scholarly journals 1145. The Role of the Plasmid-Mediated Fluoroquinolone-Resistance (PMFQR) Genes As Resistance Mechanisms in Pediatric Infections due to Enterobacterales (Ent)

2021 ◽  
Vol 8 (Supplement_1) ◽  
pp. S664-S665
Author(s):  
Claire E Pitstick ◽  
Steven Marshall ◽  
Sreenivas Konda ◽  
Rachel L Medernach ◽  
T Nicholas Domitrovic ◽  
...  
Keyword(s):  
Healthcare Setting ◽  
Antibiotic Use ◽  
Generation Cephalosporin ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Fluoroquinolone Resistance ◽  
Research Support ◽  
E Coli ◽  
Treatment And Prevention

Abstract Background Fluoroquinolones (FQs) are not commonly prescribed in children, yet the increasing incidence of multidrug resistant (MDR) Ent infections in this population often reveals FQ resistance. We sought to define the role of FQ resistance in the epidemiology of MDR Ent in children, with an overall goal to devise treatment and prevention strategies. Methods A case-control study of children (0-18 years) at 3 Chicago hospitals was performed. Cases had infections by FQ susceptible, 3rd generation cephalosporin-resistant (3GCR) and/or carbapenem-resistant (CR) Ent harboring a non or low level expressed PMFQR gene (PMFQS Ent). Controls had FQR infections due to 3GCR and/or CR Ent with expressed PMFQR genes (PMFQR Ent). We sought bla genes by PCR or DNA (BD Max Check-Points assay®) and PMFQR genes by PCR. We performed Rep-PCR, MLST, and E. coli phylogenetic grouping. Demographics; comorbidities; and device, antibiotic, and healthcare exposures were evaluated. Predictors of infection were assessed. Results Of 170 G3CR and/or CR Ent isolates, 85 (50%) were FQS; 23 (27%) had PMFQR genes (PMFQS cases). 85 (50%) were FQR; 53 (62%) had PMFQR genes (PMFQR controls). The median age for children with PMFQS Ent and PMFQR Ent were 4.3 and 6.2 years, respectively (p=NS). Of 23 PMFQS Ent, 53% were Klebsiella and of 53 PMFQR Ent, 76% were E. coli. The most common bla and PMFQR genes in PMFQS Ent were blaSHV ESBL (44%); oqxB (57%) and aac-6’1b-cr (52%) and in PMFQR Ent were blaCTX-M-1 group (76%); aac-6’1b-cr (91%) and oqxA (17%). Multivariable regression analysis showed children with PMFQS Ent infections were more likely to have hospital onset infection (OR 5.7, 95% CI 1.6-22) and isolates with multiple bla genes (OR 3.8, 95% CI 1.1-14.5). The presence of invasive devices mediated the effects of healthcare setting in the final model. Differences in demographics, comorbidities, or antibiotic use were not found. Conclusion Paradoxically, PMFQS Ent infections were often hospital onset and PMFQR Ent infections were community onset. PMFQS Ent commonly co-harbored multiple bla and PMFQR genes, affecting therapeutic options and suggesting need for contact precautions. Control of PMFQS Ent infections in children will require validating sources and risk factors. Disclosures Robert A. Bonomo, MD, entasis (Research Grant or Support)Merck (Grant/Research Support)NIH (Grant/Research Support)VA Merit Award (Grant/Research Support)VenatoRx (Grant/Research Support)

scholarly journals Community origins and regional differences highlight risk of plasmid-mediated fluoroquinolone resistant Enterobacteriaceae infections in children

2018 ◽  
Author(s):  
Latania K. Logan ◽  
Rachel L. Medernach ◽  
Jared R. Rispens ◽  
Steven H. Marshall ◽  
Andrea M. Hujer ◽  
...  
Keyword(s):  
Dna Analysis ◽  
Strong Association ◽  
Multivariable Analysis ◽  
Gene Mutations ◽  
Antibiotic Use ◽  
Generation Cephalosporin ◽  
Multidrug Resistant ◽  
Control Analysis ◽  
E Coli ◽  
Enterobacteriaceae Infections

