Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1275122 (TEM)
 21,810 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The 1990s will probably see fewer new antibiotics being registered than occurred during the 1970s and 1980s. The main reason for this is the excessive costs involved in the development of a new chemical entity. It is probable that more fluoroquinolones will be introduced and some of them will have improved antibacterial activities compared to current derivatives. Another class of antibiotics likely to develop during the next decade is the macrolides, with the emergence of drugs like azithromycin. Among the beta-lactams, new carbapenems and extended spectrum cephalosporins will be developed to meet the problems of increasing numbers of enterobacteria producing class I beta-lactamases, as well as the new broad-spectrum TEM enzymes. These resistance mechanisms against beta-lactams are also likely to give rise to a new era for beta-lactamase inhibitors. A field which presently looks less promising is that of drugs which are active against methicillin-resistant staphylococci; teicoplanin and daptomycin seem to have only minor advantages over vancomycin. Other developments that can be expected are those facilitating the administration of antibiotics, especially once-daily injectable antibiotics for intensive home care.
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PMID:Future trends in antibiotic therapy. 148 28

beta-Lactamase expression was examined in 1000 consecutive Gram-negative bacilli isolated from urine, wound swab, sputum or blood specimens received at the Microbiology Laboratory of the Royal London Hospital. This survey, performed between January and April, 1991, followed a similar study undertaken in early 1982. The distribution of species was similar in the two surveys, except that the proportion of Pseudomonas aeruginosa isolates had increased from 11% in 1982 to 17.5% in the present study. This increase was balanced by a decreased proportion of enterobacteria. Amongst plasmid-mediated beta-lactamases, TEM-1 (especially), TEM-2, SHV-1 and OXA types continued to predominate in enterobacteria. Their frequency in Escherichia coli was unchanged (46% in 1991 compared with 43% in 1982), but had increased from 5 to 22% amongst Proteus mirabilis isolates. An apparent decrease in their frequency amongst Enterobacter cloacae isolates, from 48% in 1982 to 17% in 1991, probably reflected changes to strain prevalence rather than enzyme prevalence. Plasmid type beta-lactamases were present in fewer than 2% of P. aeruginosa isolates in both surveys. In the present study, chromosomal beta-lactamase derepression (constitutive hyperproduction) was detected in 10/76 isolates of E. cloacae, Enterobacter aerogenes, Citrobacter freundii, Serratia spp. and Morganella morganii, and in 2/170 P. aeruginosa isolates. These proportions were increased, compared with those seen the 1982 survey, though the significance was borderline (P approximately 0.05; chi 2 test). Extended-spectrum plasmid mediated beta-lactamases, unknown in 1982, were found in 11/70 Klebsiellae pneumoniae isolates in the present study. Ten of these organisms, representing at least five distinct strains, produced TEM-10 enzyme, encoded by a plasmid of c. 90 kb; the remaining organism had an unidentified SHV-derived enzyme.
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PMID:Survey of the prevalence of beta-lactamases amongst 1000 gram-negative bacilli isolated consecutively at the Royal London Hospital. 149 Sep 17

Two different strains of Escherichia coli exhibiting unusual patterns of resistance to beta-lactam antibiotics were isolated from patients at Cochin Hospital. Both isolates showed a low level of resistance to amoxycillin, ticarcillin and ureidopenicillins but were susceptible to cephalosporins, aztreonam and imipenem; beta-lactamase inhibitors potentiated the activities of the beta-lactams to only a limited extent. All resistance characteristics of the strains were transferable by conjugation to E. coli K12. Resistance was shown to be due to beta-lactamases of pI 5.20 and relative molecular masses of 24,000. The hydrolytic and inhibition profiles of these enzymes were similar to each other but differed from those of broad-spectrum beta-lactamases (TEM-1). The rates of hydrolysis (Vmax) of amoxycillin (c. 200%) were higher than that for TEM-1 (84%). Ticarcillin, ureidopenicillins and cephaloridine were hydrolyzed slowly. However, as for TEM-1, no hydrolysis was observed with cefoxitin, third generation cephalosporins, aztreonam and imipenem. The high Km values demonstrated the poor affinity of these enzymes for their substrates. Unlike TEM-1, they were poorly inhibited by beta-lactamase inhibitors. These two enzymes differed from each other as follows: (i) the concentrations of clavulanic acid required for 50% beta-lactamase inhibition were 31 mumol/L for one enzyme (E-SAL) and 9.4 mumol/L for the other (E-GUER); (ii) p-chloromercuribenzoate was a more active inhibitor of E-SAL then E-GUER. The titration curve method and DNA-DNA hybridization studies demonstrated that both enzymes were structurally related to TEM-1. The novel plasmid-encoded enzymes produced by the two isolates of E. coli appeared to be almost identical and to be derived from TEM-enzymes. On the basis of their presumed phylogeny and their biological properties, we propose that these beta-lactamases be given the generic name TRI (TEM Resistant to beta-lactamase Inhibitors).
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PMID:Clinical isolates of Escherichia coli producing TRI beta-lactamases: novel TEM-enzymes conferring resistance to beta-lactamase inhibitors. 149 Sep 18

