquisition of the genes encoding 16S rRNA methylases, such as armA, rmtA, and rmtB, confers high-level resistance to aminoglycosides. However, the prevalence has not been well investigated in Japanese veterinary fields. To determine the prevalence of 16S rRNA methylases in animals, we detected 16S rRNA methylases genes in Gram-negative bacteria from animals. Here, we report the isolation of rmtB amd armA from two of the 446 Escherichia coli (0.5%) and one of the 103 Klebsiella spp. isolates (1.0%) from companion animals, respectively. However, none of the isolations were observed from 2445 E. coli isolates derived from livestock in Japan. The prevalence of 16S rRNA methylases in animals, especially in companion animals, should be carefully monitored in Japanese veterinary fields to avoid the spreading of the genes.201931061295
191830.9995Molecular Detection of Class 1 Integron-Associated Gene Cassettes in KPC-2-Producing Klebsiella pneumoniae Clones by Whole-Genome Sequencing. The dissemination of antimicrobial resistance genes and the bacterium that harbor them have increasingly become a public concern, especially in low- and middle-income countries. The present study used whole-genome sequencing to analyze 10 KPC-2-producing Klebsiella pneumoniae isolates obtained from clinical specimens originated from Brazilian hospitals. The study documents a relevant "snapshot" of the presence of class 1 integrons in 90% of the strains presenting different gene cassettes (dfrA30, dfrA15, dfrA12, dfrA14, aadA1, aadA2, and aac(6')Iq), associated or not with transposons. Two strains presented nonclassical integron (lacking the normal 3'conserved segment). In general, most strains showed a complex resistome, characterizing them as highly resistant. Integrons, a genetically stable and efficient system, confer to bacteria as highly adaptive and low cost evolution potential to bacteria, even more serious when associated with high-risk clones, indicating an urgent need for control and prevention strategies to avoid the spread of resistance determinants in Brazil. Despite this, although the class 1 integron identified in the KPC-2-producing K. pneumoniae clones is important, our findings suggest that other elements probably have a greater impact on the spread of antimicrobial resistance, since many of these important genes were not related to this cassette.201931074706
184140.9995Plasmid-Determined Colistin Resistance in the North African Countries: A Systematic Review. We have conducted a systematic review to update available information on plasmid-mediated colistin resistance (mobilized colistin resistance [mcr]) genes in North African countries. We have searched the articles of PubMed, Scopus, and Web of Science databases reporting plasmid-mediated colistin resistance bacteria isolated in North African countries. After searching and selection, 30 studies that included 208 mcr-positive isolates were included. Different mcr-positive strains frequencies were recorded and ranged from 2% in clinical isolates to 12.3% in environmental samples. Escherichia coli was the predominant species recorded and these microorganisms showed high resistance to ciprofloxacin and cotrimoxazole. IncHI2 plasmids are probably the key vectors responsible for the dissemination of mcr genes in these countries. This review highlighted that the mcr-positive isolates are circulating in different ecological niches with different frequencies. Therefore, actions should be implemented to prevent the dissemination of the mcr genes within and outside of these countries, such as microbiological and molecular surveillance programs and restriction use of colistin in farming.202132522081
184850.9995Highly Colistin-resistant Aeromonas jandaei from a Human Blood Sample. Aeromonas species are Gram-negative rods known to cause infections such as gastroenteritis, bacteremia and wound infections. Colistin is one of few treatments for multidrug-resistant Gram-negative bacteria. However, colistin-resistant bacteria carrying the mobilized colistin resistance (mcr) gene are a threat in healthcare settings worldwide. In recent years, colistin-resistant Aeromonas species have been detected in environmental and clinical samples. We analyzed the genomic characteristics of one highly colistin-resistant A. jandaei isolated from a blood sample in Nepal, which harbored four novel mcr-like genes on its chromosome. Our study strongly suggests that A. jandaei is a reservoir of colistin-resistant genes. Inappropriate use of drugs in medicine and food production should be reduced and continued global surveillance for colistin-resistant bacteria is necessary.202338855938
