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Query: UMLS:C0276640 (TEM)
 20,729 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Infections due to strains of Klebsiella pneumoniae, Escherichia coli, and Citrobacter freundii resistant to third-generation cephalosporins have been observed recently in France and the Federal Republic of Germany. This resistance phenotype is due to the production of new plasmid-mediated, broad-substrate-range beta-lactamases designated TEM-3 to TEM-7. DNA-DNA hybridization analysis with a probe specific for TEM-1 indicated that the corresponding genes blaT-3 to blaT-7 were variants of the structural genes for TEM-type beta-lactamases. In the present studies, a 2.5-kilobase BamHI plasmid DNA fragment encoding TEM-3 was cloned in E. coli, and the entire nucleotide sequence of blaT-3 was determined. The deduced amino acid sequence of TEM-3 differed in two positions from that of the TEM-2 enzyme: lysine (TEM-3) was substituted for glutamic acid (TEM-2) at residue 104 and serine (TEM-3) for glycine (TEM-2) at residue 238 in the numbering system of Ambler. Spontaneous mutants of TEM penicillinases with increased activity against third-generation cephalosporins were obtained in vitro by selection on cefotaxime or ceftazidime. It therefore appears that mutations in TEM-type beta-lactamases contribute to resistance to new-generation cephalosporins.
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PMID:Plasmid-mediated resistance to third-generation cephalosporins caused by point mutations in TEM-type penicillinase genes. 305 79

The in vitro activity of cefpirome, a new cyclopyridinium cephalosporin, was evaluated against 947 aerobic and anaerobic bacteria. Cefpirome inhibited 90% of Escherichia coli, Klebsiella spp., Citrobacter diversus, Morganella morganii, Proteus vulgaris, Proteus mirabilis, Aeromonas spp., Salmonella spp., Shigella spp. and Haemophilus and Neisseria species at less than or equal to 0.4 mg/l. It had activity comparable to that of cefotaxime, ceftizoxime, ceftazidime, aztreonam, and moxalactam against these species. Only a few Citrobacter freundii, Enterobacter spp. and Serratia marcescens had MICs above 3.1 mg/l. The activity of cefpirome against Pseudomonas aeruginosa, 90% MIC of 12.5 mg/l, was superior to piperacillin, moxalactam, cefotaxime and cefoperazone. The 90% MIC against Staphylococcus aureus was 0.8 mg/l, but methicillin-resistant staphylococci were not inhibited. Cefpirome was not significantly hydrolyzed by most plasmid beta-lactamases (TEM, SHV-1, PSE, OXA) nor by chromosomal enzymes (P99, Branhamella catarrhalis, K1). Cefpirome did not inhibit chromosomal or plasmid beta-lactamases. Mice systemically infected with E. coli, Klebsiella pneumoniae, P. aeruginosa and S. aureus were protected by concentrations of cefpirome ranging from 0.85 mg/kg for K. pneumoniae to 4.467 mg/kg for P. aeruginosa.
Infection
PMID:The in vitro activity and beta-lactamase stability of cefpirome (HR 810), a pyridine cephalosporin agent active against staphylococci, Enterobacteriaceae and Pseudomonas aeruginosa. 392 97

The MICs and MBCs of mecillinam, ticarcillin, mezlocillin, azlocillin and piperacillin were determined by the microdilution method in liquid medium using 700 strains of gram-negative bacilli and enterococci isolated from pathological sources and classified as a function of their sensitivity to ampicillin and carbenicillin. The ampicillin and carbenicillin-sensitive strains were generally sensitive to the other penicillins, although there were differences in activity. The ampicillin and carbenicillin-resistant strains of Escherichia coli that produce a TEM-type penicillinase were sensitive to mecillinam. Mezlocillin, piperacillin and azlocillin had MICs of between 32 and 64 mg/l for 40% of these strains. The Klebsiella strains, whose broad-spectrum penicillinase deactivates ampicillin and carbenicillin, remained sensitive to mecillinam. Mezlocillin, azlocillin and piperacillin had MICs of less than 8 mg/l for 50% of these strains. The carbenicillin-resistant strains of Enterobacter and Citrobacter were also resistant to the other penicillins. Piperacillin and mezlocillin displayed some activity against certain strains of carbenicillin-resistant Serratia, Proteus and Acinetobacter. Azlocillin, piperacillin and, to a lesser degree, mezlocillin were active against the strains of Pseudomonas, for which carbenicillin had an MIC of about 512 mg/l. Ampicillin, mezlocillin and azlocillin showed the best activity against the enterococci, against which mecillinam was inactive. The MBC of these antibiotics is greatly influenced by the density of the bacterial inoculum.
Infection 1982
PMID:Comparative in vitro antibacterial activity of seven semi-synthetic penicillins against aerobic gram-negative bacteria and enterococci. 715 90