AbstractBackground:Fluoroquinolones (FQs) are uncommonly prescribed in children, yet pediatric multidrug-resistant (MDR)-Enterobacteriaceae (Ent) infections often reveal FQ resistance (FQR). We sought to define the molecular epidemiology of FQR and MDR-Ent in children.Methods:A case-control analysis of children with MDR-Ent infections at 3 Chicago hospitals was performed. Cases were children with third-generation-cephalosporin-resistant (3GCR) and/or carbapenem-resistant (CR)-Ent infections. PCR and DNA analysis assessed bla and plasmid-mediated FQR (PMFQR) genes. Controls were children with 3GC and carbapenem susceptible-Ent infections matched by age, source and hospital. We assessed clinical-epidemiologic predictors of PMFQR Ent infection.Results:Of 169 3GCR and/or CR Ent isolates from children (median age 4.8 years), 85 were FQR; 56 (66%) contained PMFQR genes. The predominant organism was E. coli and most common bla gene blaCTX-M-1 group. In FQR isolates, PMFQR gene mutations included aac6’1b-cr, oqxA/B, qepA, and qnrA/B/D/S in 83%, 15%, 13% and 11% of isolates, respectively. FQR E. coli was often associated with phylogroup B2, ST43/ST131. On multivariable analysis, PMFQR Ent infections occurred mostly in outpatients (OR 33.1) of non-black-white-Hispanic race (OR 6.5). Residents of Southwest Chicago were >5 times more likely to have PMFQR-Ent infections than those in the reference region, while residence in Central Chicago was associated with a 97% decreased risk. Other demographic, comorbidity, invasive-device, antibiotic use, or healthcare differences were not found.Conclusions:The strong association of infection with MDROs showing FQR with patient residence rather than with traditional risk factors suggests that the community environment is a major contributor to spread of these pathogens in children.

scholarly journals Molecular survey of mcr1 and mcr2 plasmid mediated colistin resistance genes in Escherichia coli isolates of animal origin in Iran

2021 ◽  
Vol 14 (1) ◽  
Author(s):  
Kayhan Ilbeigi ◽  
Mahdi Askari Badouei ◽  
Hossein Vaezi ◽  
Hassan Zaheri ◽  
Sina Aghasharif ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Resistance Genes ◽  
Companion Animals ◽  
Multidrug Resistant ◽  
Animal Origin ◽  
Colistin Resistance ◽  
E Coli ◽  
High Level ◽  
Farming Industry

Abstract Objectives The emergence of colistin-resistant Enterobacteriaceae from human and animal sources is one of the major public health concerns as colistin is the last-resort antibiotic for treating infections caused by multidrug-resistant Gram-negative bacteria. We aimed to determine the prevalence of the prototype widespread colistin resistance genes (mcr-1 and mcr-2) among commensal and pathogenic Escherichia coli strains isolated from food-producing and companion animals in Iran. Results A total of 607 E. coli isolates which were previously collected from different animal sources between 2008 and 2016 used to uncover the possible presence of plasmid-mediated colistin resistance genes (mcr-1 and mcr-2) by PCR. Overall, our results could not confirm the presence of any mcr-1 or mcr-2 positive E. coli among the studied isolates. It is concluded that despite the important role of food-producing animals in transferring the antibiotic resistance, they were not the main source for carriage of mcr-1 and mcr-2 in Iran until 2016. This study suggests that the other mcr variants (mcr-3 to mcr-9) might be responsible for conferring colistin resistance in animal isolates in Iran. The possible linkage between pig farming industry and high level of mcr carriage in some countries needs to be clarified in future prospective studies.

scholarly journals Heterogeneous and Flexible Transmission ofmcr-1in Hospital-AssociatedEscherichia coli

mBio ◽  
2018 ◽  
Vol 9 (4) ◽  
Author(s):  
Yingbo Shen ◽  
Zuowei Wu ◽  
Yang Wang ◽  
Rong Zhang ◽  
Hong-Wei Zhou ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Genomic Analysis ◽  
Multidrug Resistant ◽  
Fluoroquinolone Resistance ◽  
Gram Negative Bacteria ◽  
Colistin Resistance ◽  
Gram Negative ◽  
Content Type ◽  
E Coli ◽  
Genes Encoding