253660.9995Global Burden of Colistin-Resistant Bacteria: Mobilized Colistin Resistance Genes Study (1980-2018). Colistin is considered to be an antimicrobial of last-resort for the treatment of multidrug-resistant Gram-negative bacterial infections. The recent global dissemination of mobilized colistin resistance (mcr) genes is an urgent public health threat. An accurate estimate of the global prevalence of mcr genes, their reservoirs and the potential pathways for human transmission are required to implement control and prevention strategies, yet such data are lacking. Publications from four English (PubMed, Scopus, the Cochrane Database of Systematic Reviews and Web of Science) and two Chinese (CNKI and WANFANG) databases published between 18 November 2015 and 30 December 2018 were identified. In this systematic review and meta-analysis, the prevalence of mcr genes in bacteria isolated from humans, animals, the environment and food products were investigated. A total of 974 publications were identified. 202 observational studies were included in the systematic review and 71 in the meta-analysis. mcr genes were reported from 47 countries across six continents and the overall average prevalence was 4.7% (0.1-9.3%). China reported the highest number of mcr-positive strains. Pathogenic Escherichia coli (54%), isolated from animals (52%) and harboring an IncI2 plasmid (34%) were the bacteria with highest prevalence of mcr genes. The estimated prevalence of mcr-1 pathogenic E. coli was higher in food-animals than in humans and food products, which suggests a role for foodborne transmission. This study provides a comprehensive assessment of prevalence of the mcr gene by source, organism, genotype and type of plasmid.201931623244
183270.9995Long-read sequencing reveals genomic diversity and associated plasmid movement of carbapenemase-producing bacteria in a UK hospital over 6 years. Healthcare-associated infections (HCAIs) affect the most vulnerable people in society and are increasingly difficult to treat in the face of mounting antimicrobial resistance (AMR). Routine surveillance represents an effective way of understanding the circulation and burden of bacterial resistance and transmission in hospital settings. Here, we used whole-genome sequencing (WGS) to retrospectively analyse carbapenemase-producing Gram-negative bacteria from a single hospital in the UK over 6 years (n=165). We found that the vast majority of isolates were either hospital-onset (HAI) or HCAI. Most carbapenemase-producing organisms were carriage isolates, with 71 % isolated from screening (rectal) swabs. Using WGS, we identified 15 species, the most common being Escherichia coli and Klebsiella pneumoniae. Only one significant clonal outbreak occurred during the study period and involved a sequence type (ST)78 K. pneumoniae carrying bla (NDM-1) on an IncFIB/IncHI1B plasmid. Contextualization with public data revealed little evidence of this ST outside of the study hospital, warranting ongoing surveillance. Carbapenemase genes were found on plasmids in 86 % of isolates, the most common types being bla (NDM)- and bla (OXA)-type alleles. Using long-read sequencing, we determined that approximately 30 % of isolates with carbapenemase genes on plasmids had acquired them via horizontal transmission. Overall, a national framework to collate more contextual genomic data, particularly for plasmids and resistant bacteria in the community, is needed to better understand how carbapenemase genes are transmitted in the UK.202337405394
163080.9995One Health study of mobile colistin resistance (mcr) in Salmonella enterica in Canada, 2017-2022. Colistin is a last-resort treatment for highly drug-resistant bacterial infections. Of 47,184 Salmonella isolates collected from 2017 to 2022 in Canada from human and animal/food sources, mobile colistin resistance (mcr) variants conferring colistin resistance were detected exclusively in humans (n = 15). These variants were mcr-1.1 (n = 7), mcr-3.1 (n = 5), mcr-3.2 (n = 2), and mcr-1.2 (n = 1). The most common mcr-containing serotypes were I 4,[5],12:i:- (n = 8) and Typhimurium (n = 3). The proportion of Salmonella carrying mcr genes remains low in Canada (0.03%). IMPORTANCE: Colistin can be used in combination with other drugs as salvage therapy for extensively drug-resistant infections. If mobile colistin resistance (mcr) becomes widely disseminated in Enterobacterales, colistin will no longer be an option for salvage therapy in otherwise untreatable infections. While colistin is not commonly used to treat human Salmonella infections, Salmonella represents an important reservoir of mcr genes that may be transmitted to other gram-negative bacteria. Our aim was to determine the occurrence of mcr genes in Salmonella isolates collected from humans, food animals, and retail meats in Canada.202540387317
