Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0276640 (TEM)
 20,729 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The in vitro activity of E-1040 [(6R,7R)-3-[(4-carbamoyl-1-quinuclidinio)methyl]-7-[2-(5-amino-1,2 ,4- thiadiazol-3-yl)-(Z)-2-methoxyiminoacetoamido]-8-oxo-5-thia- 1- azabicyclo(4,2,0)oct-2-ene-2-carboxylate], a novel cephalosporin, was compared with that of ceftazidime, cefpirome, cefepime, imipenem, and gentamicin. E-1040 inhibited 50% of members of the family Enterobacteriaceae, Pseudomonas aeruginosa, and Haemophilus and Neisseria species at less than or equal to 0.25 microgram/ml, and the MIC for 90% of strains tested ranged from 0.06 to 2 micrograms/ml. It was two- to fourfold more active than ceftazidime and similar in activity to cefepime and cefpirome. It inhibited Enterobacter, Citrobacter, Serratia, and Morganella species that were resistant to ceftazidime. E-1040 inhibited imipenem-, piperacillin-, aztreonam-, and tobramycin-resistant P. aeruginosa. It was less active against Xanthomonas maltophilia and P. cepacia but inhibited other Pseudomonas species. The activity of E-1040 against staphylococci and hemolytic streptococci was similar to that of ceftazidime, but E-1040 was less active than cefepime and cefpirome. It did not inhibit Bacteroides spp. There was no inoculum effect or medium effect, and MBCs were within a dilution of MICs. Plasmid beta-lactamases TEM-1, TEM-2, TEM-3 (CTX-1), SHV-1, Staphylococcus aureus, PSE, and CARB did not hydrolyze E-1040. Chromosomal beta-lactamases P99 and K-1 did not hydrolyze E-1040; E-1040 had poor affinity for these enzymes, with a Ki of greater than 100 microM.
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PMID:In vitro activity of E-1040, a novel cephalosporin with potent activity against Pseudomonas aeruginosa. 315 Sep 15

A novel beta-lactamase (beta-lactam-hydrolase, EC 3.5.2.6) was detected in a culture of Pseudomonas C, an obligatory methylotroph. This is the first beta-lactamase discovered in a methylotrophic organism. The inducible cell-bound enzyme with broad-spectrum activity against penicillins, was purified 77-fold from cell extracts of the methanol-grown bacterium, and its molecular weight was estimated to be 30,000. As a group, the isoxazolyl penicillins are the favored substrates, while cephalosporins are resistant to hydrolysis and act as mild competitive inhibitors. The activity of this M-OXA beta-lactamase focused as a single band at an acidic pI value (5.5) similar to that of PSE- and TEM-type enzymes, but can be clearly distinguished from other OXA-type beta-lactamases, all of which focus in the alkaline region. The enzyme is coded by a non-transferable gene. Based on the sum of its physical and biochemical properties, the M-OXA beta-lactamase is distinguishable from all previously described beta-lactamases, although immunological studies revealed some cross reactivity with the plasmid mediated OXA-2 enzyme.
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PMID:Inducible oxacillin-hydrolyzing beta-lactamase in a methylotrophic bacterium. 325 41

beta-Lactamase identification by colony hybridization with 32P-labeled DNA probes for TEM-1, SHV-1, OXA-1, OXA-2, PSE-1, PSE-2, and PSE-4 was compared with isoelectric focusing in 122 clinical isolates making a variety of enzyme types. All strains producing a probe-type enzyme gave a positive hybridization reaction. Cross-hybridization was observed between TEM-1 and TEM-2 or TLE-1, between SHV-1 and SHV-2, between OXA-1 and OXA-4, between OXA-2 and OXA-3 (weak), between PSE-2 and OXA-6 or OXA-5 (weak), and among PSE-1, PSE-4, and CARB-3. With allowance for such cross-hybridization, only six strains gave false-positive reactions, and the procedure was 99% specific.
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PMID:Detection of plasmid-mediated beta-lactamases with DNA probes. 325 20

