vancomycin the 50 year old "NEW" Antibiotic

• Use of vancomycin

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.”

"Because vancomycin was no longer patented by that time, it was not subjected to the intense marketing typically associated with antimicrobial agents. Nonetheless, the drug more than “sold itself” because of a very real clinical need. "

KEY POINTS

• Giving vancomycin by continuous infusion appears to offer no advantage over giving it every 12 hours.
• Therapeutic blood levels can be reached more quickly if a loading dose is given, but whether this offers a clinical advantage is unclear.
• The trough vancomycin serum concentration should be greater than 10 mg/L to prevent the development of resistance, and trough levels of 15 to 20 mg/L are recommended if the minimum inhibitory concentration (MIC) is 1 mg/L or higher.
• Whether S aureus is becoming resistant to vancomycin is not clear.
• The variable most closely associated with clinical response to vancomycin is the area under the curve (AUC) divided by the MIC (the AUC-MIC ratio), which should be greater than 400

IN THE PAST HALF-CENTURY, vancomycin has gone from near-orphan status to being one of the most often used antibiotics in our formulary. The driving force for its use is clear: the evolution of Staphylococcus aureus. At first, vancomycin was used to treat infections caused by penicillin-resistant strains. However, the discovery of methicillin curbed its use for more than 2 decades.1

Then, as methicillin-resistant S aureus (MRSA) began to spread in the 1980s, the use of vancomycin began to increase, and with the rise in community-associated MRSA infections in the 1990s, it became even more widely prescribed. The recent Infectious Diseases Society of America (IDSA) guidelines for treatment of infections due to MRSA are replete with references to the use of vancomycin.2

Another factor driving the use of vancomycin is the increased prevalence of device-associated infections, many of which are caused by coagulase-negative staphylococci and other organisms that colonize the skin.3 Many of these bacteria are susceptible only to vancomycin; they may be associated with infections of vascular catheters, cardiac valves, pacemakers, implantable cardioverter-defibrillators, orthopedic implants, neurosurgical devices, and other devices.

To use vancomycin appropriately, we need to recognize the changing minimum inhibitory concentrations (MICs), to select proper doses and dosing intervals, and to know how to monitor its use. Despite more than 50 years of experience with vancomycin, we sometimes find ourselves with more questions than answers about its optimal use.