196490.9995Antimicrobial resistance of pet-derived bacteria in China, 2000-2020. With the rapid growth of the pet industry in China, bacterial infectious diseases in pets have increased, highlighting the need to monitor antimicrobial resistance (AMR) in pet-derived bacteria to improve the diagnosis and treatment. Before the establishment of the China Antimicrobial Resistance Surveillance Network for Pets (CARPet) in 2021, a comprehensive analysis of such data in China was lacking. Our review of 38 point-prevalence surveys conducted between 2000 and 2020 revealed increasing trends in AMR among pet-derived Escherichia coli, Klebsiella pneumoniae, Staphylococcus spp., Enterococcus spp., and other bacterial pathogens in China. Notable resistance to β-lactams and fluoroquinolones, which are largely used in both pets and livestock animals, was observed. For example, resistance rates for ampicillin and ciprofloxacin in E. coli frequently exceeded 50.0%, with up to 41.3% of the isolates producing extended-spectrum β-lactamases. The emergence of carbapenem-resistant K. pneumoniae and E. coli, carrying bla(NDM) and bla(OXA) genes, highlighted the need for vigilant monitoring. The detection rate of SCCmec (Staphylococcal Cassette Chromosome mec), a genetic element associated with methicillin resistance, in Staphylococcus pseudintermedius isolated from pets in China was found to be over 40.0%. The resistance rate of E. faecalis to vancomycin was 2.1% (5/223) in East China, which was higher than the detection rate of human-derived vancomycin-resistant Enterococcus (0.1%, 12/11,215). Establishing the national AMR surveillance network CARPet was crucial, focusing on representative cities, diverse clinical samples, and including both commonly used antimicrobial agents in veterinary practice and critically important antimicrobial agents for human medicine, such as carbapenems, tigecycline, and vancomycin.202540135877
1573100.9995Genomic Analysis of a Pan-Resistant Isolate of Klebsiella pneumoniae, United States 2016. Antimicrobial resistance is a threat to public health globally and leads to an estimated 23,000 deaths annually in the United States alone. Here, we report the genomic characterization of an unusual Klebsiella pneumoniae, nonsusceptible to all 26 antibiotics tested, that was isolated from a U.S. PATIENT: The isolate harbored four known beta-lactamase genes, including plasmid-mediated bla(NDM-1) and bla(CMY-6), as well as chromosomal bla(CTX-M-15) and bla(SHV-28), which accounted for resistance to all beta-lactams tested. In addition, sequence analysis identified mechanisms that could explain all other reported nonsusceptibility results, including nonsusceptibility to colistin, tigecycline, and chloramphenicol. Two plasmids, IncA/C2 and IncFIB, were closely related to mobile elements described previously and isolated from Gram-negative bacteria from China, Nepal, India, the United States, and Kenya, suggesting possible origins of the isolate and plasmids. This is one of the first K. pneumoniae isolates in the United States to have been reported to the Centers for Disease Control and Prevention (CDC) as nonsusceptible to all drugs tested, including all beta-lactams, colistin, and tigecycline.IMPORTANCE Antimicrobial resistance is a major public health threat worldwide. Bacteria that are nonsusceptible or resistant to all antimicrobials available are of major concern to patients and the public because of lack of treatment options and potential for spread. A Klebsiella pneumoniae strain that was nonsusceptible to all tested antibiotics was isolated from a U.S. PATIENT: Mechanisms that could explain all observed phenotypic antimicrobial resistance phenotypes, including resistance to colistin and beta-lactams, were identified through whole-genome sequencing. The large variety of resistance determinants identified demonstrates the usefulness of whole-genome sequencing for detecting these genes in an outbreak response. Sequencing of isolates with rare and unusual phenotypes can provide information on how these extremely resistant isolates develop, including whether resistance is acquired on mobile elements or accumulated through chromosomal mutations. Moreover, this provides further insight into not only detecting these highly resistant organisms but also preventing their spread.201829615503
