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)

Ampicillin resistance in Haemophilus influenzae is most often due to the plasmid-mediated production of TEM beta-lactamase. We studied four strains with high-level ampicillin resistance (MIC of 32 micrograms/ml with an inoculum of 10(5) CFU on solid media) which did not produce detectable beta-lactamase activity with two different detection methods. Two of the four strains contained extrachromosomal DNA by agarose gel electrophoresis. Conjugation failed to transfer ampicillin resistance; in contrast, transformation yielded ampicillin-resistant transformants in three of the four strains. These transformants did not contain detectable extrachromosomal DNA. In addition, mobilization of the resistance determinant by transformation to, or conjugation with, recombination-deficient strains was unsuccessful. DNA-DNA hybridization experiments revealed no homology of the DNA of these strains with two R plasmids (one coding for ampicillin resistance, the other for chloramphenicol and tetracycline resistance). We conclude that the genetic basis of the non-beta-lactamase ampicillin resistance in these strains appears to be chromosomally mediated. We investigated the mechanism of resistance in these strains. Enzymatic modification of penicillin was not detected by autoradiography of a thin-layer chromatogram of cell sonic extracts of three ampicillin-resistant transformant strains incubated with [14C]penicillin. To assess changes in permeability of the cell envelope, a plasmid coding for beta-lactamase was conjugated into these strains, and the hydrolysis of penicillin by intact cells and cell sonic extracts was compared. Only one of three transformant strains had significantly diminished permeability. Outer membrane proteins of these strains analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed apparent differences in comparison with the isogenic ampicillin-susceptible recipient strain. Autofluorography of a sodium dodecyl sulfate-polyacrylamide gel electrophoresis of Sarkosyl-solubilized crude membrane (the putative inner membranes) from these ampicillin-resistant transformant strains incubated with [3H]penicillin compared with the isogenic ampicillin-susceptible recipient strain revealed reduced binding to PBP 3 and 6, 3 and 4, or 4. In addition, affinity binding studies revealed decreased affinity of PBP 4 for ampicillin of all four transformants tested. We conclude that the major mechanism of resistance in these strains is altered penicillin-binding proteins; however, other mechanisms, including permeability, may also play a role.
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PMID:Characterization of non-beta-lactamase-mediated ampicillin resistance in Haemophilus influenzae. 633 8

Two mechanisms can be assumed that are responsible for the stability of azthreonam against the attack of beta-lactamases: first, azthreonam lacks binding to the enzyme protein and second, rate of hydrolysis is extremely low, resulting even in inhibition of enzyme activity. Enzyme kinetics were studied from highly purified enzymes: azthreonam did not bind to the TEM-1 enzyme, whereas the compound revealed a time-dependent inhibition of the chromosomally mediated Enterobacter cloacae enzyme. With various cephalosporins as substrates marked discrepancies in the mode of inhibition were observed: cefacedone revealed merely noncompetitive inhibition, cefazolin and cefoperazone demonstrated mixed-inhibition kinetics, and with cephalothin as the substrate enzyme kinetics strongly suggested binding of a second azthreonam molecule. With cefacedone as the substrate KI was ascertained to be 0.8 X 10(-7) mol/l. Conjugative transfer of the TEM-mediating plasmids R6K and RP1 resulted in 20 to 50-fold increase of the MIC's for the Enterobacter cloacae and Citrobacter freundii recipients, in spite of the fact that azthreonam does not serve as a substrate for the TEM-1 enzyme. These findings have likely to be attributed to an impaired penetration of the compound through the "outer membrane" of the recipient strains.
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PMID:[The antibiotic agent azthreonam: studies on plasmid-dependent resistance formation]. 634 Dec 12

