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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 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

The interactions of a meropenem were studied with a set of beta-lactamases including the new TEM- and SHV-related plasmid-mediated enzymes that have extended-spectrum activity against third-generation cephalosporins ('cefotaximases' and 'ceftazidimases'). Meropenem and imipenem were highly resistant to the hydrolytic activity of all the TEM and SHV related beta-lactamases, and to the OXA enzymes, as were the cephamycins: cefoxitin and cefotetan. The two carbapenems were also highly stable to Class C beta-lactamases (chromosomal cephalosporinases) whereas third-generation cephalosporins and cephamycins were slowly hydrolyzed. Both carbapenems demonstrated quite similar affinities for all the enzymes studied. In some instances, and particularly with Class A (TEM- and SHV-derived) enzymes, meropenem inactivated the beta-lactamase activity. Imipenem appeared less reactive in this respect.
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PMID:Interactions of meropenem, with beta-lactamases, including enzymes with extended-spectrum activity against third-generation cephalosporins. 280 9

We determined the kinetic constants for two plasmid-mediated beta-lactamases with strong activity against third-generation cephalosporins: CTX-1 and SHV-2. The enzymes had many similar properties: their synthesis was constitutive and they were significantly active against penicillins as well as cephalosporins. The two enzymes thus differed considerably from the chromosomal cephalosporinases, but bore some resemblance to the commonly-encountered plasmid-coded penicillinases, such as TEM beta-lactamases. Moreover, like the TEM enzymes, the plasmid-mediated CTX-1 and SHV-2 enzymes were highly sensitive to the action of the inhibitors clavulanic acid and sulbactam. These inhibitors protected cefotaxime from hydrolysis by these enzymes. Both CTX-1 and SHV-2 lacked activity against the cephamycins, cefoxitin, latamoxef (moxalactam) and cefotetan. The CTX-1 and SHV-2 enzymes had a low activity against oxacillin and were not sensitive to chloride ions. Thus, they were not related to the OXA type beta-lactamases. For the third-generation cephalosporins the rates of hydrolysis were high and thus bore no relation with those observed for the other presently-known beta-lactamases, with perhaps the exceptions of those produced by K. oxytoca. Imipenem was very resistant to the action of these CTX-1 and SHV-2 beta-lactamases.
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PMID:Kinetic properties of two plasmid-mediated beta-lactamases from Klebsiella pneumoniae with strong activity against third-generation cephalosporins. 328 96

Acinetobacter calcoaceticus, a nosocomial pathogenic agent, is isolated with increasing frequency from hospitalized patients. Acinetobacter is one of the most resistant pathogens to currently available antibiotics, particularly beta-lactam antibiotics. Beta-lactamases (TEM penicillinase and cephalosporinase) and problems of permeability are the most frequent mechanisms of resistance. The authors compared the in vitro activity of ceftizoxim, ceftazidim and imipenem against 82 clinical isolates of Acinetobacter calcoaceticus. Ceftizoxim, structurally similar to cefotaxim, was highly active in vitro; MIC 50%, 90% and geometric mean were respectively 6.28, 15 and 6.9 micrograms/ml. A significant difference was observed between the anitratum and lwoffi varieties. The lwoffi variety was more susceptible to tested drugs than the anitratum variety. Ceftazidim activity was comparable with MIC 50 of 6.5 micrograms/ml and MIC 90 of 26.2 micrograms/ml. A good bactericidal activity was observed against susceptible strains (MIC less than or equal to 4 micrograms/ml). Imipenem showed the greatest activity since 0.47 microgram/ml of the drug inhibited 90% of Acinetobacter calcoaceticus.
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PMID:[Comparative activity in vitro of ceftizoxime, ceftazidime and imipenem against Acinetobacter calcoaceticus]. 353 56

