scholarly journals Role of Ceftiofur in Selection and Dissemination of blaCMY-2-Mediated Cephalosporin Resistance in Salmonella enterica and Commensal Escherichia coli Isolates from Cattle

2009 ◽  
Vol 75 (11) ◽  
pp. 3648-3655 ◽  
Author(s):  
Joshua B. Daniels ◽  
Douglas R. Call ◽  
Dale Hancock ◽  
William M. Sischo ◽  
Katherine Baker ◽  
...  

ABSTRACT Third-generation cephalosporin resistance of Salmonella and commensal Escherichia coli isolates from cattle in the United States is predominantly conferred by the cephamycinase CMY-2, which inactivates β-lactam antimicrobial drugs used to treat a wide variety of infections, including pediatric salmonellosis. The emergence and dissemination of bla CMY-2 --bearing plasmids followed and may in part be the result of selection pressure imposed by the widespread utilization of ceftiofur, a third-generation veterinary cephalosporin. This study assessed the potential effects of ceftiofur on bla CMY-2 transfer and dissemination by (i) an in vivo experimental study in which calves were inoculated with competent bla CMY-2-bearing plasmid donors and susceptible recipients and then subjected to ceftiofur selection and (ii) an observational study to determine whether ceftiofur use in dairy herds is associated with the occurrence and frequency of cephalosporin resistance in Salmonella and commensal E. coli. The first study revealed bla CMY-2 plasmid transfer in both ceftiofur-treated and untreated calves but detected no enhancement of plasmid transfer associated with ceftiofur treatment. The second study detected no association (P = 0.22) between ceftiofur use and either the occurrence of ceftiofur-resistant salmonellosis or the frequency of cephalosporin resistance in commensal E. coli. However, herds with a history of salmonellosis (including both ceftiofur-resistant and ceftiofur-susceptible Salmonella isolates) used more ceftiofur than herds with no history of salmonellosis (P = 0.03) These findings fail to support a major role for ceftiofur use in the maintenance and dissemination of bla CMY-2-bearing plasmid mediated cephalosporin resistance in commensal E. coli and in pathogenic Salmonella in these dairy cattle populations.

Author(s):  
Melissa C. MacKinnon ◽  
Scott A. McEwen ◽  
David L. Pearl ◽  
Outi Lyytikäinen ◽  
Gunnar Jacobsson ◽  
...  

Abstract Background Escherichia coli is an important pathogen in humans and is the most common cause of bacterial bloodstream infections (BSIs). The objectives of our study were to determine factors associated with E. coli BSI incidence rate and third-generation cephalosporin resistance in a multinational population-based cohort. Methods We included all incident E. coli BSIs (2014–2018) from national (Finland) and regional (Australia [Canberra], Sweden [Skaraborg], and Canada [Calgary, Sherbrooke, and western interior]) surveillance. Incidence rates were directly age and sex standardized to the European Union 28-country 2018 population. Multivariable negative binomial and logistic regression models estimated factors significantly associated with E. coli BSI incidence rate and third-generation cephalosporin resistance, respectively. The explanatory variables considered for inclusion in both models were year (2014–2018), region (six areas), age (< 70-years-old and ≥ 70-years-old), and sex (female and male). Results We identified 31,889 E. coli BSIs from 40.7 million person-years of surveillance. Overall and third-generation cephalosporin-resistant standardized rates were 87.1 and 6.6 cases/100,000 person-years, respectively, and increased 14.0% and 40.1% over the five-year study. Overall, 7.8% (2483/31889) of E. coli BSIs were third-generation cephalosporin-resistant. Calgary, Canberra, Sherbrooke, and western interior had significantly lower E. coli BSI rates compared to Finland. The significant association between age and E. coli BSI rate varied with sex. Calgary, Canberra, and western interior had significantly greater odds of third-generation cephalosporin-resistant E. coli BSIs compared to Finland. Compared to 2014, the odds of third-generation cephalosporin-resistant E. coli BSIs were significantly increased in 2016, 2017, and 2018. The significant association between age and the odds of having a third-generation cephalosporin-resistant E. coli BSI varied with sex. Conclusions Increases in overall and third-generation cephalosporin-resistant standardized E. coli BSI rates were clinically important. Overall, E. coli BSI incidence rates were 40–104% greater than previous investigations from the same study areas. Region, sex, and age are important variables when analyzing E. coli BSI rates and third-generation cephalosporin resistance in E. coli BSIs. Considering E. coli is the most common cause of BSIs, this increasing burden and evolving third-generation cephalosporin resistance will have an important impact on human health, especially in aging populations.


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.


mBio ◽  
2016 ◽  
Vol 7 (2) ◽  
Author(s):  
Nicole Stoesser ◽  
Anna E. Sheppard ◽  
Louise Pankhurst ◽  
Nicola De Maio ◽  
Catrin E. Moore ◽  
...  