1844110.9995Polymyxin E-Resistant Gram-Negative Bacteria in Tunisia and Neighboring Countries: Are There Commonalities? The current global dissemination of polymyxin E resistance constitutes a real public health threat because of the restricted therapeutic options. This review provides a comprehensive assessment of the epidemiology of polymyxin E-resistant bacteria, with special reference to colistin-resistant Gram-negative bacteria in Tunisia and neighboring countries, based on available published data to January 2020. We aimed to determine their prevalence by species and origin, shedding light on the different genes involved and illustrating their genetic support, genetic environment, and geographic distribution. We found that colistin resistance varies considerably among countries. A majority of the research has focused on Algeria (13 of 32), followed by Tunisia (nine of 32), Egypt (nine of 32), and Libya (one of 32). All these reports showed that colistin-resistant Gram-negative bacteria were dramatically disseminated in these countries, as well as in African wildlife. Moreover, high prevalence of these isolates was recorded from various sources (humans, animals, food products, and natural environments). Colistin resistance was mainly reported among Enterobacteriaceae, particularly Klebsiella pneumoniae and Escherichia coli. It was associated with chromosomal mutations and plasmid-mediated genes (mcr). Four mcr variants (mcr1, mcr2, mcr3, and mcr8), mobilized by several plasmid types (IncHI2, IncP, IncFIB, and IncI2), were detected in these countries and were responsible for their rapid spread. Countrywide dissemination of high-risk clones was also observed, including E. coli ST10 and K. pneumoniae ST101 and ST11. Intensified efforts to raise awareness of antibiotic use and legalization thereon are required in order to monitor and minimize the spread of multidrug-resistant bacteria.202134815678
1833120.9995Cracking the Code: Unveiling the Diversity of Carbapenem-Resistant Klebsiella pneumoniae Clones in the Arabian Peninsula through Genomic Surveillance. The rise of antimicrobial resistance is a global challenge that requires a coordinated effort to address. In this study, we examined the genetic similarity of carbapenem-resistant Klebsiella pneumoniae (CRKP) in countries belonging to the Gulf Cooperation Council (GCC) to gain a better understanding of how these bacteria are spreading and evolving in the region. We used in silico genomic tools to investigate the occurrence and prevalence of different types of carbapenemases and their relationship to specific sequence types (STs) of CRKP commonly found in the region. We analyzed 720 publicly available genomes of multi-drug resistant K. pneumoniae isolates collected from six GCC countries between 2011 and 2020. Our findings showed that ST-14 and ST-231 were the most common STs, and 51.7% of the isolates carried bla(OXA-48-like) genes. Additionally, we identified rare carbapenemase genes in a small number of isolates. We observed a clonal outbreak of ST-231 in Oman, and four Saudi isolates were found to have colistin resistance genes. Our study offers a comprehensive overview of the genetic diversity and resistance mechanisms of CRKP isolates in the GCC region that could aid in developing targeted interventions to combat this pressing global issue.202337508177
2260130.9995Current status of resistance to antibiotics in the Democratic Republic of the Congo: A review. A review of literature was conducted to assess the prevalence and mechanisms of antibiotic resistance to date, mainly to β-lactam antibiotics, cephalosporins, carbapenems, colistin, and tigecycline in the Democratic Republic of the Congo (DRC). English and French publications were listed and analysed using PubMed/Medline, Google Scholar, and African Journals database between 1 January 1990 and 31 December 2019. For the 30 published articles found: (1) bacterial resistance to antibiotics concerned both Gram-negative and Gram-positive bacteria; (2) multidrug resistance prevalence was the same in half of Streptococcus pneumoniae isolates; (3) a worrying prevalence of methicillin-resistant Staphylococcus aureus (MRSA) was noted, which is associated with co-resistance to several other antibiotics; and (4) resistance to third-generation cephalosporins was very high in Enterobacteriaceae, mainly because of bla(CTX-M-1) group and bla(SHV) genes. Data on carbapenem and colistin resistance were not available in DRC until recently. Further work is required to set up a surveillance system for antibiotic resistance in DRC.202032688007
