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

1997 ◽  
Vol 41 (2) ◽  
pp. 374-378 ◽  
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.

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

2014 ◽  
Vol 6 (01) ◽  
pp. 007-013 ◽  
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.

scholarly journals Prevalence of extended spectrum β-lactamase, AmpC β-lactamase and metallo β-lactamase mediated resistance in Escherichia coli from diagnostic and tertiary healthcare centers in south Bangalore, India

2018 ◽  
Vol 6 (4) ◽  
pp. 1308 ◽  
Author(s):  
Rituparna Tewari ◽  
Susweta D. Mitra ◽  
Feroze Ganaie ◽  
Nimita Venugopal ◽  
Sangita Das ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Clavulanic Acid ◽  
Multidrug Resistant ◽  
Cross Sectional Study ◽  
Beta Lactamase ◽  
Potential Threat ◽  
Cross Sectional ◽  
E Coli ◽  
Extended Spectrum ◽  
Microbiological Techniques

Background: The increasing reports on multidrug resistant Escherichia coli has become a potential threat to global health. Here, we present a cross-sectional study to characterize extended spectrum β-lactamase, AmpC β-lactamase and metallo β-lactamase producing E. coli isolated from different human clinical samples.Methods: A total of 300 clinical Gram negative bacterial isolates were collected and re-characterized for the identification of E. coli following standard microbiological techniques. The antimicrobial susceptibility of E. coli isolates was initially screened by Kirby-Bauer disk diffusion and MIC methods. The resistant isolates were confirmed to be ESBL, AmpC and MBL producers by their respective phenotypic confirmatory tests of combined disc method.Results: We identified 203 (68%) E. coli and 97 (32%) Non-E. coli isolates. The highest recovery of E. coli was from urine samples 72 (35%). Combined disc method using ceftazidime/ceftazidime+clavulanic acid and cefotaxime/cefotaxime+clavulanic acid confirmed 156 (79%) and 144 (73%) E. coli as ESBL producers, respectively. Thirty-four (34%) and 16 (27%) resistant E. coli isolates were confirmed to be AmpC and MBL producers, likewise.Conclusions: Increased prevalence of ESBL, AmpC and MBL producing E. coli were observed. Beta-lactamase mediated resistance appears to be prime mechanism in the multidrug resistant E. coli. Thus, early detection of beta lactamase producing E. coli is necessary to avoid treatment failure and prevent the spread of MDR.

scholarly journals Beta-Lactamase-Producing Escherichia coli Isolates Recovered from Pig Handlers in Retail Shops and Abattoirs in Selected Localities in Southern Nigeria: Implications for Public Health

Antibiotics ◽  
2020 ◽  
Vol 10 (1) ◽  
pp. 9
Author(s):  
Olivia Sochi Egbule ◽  
Benson C. Iweriebor ◽  
Edward Ikenna Odum
Keyword(s):  
Escherichia Coli ◽  
Clavulanic Acid ◽  
Multidrug Resistant ◽  
Beta Lactamase ◽  
Extended Spectrum Beta Lactamase ◽  
E Coli ◽  
Resistance Evolution ◽  
Resistance Patterns ◽  
Amoxicillin Clavulanic Acid ◽  
And Gender

Antibiotic resistance evolution among pathogenic microorganisms has become a huge burden globally as it has increased the burden of diseases amongst humans and animals. The prevalence of extended-spectrum beta-lactamase-producing Escherichia coli (ESBL-Ec) and metallo beta-lactamase-producing Escherichia coli (MBL-Ec) isolated from pig abattoir and handlers in retail shops was studied. In addition, the relationship between the isolates’ prevalence and the background characteristics of the butchers/retailers was also investigated. Samples from 32 hand swabs of pork sellers at retail shops and 8 butchers at abattoirs, as well as 272 swabs taken from knives, tables, floors, water troughs, and carcasses from both retail shops and abattoirs, were collected. Escherichia coli (E. coli) was isolated from hand swabs, fomites, and carcasses and were identified by standard microbiological procedures. The isolates susceptibility to nitrofurantoin (300 µg), ciprofloxacin (5 µg), ceftazidime (30 µg), cefuroxime (30 µg), gentamicin (10 µg), cefixime (5 µg), ofloxacin (5 µg), amoxicillin/clavulanic acid (30 µg), imipenem (10 µg), and meropenem (10 µg) and their ability to produce ESBL and MBL was determined by phenotypic methods. Demographic information of the handlers was retrieved by means of a structured questionnaire and, in some cases, via face to face interviews. Out of 104 E. coli isolates from both sources, 52 (50.0%) and 8 (7.7%) were ESBL and MBL producers, respectively. ESBL was more prevalent on the hands of the retailers (40.6%) and butchers (75.0%). The isolates were 100% resistant to ceftazidime, cefotaxime, and amoxicillin–clavulanic acid and 4.8% resistant to nitrofurantoin. Diverse resistance patterns were observed among ESBL-Ec and MBL-Ec. It was found that 90% of ESBL-Ec and 100% of MBL-Ec were multidrug-resistant. A possible epidemiological link between the two sources was observed. The prevalence of E. coli ESBL- and MBL-producing isolates was associated with the duty performed by handlers (p = 0.012) and gender (p = 0.012). Our results provide evidence that the handlers’ hands and abattoir environment had a great role to play in the high prevalence and resistance profiles of the microorganisms.

