RESUMEN
BACKGROUND: The ever-increasing resistance to antibiotics is a serious worldwide problem. Antibiotic strategies for appropriate use of antimicrobials in hospitals are not well defined. METHODS: A questionnaire on "ABS maturity of hospitals" was the basis of an analysis as a part of an EU project. This questionnaire was sent to 12 hospitals in Slovenia including 11 general hospitals and one university hospital. MAIN FINDINGS: All 12 hospitals returned the questionnaires. Maturity of antibiotic strategies were considered moderate (3.74). Antibiotic consumption had the highest maturity ratio (4.44), followed by diagnostics (3.96), antibiotic-related relationships (3.58), antibiotic-related personnel development (3.44) and antibiotic-related organization (3.36). The availability of data on antibiotic consumption had the highest ranking; designation of and time resources for antibiotic officers were ranked lowest. CONCLUSION: In Slovenia the maturity of antibiotic strategies in general hospitals and in one university hospital is moderate. The data provide a basis for further development of antibiotic-related issues in hospitals.
Asunto(s)
Antibacterianos/administración & dosificación , Infecciones Bacterianas/tratamiento farmacológico , Infecciones Bacterianas/epidemiología , Infección Hospitalaria/epidemiología , Infección Hospitalaria/prevención & control , Brotes de Enfermedades/estadística & datos numéricos , Hospitales/estadística & datos numéricos , Vigilancia de la Población/métodos , Antiinfecciosos , Brotes de Enfermedades/prevención & control , Farmacorresistencia Microbiana , Humanos , Incidencia , Eslovenia/epidemiología , Encuestas y CuestionariosRESUMEN
The increasing emergence of pathogenic bacterial strains with high resistance to antibiotic therapy has created an urgent need for the development of new antibacterial agents that are directed towards novel targets. We have focused our attention on the Mur ligases (MurC-F), which catalyze the early steps of bacterial peptidoglycan biosynthesis, and which to date represent under-exploited targets for antibacterial drug design. We show that some of our phosphinate inhibitors of UDP-N-acetylmuramoyl-L-alanyl:D-glutamate ligase (MurD) also inhibits UDP-N-acetylmuramoyl-L-alanyl-D-glutamate:L-lysine ligase (MurE). To obtain new information on their structure-activity relationships, three new, structurally related phosphinates were synthesized and evaluated for inhibition of MurD and MurE.
Asunto(s)
Antibacterianos/síntesis química , Inhibidores Enzimáticos/síntesis química , Péptido Sintasas/química , Ácidos Fosfínicos/síntesis química , Staphylococcus aureus/enzimología , Antibacterianos/farmacología , Simulación por Computador , Inhibidores Enzimáticos/farmacología , Modelos Moleculares , Estructura Molecular , Péptido Sintasas/antagonistas & inhibidores , Péptido Sintasas/aislamiento & purificación , Ácidos Fosfínicos/farmacología , Conformación Proteica , Relación Estructura-ActividadRESUMEN
A series of new phosphinate compounds were designed and synthesized as inhibitors of the d-glutamic acid-adding enzyme (MurD) involved in peptidoglycan biosynthesis. They were tested against the MurD enzyme from Escherichia coli, allowing initial structure-activity relationships to be deduced. Two compounds had IC(50) values near 100 microM and constitute a promising starting point for further development.
