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

The effects of acidic conditions on activities of seven beta-lactamases--TEM-1 (class A), KOXY (class A), IMP-1 (class B), AmpC (class C), MOX-1 (class C), OXA-5 (class D), and PSE-2 (class D)--and their inhibitors were measured. The enzymatic activities of KOXY, IMP-1, and MOX-1 at pH 5.8 were slightly lower than those at pH 7.5. However, the activities of PSE-2 and OXA-5 were greatly reduced at pH 5.8. All of the beta-lactamase inhibitors tested had poorer inhibitory activities at pH 5.8 than at pH 7.5 except clavulanic acid for TEM-1.
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PMID:Effect of pH on activities of novel beta-lactamases and beta-lactamase inhibitors against these beta-lactamases. 748 32

Sanfetrinem is a trinem beta-lactam which can be administered orally as a hexatil ester. We examined whether its beta-lactamase interactions resembled those of the available carbapenems, i.e., stable to AmpC and extended-spectrum beta-lactamases but labile to class B and functional group 2f enzymes. The comparator drugs were imipenem, oral cephalosporins, and amoxicillin. MICs were determined for beta-lactamase expression variants, and hydrolysis was examined directly with representative enzymes. Sanfetrinem was a weak inducer of AmpC beta-lactamases below the MIC and had slight lability, with a kcat of 0.00033 s(-1) for the Enterobacter cloacae enzyme. Its MICs for AmpC-derepressed E. cloacae and Citrobacter freundii were 4 to 8 microg/ml, compared with MICs of 0.12 to 2 microg/ml for AmpC-inducible and -basal strains; MICs for AmpC-derepressed Serratia marcescens and Morganella morganii were not raised. Cefixime and cefpodoxime were more labile than sanfetrinem to the E. cloacae AmpC enzyme, and AmpC-derepressed mutants showed much greater resistance; imipenem was more stable and retained full activity against derepressed mutants. Like imipenem, sanfetrinem was stable to TEM-1 and TEM-10 enzymes and retained full activity against isolates and transconjugants with various extended-spectrum TEM and SHV enzymes, whereas these organisms were resistant to cefixime and cefpodoxime. Sanfetrinem, like imipenem and cefixime but unlike cefpodoxime, also retained activity against Proteus vulgaris and Klebsiella oxytoca strains that hyperproduced potent chromosomal class A beta-lactamases. Functional group 2f enzymes, including Sme-1, NMC-A, and an unnamed enzyme from Acinetobacter spp., increased the sanfetrinem MICs by up to 64-fold. These enzymes also compromised the activities of imipenem and amoxicillin but not those of the cephalosporins. The hydrolysis of sanfetrinem was examined with a purified Sme-1 enzyme, and biphasic kinetics were found. Finally, zinc beta-lactamases, including IMP-1 and the L1 enzyme of Stenotrophomonas maltophilia, conferred resistance to sanfetrinem and all other beta-lactams tested, and hydrolysis was confirmed with the IMP-1 enzyme. We conclude that sanfetrinem has beta-lactamase interactions similar to those of the available carbapenems except that it is a weaker inducer of AmpC types, with some tendency to select derepressed mutants, unlike imipenem and meropenem.
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PMID:Interactions of beta-lactamases with sanfetrinem (GV 104326) compared to those with imipenem and with oral beta-lactams. 959 45

beta-Lactam resistance among Enterobacteriaceae is related primarily to the emergence of novel beta-lactamases. The class A extended-spectrum beta-lactamases hydrolyze extended-spectrum beta-lactams and are inhibited by clavulanic acid. These beta-lactamases are divided in two groups: TEM and SHV derivatives and non-TEM and non-SHV extended-spectrum beta-lactamases (CTX-M1, CTX-M2, MEN-1, PER-1, PER-2, TOHO-1, and VEB-1). The plasmid-mediated cephalosporinases (MIR-1, FOX-1, MOX-1, BIL-1, CMY-1, CMY-2, and LAT-1) hydrolyze extended-spectrum cephalosporins and cephamycins and are not inhibited by clavulanic acid. They have been reported in Europe and in the United States. The 15 inhibitor-resistant penicillinases are TEM derivatives (except for SHV-10) and plasmid mediated, and they are mainly from Escherichia coli isolates. The carbapenemases noted among Enterobacteriaceae are either the chromosomally located penicillinases (Sme-1, NmcA, IMI-1) found in rare Enterobacter cloacae or Serratia marcescens isolates or the plasmid-mediated metalloenzyme IMP-1 that is widespread in Japan. The incidence of resistance among Enterobacteriaceae related to the other more common beta-lactam-resistance mechanisms has continued to rise worldwide.
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PMID:Trends in beta-lactam resistance among Enterobacteriaceae. 971 Jun 78

