scholarly journals High rates of human faecal carriage of mcr-1-positive multi-drug resistant isolates emerge in China in association with successful plasmid families

2017 ◽  
Author(s):  
Lan-Lan Zhong ◽  
Hang TT Phan ◽  
Xi Huang ◽  
Karina Doris-Vihta ◽  
Anna E Sheppard ◽  
...  

SynopsisBackgroundmcr-1-mediated transmissible colistin resistance in Enterobacteriaceae is concerning, given colistin is frequently used as a treatment of last resort in multidrug-resistant Enterobacteriaceae infections. Reported rates of human mcr-1 gastrointestinal carriage have historically been low.ObjectivesTo identify trends in human gastrointestinal carriage of mcr-1 positive and mcr-1-positive/cefotaxime-resistant Enterobacteriaceae in Guangzhou, China, 2011-2016, and investigate the genetic contexts of mcr-1 in a subset of mcr-1-positive/cefotaxime-resistant strains using whole genome sequencing (WGS).MethodsOf 8,022 faecal samples collected, 497 (6.2%) were mcr-1- positive, and 182 (2.3%) mcr-1-positive/cefotaxime-resistant. Trends in carriage were assessed using iterative sequential regression. A subset of mcr-1-positive isolates was sequenced (Illumina), and genetic contexts of mcr-1 were characterised.ResultsWe observed marked increases in mcr-1 (now ~30% prevalence) and more recent (since January 2014) increases in mcr-1-positive/third-generation cephalosporin-resistant Enterobacteriaceae human colonisation (p<0.001). Sub-cultured mcr-1-positive/third-generation cephalosporin-resistant isolates were commonly multi-drug resistant.WGS of 50 mcr-1/third-generation cephalosporin-resistant isolates (49 Escherichia coli; 1 Klebsiella pneumoniae) demonstrated bacterial strain diversity (39 E. coli sequence types); mcr-1 in association with common plasmid backbones (IncI, IncHI2/HI2A, IncX4) and sometimes in multiple plasmids; frequent mcr-1 chromosomal integration; and loss of the mcr-1-associated insertion sequence ISApl1 in some plasmids. Significant sequence similarity with published mcr-1 plasmid sequences was consistent with spread amongst pig, chicken and human reservoirs.ConclusionsThe high positivity rate (~10%) of mcr-1 in multidrug-resistant E. coli colonising humans is a clinical threat; the diverse genetic mechanisms (strains/plasmids/insertion sequences) associated with mcr-1 have likely contributed to its dissemination, and will facilitate its persistence.

Author(s):  
Kathleen M. Kurowski ◽  
Rachel Marusinec ◽  
Heather K. Amato ◽  
Carlos Saraiva-Garcia ◽  
Fernanda Loayza ◽  
...  

Extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL), a family of bacteria that includes Escherichia coli, have emerged as a global health threat. This study examined risks associated with carriage of third-generation cephalosporin-resistant (3GC-R) E. coli, including ESBL-producing, multidrug-resistant, and extensively drug-resistant (XDR) strains in children living in semirural parishes of Quito, Ecuador. We conducted a longitudinal study with two cycles of sampling (N = 374, N = 366) that included an analysis of child fecal samples and survey questions relating to water, sanitation, and hygiene, socioeconomic status, household crowding, and animal ownership. We used multivariate regression models to assess risk factors associated with a child being colonized. Across the two cycles, 18.4% (n = 516) of the 3GC-R isolates were ESBL-producing E. coli, and 40.3% (n = 516) were XDR E. coli. Children living in households that owned between 11 and 20 backyard animals had an increased odds of being colonized with XDR E. coli (odds ratio [OR] = 1.94, 95% confidence interval [CI]: 1.05–3.60) compared with those with no animals. Households that reported smelling odors from commercial poultry had increased odds of having a child positive for XDR E. coli (OR = 1.72, 95% CI: 1.11–2.66). Our results suggest that colonization of children with antimicrobial-resistant E. coli is influenced by exposure to backyard and commercial livestock and poultry. Future studies should consider community-level risk factors because child exposures to drug-resistant bacteria are likely influenced by neighborhood and regional risk factors.


2018 ◽  
Author(s):  
Latania K. Logan ◽  
Rachel L. Medernach ◽  
Jared R. Rispens ◽  
Steven H. Marshall ◽  
Andrea M. Hujer ◽  
...  

