Extended-spectrum Cephalosporin Resistance Research Articles

Global transmission of extended-spectrum cephalosporin resistance in Escherichia coli driven by epidemic plasmids

Extended-spectrum cephalosporins (ESCs) are third and fourth generation cephalosporin antimicrobials used in humans and animals to treat infections due to multidrug-resistant (MDR) bacteria. Resistance to ESCs (ESC-R) in Enterobacterales is predominantly due to the production of extended-spectrum β-lactamases (ESBLs) and plasmid-mediated AmpC β-lactamases (AmpCs). The dynamics of ESBLs and AmpCs are changing across countries and host species, the result of global transmission of ESC-R genes. Plasmids are known to play a key role in this dissemination, but the relative importance of different types of plasmids is not fully understood. In this study, Escherichia coli with the major ESC-R genes blaCTX-M-1, blaCTX-M-15, blaCTX-M-14 (ESBLs) and blaCMY-2 (AmpC), were selected from diverse host species and other sources across Canada, France and Germany, collected between 2003 and 2017. To examine in detail the vehicles of transmission of the ESC-R genes, long- and short-read sequences were generated to obtain complete contiguous chromosome and plasmid sequences (n=192 ESC-R E.coli). The types, gene composition and genetic relatedness of these plasmids were investigated, along with association with isolate year, source and geographical origin, and put in context with publicly available plasmid sequences. We identified five epidemic resistance plasmid subtypes with distinct genetic properties that are associated with the global dissemination of ESC-R genes across multiple E.coli lineages and host species. The IncI1 pST3 blaCTX-M-1 plasmid subtype was found in more diverse sources than the other main plasmid subtypes, whereas IncI1 pST12 blaCMY-2 was more frequent in Canadian and German human and chicken isolates. Clonal expansion also contributed to the dissemination of the IncI1 pST12 blaCMY-2 plasmid in ST131 and ST117 E.coli harbouring this plasmid. The IncI1 pST2 blaCMY-2 subtype was predominant in isolates from humans in France, while the IncF F31:A4:B1 blaCTX-M-15 and F2:A-:B- blaCTX-M-14 plasmid subtypes were frequent in human and cattle isolates across multiple countries. Beyond their epidemic nature with respect to ESC-R genes, in our collection almost all IncI1 pST3 blaCTX-M-1 and IncF F31:A4:B1 blaCTX-M-15 epidemic plasmids also carried multiple antimicrobial resistance (AMR) genes conferring resistance to other antimicrobial classes. Finally, we found genetic signatures in the regions surrounding specific ESC-R genes, identifying the predominant mechanisms of ESC-R gene movement, and using publicly available databases, we identified these epidemic plasmids from widespread bacterial species, host species, countries and continents. We provide evidence that epidemic resistance plasmid subtypes contribute to the global dissemination of ESC-R genes, and in addition, some of these epidemic plasmids confer resistance to multiple other antimicrobial classes. The success of these plasmids suggests that they may have a fitness advantage over other plasmid types and subtypes. Identification and understanding of the vehicles of AMR transmission are crucial to develop and target strategies and interventions to reduce the spread of AMR. This project was supported by the Joint Programming Initiative on Antimicrobial Resistance (JPIAMR), through the Medical Research Council (MRC, MR/R000948/1), the Canadian Institutes of Health Research (CFC-150770), and the Genomics Research and Development Initiative (Government of Canada), the German Federal Ministry of Education and Research (BMBF) grant no. 01KI1709, the French Agency for food environmental and occupational health & safety (Anses), and the French National Reference Center (CNR) for antimicrobial resistance. Support was also provided by the Biotechnology and Biological Sciences Research Council (BBSRC) through the BBSRC Institute Strategic Programme Microbes in the Food ChainBB/R012504/1 and its constituent project BBS/E/F/000PR10348 (Theme 1, Epidemiology and Evolution of Pathogens in the Food Chain).

Carbapenem use in extended-spectrum cephalosporin-resistant Enterobacterales infections in US hospitals and influence of IDSA guidance: a retrospective cohort study

Disparate and rapidly changing practice recommendations from major professional infectious diseases societies for managing non-severe infections caused by extended-spectrum β-lactamase-producing Enterobacterales might hamper carbapenem stewardship. We aimed to understand the real-world management of extended-spectrum cephalosporin-resistant (ECR) Enterobacterales infections in US hospitals and factors influencing preference for carbapenems over alternative treatments. This retrospective cohort study included adults (aged ≥18 years) admitted to hospital with ECR Enterobacterales infections in the PINC AI database. Antibiotic regimens were assessed during empirical and targeted treatment periods and by infection severity and site. Likelihood of receiving targeted carbapenems over time and before or after initial release of the Infectious Diseases Society of America (IDSA) guidance on Sept 8, 2020, was established with generalised estimating equations controlling for patient, hospital, and temporal confounders. Between Jan 1, 2018, and Dec 31, 2021, 30 041 inpatient encounters with ECR Enterobacterales infections were identified at 168 US hospitals, of which 16 006 (53·3%) encounters were in women and 14 035 (46·7%) were in men, with a mean age of 67·3 years (SD 15·1). Although few patients received carbapenems empirically (5324 [17·7%] of 30 041), many did so as targeted treatment (17 518 [58·3%] of 30 041), including subgroups of patients without septic shock (3031 [45·6%] of 6651) and patients with urinary tract infections without septic shock (1845 [46·8%] of 3943) in whom specific narrower-spectrum alternatives were active. Transitions from non-carbapenem to carbapenem antibiotics occurred most often on the day that the ECR phenotype was reported, regardless of illness severity. Carbapenems were the predominant choice to treat ECR Enterobacterales infections over time (adjusted odds ratio 1·00 [95% CI 1·00-1·00]), with no additional immediate change (1·07 [0·95-1·20]) or sustained change (0·99 [0·98-1·00]) after IDSA guidance release. High carbapenem use in targeting non-severe ECR Enterobacterales infections in US hospitals predates 2020 IDSA guidance and has persisted thereafter. Efforts to increase awareness and implementation of recommendations among clinicians to use carbapenem-sparing alternatives in ECR Enterobacterales infections might decrease global carbapenem selective pressure. US National Institutes of Health Intramural Research Program, National Institute of Allergy and Infectious Diseases, and US Food and Drug Administration.

