646. Adapting the modified Carbapenem Inactivation Method to assess for possible beta-lactamase mediated resistance in Piperacillin-Tazobactam resistant/ Ceftriaxone susceptible Escherichia. coli and Klebsiella pneumoniae

Abstract Background A cluster of piperacillin-tazobactam resistant/ceftriaxone susceptible Escherichia coli and Klebsiella pneumonaie bacteremias were noted at our institution. A review of the literature suggested this resistance phenotype was mediated by a beta-lactamase. We sought to further corroborate this phenotypically. Methods We adapted the “carbapenem inactivation method” utilizing piperacillin-tazobactam and ceftriaxone discs on all E. coli and K. pneumoniae isolated from blood and demonstrating piperacillin-tazobactam resistance but with ceftriaxone susceptibility. We utilized pan-susceptible and carbapenem resistance Enterobacteriaceae reference strains as well as third generation cephalosporin resistant, piperacillin-tazobactam susceptible isolates as controls. Results 96% of the piperacillin-tazobactam resistant, ceftriaxone susceptible strains demonstrated the capacity to degrade the piperacillin-tazobactam discs while 100% spared the ceftriaxone discs. 75% of the piperacillin-tazobactam susceptible, ceftriaxone resistant control strains spared the piperacillin-tazobactam discs while degrading the ceftriaxone discs. Conclusion The resistance phenotype observed is due to beta-lactamase production and the modified carbapenem inactivation method can be adapted to probe for other beta-lactamases. Further study is required to definitively identify which beta-lactamase is responsible. Disclosures All Authors: No reported disclosures

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Activity of Cefiderocol, Ceftazidime-Avibactam, and Eravacycline against Carbapenem-Resistant Escherichia coli Isolates from the United States and International Sites in Relation to Clonal Background, Resistance Genes, Coresistance, and Region

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.00797-20 ◽

2020 ◽

Vol 64 (10) ◽

Cited By ~ 1

Author(s):

Brian D. Johnston ◽

Paul Thuras ◽

Stephen B. Porter ◽

Melissa Anacker ◽

Brittany VonBank ◽

...

Keyword(s):

Escherichia Coli ◽

Carbapenem Resistance ◽

The United States ◽

Asia Pacific ◽

Beta Lactamase ◽

Content Type ◽

Beta Lactamases ◽

E Coli ◽

Carbapenem Resistant ◽

Primary Agent

ABSTRACT Emerging carbapenem resistance in Escherichia coli, including sequence type 131 (ST131), the leading cause of extraintestinal E. coli infections globally, threatens therapeutic efficacy. Accordingly, we determined broth microdilution MICs for three distinctive newer agents, i.e., cefiderocol (CFDC), ceftazidime-avibactam (CZA), and eravacycline (ERV), plus 11 comparators, against 343 carbapenem-resistant (CR) clinical E. coli isolates, then compared susceptibility results with bacterial characteristics and region. The collection comprised 203 U.S. isolates (2002 to 2017) and 141 isolates from 17 countries in Europe, Latin America, and the Asia-West Pacific region (2003 to 2017). Isolates were characterized for phylogenetic group, resistance-associated sequence types (STs) and subsets thereof, and relevant beta-lactamase-encoding genes. CFDC, CZA, and ERV exhibited the highest percent susceptible (82% to 98%) after tigecycline (TGC) (99%); avibactam improved CZA's activity over that of CAZ (11% susceptible). Percent susceptible varied by phylogroup and ST for CFDC and CZA (greatest in phylogroups B2, D, and F, and in ST131, ST405, and ST648). Susceptibility also varied by resistance genotype, being higher with the Klebsiella pneumoniae carbapenemase (KPC) for CZA, lower with metallo-beta-lactamases for CFDC and CZA, and higher with the beta-lactamase CTX-M for ERV. Percent susceptible also varied by global region for CZA (lower in Asia-Pacific) and by U.S. region for ERV (lower in the South and Southeast). Although resistance to comparators often predicted reduced susceptibility to a primary agent (especially CFDC and CZA), even among comparator-resistant isolates the primary-agent-susceptible fraction usually exceeded 50%. These findings clarify the likely utility of CFDC, CZA, and ERV against CR E. coli in relation to multiple bacterial characteristics and geographical region.