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.


2020 ◽  
Author(s):  
Hadeel Alkofide ◽  
Abdullah Alhammad ◽  
Alya Alruwaili ◽  
Ahmed Aldemerdash ◽  
Thamer Almangour ◽  
...  

Abstract Background. Highly resistant gram-negative bacteria (GNB) is a global public health threat, especially in intensive care units (ICU). The purpose of this study is to explore the prevalence of drug resistant Enterobacteriaceae infections at an Intensive Care Unit (ICU) in Saudi Arabia. It also aims to assess the appropriateness of therapies used and whether these therapies improved clinical outcomes. Methods. A retrospective study was conducted from 2015 to 2018 in a tertiary hospital ICUs in Saudi Arabia. Positive cultures for multidrug-resistant (MDR), extensive drug resistant (XDR), and pan drug-resistant (PDR) Enterobacteriaceae: Klebsiella pneumoniae (K. pneumonia), Escherichia coli (E. coli), and Enterobacter species were included. Primary outcome was microbiological cure and 30 days in hospital mortality rates; while secondary outcome was length of hospital stay (LOS). Regression models were used to assess the relationship between appropriateness of therapy and outcomes. Results. This study included 227 Enterobacteriaceae cultures in which 60% were either MDR (n=130) or XDR (n=8) infections; no PDR Enterobacteriaceae cultures were identified. The average subjects’ age was 60.1±17.7 years and 54% were females. Half of the MDR/XDR cultures were E. coli, followed by 33% K. pneumoniae, and 16% Enterobacter infection. The most common antibiotics used were piperacillin/tazobactam (53%), followed by carbapenems (47%) and cephalosporins (21.3%). Antibiotic therapy was considered appropriate in 85 out of 138 (61.59%) subjects only. In-hospital death was 84%, microbiological cure rate was achieved in 40% of cases, and the average LOS was 27 days. Appropriateness of antibiotic therapy prescribed was not a predictor of any of the study clinical outcomes. Conclusion. In this study, there was a high prevalence of resistant Enterobacteriaceae infections, which were associated with a high mortality rate. This warrants the need to assess the effectiveness of antimicrobial stewardship program and infection prevention and control practices particularly in critically ill patients.


Trials ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Adam G. Stewart ◽  
Patrick N. A. Harris ◽  
Mark D. Chatfield ◽  
Roberta Littleford ◽  
David L. Paterson

Abstract Background Extended-spectrum beta-lactamase (ESBL) and AmpC-producing Enterobacterales are common causes of bloodstream infection. ESBL-producing bacteria are typically resistant to third-generation cephalosporins and result in a sizeable economic and public health burden. AmpC-producing Enterobacterales may develop third-generation cephalosporin resistance through enzyme hyper-expression. In no observational study has the outcome of treatment of these infections been surpassed by carbapenems. Widespread use of carbapenems may drive the development of carbapenem-resistant Gram-negative bacilli. Methods This study will use a multicentre, parallel group open-label non-inferiority trial design comparing ceftolozane-tazobactam and meropenem in adult patients with bloodstream infection caused by ESBL or AmpC-producing Enterobacterales. Trial recruitment will occur in up to 40 sites in six countries (Australia, Singapore, Italy, Spain, Saudi Arabia and Lebanon). The sample size is determined by a predefined quantity of ceftolozane-tazobactam to be supplied by Merck, Sharpe and Dohme (MSD). We anticipate that a trial with 600 patients contributing to the primary outcome analysis would have 80% power to declare non-inferiority with a 5% non-inferiority margin, assuming a 30-day mortality of 5% in both randomised groups. Once randomised, definitive treatment will be for a minimum of 5 days and a maximum of 14 days with the total duration determined by treating clinicians. Data describing demographic information, risk factors, concomitant antibiotics, illness scores, microbiology, multidrug-resistant organism screening, discharge and mortality will be collected. Discussion Participants will have bloodstream infection due to third-generation cephalosporin non-susceptible E. coli and Klebsiella spp. or Enterobacter spp., Citrobacter freundii, Morganella morganii, Providencia spp. or Serratia marcescens. They will be randomised 1:1 to ceftolozane-tazobactam 3 g versus meropenem 1 g, both every 8 h. Secondary outcomes will be a comparison of 14-day all-cause mortality, clinical and microbiological success at day 5, functional bacteraemia score, microbiological relapse, new bloodstream infection, length of hospital stay, serious adverse events, C. difficile infection, multidrug-resistant organism colonisation. The estimated trial completion date is December 2024. Trial registration The MERINO-3 trial is registered under the US National Institute of Health ClinicalTrials.gov register, reference number: NCT04238390. Registered on 23 January 2020.