The spread of pESI-mediated extended-spectrum cephalosporin resistance in Salmonella serovars-Infantis, Senftenberg, and Alachua isolated from food animal sources in the United States.

The goal of this study is to investigate the origin, prevalence, and evolution of the pESI megaplasmid in Salmonella isolated from animals, foods, and humans. We queried 510,097 Salmonella genomes under the National Center for Biotechnology Information (NCBI) Pathogen Detection (PD) database for the presence of potential sequences containing the pESI plasmid in animal, food, and environmental sources. The presence of the pESI megaplasmid was confirmed by using seven plasmid-specific markers (rdA, pilL, SogS, TrbA, ipf, ipr2 and IncFIB(pN55391)). The plasmid and chromosome phylogeny of these isolates was inferred from single nucleotide polymorphisms (SNPs). Our search resolved six Salmonella clusters carrying the pESI plasmid. Four were emergent Salmonella Infantis clusters, and one each belonged to serovar Senftenberg and Alachua. The Infantis cluster with a pESI plasmid carrying blaCTX-M-65 gene was the biggest of the four emergent Infantis clusters, with over 10,000 isolates. This cluster was first detected in South America and has since spread widely in United States. Over time the composition of pESI in United States has changed with the average number of resistance genes showing a decrease from 9 in 2014 to 5 in 2022, resulting from changes in gene content in two integrons present in the plasmid. A recent and emerging cluster of Senftenberg, which carries the blaCTX-M-65 gene and is primarily associated with turkey sources, was the second largest in the United States. SNP analysis showed that this cluster likely originated in North Carolina with the recent acquisition of the pESI plasmid. A single Alachua isolate from turkey was also found to carry the pESI plasmid containing blaCTX-M-65 gene. The study of the pESI plasmid, its evolution and mechanism of spread can help us in developing appropriate strategies for the prevention and further spread of this multi-drug resistant plasmid in Salmonella in poultry and humans.

Occurrence and persistence of multidrug-resistant Enterobacterales isolated from urban, industrial and surface water in Monastir, Tunisia

The One Health approach of antimicrobial resistance highlighted the role of the aquatic environment as a reservoir and dissemination source of resistance genes and resistant bacteria, especially due to anthropogenic activities. Resistance to extended-spectrum cephalosporins (ESC) conferred by extended-spectrum beta-lactamases (ESBLs) in E. coli has been proposed as the major marker of the AMR burden in cross-sectoral approaches. In this study, we investigated wastewater, surface water and seawater that are subjected to official water quality monitoring in Monastir, Tunisia. While all but one sample were declared compliant according to the official tests, ESC-resistant bacteria were detected in 31 (19.1 %) samples. Thirty-nine isolates, coming from urban, industrial and surface water in Monastir, were collected and characterized using antibiograms and whole-genome sequencing. These isolates were identified as 27 Escherichia coli (69.3 %) belonging to 13 STs, 10 Klebsiella pneumoniae (25.6 %) belonging to six STs, and two Citrobacter freundii (5.1 %). We observed the persistence and dissemination of clones over time and in different sampling sites, and no typically human-associated pathogens could be identified apart from one ST131. All isolates presented a blaCTX-M gene – blaCTX-M-15 (n = 22) and blaCTX-M-55 (n = 8) being the most frequent variants – which were identified on plasmids (n = 20) or on the chromosome (n = 19). In conclusion, we observed ESC resistance in rather ubiquitous bacteria that are capable of surviving in the water environment. This suggests that including the total coliform count and the ESBL count as determined by bacterial growth on selective plates in the official monitoring would greatly improve water quality control in Tunisia.

