RESUMEN
The synthesis and antibacterial activity of a series of 3-(1-substituted pyridinium-4-thiomethyl)-7 alpha-formamido cephalosporins is described. All the derivatives showed good potency and stability to bacterial beta-lactamases. The antibacterial efficacy seen with the N-alkyl pyridinium substituents was enhanced by the introduction of a catecholic side chain at C-7 and by preparation of N-(substituted amino)pyridinium derivatives.
Asunto(s)
Bacterias/efectos de los fármacos , Cefalosporinas/síntesis química , Cefalosporinas/farmacología , Pruebas de Sensibilidad Microbiana , Relación Estructura-ActividadRESUMEN
(6R,7R)-7-[2-(2-Amino-4-thiazolyl)-2-[(Z)-[(S)-carboxy(3,4- dihydroxyphenyl)methyl]oxyimino]acetamido]-3-(1-methylaminopyri dinium-4-thiomethyl)ceph-3-em-4-carboxylate sodium salt (BRL 57342, 1f) combines excellent in vitro antibacterial potency against Gram-positive and Gram-negative bacteria, including P. aeruginosa and Acinetobacter spp., with excellent stability to extended spectrum beta-lactamases. This potency is reflected in in vivo efficacy studies.
Asunto(s)
Cefalosporinas/síntesis química , Animales , Cefalosporinas/química , Cefalosporinas/farmacología , Bacterias Gramnegativas/efectos de los fármacos , Bacterias Grampositivas/efectos de los fármacos , Humanos , Ratones , Pruebas de Sensibilidad Microbiana , Saimiri , Relación Estructura-ActividadRESUMEN
Several classes of antibiotics were assessed for activity against non-growing Escherichia coli and cells grown as a biofilm. Antibiotics which had activity against non-growing cells also showed some activity against biofilms. Cephamycins were more active than other cephalosporins, but the most effective antibiotics were imipenem and ciprofloxacin, which were also active against steady state biofilms. However, none of the antibiotics studied was capable of completely eradicating a biofilm. These results suggest that growth rate plays a role in mediating resistance of biofilms to antibiotics.