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R Labia

Publications and source records attributed to R Labia.

At least 127 records · Page 7Linked to original sources
PubMed1988

Kinetic properties of two plasmid-mediated beta-lactamases from Klebsiella pneumoniae with strong activity against third-generation cephalosporins.

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.

Cephalosporins↗
PubMed1988

Comparative study of a novel plasmid-mediated beta-lactamase, CAZ-2, and the CTX-1 and CAZ-1 enzymes conferring resistance to broad-spectrum cephalosporins.

Infections caused by strains of Klebsiella pneumoniae resistant to broad-spectrum cephalosporins have been observed recently in hospitals in Clermont-Ferrand, France. beta-Lactam resistance resulted primarily from the plasmid-mediated, expanded-spectrum CTX-1 beta-lactamase. Furthermore, since 1987 some K. pneumoniae isolates more resistant to ceftazidime than to other cephalosporins have been observed. This new resistance phenotype was the result of the production of ceftazidimase CAZ-1 and, more recently, CAZ-2. As in CTX-1-producing strains, resistance to beta-lactams resulting from CAZ-2 was associated with resistance to aminoglycosides except gentamicin, sulfonamide, and tetracycline and was transferable to Escherichia coli by conjugation. Agarose gel electrophoresis of plasmid DNA from wild-type strains and transconjugants indicated that CAZ-2 production was mediated by a plasmid of 85 kilobases highly related to plasmid pCFF04 coding for CTX-1 beta-lactamase. The isoelectric point, close to 6.0, of this novel enzyme differed from those of CTX-1 and CAZ-1. Like CAZ-1, the CAZ-2 enzyme efficiently hydrolyzed ceftazidime and aztreonam, but as with CTX-1, cefotaxime gave the maximal reaction rate. For each expanded-spectrum beta-lactamase, the activity of broad-spectrum cephalosporins was restored by clavulanic acid or sulbactam.

Cefotaxime↗
PubMed1988

Novel plasmid-mediated beta-lactamase in clinical isolates of Klebsiella pneumoniae more resistant to ceftazidime than to other broad-spectrum cephalosporins.

Multiresistant Klebsiella pneumoniae strains isolated from three patients in the same intensive care unit were more resistant to ceftazidime than to cefotaxime and aztreonam but remained susceptible to moxalactam and imipenem. Resistance to beta-lactams, kanamycin, streptomycin, sulfonamides, and tetracyclines was transferable to Escherichia coli by conjugation and was lost en bloc after treatment with ethidium bromide. Agarose gel electrophoresis of wild types and transconjugants indicated that these resistances were mediated by a 150-kilobase plasmid, pCFF14. The strains constitutively produced a beta-lactamase with isoelectric point close to 5.6 and which had a higher Vmax for ceftazidime and cephalothin than for cefotaxime. The substrate profile and isoelectric point of this enzyme thus differ from those of other known plasmid-mediated beta-lactamases, including the broad-spectrum enzyme CTX-1. Hybridization studies support the derivation of the novel enzyme from a TEM-type beta-lactamase.

Ceftazidime↗
PubMed1988

alpha-Amanitin: a possible suicide substrate-like toxin involving the sulphoxide moiety of the bridged cyclopeptide.

The highly hepatotoxic natural compound, alpha-amanitin, is noteworthy for its uncommon properties: high and specific affinity for the enzyme RNA polymerase type II, and, furthermore, high potency, severity and irreversibility of the poisoning. Considering the structural uniqueness of the tryptathionine bridge bearing a sulphoxide function, a few mechanistic and biochemical observations suggest that an enzyme-induced process may underlie the characteristics of the poisoning evolution which leads to the cytolysis of the hepatocytes.

Amanitins↗
PubMed1988

The kinetics of SHV-2 plasmid-mediated beta-lactamase compared to those of the parent enzyme from which it is derived.

Kinetic constants were determined for two closely related plasmid-mediated beta-lactamases: SHV-2 and PIT-2 (also known as SHV-1). These enzymes were synthesized constitutively. They were highly sensitive to the action of the inhibitors clavulanic acid and sulbactam, and they lacked activity against cephamycins and also imipenem. Both enzymes were significantly active against penicillins and first-generation cephalosporins, and the main difference concerned the third-generation cephalosporins: SHV-2 was highly active against these compounds whereas PIT-2 was not.

Anti-Bacterial Agents↗
PubMed1987

Transferable resistance to third-generation cephalosporins in clinical isolates of Klebsiella pneumoniae: identification of CTX-1, a novel beta-lactamase.