PenA profile of Neisseria gonorrhoeae in Guangdong, China: Novel penA alleles are related to decreased susceptibility to ceftriaxone or cefixime

Resistance to extended-spectrum cephalosporins (ESCs) has become a public health concern with the spread of Neisseria gonorrhoeae and increasing antimicrobial resistance. Mutation of penA, encoding penicillin-binding protein 2, represents a mechanism of ESC resistance. This study sought to assess penA alleles and mutations associated with decreased susceptibility (DS) to ESCs in N. gonorrhoeae. In 2021, 347 gonococci were collected in Guangdong, China. Minimum inhibitory concentations (MICs) of ceftriaxone and cefixime were determined, and whole-genome sequencing and phylogenetic analysis were performed. Multi-locus sequence typing (MLST) and conventional resistance determinants such as penA, mtrR, PonA and PorB were analysed. penA was genotyped and sequence-aligned using PubMLST. Genome-wide phylogenetic analysis revealed that the prevalence of DS to ESCs was highest in Clade 11.1 (100.0%), Clade 2 (66.7%) and Clade 0 (55.7%), and the leading cause was strains with penA-60.001 or new penA alleles in clades. The penA phylogenetic tree is divided into two branches: non-mosaic penA and mosaic penA. The latter contained penA-60.001, penA-10 and penA-34. penA profile analysis indicated that A311V and T483S are closely related to DS to ESCs in mosaic penA. The new alleles NEIS1753_2840 and NEIS1753_2837 are closely related to penA-60.001, with DS to ceftriaxone and cefixime of 100%. NEIS1753_2660, a derivative of penA-10 (A486V), has increased DS to ceftriaxone. NEIS1753_2846, a derivative of penA-34.007 (G546S), has increased DS to cefixime. This study identified critical penA alleles related to elevated MICs, and trends of gonococcus-evolved mutated penA associated with DS to ESCs in Guangdong.

Genotypic Characterization of Uropathogenic Escherichia coli from Companion Animals: Predominance of ST372 in Dogs and Human-Related ST73 in Cats.

Extraintestinal pathogenic Escherichia coli (ExPEC) account for over 80% and 60% of bacterial urinary tract infections (UTIs) in humans and animals, respectively. As shared uropathogenic E. coli (UPEC) strains have been previously reported among humans and pets, our study aimed to characterize E. coli lineages among UTI isolates from dogs and cats and to assess their overlaps with human UPEC lineages. We analysed 315 non-duplicate E. coli isolates from the UT of dogs (198) and cats (117) collected in central Germany in 2019 and 2020 utilizing whole genome sequencing and in silico methods. Phylogroup B2 (77.8%), dog-associated sequence type (ST) 372 (18.1%), and human-associated ST73 (16.6%), were predominant. Other STs included ST12 (8.6%), ST141 (5.1%), ST127 (4.8%), and ST131 (3.5%). Among these, 58.4% were assigned to the ExPEC group and 51.1% to the UPEC group based on their virulence associated gene (VAG) profile (ExPEC, presence of ≥VAGs: papAH and/or papC, sfa/focG, afaD/draBC, kpsMTII, and iutA; UPEC, additionally cnf1 or hlyD). Extended-spectrum cephalosporin (ESC) resistance mediated by extended-spectrum β-lactamases (ESBL) and AmpC-β-lactamase was identified in 1.9% of the isolates, along with one carbapenemase-producing isolate and one isolate carrying a mcr gene. Low occurrence of ESC-resistant or multidrug-resistant (MDR) isolates (2.9%) in the two most frequently detected STs implies that E. coli isolated from UTIs of companion animals are to a lesser extent associated with resistance, but possess virulence-associated genes enabling efficient UT colonization and carriage. Detection of human-related pandemic lineages suggests interspecies transmission and underscores the importance of monitoring companion animals.

Performance of CHROMagar ESBL media for the surveillance of extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE) from rectal swabs in Botswana.

Introduction. Lack of laboratory capacity hampers consistent national antimicrobial resistance (AMR) surveillance. Chromogenic media may provide a practical screening tool for detection of individuals colonized by extended-spectrum beta-lactamase (ESBL)-producing organisms.Hypothesis. CHROMagar ESBL media represent an adequate screening method for the detection of extended-spectrum cephalosporin-resistant Enterobacterales (ESCrE), isolated from rectal swabs.Aim. To evaluate the performance of CHROMagar ESBL media to accurately identify ESCrE isolates from rectal swab samples attained from hospitalized and community participants.Methodology. All participants provided informed consent prior to enrolment. Rectal swabs from 2469 hospital and community participants were inoculated onto CHROMagar ESBL. The performance of CHROMagar ESBL to differentiate Escherichia coli and Klebsiella spp., Enterobacter spp. and Citrobacter spp. (KEC spp.) as well as select for extended-spectrum cephalosporin resistance were compared to matrix-assisted laser desorption/ionization-time-of-flight MS (MALDI-TOF-MS) and VITEK-2 automated susceptibility testing.Results. CHROMagar ESBL had a positive and negative agreement of 91.2 % (95 % CI, 88.4-93.3) and 86.8 % (95 % CI, 82.0-90.7) for E. coli and 88.1 % (95 % CI 83.2-92.1) and 87.6 % (95 % CI 84.7-90.2) for KEC spp. differentiation, respectively, when compared to species ID by MALDI-TOF-MS. When evaluated for phenotypic susceptibilities (VITEK-2), 88.1 % (714/810) of the isolates recovered on the selective agar exhibited resistance to third-generation cephalosporins.Conclusion. The performance characteristics of CHROMagar ESBL media suggest that they may be a viable screening tool for the identification of ESCrE from hospitalized and community participants and could be used to inform infection prevention and control practices in Botswana and potentially other low-and middle-income countries (LMICs). Further studies are required to analyse the costs and the impact on time-to-result of the media in comparison with available laboratory methods for ESCrE surveillance in the country.

Prevalence and Transmission of Extended-Spectrum Cephalosporin (ESC) Resistance Genes in Escherichia coli Isolated from Poultry Production Systems and Slaughterhouses in Denmark.