The ongoing discoveries of new beta-lactamases, mainly penicillinases, in Gram-negative bacteria has emphasized the problem of their precise identification, and thus their phylogeny. Crude extracts, prepared by sonication, of 14 plasmid beta-lactamases, types TEM, carbenicillinases (CARB or PSE) and oxacillinases (OXA) were analysed by a simple, rapid (3.5 to 4 hours) method of electrophoresis on polyacrylamide (7%) agarose (1.4%) gels, using Tris-glycine buffer at pH 8.7. Preliminary serial dilutions were made to determine enzymic activity levels. Enzymes were then characterized by their relative electrophoretic mobilities. These mobilities had coefficients of variability between 2% and 10%, ranged from 5 to 61, and were correlated with their isoelectric points (pI). Thus, the lower the pI is, the greater the mobility is. Despite the high resolving power of the polyacrylamide-agarose gel system, enzymes with similar pI's and of similar types (PSE-1 and CARB-3, or OXA-1 and OXA-4) or different types (SHV-1 and OXA-6) could not be distinguished on the basis of their mobilities. However, this technique provides for rapid and easy identification of the major penicillinases in Gram-negative bacteria. A combination of polyacrylamide-agarose gel electrophoresis and pH gradient electrophoresis (titration curve) could provide a powerful approach to the study of the molecular structure of these enzymes.
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PMID:[Electrophoretic behavior of beta-lactamases in gram-negative bacteria]. 328 89

Foramidocillin is a 6-alpha-formamido penicillin with a 6-beta-acylureido side chain. The majority of the Enterobacteriaceae were inhibited by less than or equal to 1 microgram of foramidocillin per ml, and Pseudomonas aeruginosa was inhibited by 4 micrograms/ml. Foramidocillin had activity comparable to those of ceftazidime, imipenem, and aztreonam against beta-lactamase-producing members of the Enterobacteriaceae and P. aeruginosa, and it inhibited organisms resistant to piperacillin. Foramidocillin did not inhibit gram-positive species or anaerobic gram-negative bacteria. Foramidocillin was not hydrolyzed by the common plasmid-mediated beta-lactamases TEM-1, TEM-2, OXA-2, PSE-4, and SHV-1, by the chromosomal beta-lactamases P99 of Enterobacter cloacae and K1 of Klebsiella oxytoca, or by the Sabath-Abraham enzyme of P. aeruginosa.
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PMID:Antimicrobial activity and beta-lactamase stability of foramidocillin. 348 17

The in vitro activity of CGP 31608, a new penem, against aerobic and anaerobic organisms was evaluated and compared with those of other beta-lactams. CGP 31608 inhibited Escherichia coli, Klebsiella pneumoniae, K. oxytoca, Proteus mirabilis, Citrobacter diversus, and Salmonella, Shigella, Aeromonas, and Yersinia spp. with MICs for 50% of the strains (MIC50s) of 2 to 4 micrograms/ml and MIC90s of 4 micrograms/ml, compared with cefotaxime, ceftazidime, aztreonam, and imipenem MICs of less than 0.25 microgram/ml. MIC90s were 8 micrograms/ml for Enterobacter species and C. freundii, for which other agents had MICs of 32 micrograms/ml, except imipenem, which had equal activity. The MIC90 for Proteus vulgaris, Morganella morganii, Providencia stuartii, and Providencia rettgeri was 8 micrograms/ml, compared with less than 2 micrograms/ml shown by the other agents. Acinetobacter species resistant to other agents except imipenem were inhibited by 4 micrograms/ml, as were Pseudomonas aeruginosa, including piperacillin-, ceftazidime-, and gentamicin-resistant isolates. The MIC for P. cepacia, P. fluorescens, and P. acidovorans was less than or equal to 8 micrograms/ml, but that for P. maltophilia was greater than or equal to 128 micrograms/ml. Hemolytic streptococci A, B, C, G, and F were inhibited by less than 1 micrograms/ml, but the MIC for Streptococcus faecalis was greater than or equal to 32 micrograms/ml. MICs for Staphylococcus aureus methicillin-susceptible and -resistant strains were less than or equal to 1 microgram/ml, as were those for methicillin-susceptible and -resistant S. epidermidis. Bacteroides fragilis and Clostridium species and Fusobacterium spp. were inhibited by less than or equal to 4 micrograms/ml. CGP 31608 was not hydrolyzed by plasmid beta-lactamases TEM-1, TEM-2, SHV-1, PSE-1, OXA-2, PSE-4, or by S. aureus. Chromosomal beta-lactamases of type Ia in Enterobacter cloacae P99 and Morganella morganii, Ic in P. vulgaris, K-1 in K. oxytoca, and Id in P. aeruginosa also did not hydrolyze CGP 31608. It inhibited TEM-1, but the 50% inhibitory concentration was 14.2 micrograms/ml compared with 0.15 micrograms/ml for the P99 enzyme. CGP 31608 induced beta-lactamases in P. aeruginosa, E. cloacae, C. freundii and Providencia rettgeri, but there was no increase in MICs for the isolates and it did not select strains derepressed for beta-lactamase production. Synergy of CGP 31608 and gentamicin was found against 90% P. aeruginosa, 60% Enterobacter cloacae, and 50% Serratia marcescens strains. No synergy was found with rifampin. A postantibiotic effect was found against E. coli.
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PMID:In vitro activity and beta-lactamase stability of a new penem, CGP 31608. 349 45

