Syntheses, in vitro antibacterial and cytotoxic activities of a series of 3-substituted succinimides.

We have synthesized a series of 3-substituted succinimides and their in vitro antibacterial activities have been tested towards Gram-positive and Gram-negative bacteria from the ATCC collection. Some of them possess significant antibacterial activity against Gram-positive organisms (Staphylococcus aureus ATCC 25923 and Enterococcus faecalis ATCC 29212) but all are poorly active or inactive against Gram-negative organisms (Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853). The compounds with the lowest minimal inhibitory concentrations (esters of 3-hydroxy succinimides) are also the most cytotoxic against green monkey Vero cell line (ATCC CCL-81) and could explain that perhaps apoptosis should be implicated in eukaryotic cell cytotoxicity of succinimides.

Inducible AmpC beta-lactamase of a new member Enterobacteriaceae.

Extensive biochemical testing and 16S rRNA and rpoB sequence analysis revealed that clinical strain CF01Ent1, initially identified as Buttiauxella agrestis by the use of Api 32 biochemical strips, is a new organism in the Enterobacteriaceae family. It produced an inducible AmpC-type beta-lactamase whose sequence shares 69 to 72% identity with those of the other AmpC-type beta-lactamases of ENTEROBACTERIACEAE: This enzyme exhibits an atypical high affinity for all beta-lactams tested.

Prospective survey of beta-lactamases produced by ceftazidime- resistant Pseudomonas aeruginosa isolated in a French hospital in 2000.

In 2000, at the Université d'Auvergne teaching hospital in Clermont-Ferrand, France, 44 (6.2%) strains of Pseudomonas aeruginosa were found to be resistant to ceftazidime. After genotyping, 34 strains were selected. Nine had an additional beta-lactamase: OXA-21 (n = 6), PSE-1 (CARB-2) (n = 2), or PER-1 (n = 1). Ceftazidime resistance was related solely to the overproduction of the cephalosporinase in 30 strains. Sequencing of five bla(AmpC) genes encoding cephalosporinases with different pIs showed 99% identity with the ampC gene of P. aeruginosa PAO1.

[Enzymatic resistance of Escherichia coli to beta-lactams and clinical prevalence]. / Résistance enzymatique d'Escherichia coli aux bêtalactamines et prévalence en clinique.

Escherichia coli (E. coli) is the most frequent bacterium implicated in community-acquired infection as well as in nosocomial infections. This bacterium is characterised by numerous possibilities to acquire resistance mechanisms, even during antibiotic treatment. The main mechanism of resistance is the production of beta-lactamines, enzymes hydrolysing beta-lactam ring. This paper describes enzymatic mechanisms of resistance of E. coli to beta-lactam and indicates the necessity of a good knowledge of the risk factors for resistance to have an adapted good clinical practice in using antibiotics.

Synthesis and antimicrobial activities of N-substituted imides.

In the field of our research programs concerning novel antimicrobial agents, a series of N-substituted imides was synthesized. These compounds were obtained by cyclization of amido-acids in acetic anhydride/sodium acetate or hexamethyldisilazane/zinc bromide for the hydroxy-aromatic derivatives. The hydroxy-alkyl maleimides were directly prepared by condensation of the corresponding amino-alcohol with maleic anhydride in boiling toluene. Most of N-substituted maleimides showed an interesting antimicrobial activity towards bacteria from the ATCC collection (Staphylococcus aureus ATCC 25923, Enterococcus faecalis ATCC 29212, Escherichia coli ATCC 25922 and Pseudomonas aeruginosa ATCC 27853) but the MIC values for P. aeruginosa were always high (128 microg/ml). The imides with alkyl substituents showed higher activities than aromatic analogues with MIC values in the range of 8-32 microg/ml. Comparatively, succinimides were practically inactive.

Experimental application of the median-effect principle for in vitro quantification of the combined inhibitory activities of clavulanic acid and imipenem against IRT-4 beta-lactamase.

Inhibitor-resistant TEM beta-lactamases (IRT) have been identified in Enterobacteriaceae which, however, remained susceptible to cephalosporins. We evaluated the combined inhibitory activity of clavulanic acid and imipenem at ratios of 1:1 and 1:3 against IRT-4, using the median effect principle of Chou and Talalay. The combination of the two drugs, which produced a nearly additive effect, meant their concentrations could be lowered 1.3-4.9-fold, while maintaining a 50% inhibitory effect against the IRT-4 in comparison with each drug alone. From a therapeutic point of view, such a combination is not efficient but this method of Chou and Talalay, used for the first time to assay combined inhibitory activity of beta-lactamase inhibitors, could be used to evaluate new molecules and/or strategies to inactivate beta-lactamase.

Plasmid-mediated TEM-3 extended-spectrum beta-lactamase production in Salmonella typhimurium in Casablanca.

Isolates of extended-spectrum beta-lactamase (ESBL)-producing Salmonella typhimurium were recovered from children admitted to the IbnRochd University Hospital of Casablanca in 1994. These isolates produced TEM-3 as shown by PCR, isoelectric focusing and sequencing. Production of TEM-3 and resistance to gentamicin were encoded by a 10 kb plasmid that could be transferred by conjugation and transformation. This report extends the list of ESBLs produced by S. typhimurium and stresses the need for continuous surveillance of non-typhoidal Salmonella to adapt antibiotic treatment and preventive measures.