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National Prevalence of Resistance to Third-Generation Cephalosporins in Escherichia coli Isolates from Layer Flocks in France

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.01460-13 ◽

2013 ◽

Vol 57 (12) ◽

pp. 6351-6353 ◽

Cited By ~ 13

Author(s):

Claire Chauvin ◽

Laetitia Le Devendec ◽

Eric Jouy ◽

Maena Le Cornec ◽

Sylvie Francart ◽

...

Keyword(s):

Escherichia Coli ◽

Confidence Interval ◽

Egg Production ◽

Generation Cephalosporin ◽

Gene Control ◽

Third Generation ◽

Content Type ◽

E Coli ◽

National Prevalence ◽

Third Generation Cephalosporins

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.

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Clinical and Economic Impact of Third-Generation Cephalosporin-Resistant Infection or Colonization Caused by Escherichia coli and Klebsiella pneumoniae: A Multicenter Study in China

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17249285 ◽

2020 ◽

Vol 17 (24) ◽

pp. 9285

Author(s):

Xuemei Zhen ◽

Cecilia Stålsby Lundborg ◽

Xueshan Sun ◽

Xiaoqian Hu ◽

Hengjin Dong

Keyword(s):

Escherichia Coli ◽

Klebsiella Pneumoniae ◽

Hospital Mortality ◽

Multicenter Study ◽

Generation Cephalosporin ◽

Total Hospital Cost ◽

Third Generation ◽

E Coli ◽

Significant Difference ◽

The Impact

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.

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Properties of IRT-14 (TEM-45), a newly characterized mutant of TEM-type beta-lactamases.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.41.2.374 ◽

1997 ◽

Vol 41 (2) ◽

pp. 374-378 ◽

Cited By ~ 29

Author(s):

M M Caniça ◽

M Barthélémy ◽

L Gilly ◽

R Labia ◽

R Krishnamoorthy ◽

...

Keyword(s):

Escherichia Coli ◽

Kinetic Parameters ◽

Clavulanic Acid ◽

Broad Spectrum ◽

Promoter Region ◽

Beta Lactamase ◽

Beta Lactamases ◽

Structural Modifications ◽

E Coli

IRT-14 (TEM-45) is a new mutant TEM-type beta-lactamase that was isolated from clinical Escherichia coli P37 and that confers resistance to broad-spectrum penicillins with reduced sensitivity to beta-lactamase inhibitors. The MICs of amoxicillin alone and of amoxicillin combined with 2 micrograms of clavulanic acid or 2 micrograms of tazobactam per ml were 4,096, 2,048, and 1,024 micrograms/ml, respectively. The strain was susceptible to cephalosporins, aztreonam, moxalactam, and imipenem. The enzyme was purified to homogeneity, and values of the kinetic parameters Kcat, Km, and Kcat/Km were determined for different substrates. This enzyme, with a pI of 5.2, was found to have reduced affinity for broad-spectrum penicillins and cephalosporins. The values of 50% inhibitory concentrations of clavulanic acid, sulbactam, tazobactam, and brobactam are correlated with the higher KmS for substrates. The resistance of E. coli P37 to mechanism-based inactivators results from a higher level of production of the TEM-derived enzyme due to the G-to-T substitution at position 162 (G-162-->T) in the promoter region of blaTEM and from the structural modifications resulting from the Met-69-->Leu and Arg-275-->Gln substitutions that characterize IRT-14 beta-lactamase.