The in vitro activity of FK-037, 5-amino-2-[[(6R, 7R)-7-[[(Z)-2-(2-amino-4-thiazolyl)-2- methoxyimino) acetyl] amino]-2-carboxy-8-oxo-5-thia-1- azabicyclo[4.2.0]oct-2-en-3-yl]methyl]-1-(2-hydroxyethyl)-1H-pyrazoli um hydroxide, inner salt, sulfate (1:1), a new parenteral cephem, was compared with those of cefepime, ceftazidime, imipenem, and ciprofloxacin. FK-037 inhibited methicillin-susceptible staphylocci at < or = 4 micrograms/ml. Of 98 isolates of homogenous methicillin-resistant Staphylococcus aureus, 55 (56.1%) were inhibited by 8 micrograms of FK-037 per ml, compared to 3.1% for cefepime. Imipenem was the most active beta-lactam tested against staphylococci. The MIC of FK-037 for 90% of the strains tested (MIC90) was 0.06 micrograms/ml for hemolytic streptococci, Streptococcus pneumoniae, viridans group streptococci, and Streptococcus bovis. The MIC90 for many of the members of the family Enterobacteriaceae was 1 microgram/ml, similar to that of cefepime and lower than those of ceftazidime and imipenem. The MIC90 for Klebsiella pneumoniae and Enterobacter cloacae was 8 micrograms/ml, similar to that for cefepime, but all isolates were inhibited by 2 micrograms of imipenem per ml. K. pneumoniae isolates with cefotaxime and ceftazidime MICs of > 32 micrograms/ml with Bush type 2b' beta-lactamases were inhibited by 4 micrograms of FK-037 per ml. E. cloacae, Citrobacter freundii, and S. aureus stably resistant to FK-037 could be selected by repeated transfer in the presence of FK-037. The FK-037 MIC90 for Pseudomonas aeruginosa was 4 microgram/ml, compared to 32 microgram/ml for cefepime and ceftazidime and 8 microgram/ml for imipenem. Xanthomonas maltophilia, Pseudomonas cepacia, Acinetobacter anitratus, and Bacteroides species were resistant to FK-037 (MIC, more than or equal 32 microgram/ml). MBCs were identical to or within twofold of the MICs except for a 32-fold greater MBC for P. aeruginosa. Inoculum size and acid environment did not lower the activity of FK-037. FK-037 was not appreciably hydrolyzed by Bush group 1, 2a, 2b, and 2e beta-lactamases but was hydrolyzed by 2b' and 2d enzymes at rates comparable to that of ceftazidime. Nonetheless, FK-037 inhibited bacteria possessing TEM-3, -5, and -7 and SHV -5 at less than or equal 8 microgram/ml. Overall, FK-037 has lower MICs against staphylococci and P. aeruginosa than the currently available iminomethoxy aminothiazolyl cephalosporins and has activity against members of the family Enterobacteriaceae comparable to that of cefepime.
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PMID:In vitro activity and beta-lactamase stability of FK-037, a parenteral cephalosporin. 846 Sep 25

Ten extended spectrum beta-lactamases producing strains of Klebsiella pneumoniae characterized by analytical isoelectric focusing and studied for their susceptibility to beta-lactam antibiotics, either alone or in combination with a beta-lactamase inhibitor (clavulanic acid and sulbactam) and in association with amikacin. The extended spectrum beta-lactamases were derived from either TEM (CTX-1 = TEM-3) or SHV (CAZ-4 = SHV-5). Killing curves were studied with antibiotics at clinical by achievable concentrations, at MIC and MIC x 4. At MIC, cefotetan, cefotaxime and ceftazidime lacked bactericidal activity. Imipenem was more rapidly bactericidal than meropenem or co-amoxiclav. At MIC x 4, cefotetan and cefotaxime exhibited bactericidal effect but this was less than for imipenem which gave a reduction of 4 log10 of the inoculum. Cefotaxime plus sulbactam gave no bactericidal effect compared with cefotaxime plus co-amoxiclav. A bactericidal effect with cefotaxime plus sulbactam was seen with the addition of amikacin. At clinical concentrations cefotaxime plus co-amoxiclav +/- amikacin was as efficient as imipenem +/- amikacin with a rapid bactericidal effect (5-6 log10 in 30-60 min). We proposed that cefotaxime+co-amoxiclav might be considered as an alternative to imipenem for the treatment of extended spectrum beta-lactamase associated K. pneumoniae injections.
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PMID:Bactericidal effect of beta-lactams and amikacin alone or in association against Klebsiella pneumoniae producing extended spectrum beta-lactamase. 853 74

Tazobactam is a new, irreversible inhibitor of bacterial beta-lactamases of staphylococci, plasmid-mediated beta-lactamases of the TEM and SHV types found in Escherichia coli and Klebsiella species and beta-lactamases of anerobes such as Bacteroides species. Its combination with piperacillin, a broad spectrum ureido-penicillin, would be expected to improve the activity of piperacillin against staphylococci, TEM and SHV beta-lactamase producing Gram negative bacteria and anerobes. Minimal inhibitory concentrations (MIC) of piperacillin/tazobactam were determined for 1952 individual patient isolates of Gram positive and negative bacteria causing significant infections and compared with MIC values for cefotaxime, ceftazidime, ciprofloxacin, imipenem, ticarcillin/clavulanic acid. MICs were determined by agar dilution (NCCLS 1990 and 1992). Piperacillin/tazobactam had excellent activity against methicillin susceptible staphylococci, Streptococcus pneumoniae, Haemophilus influenzae, enterococci and organisms of the Bacteroides fragilis group. It was also active against the majority of Enterobacteriaceae and Pseudomonas aeruginosa isolates tested. It was not active against extended spectrum beta-lactamase (ESBL) producing Klebsiella species and some high level TEM and SHV beta-lactamase producing E. coli and Klebsiella species. Activity against Gram negative organisms capable of producing chromosomally mediated beta-lactamases was good, since in most organisms tested, the enzymes were not induced in sufficient quantities to cause antibiotic resistance. However some Enterobacter species were derepressed hyperproducing mutants; these isolates showed resistance to piperacillin/tazobactam since tazobactam does not inhibit these Class I beta lactamases. Activity was superior to ticarcillin/clavulanic acid for Gram negative rods. Imipenem was the most active agent against ESBL producing Klebsiella species. Piperacillin/tazobactam has a suitable spectrum of activity in vitro to suggest its use in monotherapy of mixed anerobic infections, mixed respiratory infections such as aspiration pneumonia and, in combination with an aminoglycoside, it would provide Gram positive as well as Gram negative cover of febrile episodes in immunosuppressed patients.
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PMID:An evaluation of the in vitro activity of piperacillin/tazobactam. 874 25