The emergence of extended-spectrum cephalosporin (ESC)-resistant Escherichia coli is a global concern. This study aimed to assess the prevalence and transmission of ESC-resistant E. coli in the Danish broiler production system. Samples from two vertically integrated Production Systems (1 and 2) and two slaughterhouses (A and B) were analyzed (n = 943) for the occurrence of ESC-resistant E. coli from 2015 to 2018. ESC-resistant E. coli isolates were whole-genome sequenced (WGS) for characterization of the multi-locus sequence type (MLST), antibiotic resistance genes, virulence genes, and plasmid replicon types. An ad hoc core genome (cg) MLST based on 2513 alleles was used to examine the genetic relatedness among isolates. The prevalence of ESC-resistant E. coli in the conventional Production System 1 was 2.7%, while in Production System 2 the prevalence was 26.7% and 56.5% for samples from the conventional and organic production, respectively. The overall prevalence of ESC-resistant E. coli in broiler thigh and fecal samples ranged from 19.3% in Slaughterhouse A to 22.4% in Slaughterhouse B. In total, 162 ESC-resistant E. coli were isolated and shown to belong to 16 different sequence types (STs). The most prevalent STs were ST2040 (n = 85) and ST429 (n = 22). Seven ESC resistance genes were detected: blaCMY-2 (n = 119), blaTEM-52B (n = 16), blaCTX-M-1 (n = 5), blaTEM-52C (n = 3), blaCTX-M-14 (n = 1), blaSHV-12 (n = 1), and up-regulation of ampC (n = 16), with an unknown resistance gene in one isolate (n = 1). The carriage of blaCMY-2 in 119 isolates was primarily associated with IncI1 (n = 87), and IncK plasmids (n = 31). Highly similar blaCMY-2 carrying E. coli isolates from ST429 were found in production systems as well as in slaughterhouses. In conclusion, findings from this study indicate that ESC-resistant E. coli are transferred vertically from farms in the production systems to slaughterhouses with the potential to enter the food supply.

국내 개, 고양이, 사람 및 환경에서 유래된 항생제 내성 그람음성세균

The report of distribution and antimicrobial resistance rates in clinical hospitals in South Korea has been well-documented. However, the description of prevalence and antimicrobial resistance rate in veterinary hospitals is relatively rare. The aims of this study were to describe the prevalence and antimicrobial resistance rate for gram-negative bacteria originated from canines, felines, environments, and humans in South Korea. We collected bacteria from the rectal swabs of companion animals (dogs and cats), stool samples of humans (pet owners and medical staffs), and swabs of veterinary hospital surfaced in 16 veterinary hospitals. The isolates for antimicrobial susceptibility were performed by the agar disk diffusion method. Third- and fourth-generation extended-spectrum cephalosporin (ESC) resistance genes were identified by PCR and sequencing. A total of 740 Escherichia coli , 133 Klebsiella pneumoniae, 132 Acinetobacter baumannii , and 100 Pseudomonas aeruginosa isolates were recovered on MacConkey agar from companion animals, humans, and veterinary hospital environment samples for 2019 - 2020. The ESC resistant rates showed 36.3%, 40.6%, 18.2%, and 0% in E. coli , K. pneumoniae , A. baumannii , and P. aeruginosa, respectively. The most of the ESC resistance genes were blaCMY-2, blaDHA-1, and blaCTX-M-type. Our results indicate that the antimicrobial resistance rate including ESC was similar to that in the clinical field except carbapenem. In addition, the genus, species, and an timicrobial resistance determinants of gram-negative bacteria collected from samples were similar between the clinical and veterinary fields.

Clonal, Plasmidic and Genetic Diversity of Multi-Drug-Resistant Enterobacterales from Hospitalized Patients in Tripoli, Libya.

Resistance to extended-spectrum cephalosporins (ESC) and carbapenems in Enterobacterales is a major issue in public health. Carbapenem resistance in particular is associated with increased morbidity and mortality. Moreover, such resistance is often co-harbored with resistance to non-beta-lactam antibiotics, and pathogens quickly become multi-drug-resistant (MDR). Only a few studies have been published on AMR in Libyan hospitals, but all reported worrisome results. Here, we studied 54 MDR isolates that were collected from 49 patients at the Tripoli University Hospital between 2019 and 2021. They were characterized using phenotypic methods, PCR and PFGE, and a sub-set of isolates were short- and long-read whole-genome sequenced. The results showed the frequent occurrence of Klebsiella pneumoniae (49/54), among which several high-risk clones were responsible for the spread of resistance, namely, ST11, ST17, ST101 and ST147. ESC and carbapenem resistance was due to a wide variety of enzymes (CTX-M, OXA-48, NDM, KPC), with their corresponding genes carried by different plasmids, including IncF-IncHI2 and IncF-IncR hybrids. This study highlights that implementation of infection prevention, control and surveillance measures are needed in Libya to fight against AMR.

High Burden of Intestinal Colonization With Antimicrobial-Resistant Bacteria in Chile: An Antibiotic Resistance in Communities and Hospitals (ARCH) Study.

