RESUMEN
Development of new antibiotics is declining whereas antibiotic resistance is rising, heralding a post-antibiotic era. Antimicrobial peptides such as gramicidin S (GS), exclusively topically used due to its hemolytic side-effect, could still be interesting as therapeutic compounds. By modifying the amino-acid composition of GS, we synthesized GS analogues. We now show that derivative VK7 has a lower MIC (7.8-31.2 µg/ml, median 15.6 µg/ml) against strains of multi-drug resistant (MDR) Klebsiella pneumoniae, Acinetobacter baumannii, and Pseudomonas aeruginosa than GS has (3.9-62.5 µg/ml, median 31.3 µg/ml). Low MICs for both VK7 and GS were observed for Staphylococcus aureus and Enterococcus faecium. VK7 showed reduced haemolysis and less lactate dehydrogenase release. All compounds were fully bactericidal at MIC values. Modification of GS enables production of novel derivatives potentially useful for systemic treatment of human infections.
Asunto(s)
Antibacterianos/química , Antibacterianos/farmacología , Gramicidina/química , Gramicidina/farmacología , Antibacterianos/toxicidad , Línea Celular Tumoral , Eritrocitos/efectos de los fármacos , Eritrocitos/metabolismo , Gramicidina/toxicidad , Hemólisis , Humanos , Lactato Deshidrogenasas/biosíntesis , Pruebas de Sensibilidad Microbiana , Estructura MolecularRESUMEN
In 1995 the activities of Médecins sans Frontières in the Province of Kampot, Cambodia, were handed to Memisa Medicus Mundi. This happened as a part of the co-operation between the two relief agencies. Following a request from the Cambodian Ministry of Health, Memisa sent a Dutch surgeon to Kampot in order to make an inventory of the surgical care in this province and to make recommendations for improvement. Two visits of two months each were made with an intermission of one year. Special attention was given to the most adequate treatment of a few common fractures in developing countries. By asking a fixed amount of money for a treatment all in, and by providing good service the confidence of the people in the health care facilities is increased.