2013 ◽  
Vol 57 (12) ◽  
pp. 6351-6353 ◽  
Author(s):  
Claire Chauvin ◽  
Laetitia Le Devendec ◽  
Eric Jouy ◽  
Maena Le Cornec ◽  
Sylvie Francart ◽  
...  

ABSTRACTResistance ofEscherichia colito third-generation cephalosporin (3GC) in fecal samples representative of French egg production was studied. The susceptibility to cefotaxime ofE. coliisolates obtained by culture on nonselective media was determined. Twenty-two nonsusceptible isolates were obtained (7.51%; 95% confidence interval, 4.49 to 10.54%), the majority of which came from young birds. Most isolates carried ablaCTX-M-1group gene, and a few carried ablaCMY-2-like gene. Control of 3GC resistance in laying hens is needed.


Author(s):  
Xuemei Zhen ◽  
Cecilia Stålsby Lundborg ◽  
Xueshan Sun ◽  
Xiaoqian Hu ◽  
Hengjin Dong

Quantifying economic and clinical outcomes for interventions could help to reduce third-generation cephalosporin resistance and Escherichia coli or Klebsiella pneumoniae. We aimed to compare the differences in clinical and economic burden between third-generation cephalosporin-resistant E. coli (3GCREC) and third-generation cephalosporin-susceptible E. coli (3GCSEC) cases, and between third-generation cephalosporin-resistant K. pneumoniae (3GCRKP) and third-generation cephalosporin-susceptible K. pneumoniae (3GCSKP) cases. A retrospective and multicenter study was conducted. We collected data from electronic medical records for patients who had clinical samples positive for E. coli or K. pneumoniae isolates during 2013 and 2015. Propensity score matching (PSM) was conducted to minimize the impact of potential confounding variables, including age, sex, insurance, number of diagnoses, Charlson comorbidity index, admission to intensive care unit, surgery, and comorbidities. We also repeated the PSM including length of stay (LOS) before culture. The main indicators included economic costs, LOS and hospital mortality. The proportions of 3GCREC and 3GCRKP in the sampled hospitals were 44.3% and 32.5%, respectively. In the two PSM methods, 1804 pairs and 1521 pairs were generated, and 1815 pairs and 1617 pairs were obtained, respectively. Compared with susceptible cases, those with 3GCREC and 3GCRKP were associated with significantly increased total hospital cost and excess LOS. Inpatients with 3GCRKP were significantly associated with higher hospital mortality compared with 3GCSKP cases, however, there was no significant difference between 3GCREC and 3GCSEC cases. Cost reduction and outcome improvement could be achieved through a preventative approach in terms of both antimicrobial stewardship and preventing the transmission of organisms.


2008 ◽  
Vol 35 (5) ◽  
pp. 862-870 ◽  
Author(s):  
Elisabeth Meyer ◽  
Matthias Lapatschek ◽  
Andreas Bechtold ◽  
Gerhard Schwarzkopf ◽  
Petra Gastmeier ◽  
...  

2014 ◽  
Vol 77 (8) ◽  
pp. 1394-1401 ◽  
Author(s):  
KANJANA CHANGKAEW ◽  
FUANGFA UTRARACHKIJ ◽  
KANOKRAT SIRIPANICHGON ◽  
CHIE NAKAJIMA ◽  
ORASA SUTHIENKUL ◽  
...  

