scholarly journals Kinetic and physical studies of β-lactamase inhibition by a novel penem, BRL 42715

1994 ◽  
Vol 303 (3) ◽  
pp. 825-830 ◽  
Author(s):  
T H Farmer ◽  
J W J Page ◽  
D J Payne ◽  
D J C Knowles

The interactions of Staphylococcus aureus, Bacillus cereus I, TEM, Klebsiella pneumoniae K1 and Enterobacter cloacae P99 beta-lactamases with the novel penem inhibitor BRL 42715 were investigated kinetically and, in some cases, by electrospray mass spectrometry (e.s.m.s.). All the beta-lactamases were rapidly inactivated by BRL 42715, with second-order rate constants ranging from 0.17 to 6.4 microM-1.s-1. The initial stoichiometry of beta-lactamase inhibition was essentially 1:1, with the exception of the K1 enzyme. In this instance about 20 molecules of BRL 42715 were hydrolysed before the enzyme was completely inhibited. Inhibited beta-lactamases did not readily regain activity in the absence of BRL 42715, the half-lives for regeneration of free enzyme ranging from 5 min for the K1 beta-lactamase to over 2 days for the staphylococcal enzyme. Recovery of activity was incomplete for TEM-1, K1 and P99 beta-lactamases, suggesting partitioning of the inhibited enzymes to give a permanently (or at least very stable) inactivated species. Examination of the interactions of the penem with TEM, B. cereus I and P99 beta-lactamases by e.s.m.s. also showed rapid and stoichiometric binding of the inhibitor. In all cases a mass increase of 264 Da over the native enzyme was observed, corresponding to the molecular mass of BRL 42715, showing that no fragmentation of the penem occurred on reaction with the beta-lactamases.

1996 ◽  
Vol 40 (7) ◽  
pp. 1736-1740 ◽  
Author(s):  
M Gazouli ◽  
L S Tzouvelekis ◽  
E Prinarakis ◽  
V Miriagou ◽  
E Tzelepi

Cefoxitin resistance in Klebsiella pneumoniae from Escherichia coli strains isolated in Greek hospitals was found to be due to the acquisition of similar plasmids coding for group 1 beta-lactamases. The plasmids were not self-transferable but were mobilized by conjugative plasmids. These elements have also been spread to Enterobacter aerogenes. The most common enzyme was a Citrobacter freundii-derived cephalosporinase (LAT-2) which differed from LAT-1 by three amino acids.


1996 ◽  
Vol 40 (4) ◽  
pp. 1027-1029 ◽  
Author(s):  
M J Soilleux ◽  
A M Morand ◽  
G J Arlet ◽  
M R Scavizzi ◽  
R Labia

Crude extracts from 115 extended-spectrum beta-lactamase-producing Klebsiella pneumoniae isolates were analyzed biochemically. The TEM-3 type was encountered 108 times, SHV types were encountered 7 times, and the TEM-26 type was encountered only once. For the last one, the gene was identified; an adenine was detected at position 925, as in blaTEM-26B not in blaTEM-26.


2006 ◽  
Vol 84 (10) ◽  
pp. 1280-1289 ◽  
Author(s):  
Jeffery D Clarke ◽  
Keith Vaughan ◽  
Valerio Bertolasi

The reactions of a series of arene diazonium salts with 1,4,8,11-tetraazacyclotetradecane (cyclam) afford the novel compounds, the 1,4,8,11-tetra[2-aryl-1-diazenyl]-1,4,8,11-tetraazacyclotetradecanes (1a–1f), which are the first examples of tetrakistriazenes to be reported. The tetrakistriazenes were characterized by IR spectroscopy, proton and carbon NMR, elemental analysis, high resolution electrospray mass spectrometry, and X-ray crystallography. The analogous reaction of a diazonium salt with 1,4,7-triazacyclononane or 1,5,9-triazacyclododecane yields the tristriazenes 2, 3a, and 3b. The structures of compounds 1c and 1e were solved by X-ray crystallography at low temperature (150 K). Both molecules display a conformation where the four phenyltriazenyl groups point alternately upwards and downwards with respect to the mean macrocyclic plane.Key words: triazene, tetrakistriazene, cyclam, tetraazacyclotetradecane, X-ray, NMR, cyclic polyamines.