Several mechanisms render antimicrobials inactive; one of these, beta-lactamase hydrolysis of beta-lactam antimicrobials, is a common and serious problem resulting in loss of antimicrobial activity. Resistance in gram-negative organisms may be caused by chromosomally or plasmid-mediated beta-lactamases. Chromosomally mediated resistance may result from exposure to inducer compounds (induction) or by selection of stably derepressed mutants. Plasmids are extrachromosomal elements of DNA that can transfer resistance between bacteria. Common plasmid-encoded beta-lactamases are the TEM- and SHV-type enzymes, which include the newer extended-spectrum beta-lactamases. Infections caused by resistant bacteria frequently result in longer hospital stays, higher mortality, and increased cost of treatment. When bacteria develop resistance during antimicrobial therapy, therapeutic failure ensues in approximately 50% of patients. Clinical studies demonstrate that resistance mediated by beta-lactamases is a critical issue. Strategies for overcoming it include use of beta-lactam-beta-lactamase inhibitor combinations, development of new antimicrobial compounds, and use of regimens that optimize in vivo exposure to drug.
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PMID:Bacterial resistance mechanisms to beta-lactam antibiotics: assessment of management strategies. 775 92

The prevalence of ESBL was determined among isolates of Escherichia coli (n = 571) and Klebsiella spp. (n = 196) collected during a 1-week study period in 8 university and 3 large regional laboratories all over the Netherlands. 18 isolates were positive for at least one of the screening tests used, i.e., VITEK-ESBL, E-test ESBL and MIC ratio of ceftazidime/ceftazidime-clavulanic acid, cefotaxime/cefotaxime-clavulanic acid. In 5 of these 18 putative ESBLs no betalactamase production was detectable. A TEM type was found in three E. coli and two Klebsiella spp. An SHV type was present in five Klebsiella spp. In one E. coli and one Klebsiella pneumoniae both enzymes were present. In one Klebsiella oxytoca neither of the two enzymes was present. Using PCR for both ESBL TEM and ESBL SHV, an SHV ESBL was found in one E. coli and four Klebsiella isolates. The mutations at position 238 and 240 were already described. In one E. coli isolate a TEM ESBL was found with three mutations, at position 21, 164 and 265. These mutations were already described in other ESBLs but not in this combination suggesting a new TEM ESBL. The overall prevalence of ESBL producing E. coli and Klebsiella spp. was less than 1% (6 out of 767).
Infection
PMID:Occurrence of extended-spectrum betalactamases (ESBL) in Dutch hospitals. 1062 95

The prevalence of organisms producing extended-spectrum beta-lactamases(ESBLs) has been increasing all over the world. ESBLs confer resistance to cefotaxime, ceftazidime, aztreonam, extended-spectrum penicillins, and structurally related beta-lactams in clinical isolates of K. pneumoniae and E. coli. Under the influence of antimicrobial agents, bacteria that primarily produce TEM-type or SHV-type beta-lactamases developed point mutations in structural genes which served to extend the substrate specificity of the enzymes. Infections caused by ESBLs producing isolates are difficult to detect with current susceptibility tests, and are difficult to treat. This article provides an historical overview of the emergence of ESBLs carrying gram-negative rods and consider how to treat their infections.
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PMID:[Clinical characteristics of emerging multiple-drug-resistant gram-negative rods producing extended-spectrum beta-lactamases (ESBLs)]. 1130 1

Infections with bacteria that contain hydrolytic beta-lactamase enzymes are becoming a serious problem in the United States. Mutations at Met-69, an amino acid proximal to the active site Ser-70 in the TEM-1 and SHV-1 beta-lactamases, have emerged as a puzzling cause of bacterial resistance to inhibitors of beta-lactamases. Site-saturation mutagenesis of the 69 position in SHV beta-lactamase was performed to determine how mutations of this non-catalytic residue play a role in increasing 50% inhibitory concentrations (IC(50) concentrations) for clinically important beta-lactamase enzyme inhibitors. Two distinct phenotypes are evident in the variant beta-lactamases studied: significantly increased minimum inhibitory concentrations (microg/ml) and IC(50) concentrations to clavulanic acid for the Met69Ile, Leu, and Val substitutions, and unanticipated increased minimum inhibitory concentrations and hydrolytic activity toward ceftazidime, an advanced generation cephalosporin antibiotic, for the Met69Lys, Tyr- and Phe-substituted enzymes. Molecular modeling studies emphasize the conserved structure of these substitutions despite great variation in substrate specificity. This study demonstrates the key role of Met-69 in defining substrate specificity of SHV beta-lactamases and alerts us to new phenotypes that may emerge clinically.
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PMID:Unexpected advanced generation cephalosporinase activity of the M69F variant of SHV beta-lactamase. 1235 65

