Biomedical subjects

A Morand

Publications and source records attributed to A Morand.

35 records · Page 2Linked to original sources

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

[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↗

PubMed1985

Behaviour of cefmenoxime towards beta-lactamases.

Using several well-characterized beta-lactamases isolated from Gram-negative bacteria, the interactions of cefmenoxime, a new methoxy-imino-amino-2-thiazol cephalosporin were compared with those of cefotaxime, lamoxactam, cefoperazone and ceftazidime. On-line computerized microacidimetry allowed determination of the affinity of these compounds for the enzymes, which was characterized by Ki values. Microacidimetry showed poor interactions of cefmenoxime with penicillinase TEM-1 (low Vm, poor affinity) whereas it showed a high affinity for the cephalosporinases, as is also the case for cefotaxime or lamoxactam. Both cefmenoxime and cefotaxime showed relative susceptibility in Masuda's double disc technique.

Cefmenoxime↗

PubMed1984

Affinity of cefmenoxime for beta-lactamases: an analysis.

The interactions of cefmenoxime with beta-lactamases in comparison with cefotaxime, moxalactam, cefoperazone, and ceftazidime have been determined. On-line computerized microacidimetry allowed determination of the affinity of these compounds with the enzymes, which was characterized by Km values. The beta-lactamases that were used were two cephalosporinases and one penicillinase. Within these data, the cephalosporins could be classified into three groups: (1) those with high affinity for the cephalosporinases and very poor affinity for the penicillinase (cefmenoxime, cefotaxime, and moxalactam); (2) those with moderate affinity for the cephalosporinases and very poor affinity for the penicillinase (ceftazidime); (3) those with poor affinity for all enzymes (cefoperazone). In the case of the penicillinase (TEM-1), only cefoperazone was subject to some hydrolysis.

Bacteria↗

PubMed1984

[Mechanisms of azlocillin resistance in Pseudomonas aeruginosa].

The authors have evaluated the susceptibility of azlocillin to beta-lactamases habitually produced by Pseudomonas aeruginosa, i.e. TEM and CARB types penicillinases and the so-called Sabath and Abraham cephalosporinase. As all penicillins, azlocillin is liable to hydrolysis by penicillinases that also affect, through to a lesser extent, some cephalosporin. It is also degraded, albeit moderately by the Sabath and Abraham cephalosporinase. The authors have also compared the behaviour of azlocillin towards beta-lactamases to that of other beta-lactam antibiotics, notably carbenicillin, cefoperazone and cefsulodin.

Azlocillin↗

PubMed1984

The action of beta-lactamases on desacetyl-cefotaxime and cefotaxime.

Desacetyl-cefotaxime is the main cefotaxime metabolite. Its antibacterial activity is less than that of the parent molecule, but the combination of cefotaxime and desacetyl-cefotaxime is often synergistic. We analysed the hydrolysis of desacetyl-cefotaxime, in comparison with cefotaxime, by 10 beta-lactamases, mostly cephalosporinases, isolated from various Gram-negative species. From partially purified beta-lactamase preparations of high specific activity, we determined the maximum rates of hydrolysis (Vm) and the Michaelis constants (Ki and Km when possible). It appeared for 7 beta-lactamases the rate of desacetyl-cefotaxime hydrolysis was 2.1 times greater than that of cefotaxime, in terms of geometrical mean value, but with 3 enzymes no hydrolysis was shown for one compound. For 8 enzymes, the Ki, and sometimes Km, of desacetyl cefotaxime are 39 times higher than those of cefotaxime (geometric mean value), which corresponds to a lower affinity.

Cefotaxime↗

PubMed1983

Cefotetan and beta-lactamases. I. An analysis of the affinity of cefotetan for beta-lactamases.

Cefotetan is a new cephamycin whose interaction with a group of eight beta-lactamases isolated from various Gram-negative bacteria has been studied. Using computerized micro-acidimetry, cefotetan was found to be resistant to the hydrolytic action of various enzymes, including those which actively hydrolyse cefotaxime. Despite this resistance to hydrolysis, cefotetan nevertheless shows a certain affinity for these enzymes. These data were submitted to two statistical procedures consisting of correspondence analysis and ascending hierarchical classification. These techniques revealed that cefotetan behaves very much like cefoxitin (another cephamycin) and also like cefotaxime and moxalactam.