Antimicrobial resistance is a global threat, heavily impacting low- and middle-income countries. This study estimated antimicrobial-resistant gram-negative bacteria (GNB) fecal colonization prevalence in hospitalized and community-dwelling adults in Chile before the coronavirus disease 2019 pandemic. From December 2018 to May 2019, we enrolled hospitalized adults in 4 public hospitals and community dwellers from central Chile, who provided fecal specimens and epidemiological information. Samples were plated onto MacConkey agar with ciprofloxacin or ceftazidime added. All recovered morphotypes were identified and characterized according to the following phenotypes: fluoroquinolone-resistant (FQR), extended-spectrum cephalosporin-resistant (ESCR), carbapenem-resistant (CR), or multidrug-resistant (MDR; as per Centers for Disease Control and Prevention criteria) GNB. Categories were not mutually exclusive. A total of 775 hospitalized adults and 357 community dwellers were enrolled. Among hospitalized subjects, the prevalence of colonization with FQR, ESCR, CR, or MDR-GNB was 46.4% (95% confidence interval [CI], 42.9-50.0), 41.2% (95% CI, 37.7-44.6), 14.5% (95% CI, 12.0-16.9), and 26.3% (95% CI, 23.2-29.4). In the community, the prevalence of FQR, ESCR, CR, and MDR-GNB colonization was 39.5% (95% CI, 34.4-44.6), 28.9% (95% CI, 24.2-33.6), 5.6% (95% CI, 3.2-8.0), and 4.8% (95% CI, 2.6-7.0), respectively. A high burden of antimicrobial-resistant GNB colonization was observed in this sample of hospitalized and community-dwelling adults, suggesting that the community is a relevant source of antibiotic resistance. Efforts are needed to understand the relatedness between resistant strains circulating in the community and hospitals.

Escherichia coli multilocus sequence type 38 from humans and broiler production represent distinct monophyletic groups.

Escherichia coli belonging to multilocus sequence type 38 (ST38) is a well-known cause of extra-intestinal infections in humans, and are frequently associated with resistance to extended-spectrum cephalosporins (ESCs). Resistance to carbapenems, mediated by blaOXA-genes has also been reported in this ST. Recently, the European Centre for Disease Prevention and Control (ECDC) released a rapid risk assessment on the increased detection of OXA-244 producing E. coli ST38 in humans, requesting further knowledge to determine the source. ST38 is also one of the most common STs among ESC-resistant E. coli from broiler production. Our aim was to investigate the genetic characteristics and relationship between E. coli ST38 from broiler production and humans, and to investigate if there has been a potential spillover between these sources. A total of 288 E. coli ST38 genomes isolated from humans in Europe (collected 2009-2019) and from Nordic broiler production (collected 2011-2014) were analyzed. The results showed distinct monophyletic clades associated to humans and broiler production. Furthermore, there were differences in the ESC resistance genes present in E. coli ST38 from the two sources. The blaOXA-244 gene was not present in E. coli from broiler production. Our results show that ST38 from humans and broiler production belong to well-separated clades, and suggest that the increased detection of OXA-244-producing E. coli ST38 in humans is not associated with spillover from broiler production.

Impact of a Statewide Livestock Antibiotic Use Policy on Resistance in Human Urine Escherichia coli Isolates: A Synthetic Control Analysis.

On 1 January 2018, California implemented Senate Bill 27 (SB27), banning, for the first time in the United States, routine preventive use of antibiotics in food-animal production and any antibiotic use without a veterinarian's prescription. Our objective was to assess whether SB27 was associated with decreased antimicrobial resistance among E. coli isolated from human urine. We used U.S. nationwide monthly state-level data from BD Insights Research Database (Becton, Dickinson, and Co.) spanning 1 January 2013 to 30 June 2021 on antibiotic-resistance patterns of 30-d nonduplicate E. coli isolated from urine. Tested antibiotic classes included aminoglycosides, extended-spectrum cephalosporins (ESC), fluoroquinolones, and tetracyclines. Counts of tested and not-susceptible (resistant and intermediate, hereafter resistant) urine isolates were available by sex, age group (, year), month, and state. We applied a synthetic control approach to estimate the causal effect of SB27 on resistance patterns. Our approach created a synthetic California based on a composite of other states without the policy change and contrasted its counterfactual postpolicy trends with the observed postpolicy trends in California. We included E. coli urine isolates, 90% among women, across 33 states. From 2013 to 2017, the median (interquartile range) resistance percentages in California were 11.9% (7.4, 17.6), 13.8% (5.8, 20.0), 24.6% (9.6, 36.4), 7.9% (2.1, 13.1), for aminoglycosides, ESC, fluoroquinolones, and tetracyclines, respectively. SB27 was associated with a 7.1% reduction in ESC resistance (p-value for joint null: ), but no change in resistance to aminoglycosides, fluoroquinolones, or tetracyclines. Further research is needed to determine the role of SB27 in the observed reduction in ESC resistance E. coli in human populations, particularly as additional states implement similar legislation. https://doi.org/10.1289/EHP11221.

Characterization of Escherichia coli and Other Enterobacterales Resistant to Extended-Spectrum Cephalosporins Isolated from Dairy Manure in Ontario, Canada.

