STATE-OF-THE-ART CLINICAL ARTICLE Resistance to Glycopeptides in Enterococci

The development of resistance to glycopeptides (vancomycin and teicoplanin) is one of the best examples of the alternation between success and failure that spans the history of the antibiotic era. The introduction of penicillin G was revolutionary. However, the emergence in the 1950s of clinical isolates of Staphylococcus aureus that were resistant to penicillins and subsequently to erythromycin and tetracyclines stimulated the development of large-scale screening programs for new drugs. Under these circumstances, an American missionary, Reverend W. M. Bouw, provided Eli Lilly (Indianapolis) with a soil sample from Borneo [1]. The organism that produces vancomycin, Amycolatopsis orientalis, was isolated from this sample in 1954. Since vancomycin proved to be potent against grampositive bacteria, including penicillinase-producing staphylococci, it was licensed for human use in record time. However, the renal toxicity and ototoxicity associated with vancomycin therapy (due for the most part to impurities in the drug) together with the introduction of new penicillinase-resistant f3-lactams led to a rapid decline in the use of vancomycin. In the 1980s, interest in vancomycin revived because of several factors. During this period, methicillin-resistant and multiresistant staphylococci, against which vancomycin is often the only active antibiotic, were emerging worldwide. At the same time, medical advances had resulted in the prolongation of life for increasingly fragile, immunocompromised patients who are exposed to opportunistic pathogens such as multiresistant gram-positive organisms. In addition, it was determined that pseudomembranous colitis could be treated with oral vancomycin, and a new glycopeptide, teicoplanin, was introduced in 1984 in certain European countries. The apparent absence of resistance to vancomycin in grampositive bacteria and a decrease in the toxicity associated with vancomycin therapy (purified formulations of the drug had become available) led to a notable increase in the prescription of this antibiotic. In the United States, a 20-fold increase in the consumption of vancomycin was observed over a 10-year period at a university hospital [2].