1574140.9995Plethora of Resistance Genes in Carbapenem-Resistant Gram-Negative Bacteria in Greece: No End to a Continuous Genetic Evolution. Carbapenem-resistant Gram-negative bacteria are a public health threat that requires urgent action. The fact that these pathogens commonly also harbor resistance mechanisms for several other antimicrobial classes further reduces patient treatment options. The present study aimed to provide information regarding the multidrug resistance genetic background of carbapenem-resistant Gram-negative bacteria in Central Greece. Strains from a tertiary care hospital, collected during routine practice, were characterized using a DNA microarray-based assay. Various different resistance determinants for carbapenems, other beta-lactams, aminoglycosides, quinolones, trimethoprim, sulfonamides and macrolides were detected among isolates of the same sequence type. Eighteen different multidrug resistance genomic profiles were identified among the twenty-four K. pneumoniae ST258, seven different profiles among the eight K. pneumoniae ST11, four profiles among the six A. baumannii ST409 and two among the three K. oxytoca. This report describes the multidrug resistance genomic background of carbapenem-resistant Gram-negative bacteria from a tertiary care hospital in Central Greece, providing evidence of their continuous genetic evolution.202235056608
1678150.9995Molecular characterization and descriptive analysis of carbapenemase-producing Gram-negative rod infections in Bogota, Colombia. In this study, the genetic differences and clinical impact of the carbapenemase-encoding genes among the community and healthcare-acquired infections were assessed. This retrospective, multicenter cohort study was conducted in Colombia and included patients infected with carbapenem-resistant Gram-negative rods between 2017 and 2021. Carbapenem resistance was identified by Vitek, and carbapenemase-encoding genes were identified by whole-genome sequencing (WGS) to classify the alleles and sequence types (STs). Descriptive statistics were used to determine the association of any pathogen or gene with clinical outcomes. A total of 248 patients were included, of which only 0.8% (2/248) had community-acquired infections. Regarding the identified bacteria, the most prevalent pathogens were Pseudomonas aeruginosa and Klebsiella pneumoniae. In the WGS analysis, 228 isolates passed all the quality criteria and were analyzed. The principal carbapenemase-encoding gene was blaKPC, specifically blaKPC-2 [38.6% (88/228)] and blaKPC-3 [36.4% (83/228)]. These were frequently detected in co-concurrence with blaVIM-2 and blaNDM-1 in healthcare-acquired infections. Notably, the only identified allele among community-acquired infections was blaKPC-3 [50.0% (1/2)]. In reference to the STs, 78 were identified, of which Pseudomonas aeruginosa ST111 was mainly related to blaKPC-3. Klebsiella pneumoniae ST512, ST258, ST14, and ST1082 were exclusively associated with blaKPC-3. Finally, no particular carbapenemase-encoding gene was associated with worse clinical outcomes. The most identified genes in carbapenemase-producing Gram-negative rods were blaKPC-2 and blaKPC-3, both related to gene co-occurrence and diverse STs in the healthcare environment. Patients had several systemic complications and poor clinical outcomes that were not associated with a particular gene.IMPORTANCEAntimicrobial resistance is a pandemic and a worldwide public health problem, especially carbapenem resistance in low- and middle-income countries. Limited data regarding the molecular characteristics and clinical outcomes of patients infected with these bacteria are available. Thus, our study described the carbapenemase-encoding genes among community- and healthcare-acquired infections. Notably, the co-occurrence of carbapenemase-encoding genes was frequently identified. We also found 78 distinct sequence types, of which two were novel Pseudomonas aeruginosa, which could represent challenges in treating these infections. Our study shows that in low and middle-income countries, such as Colombia, the burden of carbapenem resistance in Gram-negative rods is a concern for public health, and regardless of the allele, these infections are associated with poor clinical outcomes. Thus, studies assessing local epidemiology, prevention strategies (including trials), and underpinning genetic mechanisms are urgently needed, especially in low and middle-income countries.202438629835