Standard beta-lactamases K1, P99, TEM-1, SHV-1 and beta-lactamase K-CAZ purified using FPLC through ion-exchange chromatography and filtration chromatography, were identified by determination of isoelectric points, molecular weights and substrate profiles. The results showed that the beta-lactamase stability of domestic aztreonam was very similar to that of cefotaxime, ceftazidime and much better than that of cefoperazone. Aztreonam showed a high affinity to chromosomal-mediated cephalosporinase P99, its Ki for inhibition of P99 with cephaloridine as substrate was 0.0159 microns. Aztreonam and the three third generation cephalosporins tested were not stable to beta-lactamase K-CAZ, which hydrolysed them in different degrees.
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PMID:Purification of beta-lactamases and enzyme kinetic studies on aztreonam. 149 75

In a leukaemic patient presenting a septicaemia treated with ceftazidime and amikacin, two clinical Escherichia coli isolates distinguished by their level of resistance to oxyimino-beta-lactams were isolated at an interval of 24 h. The isolates were identified by biotyping and esterase electrophoretic typing and the two host strains were shown to be identical. However, each of these strains exhibited a different transferrable extended-spectrum beta-lactamase. These enzymes had different pI values (5.25 and 5.58), but were both blaTEM-1 mutants. The enzyme with pI 5.25 was identical to TEM-101 (TEM-12) (serine 162 substitution). The enzyme with pI 5.58 showed an additional amino acid substitution (lysine residue instead of an arginine at position 237) and was denominated TEM-23. These data indicate that point-mutations can be successively cumulated in vivo by blaTEM mutants, leading to expression of beta-lactamases with increased hydrolysis rates.
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PMID:Two variants of transferrable extended-spectrum TEM-beta-lactamase successively isolated from a clinical Escherichia coli isolate. 150 39

TEM-1, OXA-1, SHV-1, and related beta-lactamases in fecal isolates from 953 infants in 22 Swedish neonatal intensive care units were studied by DNA hybridization. TEM-1- and OXA-1-positive isolates were always Escherichia coli and represented 86 and 8%, respectively, of the ampicillin-resistant isolates of this species. SHV-1 was found in 16% of the Klebsiella sp. (mainly Klebsiella pneumoniae) isolates. TEM-1 and SHV-1 occurred in 14 and 16 units and in up to 64 and 26% of the neonates, respectively. On average, two to four different biochemical phenotypes per species per ward were positive for each beta-lactamase. All but 1 of the 33 E. coli phenotypes found to be TEM-1 positive were uniformly positive for the beta-lactamase gene, whereas some of the phenotypes found to be positive for OXA-1 (2 of 3) and SHV-1 (6 of 70) were occasionally negative for the respective genes. The occurrence of the three beta-lactamases studied tended to be associated with local ampicillin usage (correlation coefficient, 0.31 to 0.39; P greater than 0.05). Of the neonates receiving ampicillin, 30% carried TEM-1-positive E. coli, compared with 13% for cephalosporin-treated neonates and 15% for untreated neonates (P less than or equal to 0.001). The corresponding rates for SHV-1 in Klebsiella spp. were 18, 13, and 9% (P less than or equal to 0.01). Ampicillin is thus a significant risk factor for the maintenance of the most prevalent gram-negative plasmid-mediated beta-lactamases in hospitalized neonates.
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PMID:Epidemiology of plasmid-mediated beta-lactamases in enterobacteria Swedish neonatal wards and relation to antimicrobial therapy. 151 Apr 25

The in vitro activity of LJC 10,627, a new carbapenem, was compared with those of imipenem, cefotaxime, ceftazidime, and gentamicin. LJC 10,627 inhibited 90% of Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Enterobacter aerogenes, Enterobacter agglomerans, Enterobacter cloacae, Hafnia alvei, Citrobacter freundii, Citrobacter diversus, Proteus mirabilis, Morganella morganii, Proteus rettgeri, Serratia marcescens, Pseudomonas cepacia, salmonellae, shigellae, aeromonas, and yersiniae at less than or equal to 2 micrograms/ml. Haemophilus influenzae was inhibited by 0.5 microgram/ml, and moraxellae were inhibited by 0.12 microgram/ml. LJC 10,627 was twofold more active than imipenem against aerobic gram-negative organisms and inhibited ceftazidime-, cefotaxime-, and gentamicin-resistant members of the genera Klebsiella, Enterobacter, Citrobacter, and Serratia at less than or equal to 2 micrograms/ml. Xanthomonas maltophilia strains were resistant to the drug. Imipenem was two- to fourfold more active than LJC 10,627 against Staphylococcus aureus and Staphylococcus epidermidis. LJC 10,627 did not inhibit most methicillin-resistant Staphylococcus aureus or methicillin-resistant Staphylococcus epidermidis strains. LJC 10,627 inhibited Streptococcus pyogenes and Streptococcus pneumoniae at 0.06 and 0.12 microgram/ml, respectively. Bacteroides fragilis and other Bacteroides spp. were inhibited by 0.5 microgram of LJC 10,627 per ml. Serum (50%) did not affect the MICs. LJC 10,627 was not hydrolyzed by plasmid-mediated beta-lactamases of Bush types 2b, 2b', TEM-1, TEM-2, TEM-3, TEM-5, TEM-7, TEM-9, and SHV-1; the chromosomal beta-lactamases of Bush type 1; P-99; a Morganella enzyme; or a Citrobacter freundii enzyme. The Bush type 2c and 2d enzymes OXA-1, OXA-2, PSE-1, PSE-2, and PSE-4 did not hydrolyze LJC 10,627, nor did the beta-lactamases of Staphylococcus aureus, Moraxella spp., Bacteroides fragilis, and Proteus vulgaris. The beta-lactamase of Xanthomonas hydrolyzed LJC 10,627, albeit at approximately one-third the rate that imipenem was hydrolyzed.
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PMID:In vitro activity and beta-lactamase stability of LJC 10,627. 151 Apr 36