A variety of 1beta-methylcarbapenem derivatives were screened to identify inhibitors of IMP-1 metallo-beta-lactamase, a class B beta-lactamase, in an automated microassay system using nitrocefin as a substrate. The structure-inhibitory-activity relationship study revealed that three types of 1beta-methylcarbapenems having benzothienylthio, dithiocarbamate, or pyrrolidinylthio moieties at the C-2 position showed good inhibitory activity. Among the compounds screened, J-110,441, having a benzothienylthio moiety at the C-2 position of 1beta-methylcarbapenem, was the most potent inhibitor of class B metallo-beta-lactamases with K(i) values of 0. 0037, 0.23, 1.00, and 0.83 microM for IMP-1 encoded by the bla(IMP) gene, CcrA from Bacteroides fragilis, L1 from Stenotrophomonas maltophilia, and type II from Bacillus cereus, respectively. In a further characterization study, J-110,441 also showed inhibitory activity against TEM-type class A serine beta-lactamase and chromosomal class C serine beta-lactamase from Enterobacter cloacae with K(i) values of 2.54 and 0.037 microM, respectively. Combining imipenem or ceftazidime with J-110,441 had a synergistic effect on the antimicrobial activity against beta-lactamase-producing bacteria. Against the isolates of IMP-1-producing Serratia marcescens, the MICs of imipenem decreased to levels ranging from 1/64 to 1/4 in the presence of one-fourth of the MIC of J-110,441. Against E. cloacae producing high levels of class C beta-lactamase, the MIC of ceftazidime decreased from 64 to 4 microg/ml in the presence of 4 microg of J-110,441 per ml. This is the first report to describe a new class of inhibitor of class B and class C beta-lactamases including transferable IMP-1 metallo-beta-lactamases.
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PMID:Carbapenem derivatives as potential inhibitors of various beta-lactamases, including class B metallo-beta-lactamases. 1050 31

A 62-year-old woman admitted for rectal carcinoma suffered from a post-operative bacterial infection. Oxy-imino-beta-lactams including cefotiam (CTM) and cefozopran (CZOP) were prescribed for this case, but the patient developed a wound abscess followed by peritonitis. She recovered from the bacterial infection after drainage and recurrent washing of the abscess. An ephemeral aggravation of infectious signs was observed just after creation of an artificial anus, and CZOP was again administered, and no evident bacterial infection occurred. The patient recovered, then was followed as an outpatient to date. A CAZ-resistant (MIC, > 16 micrograms/ml) E. coli was recovered from pus of her wound abscess. Since the CAZ-resistance decreased (MIC, 64 micrograms/ml-->0.13 microgram/ml) by the presence of clavulanate (CVA) in this isolate, this strain was speculated to be an extended spectrum beta-lactamase (ESBL) producer at an early stage of infection. A similar strain was also isolated from the feces. Therefore, we immediately took measures to block the nosocomial spread of this microorganism, and we succeeded in preventing a nosocomial outbreak of this strain. It was later confirmed by PCR analysis and DNA sequencing analysis that this CAZ-resistant E. coli strain produces an ESBL (SHV-5-2a = SHV-12). This is the first report of a case of infection with SHV-derived ESBL producing E. coli strain in Japan. We are concerned that further dissemination of this kind of microorganism might occur in the near future also in Japan, as it has been widely observed in European countries and the US. We believe that it will be very important to distinguish the type of beta-lactamases for rigorous bacterial infection control with the prudent use of antibiotics. In other words, we in Japan must recall that various gram-negative bacterial species that produce TEM-, SHV-derived ESBLs, Toho-1, AmpC, or IMP-1 are already widespread. Thus, we should take this fact into consideration when we do antibiotic susceptibility tentings and interpretation of the results for promotion of accurate chemotherapy.
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PMID:[A SHV-derived extended-spectrum beta-lactamase (SHV-12) produced by an Escherichia coli recovered from wound abscess in post operative case with rectal carcinoma]. 1074 Oct 1