Bacterial resistance to beta-lactam antibiotics, a clinically worrying and recurrent problem, is often due to the production of beta-lactamases, enzymes that efficiently hydrolyze the amide bond of the beta-lactam nucleus. Imipenem and other carbapenems escape the activity of most active site serine beta-lactamases and have therefore become very popular drugs for antibacterial chemotherapy in the hospital environment. Their usefulness is, however, threatened by the appearance of new beta-lactamases that efficiently hydrolyze them. This study is focused on the structure and properties of two recently described class A carbapenemases, produced by Serratia marcescens and Enterobacter cloacae strains and leads to a better understanding of the specificity of beta-lactamases. In turn, this will contribute to the design of better antibacterial drugs. Three-dimensional models of the two class A carbapenemases were constructed by homology modeling. They suggested the presence, near the active site of the enzymes, of a disulfide bridge (C69-C238) whose existence was experimentally confirmed. Kinetic parameters were measured with the purified Sme-1 carbapenemase, and an attempt was made to explain its specific substrate profile by analyzing the structures of minimized Henri-Michaelis complexes and comparing them to those obtained for the "classical" TEM-1 beta-lactamase. The peculiar substrate profile of the carbapenemases appears to be strongly correlated with the presence of the disulfide bridge between C69 and C238.
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PMID:A disulfide bridge near the active site of carbapenem-hydrolyzing class A beta-lactamases might explain their unusual substrate profile. 903 11

The in vivo activities of piperacillin-tazobactam and cefepime were compared with those of ticarcillin-clavulanate, ceftazidime, cefotaxime, and imipenem in a rat model of intra-abdominal abscess with a strain of Klebsiella pneumoniae elaborating an extended-spectrum beta-lactamase (TEM-26). With the exception of ceftazidime, all of the antimicrobial agents significantly reduced bacterial counts within abscesses at the end of therapy compared with those in untreated controls. Residual viable cell counts (mean +/- standard deviation in log10 CFU/gram) were as follows: control, 8.76 +/- 0.97; ceftazidime, 8.00 +/- 0.76; piperacillin-tazobactam, 3.87 +/- 1.72; ticarcillin-clavulanate, 3.74 +/- 1.34; cefepime, 3.15 +/- 1.19; cefotaxime, 2.61 +/- 0.77; imipenem, 2.41 +/- 0.93. Imipenem was more effective than either of the inhibitor combinations (P < 0.05). Cefotaxime was unexpectedly effective given its poor in vivo activity against this organism in our earlier studies, which used a different dose and total duration of therapy (L. B. Rice, J. D. C. Yao, K. Klimm, G. M. Eliopoulos, and R. C. Moellering, Jr., Antimicrob. Agents Chemother. 35:1243-1244, 1991). These observations suggest that the effectiveness of cephalosporins in the treatment of experimental infections caused by extended-spectrum beta-lactamase-producing K. pneumoniae may be highly dependent on dosing regimens, even for a specific organism and site of infection.
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PMID:Efficacies of piperacillin-tazobactam and cefepime in rats with experimental intra-abdominal abscesses due to an extended-spectrum beta-lactamase-producing strain of Klebsiella pneumoniae. 914 68

Bacterial resistance to antibiotic is the inevitable consequence of the utilization of antimicrobial agents all over the world, particularly in developed countries. It is particularly evident with beta-lactam agents because they are among most frequently prescribed drugs. The resistance is mainly attributable to production of various types of beta-lactamases but other mechanisms like alterations in PBP molecules or in outer membrane proteins can play a significant role. Increased resistance can be seen among fastidious gram-negative bacteria like Haemophilus influenzae or Moraxella catarrhalis. The percentage of M. catarrhalis isolates producing beta-lactamases has increased to over 90%. Among Enterobacteriaceae E. coli and Klebsiella pneumoniae pose a very serious problem because of the production of extended-spectrum beta-lactamases which confer resistance to third generation cephalosporins. The percentage of ampicillin resistant E. coli among hospital isolates has rosen to 78% in U.S.A. nowadays. Recently, the emergence of E. coli strain resistant to combination of amoxycillin and clavulanate, due to hyperproduction of TEM-1 beta-lactamase, was observed. Inducible beta-lactamases mediate beta-lactam resistance in Pseudomonas aeruginosa which often develops during therapy of P. aeruginosa infections. Imipenem resistance is increasingly prevalent among P. aeruginosa isolates nowadays, but can be detected in K. pneumoniae due to the production of novel beta-lactamases and changes in outer membrane proteins.
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PMID:[Development of beta-lactam antibiotic resistance in gram-negative bacteria and the impact of resistance on therapy]. 1057 61


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