Approximately 10% (89 isolates) of Klebsiella pneumoniae isolated in 1985 from patients in intensive care units in Clermont-Ferrand exhibited a complex resistance phenotype towards antibiotics. They were resistant to amino-, carboxy- and ureidopenicillins, aminoglycosides (except gentamicin), chloramphenicol, sulphonamides, tetracyclines and, most importantly, to cephalosporins (except cefoxitin and latamoxef) and to aztreonam. The metabolic profile of fifty isolates was identical and seven were selected for further study. All the resistance characters in these isolates were transferable to Escherichia coli by conjugation and were lost en bloc after treatment with ethidium bromide. Agarose gel electrophoresis of crude lysates of the wild types and their transconjugants indicated that the multiple resistances were mediated by a 95kb plasmid, pCF04. The seven isolates selected for study and their corresponding transconjugants, constitutively produced a plasmid-mediated beta-lactamase with a pI of 6.3 that was much more active against third-generation cephalosporins than against cephalothin. The substrate profile and the isoelectric-focusing behaviour of this enzyme differed from those of other known plasmid-mediated beta-lactamases, and the enzyme was designated CTX-1. A chromosomally-encoded SHV-1 (PIT-2) penicillinase (pI 7.7) was also present in the seven K. pneumoniae isolates but did not transfer. Resistance to aminoglycosides in the K. pneumoniae isolates was due to synthesis of a 6'-aminoglycoside acetyltransferase type IV. Our data indicate an epidemic of antibiotic multiply-resistant strains of K. pneumoniae producing a new beta-lactamase.

Cephalosporins↗
PubMed1987

[Effects of beta-lactamases on the antibacterial activity of carumonam and aztreonam against Klebsiella sp. in comparison with 4 other beta-lactams].

Carumonam and aztreonam are two similar monocyclic beta lactam antibiotics. We have studied their antibacterial activities on Klebsiella, in comparison with cefotaxime, cefoxitin, cefotetan and imipenem. In the case of K. pneumoniae (53 strains) the antibacterial activities of the two monobactams are very similar. On the contrary, with K. oxytoca (22 strains) carumonam is significantly more active. This situation seems to be justified by an improved stability of carumonam to beta lactamases. In addition, the antibacterial activities of imipenem and of cephamycins remain quite constant within all the strains. Then the antibacterial activity of cefotaxime is fluctuant, which is in relation with a clear susceptibility to the Klebsiella beta lactamases.

Anti-Bacterial Agents↗
PubMed1986

[Enzymologic aspect of piperacillin combinations].

Like all penicillins, piperacillin exhibits some susceptibility to beta-lactamases of the penicillinase type, including those produced by Staphylococcus aureus and the TEM, OXA and CARB enzymes isolated from Gram-negative bacilli. Piperacillin is very slightly hydrolyzed by cephalosporinases, which makes it similar to 3rd generation cephalosporins. When tested with Enterobacter cloacae GN 5797 and Pseudomonas aeruginosa NTC 8303, two strains which produce inducible cephalosporinases, piperacillin had moderate inductive activity compared to cefoxitin, a potent inducer. Induction was very low with Enterobacter, but the drug was slightly more sensitive to Pseudomonas. Inhibition of this type of beta-lactamase synthesis was very strong when piperacillin was combined with amikacin and weaker when it was combined with pefloxacin. The piperacillin-amikacin combination prevented the development of piperacillin-resistant mutants of Enterobacter and Pseudomonas and, probably, of all Gram-negative bacilli. In our tests, the piperacillin-pefloxacin combination was of interest only against Enterobacter, and probably against all enterobacteria, since Pseudomonas mutants that resist pefloxacin are fairly easily obtained in vitro.

Amikacin↗
PubMed1986

Timentin and beta-lactamases.

Ticarcillin is resistant to the action of cephalosporinases, which explains its biological activity on a large number of bacterial species, including cephalosporinase-producing Enterobacteriaceae and Pseudomonas aeruginosa. Nevertheless, its antibacterial activity is often limited by the action of some beta-lactamases, mostly plasmid-mediated penicillinases. Clavulanic acid by itself has poor antibacterial activity, but its most important property is to inhibit and inactivate beta-lactamases. The inhibitory properties of clavulanic acid were studied on a large number of beta-lactamases. The penicillinases produced by Staphylococcus aureus, the plasmid-mediated beta-lactamases such as the TEM-type, the chromosomally-mediated penicillinases from Klebsiella pneumoniae and other closely-related beta-lactamases, and a few chromosomally-mediated cephalosporinases, such as that produced by Proteus vulgaris, are powerfully inhibited by clavulanic acid. The plasmid-mediated penicillinases of OXA type and most of the chromosomally-mediated cephalosporinases, such as that produced by Escherichia coli (Amp C), are less or poorly inhibited. Moreover, clavulanic acid has some cephalosporinase-inducing properties. These properties are in good agreement with the bacteriological properties of Timentin.

Bacterial Proteins↗
PubMed1986

Beta-lactamase stability of imipenem.