Extended-spectrum cephalosporins (ESCs) resistance genes, such as blaCTX-M, blaCMY, and blaSHV, have been found regularly in bacteria from livestock. However, information on their distribution in dairy cattle in Canada and on the associated genome sequences of ESC-resistant Enterobacterales is sparse. In this study, the diversity and distribution of ESC-resistant Escherichia coli throughout manure treatments in six farms in Southern Ontario were assessed over a one-year period, and their ESC-resistance plasmids were characterized. The manure samples were enriched using selective media. The resulting isolates were screened via polymerase chain reaction for blaCTX-M, blaCMY, and blaSHV. No E. coli carrying blaSHV were detected. Escherichia coli (n = 248) carrying blaCTX-M or blaCMY underwent whole-genome sequencing using an Illumina MiSeq/NextSeq. These isolates were typed using multilocus sequence typing (MLST) and their resistance gene profiles. A subset of E. coli (n = 28) were sequenced using Oxford Nanopore Technologies. Plasmids were assembled using Unicycler and characterized via the resistance genes pattern, replicon type, plasmid MLST, phylogenetic analysis, and Mauve alignments. The recovery of ESC-resistant Enterobacterales (18 species, 8 genera) was drastically reduced in manure outputs. However, multiple treatment stages were needed to attain a significant reduction. 62 sequence types were identified, with ST10, ST46, ST58, ST155, ST190, ST398, ST685, and ST8761 being detected throughout the treatment pipeline. These STs overlapped with those found on multiple farms. The ESC-resistance determinants included CTX-M-1, -14, -15, -17, -24, -32, -55, and CMY-2. The plasmids carrying blaCTX-M were more diverse than were the plasmids carrying blaCMY. Known "epidemic plasmids" were detected for both blaCTX-M and blaCMY. IMPORTANCE The increase in antimicrobial resistance is of concern for human and animal health, especially when resistance is conferred to extended-spectrum cephalosporins, which are used to treat serious infections in both human and veterinary medicine. Bacteria carrying extended-spectrum cephalosporin resistance genes, including blaCTX-M and blaCMY, are frequently found in dairy manure. Manure treatment influences the loads and diversity of bacteria, including those carrying antimicrobial resistance genes, such as Enterobacterales and Escherichia coli. Any bacteria that survive the treatment process are subsequently applied to the environment. Enterobacterales carrying blaCTX-M or blaCMY can contaminate soil and crops consumed by humans and animals, thereby increasing the potential for antimicrobial resistance genes to integrate into the human gut microflora through horizontal gene transfer. This furthers the dissemination of resistance. Therefore, it is imperative to understand the effects manure treatments have on ESC-resistance in environmentally applied manure.

Antimicrobial resistance in Escherichia coli isolates from Japanese raccoon dogs (Nyctereutes viverrinus) in Kanagawa Prefecture, Japan: Emergence of extended-spectrum cephalosporin-resistant human-related clones.

Introduction. Wild animals are one of the putative reservoirs of antimicrobial-resistant bacteria, but the significance of raccoon dogs remains to be investigated.Hypothesis. Raccoon dogs can be a reservoir of antimicrobial-resistant bacteria.Aim. This study aimed to explore the prevalence of antimicrobial resistance, mainly extended-spectrum cephalosporins resistance, in Escherichia coli isolates from faeces of 80 Japanese raccoon dogs in Kanagawa Prefecture, Japan.Methodology. All of the 80 faecal samples were streaked onto deoxycholate-hydrogen sulfate-lactose (DHL) and cefotaxime (CTX)-supplemented DHL (DHL-CTX) agars. Susceptibilities to ten antimicrobials were determined using the agar dilution method. Additionally, extended-spectrum β-lactamases (ESBLs) and AmpC-type β-lactamases (ABLs) were identified in addition to sequence types (STs), in ESC-resistant isolates by a polymerase chain reaction and sequencing.Results. Out of all the samples, 75 (93.8 %) and 20 (25.0 %) E. coli isolates were isolated by DHL and DHL-CTX agars, respectively. Significantly higher resistance rates to most of the drugs were found in DHL-CTX-derived isolates than DHL-derived isolates (P<0.01). Genetic analysis identified CTX-M-14 (n=6), CTX-M-2 (n=2), CTX-M-1 (n=1) and CTX-M-55 (n=1) as ESBLs, and CMY-2 (n=8) and DHA-1 (n=1) as ABLs in 20 DHL-CTX-derived isolates. Most of the detected STs were related to Japanese humans (i.e. ST10, ST58, ST69, ST131, ST357, ST648 and ST4038). Notably, this is the first report on ST69, ST131, ST155 and ST648, which are well-known international high-risk clones in Japanese raccoon dogs.Conclusion. Our findings underscore the need to understand the significance of raccoon dogs as an antimicrobial-resistant bacteria reservoir using one health approach.

427. Trends in Hospital-onset Escherichia coli Infections Resistant to Fluoroquinolones and Extended-spectrum Cephalosporins, 2012-2020