ABSTRACT Escherichia coli sequence type 131 (ST131) has emerged globally as the most predominant extraintestinal pathogenic lineage within this clinically important species, and its association with fluoroquinolone and extended-spectrum cephalosporin resistance impacts significantly on treatment. The evolutionary histories of this lineage, and of important antimicrobial resistance elements within it, remain unclearly defined. This study of the largest worldwide collection ( n = 215) of sequenced ST131 E. coli isolates to date demonstrates that the clonal expansion of two previously recognized antimicrobial-resistant clades, C1/ H 30R and C2/ H 30Rx, started around 25 years ago, consistent with the widespread introduction of fluoroquinolones and extended-spectrum cephalosporins in clinical medicine. These two clades appear to have emerged in the United States, with the expansion of the C2/ H 30Rx clade driven by the acquisition of a bla CTX-M-15 -containing IncFII-like plasmid that has subsequently undergone extensive rearrangement. Several other evolutionary processes influencing the trajectory of this drug-resistant lineage are described, including sporadic acquisitions of CTX-M resistance plasmids and chromosomal integration of bla CTX-M within subclusters followed by vertical evolution. These processes are also occurring for another family of CTX-M gene variants more recently observed among ST131, the bla CTX-M-14/14-like group. The complexity of the evolutionary history of ST131 has important implications for antimicrobial resistance surveillance, epidemiological analysis, and control of emerging clinical lineages of E. coli . These data also highlight the global imperative to reduce specific antibiotic selection pressures and demonstrate the important and varied roles played by plasmids and other mobile genetic elements in the perpetuation of antimicrobial resistance within lineages. IMPORTANCE Escherichia coli , perennially a major bacterial pathogen, is becoming increasingly difficult to manage due to emerging resistance to all preferred antimicrobials. Resistance is concentrated within specific E. coli lineages, such as sequence type 131 (ST131). Clarification of the genetic basis for clonally associated resistance is key to devising intervention strategies. We used high-resolution genomic analysis of a large global collection of ST131 isolates to define the evolutionary history of extended-spectrum beta-lactamase production in ST131. We documented diverse contributory genetic processes, including stable chromosomal integrations of resistance genes, persistence and evolution of mobile resistance elements within sublineages, and sporadic acquisition of different resistance elements. Both global distribution and regional segregation were evident. The diversity of resistance element acquisition and propagation within ST131 indicates a need for control and surveillance strategies that target both bacterial strains and mobile genetic elements.


1993 ◽  
Vol 27 (7-8) ◽  
pp. 870-873 ◽  
Author(s):  
Sandra L. Preston ◽  
Laurie L. Briceland

OBJECTIVE: To report a case of gram-negative bacillary meningitis (GNBM) secondary to cephalosporin-resistant Escherichia coli that was treated with intrathecal and intravenous amikacin and intravenous imipenem/cilastatin (I/C). CASE SUMMARY: A patient who had undergone two recent neurosurgical procedures developed GNBM and bacteremia. He was treated empirically with ceftazidime. Both bloodstream and cerebrospinal fluid isolates were identified as E. coli, resistant to third-generation cephalosporins, penicillins, tobramycin, and gentamicin. The patient was subsequently treated with intravenous and intrathecal amikacin plus intravenous I/C He experienced subjective and objective improvement on days 2–4 of antimicrobial therapy; two generalized tonic-clonic seizures occurred on days 7 and 12. Intrathecal amikacin was discontinued after 6 days, and intravenous amikacin and I/C were discontinued after 23 and 27 days, respectively. The patient's mental status did not completely return to premeningitis baseline. DISCUSSION: Third-generation cephalosporins are the treatment of choice for GNBM. In the case reported herein, bacterial resistance to these agents prompted the use of a therapy that has not been well studied and is also considered to be less safe and perhaps less efficacious. Treatment of GNBM with an intrathecally administered aminoglycoside or with intravenous I/C plus an aminoglycoside is reviewed. CONCLUSIONS: Patients with GNBM secondary to third-generation cephalosporin-resistant organisms may require therapies that may be less effective and more toxic. Further study of alternative agents is warranted.


2020 ◽  
Vol 75 (9) ◽  
pp. 2471-2479 ◽  
Author(s):  
Maryam Alzayn ◽  
Jacqueline Findlay ◽  
Hannah Schubert ◽  
Oliver Mounsey ◽  
Virginia C Gould ◽  
...  

Abstract Objectives To characterize putative AmpC-hyperproducing third-generation cephalosporin-resistant E. coli from dairy farms and their phylogenetic relationships; to identify risk factors for their presence; and to assess evidence for their zoonotic transmission into the local human population. Methods Proteomics was used to explain differences in antimicrobial susceptibility. WGS allowed phylogenetic analysis. Multilevel, multivariable logistic regression modelling was used to identify risk factors. Results Increased use of amoxicillin/clavulanate was associated with an increased risk of finding AmpC hyperproducers on farms. Expansion of cephalosporin resistance in AmpC hyperproducers was seen in farm isolates with marR mutations (conferring cefoperazone resistance) or when AmpC was mutated (conferring fourth-generation cephalosporin and cefoperazone resistance). Phylogenetic analysis confirmed the dominance of ST88 amongst farm AmpC hyperproducers but there was no evidence for acquisition of farm isolates by members of the local human population. Conclusions Clear evidence was found for recent farm-to-farm transmission of AmpC-hyperproducing E. coli and of adaptive mutations to expand resistance. Whilst there was no evidence of isolates entering the local human population, efforts to reduce third-generation cephalosporin resistance on dairy farms must address the high prevalence of AmpC hyperproducers. The finding that amoxicillin/clavulanate use was associated with an increased risk of finding AmpC hyperproducers is important because this is not currently categorized as a highest-priority critically important antimicrobial and so is not currently targeted for specific usage restrictions in the UK.


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