ABSTRACTThe recent emergence of a transferable colistin resistance mechanism, MCR-1, has gained global attention because of its threat to clinical treatment of infections caused by multidrug-resistant Gram-negative bacteria. However, the possible transmission route ofmcr-1amongEnterobacteriaceaespecies in clinical settings is largely unknown. Here, we present a comprehensive genomic analysis ofEscherichia coliisolates collected in a hospital in Hangzhou, China. We found thatmcr-1-carrying isolates from clinical infections and feces of inpatients and healthy volunteers were genetically diverse and were not closely related phylogenetically, suggesting that clonal expansion is not involved in the spread ofmcr-1. Themcr-1gene was found on either chromosomes or plasmids, but in most of theE. coliisolates,mcr-1was carried on plasmids. The genetic context of the plasmids showed considerable diversity as evidenced by the different functional insertion sequence (IS) elements, toxin-antitoxin (TA) systems, heavy metal resistance determinants, and Rep proteins of broad-host-range plasmids. Additionally, the genomic analysis revealed nosocomial transmission ofmcr-1and the coexistence ofmcr-1with other genes encoding β-lactamases and fluoroquinolone resistance in theE. coliisolates. These findings indicate thatmcr-1is heterogeneously disseminated in both commensal and pathogenic strains ofE. coli, suggest the high flexibility of this gene in its association with diverse genetic backgrounds of the hosts, and provide new insights into the genome epidemiology ofmcr-1among hospital-associatedE. colistrains.IMPORTANCEColistin represents one of the very few available drugs for treating infections caused by extensively multidrug-resistant Gram-negative bacteria. The recently emergentmcr-1colistin resistance gene threatens the clinical utility of colistin and has gained global attention. Howmcr-1spreads in hospital settings remains unknown and was investigated by whole-genome sequencing ofmcr-1-carryingEscherichia coliin this study. The findings revealed extraordinary flexibility ofmcr-1in its spread among genetically diverseE. colihosts and plasmids, nosocomial transmission ofmcr-1-carryingE. coli, and the continuous emergence of novel Inc types of plasmids carryingmcr-1and newmcr-1variants. Additionally,mcr-1was found to be frequently associated with other genes encoding β-lactams and fluoroquinolone resistance. These findings provide important information on the transmission and epidemiology ofmcr-1and are of significant public health importance as the information is expected to facilitate the control of this significant antibiotic resistance threat.

scholarly journals Activity of Ceftolozane-Tazobactam (C/T) against Escherichia coli Isolates from U.S. Veterans in Relation to Co-resistance and Sequence Type 131 (ST131) H30/H30Rx Status

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S374-S374
Author(s):  
Brian D Johnston ◽  
Paul Thuras ◽  
James R Johnson
Keyword(s):  
Significant Variation ◽  
Multidrug Resistant ◽  
Sequence Type ◽  
Clinical Isolates ◽  
The Novel ◽  
Total Resistance ◽  
Research Support ◽  
E Coli ◽  
The U.S ◽  
Research Grant

Abstract Background E. coli ST131, with its resistance-associated H30 and H30Rx clonal subsets, causes most antimicrobial-resistant E. coli infections, especially among veterans. The activity of the novel combination agent C/T against ST131 is undefined. Methods E. coli clinical isolates (n = 595), including (per VAMC) 10 each ciprofloxacin-resistant and susceptible isolates, plus archived ESBL isolates, were collected from 24 VAMCs across the U.S. (2011). ST131, H30, and H30Rx were detected by clonal PCR. Microdilution MICs were determined for C/T and 5 comparators (piperacillin-tazobactam [TZP], levofloxacin [LVX], gentamicin [GEN], ceftazidime [CAZ], and meropenem [MEM]). Categorical resistance and MICs were compared statistically with resistance category and H30/H30Rx status. Results Total resistance prevalence was < 5% for C/T (3.5%) and MEM (0%), vs. from 7.9% (TZP) to 59% (LVX) for other comparators (Table 1). Resistance prevalence generally increased by resistance category from FQ-S through FQ-R to ESBL, and by clonal subgroup from non-H30 through H30 to H30Rx. Conclusion C/T is broadly active against E. coli clinical isolates from veterans, notwithstanding significant variation by resistance category and ST131-H30/H30Rx status; it outperformed all non-carbapenem comparators. C/T should prove useful as a carbapenem-sparing agent against multidrug-resistant E. coli ST131 infections. Disclosures B. D. Johnston, Merck Sharpe & Dohme, Corp.: Collaborator, Research support Actavis: Collaborator, Research support; J. R. Johnson, Merck: Grant Investigator, Research grant Grant Investigator, Research grant