The in vitro activity of CGP 31523A, an aminothiazolyl cephem, was compared to that of other cephalosporins--imipenem, aztreonam, carbenicillin, and gentamicin. CGP 31523A inhibited E. coli, K. pneumoniae, P. mirabilis, C. diversus, K. oxytoca, P. stuartii, Salmonella and Shigella at less than or equal to 0.25 micrograms/ml. It was equal or 2-fold more active than cefotaxime and ceftazidime, and 4-fold more active than imipenem against these organisms. It inhibited all carbenicillin and gentamicin-resistant isolates of these species. Neisseria and Haemophilus were inhibited by less than or equal to 0.12 micrograms/ml. Some C. freundii, E. cloacae, E. aerogenes, P. vulgaris, and P. penneri had MICs greater than or equal to 16 micrograms/ml similar to cefotaxime, ceftazidime and aztreonam. Pseudomonas were resistant, MIC 128 micrograms/ml. CGP 31523A inhibited streptococci at less than or equal to 0.25 micrograms/ml with the exception of S. faecalis, and staphylococci were inhibited by 0.5 micrograms/ml but methicillin-resistant isolates were resistant. Bacteroides and some Clostridium had MICs greater than or equal to 16 micrograms/ml. CGP 31523A was less stable than cefotaxime and ceftazidime to the plasmid TEM/SHV/PSE-4 beta-lactamases. Like cefotaxime it was hydrolyzed by the P. vulgaris type Ic beta-lactamase but not by the type Ia enzymes. CGP 31523A was not an effective beta-lactamase inhibitor nor did it induce beta-lactamases. It had overall activity comparable to available extended spectrum cephalosporins.
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PMID:Comparative in vitro activity and beta-lactamase stability of CGP 31523A, a new aminothiazolyl cephalosporin. 351 67

We studied the plasmid and antibiotic resistance characteristics of 35 strains of Enterobacteriaceae recovered from faecal specimens of children with diarrhoea in Central General Hospital, Bandung, Indonesia. Twenty three Escherichia coli, three Providencia, three Proteus, three Klebsiella, two Enterobacter and one Citrobacter were examined. All strains were multiply resistant, many carrying six to nine antibiotic resistances. Most of these resistances were transferable to a laboratory E. coli strain and were carried on large-sized plasmids. All recently-described tetracycline resistance determinants (Classes A----D) were represented; the most common was the Class B, or TN10 type. The TEM-1 beta-lactamase was detected in 17 out of 21 ampicillin-resistant strains examined. The OXA-1, PSE-1, and SHV-1 enzymes were also found. Of 23 plasmids tested, all could be classified into one of eight different incompatibility groups: IncFII, IncN, IncB, IncF1, IncI1, IncI2, IncH2 and IncT. These studies demonstrate the existence of large multiresistant transferable plasmids representing common incompatibility groups and bearing common tetracycline and ampicillin resistance determinants in enteric strains isolated from children hospitalized in Indonesia.
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PMID:Multiple antibiotic resistance plasmids in Enterobacteriaceae isolated from diarrhoeal specimens of hospitalized children in Indonesia. 387 28