The beta-lactamase stability and interactions of imipenem were analysed in comparison with those of cefazolin, cefuroxime, cefoxitin, cefotaxime, ceftazidime, mezlocillin, piperacillin and penicillin G for a set of representative beta-lactamases. These enzymes included penicillinases such as those obtained from Staphylococcus aureus, Escherichia coli and other Enterobacteriaceae (TEM-1 and similar enzymes) (group A); cephalosporinases produced by Esch. coli (Amp C type), Serratia liquefaciens, Enterobacter cloacae, Pseudomonas aeruginosa (group B); and beta-lactamases produced by Klebsiella spp., Proteus vulgaris and Bacteroides fragilis and with a high hydrolytic activity for the newer cephalosporins (group C). Enzymes of group A were demonstrated to be highly active against penicillins and also against the early cephalosporins; enzymes of group B showed hydrolytic activity for all other tested compounds, including the newer cephalosporins and cephamycins, but not imipenem, whereas enzymes of group C were highly active against the new cephalosporins but not against cephamycins and imipenem. In conclusion, imipenem shows a moderate affinity for all these enzymes but no detectable hydrolysis.

Enzyme Stability↗
PubMed1986

Classification of beta-lactamases from Branhamella catarrhalis in relation to penicillinases produced by other bacterial species.

Branhamella catarrhalis strains resistant to commonly used penicillins, and presently isolated, produce a beta-lactamase. Most of these enzymes are chromosomally mediated, but a plasmid-mediated beta-lactamase has been described (enzyme BRO-1). With reference to isoelectric points, 7 different enzymes have been identified: 6 chromosomally mediated and 1 plasmid-mediated. Nevertheless, they have many common properties, such as being biosynthesised constitutively but with a low level of production. They have a penicillinase-type profile, and are strongly inhibited by clavulanic acid.

Bacteria↗
PubMed1986

[Inhibition of cephalosporinase of enterobacteria by ceftriaxone].

Resistance of ceftriaxone, cefotaxime and cefmenoxime to inactivation by the chromosomal constitutive cephalosporinases of Enterobacter cloacae P99, Morganella morganii GN 1510 and Serratia liquefaciens 132 was determined using high performance liquid chromatography. The inhibitory properties of ceftriaxone against the same cephalosporinases were studied by determining the residual amount of cephalothin used as the substrate. With a 1:50 cephalosporinase-cephalosporin ratio, ceftriaxone was less resistant to hydrolysis than cefotaxime of cefmenoxime but showed stronger inhibitory properties.

Cefmenoxime↗
PubMed1986

[Klebsiella oxytoca beta-lactamases: study of their action on 3d-generation cephalosporins].

Indole-positive Klebsiella pneumoniae or K. oxytoca are usually resistant to penicillins as a result of the production of a chromosomally-mediated beta-lactamase with a low level of synthesis (specific activity approximately 50 to 100 mU/mg). Although most strains are susceptible to the majority of cephalosporins, some strains exhibit resistance to cephalosporins including third-generation drugs. These resistant strains produce a chromosomally-mediated beta-lactamase with a high level of synthesis (specific activity approximately 5,000 mU/mg or higher). Four beta-lactamases have been identified on the basis of their isoelectric points: pI = 5.5, 5.7, 6.0 and 6.3; nevertheless they have similar kinetic constants, and are inhibited by clavulanic acid. These enzymes hydrolyze most third-generation cephalosporins, in the following order of decreasing velocities: cefoperazone, ceftriaxone, cefotaxime, cefodizime, cefpirome; ceftazidime, and cefoxitin, cefotetan, latamoxef, cephamycins which are totally resistant to these enzymes.

Cephalosporins↗
PubMed1986

[Interactions of ceftriaxone with beta-lactamases including those which hydrolyze cefotaxime].

As it occurs with most of 3rd generation cephalosporins, ceftriaxone has few, if any, interactions with penicillinase-type beta-lactamases, such as TEM-1, TEM-2 or PIT-2. These poor interactions are characterized by an extremely low hydrolysis, associated to a poor affinity of these compounds for the penicillinases. Conversely, ceftriaxone, as cefotaxime, shows a high affinity for chromosomally-mediated cephalosporinases (indole-positive Proteus, Enterobacter, Pseudomonas...), which is characterized by Ki values ranging from about 0.05 to 1 microM. Within these beta-lactamases, the hydrolysis of ceftriaxone, as that of cefotaxime, is always low, but significant. Then few beta-lactamases are able to hydrolyze more efficiently cefotaxime, as cefuroxime, such as those produced by P vulgaris and K oxytoca. Within these enzymes, ceftriaxone is also hydrolyzed, in a way quite similar to that of cefotaxime.

Cefotaxime↗