Abstract Background Inpatient and outpatient fluoroquinolone (FQ) use has decreased substantially in the last decade; however, the impact of this trend on FQ resistance is less clear. During this period, extended-spectrum β-lactamase (ESBL) Escherichia coli infections have increased. We examined hospital-onset (HO) E. coli clinical culture trends and resistance patterns among hospitalized adult patients in the United States. Methods We measured the incidence of positive clinical cultures from inpatient encounters in a cohort of hospitals submitting data to the Premier Healthcare Database from 2012-2020. We included E. coli cultures with susceptibility testing to FQs or extended-spectrum cephalosporins (ESC). ESC resistance was defined as non-susceptibility to cefotaxime, ceftriaxone, ceftazidime, or cefepime and FQ resistance as resistance to ciprofloxacin, levofloxacin, or moxifloxacin. Co-resistance was defined as both ESC and FQ resistance in the same E. coli isolate. Isolates were classified as FQ resistant only (and not ESC), ESC resistant only (and not FQ), co-resistant, or neither FQ nor ESC resistant. Results The overall proportion of HO E. coli with any FQ resistance decreased 12.3% (from 36.7% in 2012 to 32.2% in 2020). The proportion of HO E. coli with only FQ resistance decreased by 39.8% (from 27.9% in 2012 to 16.8% in 2020); the proportion with only ESC resistance increased by 112.5% (from 2.4% to 5.1%), and co-resistance increased by 75.0% (from 8.8% to 15.4%) (Figure). Figure.Proportion of hospital-onset E. coli infections with selected antibiotic resistance patterns, 2012-2020 Conclusion These results suggest that declining FQ use has been accompanied by declining FQ resistance in E. coli. Increases in FQ and ESC co-resistance may be due to factors including increases in the use of non-FQ antibiotics such as cephalosporins and increased transmission of E. coli strains such as ST131 in which co-resistance is prevalent. Antibiotic stewardship across multiple antibiotic classes combined with infection control measures are likely necessary to reduce multidrug resistant E. coli infections. Disclosures All Authors: No reported disclosures.

1182. Risk factors for colonization with extended-spectrum cephalosporin resistant and carbapenem resistant Enterobacterales among community adults, Bangladesh: An Antibiotic Resistance in Communities and Hospitals (ARCH) study

Abstract Background Antimicrobial resistant (AMR) organisms are an increasing global health threat that are spreading within communities. Understanding the risk factors for colonization with AMR organisms is critical for implementing prevention and control strategies, particularly in resource-limited settings such as Bangladesh. Methods During 2019, we conducted a population-based observational study in Dhaka (surveillance site of icddr,b). We collected stool samples from randomly selected adults and tested for Enterobacterales with extended-spectrum cephalosporin resistance (ESCrE) and carbapenem resistance (CRE) using selective media followed by VITEK-2 confirmation. Participants completed demographic surveys assessing food consumption, animal contact, sanitation, water sources, and healthcare exposure. We identified factors associated with ESCrE and CRE colonization using bivariable and multivariable logistic regression, adjusting for potential confounders and clustering. Results Of 714 enrolled individuals, 557 (78%) were colonized with ESCrE and 66 (9%) with CRE. In bivariable analysis, factors associated with ESCrE colonization included fresh fruit consumption in the past week (OR 1.8, 95% CI 1.2-2.9), public tap as main source of drinking water compared with basic improved source (OR 3.3, 1.0-11.0), and unimproved toilet (pour/flush to open drain, pit latrine without slab) compared with basic improved toilet (OR 11, 2.9-42.0). Only consumption of fresh fruit was significant in the multivariable analysis (aOR 2.0, 1.3-3.2). Factors associated with CRE colonization in bivariable analysis were hospitalization in the last 3 months (OR 3.2, 1.2-8.6), limited sanitation facility (improved toilet shared with other households) (OR 2.0, 1.0-3.8), and limited hygiene (availability of handwashing facility on premises without soap and/or water) (OR 3.3, 1.4-7.7). The only factor that was significant in multivariable analysis was hospitalization in the last 3 months (aOR 3.0, 1.0-8.7). Conclusion While ESCrE colonization is common in urban communities, hospitals may be contributing to community spread of CRE. Targeted interventions focused on healthcare facilities may be needed to mitigate the transmission of AMR organisms. Disclosures All Authors: No reported disclosures.

2056. Trends in the Rates of Multidrug-resistant Bacteria Commonly Associated with Healthcare in U.S. Acute Care Hospitals, 2019-June 2021

Abstract Background Several studies demonstrated an increase in hospital-onset (HO) infections during the COVID-19 pandemic. We examined trends in the rates of multidrug-resistant (MDR) infections among acute care hospitals in the United States (U.S.) for bacteria commonly associated with healthcare: methicillin-resistant Staphylococcus aureus (MRSA), extended-spectrum cephalosporin resistance in Enterobacteriaceae suggestive of extended-spectrum beta-lactamase production (ESBL), vancomycin resistant Enterococcus (VRE), MDR Pseudomonas aeruginosa, carbapenem resistant Enterobacteriaceae (CRE), and carbapenem-resistant Acinetobacter species (CRAB). Methods We measured incidence of clinical cultures yielding the bacterial species of interest among hospitalized patients in a dynamic cohort of hospitals submitting data to the Premier Healthcare Database Special COVID-19 Release during 2019-June 2021. Community-onset (CO) cultures were obtained ≤ day 3 of hospitalization; HO were obtained ≥ day 4. We determined monthly hospital-specific rates for each species. We used generalized estimating equations (GEE) multivariable negative binomial regression models adjusting for hospital characteristics to examine trends. Results From 2019-June 2021, the overall number of hospitals contributing data was 318. Rates for each pathogen are shown in Figures 1 and 2. All pathogens’ HO rates were significantly higher in 2021 compared with 2019. The rates of ESBL, VRE, and CRE were also significantly higher in 2021 when compared to 2020 (Table 1a). For CO rates, we found that MRSA rates decreased significantly during the study period, while ESBL, VRE, and CRE increased with varying degree of significance (Table 1b). Rates of CO MDR Pseudomonas and CO CRAB did not significantly change. Conclusion Our study confirmed that the rates of several MDR infections increased during the COVID-19 pandemic through June 2021, especially HO infections. CO MRSA was the only pathogen with consistent and significant decline. As infections caused by MDR pathogens represent a serious threat to patient safety, further study of factors contributing to the emerging trends may inform prevention strategies during a pandemic. Disclosures All Authors: No reported disclosures.