scholarly journals High Prevalence and Diversity of Cephalosporin-Resistant Enterobacteriaceae Including Extraintestinal Pathogenic E. coli CC648 Lineage in Rural and Urban Dogs in Northwest Spain

Antibiotics ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 468 ◽  
Author(s):  
Fátima Abreu-Salinas ◽  
Dafne Díaz-Jiménez ◽  
Isidro García-Meniño ◽  
Pilar Lumbreras ◽  
Ana María López-Beceiro ◽  
...  
Keyword(s):  
High Risk ◽  
Antimicrobial Resistance ◽  
One Health ◽  
Potential Role ◽  
Multidrug Resistant ◽  
E Coli ◽  
Rural And Urban ◽  
High Prevalence ◽  
Healthy Dogs

The aim of this work was to assess the prevalence of extended spectrum-β-lactamase (ESBL)- and carbapenemase-producing Enterobacteriaceae in fecal samples recovered from rural and urban healthy dogs in Northwest Spain (Galicia) to identify potential high-risk clones and to molecularly characterize positive isolates regarding the genes coding for ESBL/pAmpC resistance and virulence. Thirty-five (19.6%) out of 179 dogs were positive for cephalosporin-resistant Enterobacteriaceae, including Escherichiacoli and Klebsiella pneumoniae (39 and three isolates, respectively). All the isolates were multidrug resistant, with high rates of resistance to different drugs, including ciprofloxacin (71.4%). A wide diversity of ESBL/pAmpC enzymes, as well as E. coli phylogroups (A, B1, C, D, E, F and clade I) were found. The eight isolates (20.5%) found to conform to the ExPEC status, belonged to clones O1:H45-clade I-ST770 (CH11-552), O18:H11-A-ST93-CC168 (CH11-neg), O23:H16-B1-ST453-CC86 (CH6-31), and O83:H42-F-ST1485-CC648 (CH231-58), with the latter also complying the uropathogenic (UPEC) status. The three K. pneumoniae recovered produced CTX-M-15 and belonged to the ST307, a clone previously reported in human clinical isolates. Our study highlights the potential role of both rural and urban dogs as a reservoir of high-risk Enterobacteriaceae clones, such as the CC648 of E. coli and antimicrobial resistance traits. Within a One-Health approach, their surveillance should be a priority in the fight against antimicrobial resistance.

scholarly journals An Early Response to Environmental Stress Involves Regulation of OmpX and OmpF, Two Enterobacterial Outer Membrane Pore-Forming Proteins

2007 ◽  
Vol 51 (9) ◽  
pp. 3190-3198 ◽  
Author(s):  
Myrielle Dupont ◽  
Chloë E. James ◽  
Jacqueline Chevalier ◽  
Jean-Marie Pagès
Keyword(s):  
Outer Membrane ◽  
Early Response ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Membrane Pore ◽  
Bacterial Response ◽  
External Stresses ◽  
Resistant Strains ◽  
Pore Forming Proteins

ABSTRACT Bacterial adaptation to external stresses and toxic compounds is a key step in the emergence of multidrug-resistant strains that are a serious threat to human health. Although some of the proteins and regulators involved in antibiotic resistance mechanisms have been described, no information is available to date concerning the early bacterial response to external stresses. Here we report that the expression of ompX, encoding an outer membrane protein, is increased during early exposure to drugs or environmental stresses. At the same time, the level of ompF porin expression is noticeably affected. Because of the role of these proteins in membrane permeability, these data suggest that OmpF and OmpX are involved in the control of the penetration of antibiotics such as β-lactams and fluoroquinolones through the enterobacterial outer membrane. Consequently, the early control of ompX and ompF induced by external stresses may represent a preliminary response to antibiotics, thus triggering the initial bacterial line of defense against antibiotherapy.

