Vancomycin: A 50-Year Reassessment

Extract

More than half a century ago, the compound now known as vancomycin was isolated from a soil sample collected deep in the interior jungle of Borneo. The isolation was performed by Dr. E. C. Kornfeld, an organic chemist at Eli Lilly, which had begun a major program to discover new antimicrobial agents with activity against staphylococci [1]. Although it had been only 15 years since the initial deployment of penicillin and the subsequent discovery of macrolides and tetracyclines, staphylococcal resistance to these compounds was already a major problem in hospitals throughout the world.

The soil sample from Borneo contained an organism (subsequently named “Streptomyces orientalis”) that yielded a compound in broth fermentation with a high degree of bactericidal activity against staphylococci. The initial compound was labeled 05865, and early laboratory studies showed that staphylococci failed to develop significant resistance to 05865 on serial passage in culture media containing the drug. Because of the growing menace of drug-resistant staphylococci, the US Food and Drug Administration essentially “fast-tracked” approval of compound 05865, which was subsequently given the generic name “vancomycin,” a term derived from the word “vanquish.” The original preparations of vancomycin from fermentation broth contained a number of impurities, and, because of the brown color of the material, it was nicknamed “Mississippi mud” by scientists at Eli Lilly [1]. Despite its early promise, however, vancomycin was not widely used in the decade following its discovery. The major reason was that methicillin and, subsequently, other antistaphylococcal penicillins were discovered and became the drugs of choice for treating staphylococcal infections. Vancomycin was relegated to a secondary role, in large part, on the basis of results of early studies performed during the mid-1950s that showed it to be ototoxic and nephrotoxic [1]. It is very likely that whatever ototoxicity and nephrotoxicity resulted from the use of vancomycin were related to the presence of impurities in the earlier preparations; when newer, purer preparations were retested in the late 1970s, they produced no ototoxicity and little nephrotoxicity in the animal models, unless given in combination with aminoglycosides [2, 3]. Because of the possible toxicity of vancomycin, it was not heavily marketed during the 1960s and 1970s and was relegated to a secondary role in antibacterial chemotherapy.