The in vitro activity of cefotetan was assessed against beta-lactamase producing clinical isolates. The majority of Enterobacteriaceae were inhibited by less than or equal to 8 micrograms/ml with 50% of isolates inhibited by less than or equal to 1 microgram/ml. Cefotetan inhibited organisms resistant to cefazolin, cefonicid and cefoperazone, but not isolates of Enterobacter, Citrobacter or Serratia resistant to ceftizoxime. Cefotetan inhibited beta-lactamase producing Haemophilus influenzae and Neisseria gonorrhoeae at less than or equal to 1 microgram/ml, but it did not inhibit Acinetobacter or Pseudomonas aeruginosa. Cefotetan was as active as cefoxitin against anaerobic species such as Bacteroides fragilis and Clostridium. Cefotetan was not hydrolyzed by Richmond-Sykes plasmid beta-lactamases of type III such as TEM and SHV, nor by the OXA or PSE beta-lactamases. It also was not hydrolyzed by cephalosporinases of Richmond-Sykes type Ia or Id. Cefotetan inhibited beta-lactamases of the type Ia and Id, but it also induced these beta-lactamases in P. aeruginosa, E. cloacae and C. freundii.
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PMID:The activity and beta-lactamase stability of cefotetan compared to other beta-lactam antibiotics. 387 87

There has been remarkable progress in the development of new antimicrobial agents as the result of structural modifications of the cephalosporin nucleus. It has been possible to predict many aspects of the antimicrobial activity of new agents and to recognize the structural modifications that contribute to overcoming the continued problem of bacterial resistance. The activity of beta-lactams against gram-positive species depends primarily on their affinity for the enzymes referred to as penicillin-binding proteins. Resistance of gram-positive species to beta-lactams is either due to altered penicillin-binding proteins or, more commonly, due to the presence of beta-lactamases, which are usually plasmid-mediated and inducible. The activity of beta-lactams against gram-negative aerobic and anaerobic bacteria is the result of the way in which the compounds pass through the porin channels in the outer wall, resist inactivation by beta-lactamases, and bind to the penicillin-binding proteins. The basic cephalosporin nucleus consists of the essential beta-lactam ring fused to a dihydrothiazine ring. It is possible to modify this structure to increase antibacterial activity. Changes in moieties at position 3 affect pharmacologic activity but can also cause a marked increase or decrease in activity against staphylococci and Pseudomonas species. The presence of the thiomethyltetrazole group at position 3 has been associated with an alteration in prothrombin synthesis and with disulfiram reactions. Modifications of the cephem nucleus at position 7 by addition of methoxy groups increase beta-lactamase stability but decrease activity against gram-positive species because of lower affinity for penicillin-binding proteins. The more useful acyl side chains have been those that contain a 2-aminothiazolyl moiety, which causes increased affinity of the molecules for penicillin-binding proteins of gram-negative bacteria and streptococcal species. Iminomethoxy groups provide beta-lactamase stability against the common plasmid beta-lactamases such as those of Staphylococcus aureus and the TEM, SHV-1, OXA, and PSE enzymes found in Enterobacteriaceae and Pseudomonas aeruginosa, as well as the chromosomally mediated K-1 and P99 enzymes of Enterobacter. A propylcarboxy group increases beta-lactamases stability and also provides activity against P. aeruginosa and some Acinetobacter. Conversely, this particular grouping reduces the beta-lactamase induction capabilities of a compound, as well as its ability to function as a beta-lactamase inhibitor.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Relation of structural properties of beta-lactam antibiotics to antibacterial activity. 389 15


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