scholarly journals Effects of Therapeutic Ceftiofur Administration to Dairy Cattle on Escherichia coli Dynamics in the Intestinal Tract

2008 ◽  
Vol 74 (22) ◽  
pp. 6956-6962 ◽  
Author(s):  
Randall S. Singer ◽  
Sheila K. Patterson ◽  
Richard L. Wallace
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Treatment ◽  
Antibiotic Use ◽  
Multidrug Resistant ◽  
Causal Link ◽  
Susceptible Population ◽  
E Coli ◽  
Genetic Groups ◽  
Susceptibility Profiles ◽  
Cessation Of Treatment

ABSTRACT The goal of this study was to follow ceftiofur-treated and untreated cattle in a normally functioning dairy to examine enteric Escherichia coli for changes in antibiotic resistance profiles and genetic diversity. Prior to treatment, all of the bacteria cultured from the cows were susceptible to ceftiofur. Ceftiofur-resistant E. coli was only isolated from treated cows during and immediately following the cessation of treatment, and the 12 bla CMY-2-positive isolates clustered into two genetic groups. E. coli bacterial counts dropped significantly in the treated animals (P < 0.027), reflecting a disappearance of the antibiotic-susceptible strains. The resistant bacterial population, however, did not increase in quantity within the treated cows; levels stayed low and were overtaken by a returning susceptible population. There was no difference in the genetic diversities of the E. coli between the treated and untreated cows prior to ceftiofur administration or after the susceptible population of E. coli returned in the treated cows. A cluster analysis of antibiotic susceptibility profiles resulted in six clusters, two of which were multidrug resistant and were comprised solely of isolates from the treated cows immediately following treatment. The antibiotic treatment provided a window to detect the presence of ceftiofur-resistant E. coli but did not appear to cause its emergence or result in its amplification. The finding of resistant isolates following antibiotic treatment is not sufficient to estimate the strength of selection pressure nor is it sufficient to demonstrate a causal link between antibiotic use and the emergence or amplification of resistance.

scholarly journals Post-antibiotic era in hemodialysis? Two case reports of simultaneous colonization and bacteremia by multidrug-resistant bacteria

2020 ◽  
Author(s):  
Johanna M. Vanegas ◽  
Lorena Salazar-Ospina ◽  
Gustavo A. Roncancio ◽  
Julián Builes ◽  
Judy Natalia Jiménez
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Bacterial Infections ◽  
Case Reports ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Control Measures ◽  
Resistant Bacteria ◽  
Multidrug Resistant Bacteria ◽  
E Coli ◽  
Carbapenem Resistant

ABSTRACT The emergence of resistance mechanisms not only limits the therapeutic options for common bacterial infections but also worsens the prognosis in patients who have conditions that increase the risk of bacterial infections. Thus, the effectiveness of important medical advances that seek to improve the quality of life of patients with chronic diseases is threatened. We report the simultaneous colonization and bacteremia by multidrug-resistant bacteria in two hemodialysis patients. The first patient was colonized by carbapenem- and colistin-resistant Klebsiella pneumoniae, carbapenem-resistant Pseudomonas aeruginosa, and methicillin-resistant Staphylococcus aureus (MRSA). The patient had a bacteremia by MRSA, and molecular typing methods confirmed the colonizing isolate was the same strain that caused infection. The second case is of a patient colonized by extended-spectrum beta-lactamases (ESBL)-producing Escherichia coli and carbapenem-resistant Pseudomonas aeruginosa. During the follow-up period, the patient presented three episodes of bacteremia, one of these caused by ESBL-producing E. coli. Molecular methods confirmed colonization by the same clone of ESBL-producing E. coli at two time points, but with a different genetic pattern to the strain isolated from the blood culture. Colonization by multidrug-resistant bacteria allows not only the spread of these microorganisms, but also increases the subsequent risk of infections with limited treatments options. In addition to infection control measures, it is important to establish policies for the prudent use of antibiotics in dialysis units.

scholarly journals Outpatient prescribing of four major antibiotic classes and prevalence of antimicrobial resistance in US adults