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

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.

scholarly journals Occurrence and Detection of AmpC Beta-Lactamases among Escherichia coli, Klebsiella pneumoniae, and Proteus mirabilis Isolates at a Veterans Medical Center

2000 ◽  
Vol 38 (5) ◽  
pp. 1791-1796 ◽  
Author(s):  
Philip E. Coudron ◽  
Ellen S. Moland ◽  
Kenneth S. Thomson
Keyword(s):  
Escherichia Coli ◽  
Klebsiella Pneumoniae ◽  
Isoelectric Focusing ◽  
Proteus Mirabilis ◽  
Medical Center ◽  
Three Dimensional ◽  
Beta Lactamase ◽  
True Rate ◽  
Beta Lactamases ◽  
E Coli

AmpC beta-lactamases are cephalosporinases that confer resistance to a wide variety of β-lactam drugs and that may thereby create serious therapeutic problems. Although reported with increasing frequency, the true rate of occurrence of AmpC beta-lactamases inEscherichia coli, Klebsiella pneumoniae, andProteus mirabilis remains unknown. We tested a total of 1,286 consecutive, nonrepeat isolates of these three species and found that, overall, 45 (3.5%) yielded a cefoxitin zone diameter less than 18 mm (screen positive) and that 16 (1.2%) demonstrated AmpC bands by isoelectric focusing. Based on the species, of 683 E. coli, 371 K. pneumoniae, and 232 P. mirabilisisolates tested, 13 (1.9%), 28 (7.6%), and 4 (1.7%), respectively, demonstrated decreased zone diameters and 11 (1.6%), 4 (1.1%), and 1 (0.4%), respectively, demonstrated AmpC bands. Cefoxitin resistance was transferred for all but 8 (E. coli) of the 16 AmpC producers. We also describe a three-dimensional extract test, which was used to detect phenotypically isolates that harbor AmpC beta-lactamase. Of the 45 cefoxitin-resistant isolates, the three-dimensional extract test accurately identified all 16 AmpC producers and 28 of 29 (97%) isolates as non-AmpC producers. Interestingly, most (86%) isolates in the latter group were K. pneumoniae isolates. These data confirm that, at our institution, E. coli, K. pneumoniae, and P. mirabilis harbor plasmid-mediated AmpC enzymes.

scholarly journals ESBL and AmpC beta-lactamase-producing Enterobacteriaceae in poultry in the Czech Republic

2010 ◽  
Vol 55 (No. 3) ◽  
pp. 119-124 ◽  
Author(s):  
M. Kolar ◽  
J. Bardon ◽  
M. Chroma ◽  
K. Hricova ◽  
T. Stosova ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Czech Republic ◽  
Molecular Characteristics ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
The Czech Republic ◽  
Beta Lactamases ◽  
E Coli ◽  
Beta Lactam Antibiotics ◽  
Composite Samples

A major reason for resistance of <I>Enterobacteriaceae</I> to beta-lactam antibiotics is production of ESBLs and AmpC beta-lactamases. As their more detailed description in poultry is unavailable in the Czech Republic, the presented study aimed at assessing their occurrence and molecular characteristics. A total of 154 composite samples from broilers and 150 cloacal swabs from turkeys were examined. Production of ESBLs was detected in seven <I>Escherichia coli</I> isolates and AmpC enzymes in two <I>E. coli</I> isolates. The most frequent ESBL types were CTX-M-1 and SHV-12 and the most common AmpC enzymes were the CMY-2 types.

scholarly journals 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

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S382-S382
Author(s):  
Alexander Lawandi ◽  
Samuel De L’Etoile-Morel ◽  
Gleice C Leite ◽  
Todd C Lee
Keyword(s):  
Escherichia Coli ◽  
Carbapenem Resistance ◽  
Generation Cephalosporin ◽  
Third Generation ◽  
Beta Lactamase ◽  
Review Of The Literature ◽  
Beta Lactamases ◽  
Resistance Phenotype ◽  
E Coli ◽  
Reference Strains

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

scholarly journals Beta-lactamase inhibitors from laboratory to clinic.

