Implications on Emergence of Antimicrobial Resistance as a Critical Aspect in the Design of Oral Sustained Release Delivery Systems of Antimicrobials

Autor: Ehud Horwitz, Amnon Hoffman, Mervyn Shapiro, Ronit Cohen-Poradosu, Shmuel Hess, Anna Edelberg, Lilach Kleinberg
Rok vydání: 2007
Předmět:
Zdroj: Pharmaceutical Research. 25:667-671
ISSN: 1573-904X
0724-8741
DOI: 10.1007/s11095-007-9373-6
Popis: To assess the effects of the unabsorbed fraction of an orally administered antimicrobial drug which enters the colon on the emergence of resistance among the natural microflora, a phenomenon largely overlooked so far despite its clinical importance, especially when sustained release formulations are used.Effects of an orally administered model beta-lactam antibiotic (amoxicillin) on emergence of resistant bacteria were assessed using a microbiological assay for qualitative and quantitative determination of resistant bacteria in fecal samples of rats following gastric administration of the drug to rats for 4 consecutive days. Time- and site-controlled administration of a beta-lactamase to the rat colon was assessed as a potential strategy for prevention the emergence of resistant bacteria following oral administration of incompletely absorbed antimicrobials.Emergence of resistant bacteria was demonstrated following oral administration of amoxicillin to rats, whereas de-activation of the beta-lactam prior to entering the colon, by infusion of a beta-lactamase into the lower ileum, was shown to prevent the emergence of resistant colonic bacteria.This study illustrates the need to consider the emergence of antimicrobial resistance as a goal equally important to microbiological and clinical cure, when designing oral sustained-release delivery systems of antimicrobial drugs.
Databáze: OpenAIRE