Antimicrobial resistance in bacteria associated with food and water is a global concern. To survey the risk, 312 Escherichia coli isolates from shrimp farms and markets in Thailand were examined for susceptibility to 10 antimicrobials. The results showed that 17.6% of isolates (55 of 312) were resistant to at least one of the tested drugs, and high resistance rates were observed to tetracycline (14.4%; 45 of 312), ampicillin (8.0%; 25 of 312), and trimethroprim (6.7%; 21 of 312); 29.1% (16 of 55) were multidrug resistant. PCR assay of the tet(A), tet(B), tet(C), tet(D), tet(E), and tet(G) genes detected one or more of these genes in 47 of the 55 resistant isolates. Among these genes, tet(A) (69.1%; 38 of 55) was the most common followed by tet(B) (56.4%; 31 of 55) and tet(C) (3.6%; 2 of 55). The resistant isolates were further investigated for class 1 integrons. Of the 55 resistant isolates, 16 carried class 1 integrons and 7 carried gene cassettes encoding trimethoprim resistance (dfrA12 or dfrA17) and aminoglycosides resistance (aadA2 or aadA5). Two class 1 integrons, In54 (dfrA17-aadA5) and In27 (dfrA12-orfF-aadA2), were found in four and three isolates, respectively. These results indicate a risk of drug-resistant E. coli contamination in shrimp farms and selling places. The occurrence of multidrug-resistant E. coli carrying tet genes and class 1 integrons indicates an urgent need to monitor the emergence of drug-resistant E. coli to control the dissemination of drug-resistant strains and the further spread of resistance genes to other pathogenic bacteria.


2013 ◽  
Vol 79 (18) ◽  
pp. 5559-5565 ◽  
Author(s):  
Can Zhang ◽  
Wenli Li ◽  
Wenhua Liu ◽  
Ling Zou ◽  
Chen Yan ◽  
...  

ABSTRACTChicken-pathogenicEscherichia coliis severely endangering the poultry industry in China and worldwide, and antibiotic therapy is facing an increasing problem of antibiotic resistance. Bacteriophages can kill bacteria with no known activity in human or animal cells, making them an attractive alternative to antibiotics. In this study, we present the characteristics of a novel virulent bacteriophage, Bp7, specifically infecting pathogenic multidrug-resistantE. coli. Phage Bp7 was isolated from chicken feces. Bp7 belongs to the familyMyoviridae, possessing an elongated icosahedral head and contractile sheathed tail. It has a 168-kb double-stranded DNA genome. For larger yields, its optimal multiplicity of infection (MOI) to infectE. coliwas about 0.001. The latent period was 10 to 15 min, and the burst size was 90 PFU/infected cell. It was stable both at pH 5.0 to 10.0 and at 40°C or 50°C for at least 1 h. Bp7 could infect 46% of pathogenic clinicalE. colistrains. Bp7 harbored 791 open reading frames (ORFs) and 263 possible genes. Among the 263 genes, 199 possessed amino acid sequence identities with ORFs of phage T4, 62 had identities with other T4-like phages, and only one lacked any database match. The genome of Bp7 manifested obvious division and rearrangement compared to phages T4, JS98, and IME08. Bp7 is a new member of the “T4-like” genus, familyMyoviridae. Its wide host range, strong cell-killing activity, and high stability to pH make it an alternative to antimicrobials for controlling drug-resistantE. coliin chickens.


Antibiotics ◽  
2021 ◽  
Vol 11 (1) ◽  
pp. 23
Author(s):  
Andrea Feuerstein ◽  
Nelly Scuda ◽  
Corinna Klose ◽  
Angelika Hoffmann ◽  
Alexander Melchner ◽  
...  

Worldwide, enterotoxigenic Escherichia coli (ETEC) cause neonatal diarrhea and high mortality rates in newborn calves, leading to great economic losses. In Bavaria, Germany, no recent facts are available regarding the prevalence of virulence factors or antimicrobial resistance of ETEC in calves. Antimicrobial susceptibility of 8713 E. coli isolates obtained from 7358 samples of diseased or deceased diarrheic calves were investigated between 2015 to 2019. Considerably high rates of 84.2% multidrug-resistant and 15.8% extensively drug-resistant isolates were detected. The resistance situation of the first, second and third line antimicrobials for the treatment, here amoxicillin-clavulanate, enrofloxacin and trimethoprim-sulfamethoxazole, is currently acceptable with mean non-susceptibility rates of 28.1%, 37.9% and 50.0% over the investigated 5-year period. Furthermore, the ETEC serotypes O101:K28, O9:K35, O101:K30, O101:K32, O78:K80, O139:K82, O8:K87, O141:K85 and O147:K89, as well as the virulence factors F17, F41, F5, ST-I and stx1 were identified in a subset of samples collected in 2019 and 2020. The substantially high rates of multi- and extensively drug-resistant isolates underline the necessity of continuous monitoring regarding antimicrobial resistance to provide reliable prognoses and adjust recommendations for the treatment of bacterial infections in animals.


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