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Extended-spectrum beta-lactamases producing Escherichia coli and Klebsiella pneumoniaei: A Multi-centric Study Across Karnataka

Journal of Laboratory Physicians ◽

10.4103/0974-2727.129083 ◽

2014 ◽

Vol 6 (01) ◽

pp. 007-013 ◽

Cited By ~ 13

Author(s):

Sridhar PN Rao ◽

Prasad Subba Rama ◽

Vishwanath Gurushanthappa ◽

Radhakrishna Manipura ◽

Krishna Srinivasan

Keyword(s):

Escherichia Coli ◽

Clinical Isolates ◽

Beta Lactamase ◽

Beta Lactam ◽

Esbl Production ◽

Beta Lactamases ◽

E Coli ◽

Karnataka State ◽

Extended Spectrum Beta Lactamases ◽

Esbl Producers

ABSTRACT Background: There are sporadic reports on detection of extended-spectrum beta-lactamases (ESBL) producers from Karnataka; hence, this is a first multicentric study across Karnataka state to determine the prevalence of ESBL production among clinical isolates of Escherichia coli and Klebsiella pneumoniaei. Aims and objectives: To determine the prevalence of ESBL producing clinical isolates of E. coli and K. pneumoniae from five geographically distributed centers across Karnataka, to study the susceptibility of ESBL producing isolates to other beta-lactam and beta-lactam-beta-lactamase inhibitors and to demonstrate transferability of plasmids coding for ESBL phenotype. Materials and Methods: Two hundred isolates of E. coli and K. pneumoniae each were collected from each of the five centers (Bellary, Dharwad, Davangere, Kolar and Mangalore). They were screened for resistance to screening agents (ceftazidime, cefotaxime, ceftriaxone, aztreonam) and positive isolates were confirmed for ESBL production by test described by Clinical and Laboratory Standards Institute . Co-production of ESBL and AmpC beta-lactamase was identified by using amino-phenylboronic acid disk method. Susceptibility of ESBL producers to beta-lactam antibiotics and beta-lactamase inhibitors was performed. Transferability of plasmids was performed by conjugation experiment. Results: Overall prevalence of ESBL production among E. coli and K. pneumoniae across five centers of the state was 57.5%. ESBL production was found to be 61.4% among E. coli and 46.2% among K. pneumoniae. ESBL production was significantly more among E. coli than K. pneumoniae. Significant variations in distribution of ESBL across the state was observed among E. coli isolates, but not among K. pneumoniae isolates. All ESBL producers demonstrated minimum inhibitory concentration levels ≥2 μg/ml towards cefotaxime, ceftazidime and ceftriaxone. Conclusion: Overall prevalence of ESBL production among clinical isolates of E. coli and K. pneumoniae across Karnataka state was high. The prevalence of ESBL production was significantly higher with E. coli than K. pneumoniae isolates. Higher rates of resistance to ceftriaxone and cefotaxime than to ceftazidime suggests the possibility of presence of CTX-M type ESBLs. Of all the beta-lactam/beta-lactamase inhibitor combinations tested, cefepime-tazobactam demonstrated highest in-vitro activity against ESBL producers. There was no statistical difference in the transferability of plasmids among E. coli and K. pneumoniae.

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Intrathecal Administration of Amikacin for Treatment of Meningitis Secondary to Cephalosporin-Resistant Escherichia Coli

Annals of Pharmacotherapy ◽

10.1177/106002809302700709 ◽

1993 ◽

Vol 27 (7-8) ◽

pp. 870-873 ◽

Cited By ~ 19

Author(s):

Sandra L. Preston ◽

Laurie L. Briceland

Keyword(s):

Escherichia Coli ◽

Bacterial Resistance ◽

Generation Cephalosporin ◽

Intrathecal Administration ◽

Neurosurgical Procedures ◽

Third Generation ◽

E Coli ◽

Efficacious Treatment ◽

Clonic Seizures ◽

Third Generation Cephalosporins

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.

