scholarly journals Uncovering novel susceptibility targets to enhance the efficacy of third-generation cephalosporins against ESBL-producing uropathogenic Escherichia coli

2020 ◽  
Vol 75 (6) ◽  
pp. 1415-1423 ◽  
Author(s):  
Minh-Duy Phan ◽  
Amy L Bottomley ◽  
Kate M Peters ◽  
Elizabeth J Harry ◽  
Mark A Schembri

Abstract Background Uropathogenic Escherichia coli (UPEC) are a major cause of urinary tract infection (UTI), one of the most common infectious diseases in humans. UPEC are increasingly associated with resistance to multiple antibiotics. This includes resistance to third-generation cephalosporins, a common class of antibiotics frequently used to treat UTI. Methods We employed a high-throughput genome-wide screen using saturated transposon mutagenesis and transposon directed insertion-site sequencing (TraDIS) together with phenotypic resistance assessment to identify key genes required for survival of the MDR UPEC ST131 strain EC958 in the presence of the third-generation cephalosporin cefotaxime. Results We showed that blaCMY-23 is the major ESBL gene in EC958 responsible for mediating resistance to cefotaxime. Our screen also revealed that mutation of genes involved in cell division and the twin-arginine translocation pathway sensitized EC958 to cefotaxime. The role of these cell-division and protein-secretion genes in cefotaxime resistance was confirmed through the construction of mutants and phenotypic testing. Mutation of these genes also sensitized EC958 to other cephalosporins. Conclusions This work provides an exemplar for the application of TraDIS to define molecular mechanisms of resistance to antibiotics. The identification of mutants that sensitize UPEC to cefotaxime, despite the presence of a cephalosporinase, provides a framework for the development of new approaches to treat infections caused by MDR pathogens.

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.


2015 ◽  
Vol 53 (9) ◽  
pp. 3035-3038 ◽  
Author(s):  
Ryuji Kawahara ◽  
Kazuko Seto ◽  
Masumi Taguchi ◽  
Chie Nakajima ◽  
Yuko Kumeda ◽  
...  

We isolated Shiga toxin-producingEscherichia coliO157:H7 strains resistant to third-generation cephalosporins. The resistant strains harboredblaCMY-2, a plasmid-mediated AmpC β-lactamase. Genotyping of isolates revealed the possible spread of this problematic bacterium. Results suggested the importance of the investigation and surveillance of enterobacteria with plasmids harboringblaCMY-2.


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.


2012 ◽  
Vol 73 (1) ◽  
pp. 31-38 ◽  
Author(s):  
Andrea Endimiani ◽  
Alexandra Rossano ◽  
Daniel Kunz ◽  
Gudrun Overesch ◽  
Vincent Perreten

Author(s):  
Dabor Résière ◽  
Claude Olive ◽  
Hatem Kallel ◽  
André Cabié ◽  
Rémi Névière ◽  
...  

In Martinique, Bothrops lanceolatus snakebite, although relatively uncommon (~30 cases/year), may result in serious complications such as systemic thrombosis and local infections. Infections have been hypothesized to be related to bacteria present in the snake’s oral cavity. In this investigation, we isolated, identified, and studied the susceptibility to beta-lactams of bacteria sampled from the oral cavity of twenty-six B. lanceolatus specimens collected from various areas in Martinique. Microbiota from B. lanceolatus oral cavity was polymicrobial. Isolated bacteria belonged to fifteen different taxa; the most frequent being Aeromonas hydrophyla (present in 50% of the samples), Morganella morganii, Klebsiella pneumoniae, Bacillus spp., and Enterococcus spp. Analysis of antibiotic susceptibility revealed that 66.7% of the isolated bacteria were resistant to amoxicillin/clavulanate. In contrast, the majority of isolated bacteria were susceptible to the third-generation cephalosporins (i.e., 73.3% with cefotaxime and 80.0% with ceftazidime). Microbiota from B. lanceolatus oral cavity is polymicrobial with bacteria mostly susceptible to third-generation cephalosporins but rarely to amoxicillin/clavulanate. In conclusion, our findings clearly support that first-line antibiotic therapy in the B. lanceolatus-bitten patients, when there is evidence of infection, should include a third-generation cephalosporin rather than amoxicillin/clavulanate.