1843160.9995Chromosome-Based blaOXA-48-Like Variants in Shewanella Species Isolates from Food-Producing Animals, Fish, and the Aquatic Environment. Carbapenems are considered last-resort antibiotics in health care. Increasing reports of carbapenemase-producing bacteria in food-producing animals and in the environment indicate the importance of this phenomenon in public health. Surveillance for carbapenemase genes and carbapenemase-producing bacteria in Dutch food-producing animals, environmental freshwater, and imported ornamental fish revealed several chromosome-based bla(OXA-48)-like variants in Shewanella spp., including two new alleles, bla(OXA-514) and bla(OXA-515) Carbapenemase genes were not associated with mobile genetic elements or Enterobacteriaceae.201727855066
2531170.9995Carbapenemase producing bacteria in the food supply escaping detection. Carbapenem antimicrobials are critically important to human health and they are often the only remaining effective antibiotics for treating serious infections. Resistance to these drugs mediated by acquired carbapenemase enzymes is increasingly encountered in gram-negative bacteria and is considered a public health emergency. Animal origin food products are recognized as a potential source of resistant organisms, although carbapenem resistance has only recently been reported. In western countries there are active resistance surveillance programs targeting food animals and retail meat products. These programs primarily target beef, pork and poultry and focus exclusively on E. coli, Salmonella, Campylobacter spp. and Enterococcus spp. This global surveillance strategy does not capture the diversity of foods available nor does it address the presence of resistance gene-bearing mobile genetic elements in non-pathogenic bacterial taxa. To address this gap, a total of 121 seafood products originating in Asia purchased from retail groceries in Canada were tested. Samples were processed using a taxa-independent method for the selective isolation of carbapenem resistant organisms. Isolates were characterized by phenotypic antimicrobial susceptibility testing, PCR and DNA sequencing. Carbapenemase producing bacteria, all blaOXA-48, were isolated from 4 (3.3%) of the samples tested. Positive samples originated from China (n=2) and Korea (n=2) and included squid, sea squirt, clams and seafood medley. Carbapenemase producing organisms found include Pseudomonas, Stenotrophomonas and Myroides species. These findings suggest that non-pathogenic bacteria, excluded from resistance surveillance programs, in niche market meats may serve as a reservoir of carbapenemase genes in the food supply.201525966303
1689180.9995Occurrence and Characteristics of Mcrs among Gram-Negative Bacteria Causing Bloodstream Infections of Infant Inpatients between 2006 and 2019 in China. The aim of this study was to determine the occurrence of mobilized colistin resistance (mcr) genes in Gram-negative bacteria causing bloodstream infections of child inpatients in China. Bacteria were collected between 2006 and 2019 in a maternal and child health hospital, and mcr genes were screened by PCR. Five of 252 isolates were mcr-positive, including one mcr-1-positive colistin-resistant Escherichia coli isolate, two mcr-9-positive colistin-susceptible Salmonella enterica isolates, and two mcr-9-positive colistin-susceptible Enterobacter hormaechei isolates. These were obtained from two neonate and three infant patients admitted between 2009 and 2018. The E. coli isolate was obtained from a neonate aged 20 min, suggestive of a possible mother-to-neonate transmission. The five mcr-positive isolates were multidrug resistant, and two S. enterica and one E. hormaechei isolate showed a hypervirulent phenotype compared to a hypervirulent Klebsiella pneumoniae type strain in a Galleria mellonella infection model. The mcr-1 gene was carried by an IncX4-type pA1-like epidemic plasmid, and the mcr-9 gene was detected on IncHI2/2A-type novel