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

Applied and Environmental Microbiology ◽

10.1128/aem.02435-08 ◽

2009 ◽

Vol 75 (11) ◽

pp. 3648-3655 ◽

Cited By ~ 56

Author(s):

Joshua B. Daniels ◽

Douglas R. Call ◽

Dale Hancock ◽

William M. Sischo ◽

Katherine Baker ◽

...

Keyword(s):

Escherichia Coli ◽

The United States ◽

Generation Cephalosporin ◽

Plasmid Transfer ◽

Third Generation ◽

Antimicrobial Drugs ◽

E Coli ◽

History Of ◽

Cephalosporin Resistance

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.

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Novel extended-spectrum TEM-type beta-lactamase from an Escherichia coli isolate resistant to ceftazidime and susceptible to cephalothin.

Antimicrobial Agents and Chemotherapy ◽

10.1128/aac.41.3.715 ◽

1997 ◽

Vol 41 (3) ◽

pp. 715-716 ◽

Cited By ~ 11

Author(s):

C Chanal-Claris ◽

D Sirot ◽

L Bret ◽

P Chatron ◽

R Labia ◽

...

Keyword(s):

Escherichia Coli ◽

Amino Acid ◽

Amino Acid Sequence ◽

Beta Lactamase ◽

Beta Lactamases ◽

Coli Isolate ◽

Resistance Phenotype ◽

Numbering Scheme ◽

Extended Spectrum

A novel extended-spectrum TEM-type beta-lactamase was detected in an Escherichia coli isolate which was resistant to ceftazidime and susceptible to cephalothin. The corresponding bla gene was sequenced. The deduced amino acid sequence showed the following three amino acid replacements with respect to the TEM-2 sequence: Glu-->Lys-104, Arg-->Ser-164, and Glu-->Lys-240. Since it confers a ceftazidimase-type resistance phenotype, we propose for this novel enzyme the designation CAZ-9, corresponding to TEM-46 in the sequential numbering scheme of TEM beta-lactamases.

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Carriage of ESBL and Amp-C -b -lactamase among Escherichia coli strains isolated from dogs in kennels Dak Lak province

Science and Technology Development Journal - Natural Sciences ◽

10.32508/stdjns.v5i2.996 ◽

2021 ◽

Vol 5 (2) ◽

pp. 1198-1207

Author(s):

Kien Chi Le ◽

Cuong Quoc Vo ◽

Xuan Thanh Tran ◽

Hung Manh Dang ◽

Huyen Ngoc My Nguyen ◽

...

Keyword(s):

Escherichia Coli ◽

Antimicrobial Resistance ◽

Viet Nam ◽

Beta Lactamase ◽

Sensitivity Testing ◽

Beta Lactamases ◽

E Coli ◽

Antimicrobial Sensitivity ◽

Extended Spectrum ◽

Genes Encoding

The global prevalence of antimicrobial resistance and Extended-Spectrum and AmpC Beta- Lactamases is continuously widespread among Escherichia coli during recent years, especially in Viet Nam. In Viet Nam, there have been researches on ESBL and AmpC-carrying E. coli inhabiting animal and human. However, studies of antimicrobial resistance in E. coli residing in pets, especially dogs are unavailable. The aim of the study was to investigate the antimicrobial sensitivity testing (AST), the resistance to 3rd cephalosporin and penicillin, also to assess the molecular detection of ESBL and Amp-C-beta -lactamase in E. coli isolates inhabiting the digestive tract of dogs at kennels Dak Lak. By using double disk synergy test (DDST), and ceftazidime-imipenem antagonism test (CIAT) to detect phenotypic characteristic of E. coli strains producing extended-spectrum beta- lactamases (ESBLs) and plasmid-mediated Amp-C-beta -lactamase, and by using multiplex polymerase chain reaction (multiplex PCR) to confirm the presence of ESBL genes (class A): blaCTX-M(1;2;8;9;25), bla TEM, bla SHV , bla OXA and genes encoding AmpC-type beta lactamase (class C): bla MOX-1;2 , bla CMY- (1;2-7;8-11) , blaLAT-(1;4) ,bla DHA-(1;2), bla ACC, bla FOX-(1-5B) ,bla MIR-1 ,bla ACT-1. From of three hundred twelve bacteial strains isolated from sixty-four rectal swabs two hundred sixty-nine E. Coli, isolates accounting for 86%, were identified and isolated, forty-four (16%) and twelve (4%) E. coli isolates encoding with ESBL and Amp-C-beta -lactamases. From molecular diagnosis with regard to phenotype, production of ESBL was shown in thirty-nine (15%) E. coli isolates and Amp-C enzymes in eight (3%) E. coli isolates. The high percentage of E. coli exhibiting antibiotic resistance revealed the accelerated overuse of antibiotics. Result of this study will contribute to the monitoring of epidemiologic resistance.