2019 ◽  
Vol 12 (11) ◽  
pp. e232884 ◽  
Author(s):  
Ashley Ferro ◽  
Meryl Griffiths ◽  
Rona Smith ◽  
Andrew Fry

We present the case of ceftazidime-induced immune-mediated haemolysis with associated acute kidney injury in a 43-year-old woman. The patient initially presented to the regional cystic fibrosis centre for treatment of an infective exacerbation of cystic fibrosis. After initiation of ceftazidime (a third-generation cephalosporin), renal function rapidly deteriorated and a fall in haemoglobin was noted. On transfer to our care, a haemolysis screen identified immune-mediated haemolysis, and renal biopsy confirmed the finding of acute tubular necrosis secondary to haem pigment. The patient’s renal function deteriorated such that she required haemodialysis, although she subsequently recovered and is now dialysis-independent. Although acute haemolytic reactions are recognised with third-generation cephalosporins, this is the first reported case of ceftazidime-induced immune-mediated haemolysis with acute kidney injury. Given the increased frequency of cephalosporin usage, it is important for both nephrologists and general physicians to be aware of this rare but very serious complication.


2017 ◽  
Vol 61 (9) ◽  
Author(s):  
Jin Seok Kim ◽  
Jungsun Park ◽  
Eunkyung Shin ◽  
Soojin Kim ◽  
Sung Suck Oh ◽  
...  

ABSTRACT We investigated an outbreak of enterotoxigenic Escherichia coli (ETEC) O159:H20 associated with the consumption of a tossed-noodle dish in a high school in 2016. Thirty-three ETEC strains isolated from clinical and food samples were genetically indistinguishable. The outbreak strains were resistant to third-generation cephalosporins and harbored a bla CTX-M-15 gene on a 97-kb self-transferable IncK plasmid. This is the first outbreak caused by CTX-M-15-producing ETEC strains.


2018 ◽  
Vol 2018 ◽  
pp. 1-7 ◽  
Author(s):  
Fanta Gashe ◽  
Eshetu Mulisa ◽  
Mekidim Mekonnen ◽  
Gemechu Zeleke

Background. Drug resistant microorganisms lead to an increase in morbidity and mortality as they boost the risk of inappropriate therapy. Hence, data on antimicrobial resistance help define the best possible treatment for individual patients. Therefore, this study aimed to screen the antimicrobial resistant profile of 3rd generation cephalosporin drugs in Jimma University Specialized Teaching Hospital. Methods. A hospital based prospective cross-sectional study was conducted in Jimma University Specialized Hospital (JUSH) from April to August 2016. The clinical samples such as wound swab, urine, sputum, and stool were collected from hospitalized patients. Then, bacterial species were isolated and identified as per the standard microbiological methods. Antimicrobial susceptibility tests were carried out using various antimicrobial discs by Kirby–Bauer disc diffusion method. Results. Totally, 248 bacterial isolates were obtained from 154 (62.1%) male and 94 (37.9%) female patients. Escherichia coli (25.4%) and Staphylococcus aureus (19.0 %) were the predominant organisms isolated from specimens. About 140 (56.5%) and 149 (60.1%) of the total bacterial isolates were found to be resistant to ceftriaxone and ceftazidime, respectively. The majority of Escherichia coli isolates 46 (73%) were resistant to ceftriaxone and 41 (65%) of them were resistant to ceftazidime. Staphylococcus aureus, which accounted 19% of the total bacterial isolates, showed 23.4% and 34% resistance to ceftriaxone and ceftazidime, respectively. Among the bacterial strains revealing resistant to ceftriazone and ceftazidime, about 109 (44%) and 108 (43.5%) of them were resistant to two, three, or four other drugs, respectively. Conclusion. Bacterial resistance towards third-generation cephalosporin (ceftriaxone and ceftazidime) is escalating as more than half of the isolated strains demonstrated resistance to these drugs. Moreover, these strains also revealed multidrug resistance mainly against clinically used drugs which could render therapy unsuccessful. Therefore, in clinical use appropriate medications should be selected based on the data obtained from antimicrobial susceptibility tests.


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