Anti-Bacterial Agents↗

PubMed1983

Cefotetan and beta-lactamases. II. An unusual property: the inactivation of some beta-lactamases by cefotetan.

Initially, cefotetan interacts with beta-lactamases to form a classical Michaelis complex characterized by a term Ki (the inhibition constant). In a second phase, this complex develops with time to form a new entity devoid of enzymic activity. This new entity may have the structure of an acyl enzyme with variable stability. In the case of TEM-1 and TEM-2 beta-lactamases, the process is progressively and totally reversible. The same phenomena were observed in varying degrees for Pitton's type 2 (PIT-2) penicillinase, OXA-1 and CARB-1. The Klebsiella oxytoca and Proteus vulgaris beta-lactamases are also inactivated by this same process. However, four other cephalosporinases appear to be unaffected by this mechanism.

Anti-Bacterial Agents↗

PubMed1982

[Mezlocillin and beta-lactamases (author's transl)].

Like all penicillins, mezlocillin is degraded by beta-lactamases of the penicillinase type. It is also degraded to some extent by beta-lactamases of the cephalosporinase type. Yet in both cases mezlocillin behaves approximately like the first and second generation cephalosporins. This, together with good intrinsic activity, accounts for the valuable antibacterial properties of the antibiotic, particularly against Enterobacteriacaea.

Cephalosporinase↗

PubMedDate not supplied

Interactions of new plasmid-mediated beta-lactamases with third-generation cephalosporins.

The kinetic constants of three recently identified plasmid-mediated beta-lactamases--SHV-2, CTX-1, and CAZ-1--markedly active against third-generation cephalosporins were analyzed in comparison with three better-characterized beta-lactamases--two plasmid-mediated enzymes, TEM-2 and PIT-2/SHV-1, and R-30, a beta-lactamase from Klebsiella oxytoca that has few similarities to the newer enzymes. All of these enzymes are synthesized constitutively, demonstrate efficient hydrolysis of penicillins, are highly susceptible to the action of clavulanic acid and sulbactam, and have no detectable activity against the cephamycins and imipenem. With the methoxyimino cephalosporins, including those of the third generation, the rates of hydrolysis observed for the SHV-2, CTX-1, and CAZ-1 enzymes are high and show no relation to those observed for the other presently known beta-lactamases. Structure-activity relations suggest that the oxime substituent of these cephalosporins is a major structural factor in the catalytic process observed with the three new beta-lactamases.

Cephalosporins↗

PubMedDate not supplied

Sulbactam: biochemical factors involved in its synergy with ampicillin.

Sulbactam is a time-dependent irreversible inhibitor of various beta-lactamases by reversible formation of a Michaelis-type enzyme-inhibitor complex and progressive evolution of this complex into inactivated protein(s). This process is either irreversible (true inactivation) or quasi-irreversible (stable acyl-enzyme). In this way, sulbactam efficiently protects ampicillin from degradation by beta-lactamases. Sulbactam itself exhibits a moderate antibacterial activity that is related to an affinity for the penicillin-binding proteins of various bacterial strains, which is similar to the affinity of penicillins such as ampicillin. However, sulbactam binding differs according to the bacterial species involved. In strains producing either low levels of beta-lactamase or none at all, a synergistic effect, minor but not negligible, can be observed when sulbactam is associated with a beta-lactam antibiotic with a complementary affinity for the target sites.

Ampicillin↗

PubMedDate not supplied

[Sheehan syndrome].

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Adult↗

PubMedDate not supplied

[Affinity of N-formimidoyl-thienamycin (MK-0787) for beta-lactamases, analysis by a statistical method: correspondence analysis].

N-formimidoyl-thienamycin (MK-0787) is not subject to beta-lactamase hydrolysis. Nevertheless, this compound does show some affinity for the TEM-type penicillinases, cephalosporinases and a few other beta-lactamases. Surprisingly no affinity was found for the penicillinases of the CARB-type. The results thus obtained for affinity constants Ki and Km were submitted to a statistical analysis treatment, i.e. correspondence analysis and hierarchic ascendent classification. This confirms the fact that MK-0787 presents an unusual behaviour towards beta-lactamases.

Cephalosporinase↗