Studies were performed to determine the effects of BRL 42715, a potent beta-lactamase inhibitor, on the activity of cefazolin and piperacillin against experimental intraperitoneal infections caused by either Escherichia coli or Serratia marcescens in rats. Compounds were administered to rats as a continuous infusion of an exponentially diluted solution to simulate in rat plasma the concentration-versus-time curves obtained for humans following intravenous bolus administration. A simulated 1-g dose of cefazolin was ineffective in reducing the bacterial counts in blood and peritoneal fluid samples of animals infected with S. marcescens US20, which produced class Ia beta-lactamase, and as a result, mortality was similar to that of infected controls. Similarly, a simulated 2-g dose of piperacillin was ineffective in reducing bacterial numbers and mortality in animals infected with E. coli 41548, producing a TEM-1 beta-lactamase. However, when the antibiotics were coadministered with BRL 42715, bacterial numbers were reduced significantly and all animals survived at least 16 h after infection. These data demonstrate the ability of BRL 42715 to potentiate the activity of cefazolin and piperacillin against beta-lactamase-producing bacteria that would otherwise be resistant to these antibiotics and illustrate the application of a model to simulate human serum concentrations in conscious rats.
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PMID:Simulation of human serum pharmacokinetics of cefazolin, piperacillin, and BRL 42715 in rats and efficacy against experimental intraperitoneal infections. 151 Apr 38

Phenotypic resistance to beta-lactam antibiotics is mainly due to the prevalence of beta-lactamases. The most common enzymes responsible for resistance to aminopenicillins and older (1st generation) cephalosporins are the TEM-1, TEM-2, OXA-1 and SHV-1 enzymes, all of which are plasmid-mediated. The recent development of oral cephalosporins sharing structural features and an antimicrobial spectrum comparable to that of 3rd-generation cephalosporins has provided highly active compounds for the management of outpatient infections. Two principal mechanisms, however, may cause resistance to these new compounds: the overproduction of chromosomally encoded beta-lactamases with predominating cephalosporinase activity, and the recently observed extended-spectrum beta-lactamases. The overproduction of chromosomally mediated beta-lactamases has been observed only in some species (Enterobacter cloacae, Citrobacter freundii, Serratia spp.) which cause mainly nosocomial infections and are therefore of minor importance in outpatients. The extended-spectrum beta-lactamases TEM-3 to TEM-12 and SHV-2 to SHV-7 have been observed in various countries, they derived from the original enzymes by point mutations and occurred in intensive-care units. These enzymes may cause resistance to 3rd-generation cephalosporins including the recently developed orally active compounds. Moderate resistance to cefetamet is observed only in strains producing either the TEM-3 or the TEM-4 enzyme, whereas the prevalence of the other enzymes is of no consequence for the activity of cefetamet. Consequently, cefetamet will not exhibit a marked selection pressure favoring the spread of extended-spectrum beta-lactamase-producing strains.
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PMID:The threat of resistance to the new oral cephalosporins. 151 58

Ten clinical isolates and the type strain (H37Rv) of Mycobacterium tuberculosis were shown to produce an intracellular beta-lactamase. Crude enzyme preparations were extracted from acetone cell powders by grinding with zirconium beads in 0.133 M glycine with 1.0% Triton X-100. The enzymes had identical patterns on isoelectric focusing, with two major bands at isoelectric points of 4.9 and 5.1. The beta-lactamase was highly susceptible to the new beta-lactamase inhibitor BRL 42715, with an I50 of 0.0001 microgram/ml. The enzyme was also susceptible to clavulanic acid with an I50 (0.05 microgram/ml), which was similar to the value for the common bacterial beta-lactamase TEM-1 (0.01 microgram/ml). The latter result is consistent with previous MIC studies with M. tuberculosis, which have shown synergy between clavulanic acid and amoxicillin. BRL 42715 and clavulanic acid were more active than sulbactam, tazobactam, and cloxacillin. These studies support the potential value of penicillin/clavulanic acid and penicillin/BRL 42715 combinations in the treatment of tuberculosis.
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PMID:beta-Lactamase inhibitors and the inducibility of the beta-lactamase of Mycobacterium tuberculosis. 154 47


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