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Molecular Epidemiology of Escherichia coli Producing CTX-M and pAmpC β-Lactamases from Dairy Farms Identifies a Dominant Plasmid Encoding CTX-M-32 but No Evidence for Transmission to Humans in the Same Geographical Region

Applied and Environmental Microbiology ◽

10.1128/aem.01842-20 ◽

2020 ◽

Vol 87 (1) ◽

Author(s):

Jacqueline Findlay ◽

Oliver Mounsey ◽

Winnie W. Y. Lee ◽

Nerissa Newbold ◽

Katy Morley ◽

...

Keyword(s):

Escherichia Coli ◽

Geographical Location ◽

Dairy Farms ◽

Generation Cephalosporin ◽

Sequencing Analysis ◽

Third Generation ◽

Content Type ◽

E Coli ◽

Animal Populations ◽

Close Relatives

ABSTRACT Third-generation cephalosporin resistance (3GC-R) in Escherichia coli is a rising problem in human and farmed-animal populations. We conducted whole-genome sequencing analysis of 138 representative 3GC-R isolates previously collected from dairy farms in southwest England and confirmed by PCR to carry acquired 3GC-R genes. This analysis identified blaCTX-M (131 isolates encoding CTX-M-1, -14, -15, -and 32 and the novel variant CTX-M-214), blaCMY-2 (6 isolates), and blaDHA-1 (1 isolate). A highly conserved plasmid was identified in 73 isolates, representing 27 E. coli sequence types. This novel ∼220-kb IncHI2 plasmid carrying blaCTX-M-32 was sequenced to closure and designated pMOO-32. It was found experimentally to be stable in cattle and human transconjugant E. coli even in the absence of selective pressure and was found by multiplex PCR to be present on 26 study farms representing a remarkable range of transmission over 1,500 square kilometers. However, the plasmid was not found among human urinary E. coli isolates we recently characterized from people living in the same geographical location, collected in parallel with farm sampling. There were close relatives of two blaCTX-M plasmids circulating among eight human and two cattle isolates, and a closely related blaCMY-2 plasmid was found in one cattle and one human isolate. However, phylogenetic evidence of recent sharing of 3GC-R strains between farms and humans in the same region was not found. IMPORTANCE Third-generation cephalosporins (3GCs) are critically important antibacterials, and 3GC resistance (3GC-R) threatens human health, particularly in the context of opportunistic pathogens such as Escherichia coli. There is some evidence for zoonotic transmission of 3GC-R E. coli through food, but little work has been done examining possible transmission via interaction of people with the local near-farm environment. We characterized acquired 3GC-R E. coli found on dairy farms in a geographically restricted region of the United Kingdom and compared these with E. coli from people living in the same region, collected in parallel. While there is strong evidence for recent farm-to-farm transmission of 3GC-R strains and plasmids—including one epidemic plasmid that has a remarkable capacity to be transmitted—there was no evidence that 3GC-R E. coli found on study farms had a significant impact on circulating 3GC-R E. coli strains or plasmids in the local human population.

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