In 1996, Serratia marcescens KU3838 was isolated from the urine of a patient with a urinary tract infection at a hospital in northern Japan and was found to contain the plasmid pKU501. Previously, we determined that pKU501 carries bla(IMP) and the genes for TEM-1-type beta-lactamases as well as producing both types of beta-lactamases (H. Yano, A. Kuga, K. Irinoda, R. Okamoto, T. Kobayashi, and M. Inoue, J. Antibiot. 52:1135-1139, 1999). pKU502 is a recombinant plasmid that contains a 1.5-kb DNA fragment, including the metallo-beta-lactamase gene, and is obtained by PCR amplification of pKU501. The sequence of the metallo-beta-lactamase gene in pKU502 was determined and revealed that this metallo-beta-lactamase gene differed from the gene encoding IMP-1 by one point mutation, leading to one amino acid substitution: 640-A in the base sequence of the IMP-1 gene was replaced by G, and Ser-196 was replaced by Gly in the mature enzyme. This enzyme was designated IMP-6. The strains that produced IMP-6 were resistant to carbapenems. The MICs of panipenem and especially meropenem were higher than the MIC of imipenem for these strains. The k(cat)/K(m) value of IMP-6 was about sevenfold higher against meropenem than against imipenem, although the MIC of meropenem for KU1917, which produced IMP-1, was lower than that of imipenem, and the MIC of panipenem was equal to that of imipenem. These results support the hypothesis that IMP-6 has extended substrate profiles against carbapenems. However, the activity of IMP-6 was very low against penicillin G and piperacillin. These results suggest that IMP-6 acquired high activity against carbapenems, especially meropenem, via the point mutation but in the process lost activity against penicillins. Although IMP-6 has reduced activity against penicillins due to this point mutation, pKU501 confers resistance to a variety of antimicrobial agents because it also produces TEM-1-type enzyme.
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PMID:Plasmid-encoded metallo-beta-lactamase (IMP-6) conferring resistance to carbapenems, especially meropenem. 1130 93

The diagnostic ability of the restriction fragment length dimorphism-polymerase chain reaction (RFLD-PCR) method was evaluated. Seven primer pairs, newly designed from 44 beta-lactamase genes encoding extended-spectrum beta-lactamases not related to TEM- and SHV-types, were used to differentiate OXA-2, FOX-3, CMY-3, IMP-1, and IMI-1 beta-lactamases. The RFLD-PCR was carried out successfully, and these genes were differentiated by the sizes of their PCR products and by the difference in restriction fragment length when each amplicon was digested with a unique restriction enzyme. This discriminatory detection of the genes was confirmed by sequencing the PCR products.
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PMID:Restriction fragment length dimorphism-PCR method for the detection of extended-spectrum beta-lactamases unrelated to TEM- and SHV-types. 1142 68

TEM- or SHV-type extended-spectrum beta-lactamases (ESBLs) are of clinical concern in Europe and the United States, whereas bacterial strains producing such types of ESBLs have not been reported in Japan. We report here two cases of infection due to Klebsiella pneumoniae resistant to extended-spectrum cephalosporins in Japan. A ceftadizime-resistant K. pneumoniae strain (minimum inhibitory concentration; 32 &mgr;g/ml) was isolated transiently from the sputum of an 87-year-old woman with acute myocardial infarction and pneumonia (patient 1). Ceftadizime-susceptible and -resistant (minimum inhibitory concentration; >/=8 &mgr;g/ml) K. pneumoniae strains were isolated over a month from the blood, ascites, and feces of a 44-year-old man after bone marrow transplantation for acute lymphoblastic leukemia (patient 2); this patient died of K. pneumoniae sepsis and peritonitis followed by multiple organ failure. These isolates produced penicillinase, which was inhibited by clavulanic acid. A polymerase chain reaction (PCR) study showed that both isolates carried the SHV or LEN genes, but not the TEM, Toho-1, and IMP-1 genes. The pulsed-field gel electrophoresis profile of the strain isolated from patient 1 was genetically distinguishable from the profiles of the strains isolated from patient 2. It appeared that mutation of the beta-lactamase gene may have occurred in the body of patient 2, since the genotypes of the ceftadizime-susceptible and -resistant isolates from this patient were identical. Another 12 strains of K. pneumoniae, isolated from other patients in the same wards during the period in which the K. pneumoniae strains were isolated from patients 1 and 2, did not produce ESBLs and showed different genotypes. The results suggest that these isolates of resistant K. pneumoniae did not spread by cross transmission in the hospital and that the two cases were sporadic. Surveillance of these types of resistant bacteria is necessary, since they may well be present in other hospitals in Japan. Although the organisms are suspected to produce SHV-type ESBLs or LEN-1 variant beta-lactamases, further studies are necessary to specify the resistance genes.
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PMID:Two sporadic cases of infections due to Klebsiella pneumoniae resistant to expanded-spectrum cephalosporins in Japan. 1181 Apr 97