plasmids co-carrying multiple resistance genes. The four IncHI2/2A-type plasmids shared a backbone and a high similarity (≥77% coverage and ≥ 90% nucleotide identity), suggesting that they were derived from a common ancestor with cross-species transmission and have circulated locally over a long period. The conjugation assay showed that the mcr-1-encoding plasmid and one mcr-9-encoding plasmid were self-transmissible to E. coli with high conjugation frequencies. Our findings demonstrate that mcr genes have disseminated in the community and/or hospitals, mediated by epidemic/endemic plasmids over a long period. The study shows that continuous monitoring of mcr genes is imperative for understanding and tackling their dissemination. IMPORTANCE Antimicrobial resistance, especially the spread of carbapenemase-producing Enterobacteriaceae (CPE), represents one of the largest challenges to One Health coverage of environmental, animal, and human sectors. Colistin is one of the last-line antibiotics for clinical treatment of CPE. However, the emergence of the mobilized colistin resistance (mcr) gene largely threatens the usage of colistin in the clinical setting. In this study, we investigated the existence of mcr genes in 252 Gram-negative bacteria collected between 2006 and 2019 which caused bloodstream infections of child inpatients in China. We found a high prevalence of mcr carriage among children inpatients in the absence of professional exposure, and mcr might have widely disseminated in the community via different routes. This study emphasizes the importance of rational use of colistin in the One Health frame, and highlights both the urgent need for understanding the prevalence and dissemination of mcr genes in different populations and the importance of effective measures to control their spread.202235138190
2254190.9995Hospitalized Pets as a Source of Carbapenem-Resistance. The massive and irrational use of antibiotics in livestock productions has fostered the occurrence and spread of resistance to "old class antimicrobials." To cope with that phenomenon, some regulations have been already enforced in the member states of the European Union. However, a role of livestock animals in the relatively recent alerts on the rapid worldwide increase of resistance to last-choice antimicrobials as carbapenems is very unlikely. Conversely, these antimicrobials are increasingly administered in veterinary hospitals whose role in spreading bacteria or mobile genetic elements has not adequately been addressed so far. A cross-sectional study was carried out on 105 hospitalized and 100 non-hospitalized pets with the aim of measuring the prevalence of carbapenem-resistant Gram-negative bacteria (GNB) colonizing dogs and cats, either hospitalized or not hospitalized and estimating the relative odds. Stool samples were inoculated on MacConkey agar plates containing 1 mg/L imipenem which were then incubated aerobically at 37°C ± 1 for 48 h. Isolated bacteria were identified first by Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and were confirmed by 16S rRNA sequencing. The genetic basis of resistance was investigated using PCR methods, gene or whole genome sequencing (WGS). The prevalence of pets harboring carbapenem-resistant bacteria was 11.4 and 1.0% in hospitalized and not-hospitalized animals, respectively, with an odds ratio of 12.8 (p < 0.01). One pet carried two diverse isolates. Overall, 14 gram-negative non-fermenting bacteria, specifically, one Acinetobacter radioresistens, five Acinetobacter baumannii, six Pseudomonas aeruginosa and two Stenotrophomonas maltophilia were isolated. The Acinetobacter species carried acquired carbapenemases genes encoded by bla (NDM-1) and bla (OXA-23). In contrast, Pseudomonas phenotypic resistance was associated with the presence of mutations in the oprD gene. Notably, inherent carbapenem-resistant isolates of S. maltophilia were also resistant to the first-line recommended chemotherapeutic trimethoprim/sulfamethoxazole. This study estimates the risk of colonization by carbapenem-resistant non-fermenting GNB in pets hospitalized in veterinary tertiary care centers and highlights their potential role in spreading resistance genes among the animal and human community. Public health authorities should consider extending surveillance systems and putting the release of critical antibiotics under more strict control in order to manage the infection/colonization of pets in veterinary settings.201830574124