Clinical isolates of Oxa-1 and TEM-1 producing strains of E. coli were studied. Susceptibility to piperacillin was determined by the agar and broth dilution procedure, and beta-lactam hydrolysis rates measured by the iodometric method. The beta-lactamases were identified by isoelectric focusing. Our data on TEM-1 producing strains showed a statistically significant correlation between the MIC, if determined by the agar dilution test, and the specific beta-lactamase activity. The majority of Oxa-1 producing E. coli was resistant to piperacillin although the inactivation rate of piperacillin was usually low. Cell wall permeability of TEM-1 producing strains of E. coli to piperacillin was below the lower limit of detectability, but preincubation of the E. coli strains in piperacillin containing broth led to increased cell wall permeability. Bactericidal kinetics of an Oxa-1 and TEM-1 E. coli were studied. It revealed that regrowth of the Oxa-1 strain in piperacillin containing broth was associated with a 25% decrease of piperacillin concentrations without the formation of degradation products, suggesting binding of piperacillin to bacterial cells. The TEM-1 plasmid bearing strain inactivated piperacillin, and the degradation products (penicilloate) could be detected.
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PMID:Different mechanisms of TEM-1 and Oxa-1 mediated resistance to piperacillin in E. coli. 639 46

Comparison of the activity of cefoperazone, cefamandole, cefotaxime, cephalothin and moxalactam against Enterobacteriaceae showed cefoperazone to be twofold (Escherichia coli, Klebsiella) to eigthfold (Enterobacter) more active than cefamandole. The lowes MIC values were found for cefotaxime (0.03 - 0.25 microgram/ml) followed by moxalactam (0.06 - 0.25 microgram/ml). Cefoperazone stood out in activity against Pseudomonas aeruginosa (MIC50 4 microgram/ml). Cephalothin resistance affected the MIC values of cefoperazone and moxalactam only to a small degree. From beta-lactamase susceptibility studies it was concluded that cefoperazone may be hydrolyzed by TEM type beta-lactamases, but that the cephalosporinases (class I) and the chromosomal broad-spectrum beta-lactamases (class IV) only have little effect on this antibiotic. Moxalactam was not degraded by any of the beta-lactamase preparations tested.
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PMID:Activity and specific beta-lactamase susceptibility of cefoperazone and moxalactam. Comparison with other cephalosporins. 645 58

The MICs and MBCs of mezlocillin, ticarcillin and piperacillin were determined by microdilution in liquid medium against 700 strains of Gram-negative bacilli and enterococci isolated from pathological materials and classified according to their sensitivity of ampicillin and carbenicillin. Strains sensitive to ampicillin and carbenicillin were usually sensitive to the other penicillins with weight for weight differences in activity. The MIC pf mezlocillin against 40% of ampicillin - and carbenicillin-resistant TEM-producing strains of E. coli ranged fron 32 to 64 micrograms/ml. In 50% of Klebsiella strains producing a broad-spectrum penicillinase which inhibited ampicillin and carbenicillin, the MIC of mezlocillin was equal or inferior to 8 micrograms/ml. Carbenicillin-resistant Enterobacter and Citrobacter strains were also resistant to the other penicillins under study. Mezlocillin and piperacillin showed some activity on a few strains of carbenicillin-resistant Serratia, Proteus and Acinetobacter spp. Piperacillin and, to a lesser degree, mezlocillin were active against those strains of Pseudomonas spp for which the MIC of carbenicillin was around 512 micrograms/ml. Mezlocillin and ampicillin were the most active of the antibiotics tested against Enterococci. The MBCs of all antibiotics in this study were strongly influenced by the size of the inoculum.
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PMID:[Comparative in vitro activity of 5 semi-synthetic penicillins against aerobic Gram-negative bacilli and enterococci (author's transl)]. 646 Sep 67

The activity in vitro of the new parenteral penicillin, temocillin, was determined by an agar dilution technique at two inocula against 201 recent clinical isolates and also against reference strains that produced characterized beta-lactamases. Ampicillin, ticarcillin, latamoxef (moxalactam) and cefoxitin were used as comparative agents. Temocillin showed no useful activity against Pseudomonas aeruginosa or the Bacteroides fragilis group but was highly active against the Enterobacteriaceae, inhibiting all isolates (Serratia marcescens excepted) at less than or equal to 8 mg/l. The MIC50 and MIC90 were usually within one dilution and results with both inoculum sizes were similar. Temocillin also had good activity against Haemophilus influenzae and beta-lactamase producing strains were as susceptible as non-beta-lactamase producers. Neither for the Enterobacteriaceae nor for H. influenzae did a 1000-fold increase in inoculum result in a greater than two-fold increase in MIC. The above results implied excellent stability to beta-lactamases and this was borne out by the activity of temocillin against strains containing chromosomal cephalosporinases, the 'broad-spectrum' Class IV enzyme and the plasmid mediated enzymes TEM-1, OXA-1 and SHV-1. The protein binding of temocillin was found to be 87%.
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PMID:Comparative in-vitro activity of temocillin (BRL 17421), a new penicillin. 660 23