Infections due to extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli (ESBLEC) in nonhospitalized patients seem to be emerging in different countries. Their incidence, epidemiology, and clinical impact in the community have not been studied. We describe the epidemiology and clinical features of infections caused by ESBLEC in nonhospitalized patients in Spain and the results of a case-control study performed to investigate the risk factors associated with the acquisition of these organisms. The clonal relatedness of the organisms was assessed by repetitive extragenic palindromic sequence PCR. The ESBLs and the genes encoding the ESBLs were initially characterized by isoelectric focusing and PCR, respectively. Forty-nine patients (76% with urinary tract infections, 22% with asymptomatic bacteriuria, and 2% with acute cholangitis) were included. Six patients were bacteremic. Diabetes mellitus (odds ratio, 5.5; 95% confidence interval, 1.6 to 18.7), previous fluoroquinolone use (odds ratio, 7.6; 95% confidence interval, 1.9 to 30.1), recurrent urinary tract infections (odds ratio, 4.5; 95% confidence interval, 1.3 to 15.1), a previous hospital admission (odds ratio, 18.2; 95% confidence interval, 5.3 to 61.1), and older age in male patients (odds ratio per year, 1.03; 95% confidence interval, 1.03 to 1.05) were identified as risk factors by multivariate analysis. The ESBLEC isolates were not clonally related. The ESBLs were characterized as members of the CTX-M-9 group, the SHV group, and the TEM group in 64, 18, and 18% of the isolates, respectively. ESBLEC is an emergent cause of urinary tract infections in nonhospitalized patients. There was no evidence of horizontal transmission of ESBLEC strains. Avoidance of fluoroquinolone use in high-risk patients should be considered whenever possible in order to avoid the selection of these organisms.
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PMID:Epidemiology and clinical features of infections caused by extended-spectrum beta-lactamase-producing Escherichia coli in nonhospitalized patients. 1500 58

Beta-lactam antimicrobial agents represent the most common treatment for bacterial infections and continue to be the leading cause of resistance to beta-lactam antibiotics among Gram-negative bacteria worldwide. The persistent exposure of bacterial strains to a multitude of beta-lactams has induced dynamic and continuous production and mutation of beta-lactamases in these bacteria, expanding their activity even against the newly developed beta-lactam antibiotics. These enzymes are known as extended-spectrum beta-lactamases (ESBLs). The majority of ESBLs are derived from the widespread broad-spectrum beta-lactamases TEM-1 and SHV-1. There are also new families of ESBLs, including the CTX-M and OXA-type enzymes as well as novel unrelated beta-lactamases. In recent years, there has been an increased incidence and prevalence of ESBLs. ESBLs are mainly found in strains of Escherichia coli and Klebsiella pneumoniae but have also been reported in other Enterobacteriaceae strains and Pseudomonas aeruginosa. Infections with ESBL-producing bacterial strains are encountered singly or in outbreaks, especially in critical care units in hospitals, resulting in increasing cost of treatment and prolonged hospital stays. Not only may nursing home patients be an important reservoir of ESBL-containing multiple antibiotic-resistant organisms, but ambulatory patients with chronic conditions may also harbor ESBL-producing organisms.
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PMID:Characteristics, epidemiology and clinical importance of emerging strains of Gram-negative bacilli producing extended-spectrum beta-lactamases. 1524 58

Beta-lactamases are the commonest cause of bacterial resistance to beta-lactam antibiotics. They have been classified phenotypically by their isoelectric point, substrate profile, susceptibility to inhibitors and genetic origin. Chromosomal beta-lactamases are typical for certain bacterial species and plasmid beta-lactamases are transferable between different species and genera. Sequencing of beta-lactamase genes enabled to divide them into four classes: A, B, C and D. The ability of a beta-lactamase to confer resistance depends on its location, kinetics, quantity and physicochemical conditions. First beta-lactamases were described soon after introduction of penicillin. Plasmid-mediated broad-spectrum beta-laktamases appeared in the middle 60-s of the XX century and confer resistance to penicillins and some first generation cephalosporins. They include TEM-1, TEM-2, SHV-1, ROB, BRO, OXA and PSE beta-lactamases and are transferred by conjugation between different species and strains of Gram-negative bacteria. The new beta-lactam agents nowadays are compromised mostly by extended-spectrum beta-lactamases, inhibitor-resistant beta-lactamases and carbapenemases. Extended-spectrum beta-lactamases (ESBLs) were described for the first time 20 years ago and are derived from the parental TEM and SHV-1 beta-lactamases by mutations that alter the configuration of the active site to expand their spectrum of activity. They hydrolyse oxymino-cephalosporins and aztreonam. The rapid and accurate laboratory detection of ESBLs is important for choosing appropriate antibiotic therapy. Infections caused by Enterobacteriaceae producing ESBLs pose a therapeutic problem due to multiple antibiotic resistance which includes non-beta-lactam antibiotics as well. Carbapenems are the first-line antibiotics for treatment of such infections.
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PMID:[Beta-lactamases in laboratory and their role in resistance Part I.: Evolution of bacterial resistance mediated by beta-lactamases]. 1608 90


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