With clever chemical tweaks, an old antibiotic can dole out any of three lethal blows to some of the deadliest bacteria—and give evolution one nasty concussion.

The antibiotic, vancomycin, has always been a heavy hitter against odious germs; it uses one crafty maneuver that can take out even drug-resistant foes and is often used as a last resort. But, with three chemical modifications, reported this week in PNAS, the drug now has three distinct molecular moves to take out pathogens. The menacing modifications render vancomycin at least 25,000 times deadlier. And with that level of potency, dazed bacteria stumble at developing resistance when given the chance in lab experiments.

And maybe that should be the real goal in the war against drug-resistant microbes, the authors of the new study—chemists at The Scripps Research Institute in La Jolla, California—argue.