2018 ◽  
Author(s):  
Edward Goldstein ◽  
Derek R. MacFadden ◽  
Robyn S. Lee ◽  
Marc Lipsitch
Keyword(s):  
Antibiotic Resistance ◽  
Age Groups ◽  
Antibiotic Use ◽  
Fluoroquinolone Resistance ◽  
Limited Information ◽  
E Coli ◽  
Atlas Data ◽  
Average Annual Temperature ◽  
The Us ◽  
Tract Infections

AbstractBackgroundThere is limited information on the relation between antibiotic use and antibiotic resistance in the US.MethodsWe used multivariable logistic regression to relate state-specific rates of outpatient prescribing overall for fluoroquinolones, penicillins, macrolides, and cephalosporins between 2011-2014 to state-specific prevalence of resistance for select combinations of antibiotics/bacteria among catheter-associated urinary tract infections (CAUTIs) in the CDC Patient Safety Atlas data between 2011-2014 for adults aged 65+y and 19-64y, adjusting for potential confounders.ResultsRates of fluoroquinolone prescribing were positively associated with prevalence of fluoroquinolone resistance in Escherichia coli and Pseudomonas aeruginosa (both age groups), resistance to extended-spectrum (ES) cephalosporins in E. coli (aged 19-64y), and resistance to methicillin in Staphylococcus aureus (aged 19-64y). Rates of penicillin prescribing were positively associated with prevalence of resistance to fluoroquinolones in E. coli (aged 65+) and P. aeruginosa (both age groups), and resistance to ES cephalosporins in Klebsiella spp. (both age groups). Rates of cephalosporin prescribing were negatively associated with prevalence of resistance to fluoroquinolones in E. coli and resistance to ES cephalosporins in Klebsiella spp. (both age groups). Average annual temperature was positively associated with prevalence of resistance to ES cephalosporins in E. coli and P. aeruginosa, and resistance to fluoroquinolones in E. coli.ConclusionsOur results suggest that prescribing of fluoroquinolones and penicillins to US adults is associated with prevalence of antibiotic resistance, including ESBLs and MRSA. Further work is needed to understand the potential benefit of replacing fluoroquinolones and penicillins by other antibiotics for reducing prevalence of antibiotic resistance.

scholarly journals Review of Ceftazidime-Avibactam for the Treatment of Infections Caused by Pseudomonas aeruginosa

Antibiotics ◽  
2021 ◽  
Vol 10 (9) ◽  
pp. 1126
Author(s):  
George L. Daikos ◽  
Clóvis Arns da da Cunha ◽  
Gian Maria Rossolini ◽  
Gregory G. Stone ◽  
Nathalie Baillon-Plot ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Multidrug Resistant ◽  
Resistance Mechanisms ◽  
Real World Data ◽  
Serious Infections ◽  
Tract Infections ◽  
Abdominal Infections ◽  
Hospital Acquired

Pseudomonas aeruginosa is an opportunistic Gram-negative pathogen that causes a range of serious infections that are often challenging to treat, as this pathogen can express multiple resistance mechanisms, including multidrug-resistant (MDR) and extensively drug-resistant (XDR) phenotypes. Ceftazidime–avibactam is a combination antimicrobial agent comprising ceftazidime, a third-generation semisynthetic cephalosporin, and avibactam, a novel non-β-lactam β-lactamase inhibitor. This review explores the potential role of ceftazidime–avibactam for the treatment of P. aeruginosa infections. Ceftazidime–avibactam has good in vitro activity against P. aeruginosa relative to comparator β-lactam agents and fluoroquinolones, comparable to amikacin and ceftolozane–tazobactam. In Phase 3 clinical trials, ceftazidime–avibactam has generally demonstrated similar clinical and microbiological outcomes to comparators in patients with complicated intra-abdominal infections, complicated urinary tract infections or hospital-acquired/ventilator-associated pneumonia caused by P. aeruginosa. Although real-world data are limited, favourable outcomes with ceftazidime–avibactam treatment have been reported in some patients with MDR and XDR P. aeruginosa infections. Thus, ceftazidime–avibactam may have a potentially important role in the management of serious and complicated P. aeruginosa infections, including those caused by MDR and XDR strains.

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