2012 ◽  
Vol 6 (05) ◽  
pp. 457-461 ◽  
Author(s):  
Rima I El-Herte ◽  
George F Araj ◽  
Ghassan M Matar ◽  
Maysa Baroud ◽  
Zeina A Kanafani ◽  
...  

Carbapenem resistance has been encountered globally with poor outcome of infected patients. NDM-1 (New Delhi metallo-beta-lactamase) gene containing organisms have emerged and are now spreading in all continents. This is the first report of Iraqi patients referred to Lebanon from whom carbapenem resistant Enterobacteriaceae were recovered. The genes involved in carbapenem resistance were bla-OXA-48   and the novel NDM-1. This report highlights the alarming introduction of such resistance among Enterobacteriaecae to this country.


2020 ◽  
Vol 3 (2) ◽  
pp. 96
Author(s):  
Isna Romadhona ◽  
Fauna Herawati ◽  
Rika Yulia

Antibiotik merupakan obat yang digunakan untuk mengatasi dan mencegah infeksi bakteri. Penggunaan antibiotik yang tidak tepat dapat menimbulkan berbagai masalah, diantaranya pengobatan akan lebih mahal dan juga risiko terjadinya resistensi bakteri terhadap antibiotik. Penelitian ini bertujuan untuk mengetahui profil penggunaan antibiotik dan profil peta kuman pada pasien gangren diabetes melitus di sebuah RSUD di Kabupaten Gresik serta untuk mengetahui kesesuaian penggunaan antibiotik dengan mengacu pada Permenkes Republik Indonesia No. 2406/Menkes/PER/XII/2011. Data penggunaan antibiotik diperoleh dari catatan Rekam Medis pada periode Januari – November 2017. Data penggunaan antibiotik dihitung dengan menggunakan rumus DDD/100 pasien-hari rawat. Hasil perhitungan DDD/100 pasien-hari rawat menunjukkan hasil sebesar 470,11 DDD/100 pasien-hari rawat. Peta kuman pada pasien gangren, melaporkan adanya bakteri Enterobacter cloacae 24%, Escherichia coli 18%, Staphylococcus aureus 15%, Acinetobacter baumannii 9%, Pseudomonas aeruginosa 6%, Citrobacter youngae 6%, Enterobacter aerogenes 6%, Proteus vulgaris 6%, Staphylococcus schleiferi 6%, Klebsiella pneumoniae 3%, dan Proteus mirabilis 3% . Penggunaan antibiotik seftriakson dan metronidazol pada pasien gangren diabetes melitus di sebuah RSUD di Kabupaten Gresik pada periode Januari – November 2017 telah sesuai dengan pedoman penggunaan antibiotik berdasarkan Permenkes Republik Indonesia No. 2406/Menkes/PER/ XII/2011, yaitu antibiotik golongan sefalosporin generasi III yang lebih aktif terhadap Enterobacteriaceae dan antibiotik golongan nitroimidazol yang dapat mengobati infeksi bakteri basil anerob Gram-Negatif.


1994 ◽  
Vol 12 (2) ◽  
pp. 69-83 ◽  
Author(s):  
Joseph Banoub ◽  
Emmanuel Gentil ◽  
Bougrine Tber ◽  
Nour-Eddine Fahmi ◽  
Gino Ronco ◽  
...  

Electrospray mass spectrometry has aided the structural characterization of 3'-azido-2',3'-dideoxythymidine (AZI) and the novel series of 3'-azido-2',3',4'trideoxy-4'-thio-S-(bromo, chi oro or fluoro )uridine nucleosides and their respective α.anomers. Low energy CAD MS/MS analysis of the protonated molecules [M+H]+confmned the predicted fragmentation route for AZT and a series of related 4'-thio-S-halogenouridines. This MSIMS study also provided characteristic fingerprint patterns which permitted differentiation of anomers within the series of 3'-azido-2' ,3' ,4' -trideoxy-4' -thio-S-halogenouridine nucleosides.


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