1988 ◽  
Vol 1 (1) ◽  
pp. 109-123 ◽  
Author(s):  
K Bush
Keyword(s):  
Side Effects ◽  
Clavulanic Acid ◽  
Broad Spectrum ◽  
Pathogenic Bacteria ◽  
Defense Mechanism ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Beta Lactamases ◽  
Beta Lactam Antibiotics ◽  
Tract Infections

beta-Lactamases constitute the major defense mechanism of pathogenic bacteria against beta-lactam antibiotics. When the beta-lactam ring of this antibiotic class is hydrolyzed, antimicrobial activity is destroyed. Although beta-lactamases have been identified with clinical failures for over 40 years, enzymes with various abilities to hydrolyze specific penicillins or cephalosporins are appearing more frequently in clinical isolates. One approach to counteracting this resistance mechanism has been through the development of beta-lactamase inactivators. beta-Lactamase inhibitors include clavulanic acid and sulbactam, molecules with minimal antibiotic activity. However, when combined with safe and efficacious penicillins or cephalosporins, these inhibitors can serve to protect the familiar beta-lactam antibiotics from hydrolysis by penicillinases or broad-spectrum beta-lactamases. Both of these molecules eventually inactivate the target enzymes permanently. Although clavulanic acid exhibits more potent inhibitory activity than sulbactam, especially against the TEM-type broad-spectrum beta-lactamases, the spectrum of inhibitory activities are very similar. Neither of these inhibitors acts as a good inhibitor of the cephalosporinases. Clavulanic acid has been most frequently combined with amoxicillin in the orally active Augmentin and with ticarcillin in the parenteral beta-lactam combination Timentin. Sulbactam has been used primarily to protect ampicillin from enzymatic hydrolysis. Sulbactam has been used either in the orally absorbed prodrug form as sultamicillin or as the injectable combination ampicillin-sulbactam. Synergy has been demonstrated for these combinations for most members of the Enterobacteriaceae, although those organisms that produce cephalosporinases are not well inhibited. Synergy has also been observed for Neisseria gonorrhoeae, Haemophilus influenzae, penicillinase-producing Staphylococcus aureus, and anaerobic organisms. These antibiotic combinations have been used clinically to treat urinary tract infections, bone and soft-tissue infections, gonorrhea, respiratory infections, and otitis media. Gastrointestinal side effects have been reported for Augmentin and sultamicillin; most side effects with these agents have been mild. Although combination therapy with beta-lactamase inactivators has been used successfully, the problem of resistance development to two agents must be considered. Induction of cephalosporinases can occur with clavulanic acid. Permeability mutants could arise, especially with added pressure from a second beta-lactam.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals 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

2020 ◽  
Vol 64 (10) ◽  
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.

scholarly journals Phenotypic Characterization of Multidrug-resistant Escherichia Coli with Special Reference to Extended-spectrum-beta-lactamases and Metallo-beta-lactamases in a Tertiary Care Center

2015 ◽  
Vol 53 (198) ◽  
pp. 83-88 ◽  
Author(s):  
Basudha Shrestha ◽  
Shovita Shrestha ◽  
Shyam Kumar Mishra ◽  
Hari Prasad Kattel ◽  
Tatsuya Tada ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Multidrug Resistance ◽  
Resistance Mechanism ◽  
Multidrug Resistant ◽  
Confirmatory Test ◽  
Beta Lactamase ◽  
Beta Lactamases ◽  
Extended Spectrum Beta Lactamase ◽  
E Coli ◽  
Extended Spectrum

Introduction: The increasing reports on extended-spectrum-beta-lactamase and metallo-betalactamase producing Escherichia coli have addressed a potential threat to global health since it is found to be highly resistance to most of the currently available antibiotics including carbapenems. The present study was aimed to determine the antibiogram of extended-spectrum-beta-lactamase and metallo-beta-lactamase producing MDR E. coli isolates from various clinical samples. Methods: This was a cross-sectional study conducted over a period of seven months (December 2013 to July 2014) at bacteriology laboratory of Tribhuvan University Teaching Hospital. A total of 250 clinical specimens (urine, pus, sputum, blood, body fluid, bile, tissue and central venous pressure line tip) were processed from inpatients, with multidrug-resistant Escherichia coli infections. Standard microbiological techniques were used for isolation and identification of the isolates. The presence of extended-spectrum-beta-lactamase was detected by phenotypic confirmatory test recommended by Clinical and Laboratory Standards Institute and imipenem (IMP) /EDTA combined disc method was performed to detect metallo-beta-lactamase mediated resistance mechanism. Results: We found high level of beta lactamase mediated resistance mechanism as part of multidrug resistance. Among 250 MDR isolates, 60% isolates were extended-spectrum-beta-lactamase producers and 17.2% isolates were metallo-beta-lactamase producers. Co-existence of extended-spectrum-betalactamase and metallo-beta-lactamase identified in 6.8% isolates. Conclusions: Beta-lactamase mediated resistance mechanisms are accounting very high in the multidrug resistant isolates of E. coli. Therefore, early detection of beta lactamase mediated resistant strains and their current antibiotic susceptibility pattern is necessary to avoid treatment failure and prevent the spread of MDR.  Keywords: e. coli; extended-spectrum-β-lactamase; metallo-β-lactamase; multidrug-resistance.

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