Merck Tries New
Resistance-Free Antibiotic
WASHINGTON - Scientists at drug giant Merck and Co. Inc. said on Thursday they had redesigned a drug in a way they hope will help make it harder for bacterial "superbugs'' to develop resistance against.
Tests in monkeys show it worked against several strains of drug-resistant bacteria, including those that can evade last line of defence drugs such as vancomycin.
Writing in the journal Science, they said the new drug blocked the mechanism the bacteria use to fight off penicillin and related drugs.
Hugh Rosen and colleagues at Merck Research Laboratories in Rahway, New Jersey have been working on a class of drugs known as carbapenems, which are related to penicillin. The carbapenems are strong drugs and hard for the bacteria to evolve resistance to.
But they often do. Bacteria reproduce so quickly that they can evolve new forms in just a few years.
Antibiotics are so widely used " and misused " that plenty of bacteria have had enough exposure to them to develop resistance, without actually being killed.
The new drug, called by its experimental name L-786,392, targets a bacterial protein known as PBP2a (short for penicillin-binding protein). It is found in drug-resistant staphylococci and enterococci, and essentially blocks the chemical doorways that penicillin usually uses to get into and kill bacteria.
Rosen's lab has been working for years to modify the drug so it can get around this protein. But previous attempts have resulted in a drug that also activates an improper immune response.
This time they think they have cracked the problem. The new drug killed the bacteria and did not activate the immune systems of the monkeys they tested.
"L-786,392 was well tolerated in animal safety studies,'' they wrote in a report in Science. They said it had "significant'' action against staphylococci that have evolved resistance against methicillin and vancomycin, as well as against vancomycin-resistant enterococci.
Human tests are still some way off. But doctors are anxious for new antibiotics.
Last year, the Institute of Medicine noted that 90 percent of all strains of Staphylococcus aureus, the most common cause of infections, some of them deadly, now resisted penicillin.
Dr. Jeffery Koplan, director of the Centres for Disease Control and Prevention (CDC), says 70 percent of bacteria involved in infections that people get in hospitals are now resistant to at least one antibiotic.
The CDC says 50 million unnecessary prescriptions are written for antibiotics in the United States every year.