HR810 (Hoechst-Roussel Pharmaceuticals Inc., Somerville, N.J.) is a new, cyclical-pyridinium cephalosporin that appeared superior to numerous comparison drugs against 658 strains of aerobic and facultative anaerobic bacteria. Seventeen Enterobacteriaceae spp. were tested by broth microdilution methods, and the 50% MICs (MIC50S) and 90% MICs (MIC90s) were 0.03 to 0.12 and 0.03 to 2.0 micrograms/ml, respectively. Only one strain had an MIC greater than 8.0 micrograms/ml (99.6% is considered susceptible). HR810 inhibited 98% of Pseudomonas aeruginosa isolates at less than or equal to 16 micrograms/ml, and the MIC90 for Acinetobacter spp. was 4.0 micrograms/ml. It was also very active against Pseudomonas spp. and Staphylococcus aureus (MIC90, 0.5 micrograms/ml) but marginally active against methicillin-resistant staphylococcal strains (MIC90, 16 micrograms/ml) and enterococcus (MIC90, 32 micrograms/ml). Non-enterococcal streptococci had MIC50s ranging from 0.008 micrograms/ml for Streptococcus pyogenes to 0.12 micrograms/ml for pneumococci. All MICs of HR810 against Haemophilus and Neisseria spp. were less than or equal to 0.03 micrograms/ml (MIC50, 0.002 to 0.008 micrograms/ml). HR810 poorly inhibited beta-lactamases and was very stable against 11 tested beta-lactamases of plasmid (TEM, OXA, SHV-1, and PSE) and chromosomal (K1, K14, P99) types.
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PMID:In vitro evaluation of HR810, a new wide-spectrum aminothiazolyl alpha-methoxyimino cephalosporin. 661 Nov 35

A list of 117 strains of Pseudomonas aeruginosa has been selected for the resistance to carbenicillin. The study of these strains has shown that 22 p. cent were producing a constitutive beta-lactamase. These enzymes could be classified in CARB, TEM-type enzyme and OXA. A relation between their production of beta-lactamases and the MIC has been established.
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PMID:[In vitro action of new beta-lactams on hospital strains of Pseudomonas aeruginosa producing beta-lactamases ]. 681 4

Twenty clinical isolates of ampicillin- and carbenicillin-resistant or susceptible (two strains) Gram-negative rods, producing at least one beta-lactamase, were examined for susceptibility to a combination of ampicillin or carbenicillin with clavulanic acid (enzymatic inhibitor). Synergy was evaluated by the reduction of the beta-lactam agar dilution MIC and by the measurement of intracellular AYP using firefly bioluminescence. The potentiation effect of clavulanic acid was variable, depending on resistance levels, species and types of beta-lactamase (TEM, SHV-1, CARB, OXA, MAL and Cpase). The synergy was significant, with 10 mg/l of inhibitor for all the strains producing TEM-1, TEM-2 and Carb-2 except for one strain of Serratia marcescens (TEM-2). The synergy was weak for Levinea strains (Citrobacter diversus biotype b), biosynthesizing specific penicillinases as MAL-1. No potentiation effect was observed for strains producing a cephalosporinase, such as Escherichia coli and Pseudomonas aeruginosa. This effect appeared to be variable for strains producing the oxacillin-hydrolysing enzyme (OXA-1), such as E. coli and P. aeruginosa. A positive correlation was clearly demonstrated between the MIC values and the intracellular ATP concentration in bacteria within 2 h. The opportunity of using the firefly assay for the rapid determination of synergy between beta-lactam antibiotics and clavulanic acid is discussed.
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PMID:[Rapid determination of the synergy of clavulanic acid and beta lactams by measuring the intracellular ATP by bioluminescence]. 681 96

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.
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PMID:Comparative in vitro antibacterial activity of seven semi-synthetic penicillins against aerobic gram-negative bacteria and enterococci. 715 90


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