2050. Proportion of hospital-onset infections expressing antibiotic resistant (AR) phenotypes in US Hospitals, 2018 – 2020

Abstract Background Reports suggest the COVID-19 pandemic in 2020 was associated with increases in hospital-onset AR infections, including methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus spp., carbapenem-resistant Enterobacterales (E. coli, Klebsiella spp., and Enterobacter spp.) (CRE) and Acinetobacter spp. (CRAsp), extended-spectrum cephalosporin resistance suggestive of extended-spectrum β-lactamase producing Enterobacterales (ESBL-E), and multidrug-resistant Pseudomonas aeruginosa (MDR-PA). To evaluate whether trends were similar for susceptible and resistant strains, we estimated the proportions of these resistant phenotypes in U.S. hospitals. Figure 1.Proportion of hospital-onset pathogens expressing resistant phenotypes, 2018 – 2020 Methods We analyzed 2018–2020 hospital microbiology data in the Premier Healthcare and BD Insights Research Databases. Hospital-onset (HO) infections were those with positive cultures collected after hospital day 3. We used a raking procedure to produce weights to match national hospital characteristics, specifically: U.S. census division, bed size, teaching status, age, gender and urban/rural designation. We used a weighted means survey procedure for annual national estimates and generated annual comparisons with multivariable logistic regression adjusted by hospital characteristics. Results In 589 hospitals, the percentages of HO ESBL-E and CRAsp increased from 2019 to 2020 (Table). Among enterococci, the percentage with vancomycin resistance decreased. The percentages of MRSA, CRE, and MDR-PA did not change. Conclusion Our findings suggest pandemic-related factors, such as changes in antibiotic use or infection control, may have differentially affected susceptible and resistant phenotypes of hospital pathogens. Increases in the percentages of HO CRAsp and ESBL-E suggest these resistant phenotypes may have had a selective advantage over susceptible strains during the pandemic. In contrast, no changes in the percentages of HO MRSA or MDR-PA were observed, suggesting that infection rates increased similarly for resistant and susceptible strains. These findings underscore the importance of strategies to prevent hospital-associated infections and AR that are resilient to pandemic-related stresses on the healthcare system. Disclosures All Authors: No reported disclosures.

2229. Antibiotic Resistance in Gram-Negative Community-Onset Urinary Tract Infections Among Adults Presenting to Hospitals, United States, 2012-2020

Abstract Background Choosing empiric therapy for patients with community-onset urinary tract infections (CO-UTI) presenting to hospitals for treatment is challenging without understanding local antimicrobial susceptibility patterns. We investigated changes over time in antimicrobial resistance among CO-UTI pathogens and identified patient-level factors associated with higher levels of resistance. Methods We used non-duplicate positive urine cultures in the 2012-2020 Premier Healthcare Database as a proxy for CO-UTI in patients ≥ 18 years old presenting to hospitals receiving care categorized as community-onset inpatient (CO-INPT) or observation/emergency department (OBS/ED). We included cultures positive for Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, and Pseudomonas aeruginosa obtained within 3 days of admission. Phenotypes investigated include resistance to extended-spectrum cephalosporins (ESC), fluoroquinolones (FLQ), and trimethoprim-sulfamethoxazole (TMP-SX). Logistic regression analyses were performed. Results Among 1,987,605 urine cultures meeting study criteria from 432 hospitals, &amp;gt; 66% were E. coli. Antibiotic resistance (AR) was highest to FLQ among CO-INPT E. coli (31.7%) and P. mirabilis (29.3%) in 2020. ESC resistance increased from 2012 to 2020 among E. coli and K. pneumoniae in both CO-INPT and OBS/ED (p&amp;lt; 0.001). TMP-SX resistance remained &amp;gt; 20% among E. coli in CO-INPT and OBS/ED and P. mirabilis in CO-INPT throughout the study period. All AR phenotypes were significantly higher among CO-INPT than OBS/ED (p&amp;lt; 0.001), and higher among males than females (p&amp;lt; 0.001). FLQ resistance among E. coli, P. mirabilis, and P. aeruginosa was &amp;gt; 20% among males (28.2%, 30.4%, 21.9% respectively) but not females (17.5%, 15.1%, 14.5%) in OBS/ED, while it was &amp;gt; 20% among both males (37.2%, 37.3%, 24.6%) and females (31.2%, 33.9%, 21.9%) in CO-INPT. Figure 1.% Resistance to extended-spectrum cephalosporins by year and acute care setting.Figure 2.% Resistance to fluoroquinolones by year and acute care setting.Figure 3.% Resistance to trimethoprim-sulfamethoxazole by year and acute care setting. Conclusion Resistance to TMP-SX in both CO-INPT and OBS/ED, and FLQ in CO-INPT, was elevated suggesting alternative empiric therapy might be necessary for CO-UTI presenting to hospitals. Increasing resistance to ESC among pathogens in CO-INPT cultures warrants further evaluation of local resistance levels. Gender and need for inpatient therapy are factors to consider in developing local treatment recommendations. Disclosures All Authors: No reported disclosures.