The stability of cefcapene and cefpodoxime, oral antibacterial cephalosporins, toward different classes of beta-lactamases was evaluated. For the class A beta-lactamases, TEM-1, SHV-1, and NMC-A, only the steady-state kinetic parameter ( k(cat)/ Km) values were calculated (3100 - 1.1 x 10(7) M(-1) x s(-1)), because these enzymes have very high Km values for cefpodoxime and cefotaxime. As for class B beta-lactamases L1, IMP-1, and CcrA, in general, similar k(cat)/ Km values were obtained. However, regarding class C beta-lactamases from Enterobacter cloacae, Escherichia coli, Pseudomonas aeruginosa, and Citrobacter freundii, we found major differences in stability between the two compounds. Cefpodoxime acted as a good substrate for the class C beta-lactamases, except for the enzyme from E. cloacae; its k(cat) and Km values were successfully calculated ( k(cat)/ Km, 1.8 x 10(5) - 1.2 x 10(7) M(-1) x s(-1)). On the other hand, cefcapene acted as a poor substrate or an inactivator for class C beta-lactamases; its k(2)/ K value was successfully calculated (8.7 x 10(5) - 7.0 x 10(6) M(-1) x s(-1)). In addition, k(3) values were determined for beta-lactamases from P. aeruginosa (2.3 x 10(-2) x s(-1)) and C. freundii (2.1 x 10(-1) x s(-1)). Even though these values could be calculated, transient inactivation as an enzyme reactivation reaction for all these enzymes was observed. These findings suggest the potential of cephem compounds as inhibitors of class C beta-lactamases.
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PMID:Cefcapene inactivates chromosome-encoded class C beta-lactamases. 1237 82

Enterobacteria produce elementary chromosomal enzymes, Beta-lactamases of class A: TEM and SHV (Escherichia coli, Klebsiella pneumoniae). These can give rise to plasmid-coded broad-spectrum Beta-lactamases (ESBL) discovered in 1980 (E. coli, K. pneumoniae, Enterobacter cloacae). The first cefotaximase (CTX-M, MEN-1) was reported in Europe in 1990. This enzyme is far more active against cefotaxime than against ceftazidime and aztreonam. Chromosomal hyperpoduction of K1 Beta-lactamase differs from all other ESBLs due its sensitivity to ceftazidime (Klebsiella oxytoca). However, not all enterobacteria are resistant only because of ESBLs, but also as a result of the action of chromosomally or plasmid coded AmpC Beta-lactamase of class C (MIR-1, CMY-1, BIL-1, FOX-1, MOX-1, DHA-1, ACC-1), resistant to Beta-lactamase inhibitors and to cefoxitin (Enterobacter spp., Proteus vulgaris, Citrobacter freundii, Morganelle spp., Serratia spp.). With the loss of outside-membrane porins (OMP) they can become resistant to carbapenem an tibiotics. The 100% resistance of enterobacteria to carbapenems that so far exists in this country is elsewhere in the world compromised by the incidence of carbapenem-hydrolysing plasmid-determined Beta-lactamase of class B (IMP-1, VIM-1) and of class A (KPC-1) in K. pneumoniae, (SME-1) in Serratia marcescens and (IMI-1, NMC-A) in E. clocae. Carbapenemases in enterobacteria are only effective in the presence of impermeability and other resistance mechanisms.
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PMID:[Development of Beta-lactamase resistance in enterobacteria]. 1705 71


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