Cancer chemotherapy usually involves unpleasant encounters with multiple drugs. This is because painstaking trials on actual humans have shown that several agents in combination are more effective than single drugs acting alone.
Not so with bacterial infections, where pharmacologic chemicals are generally more successful when acting on their own. This is most often explained when two drugs antagonize each other’s effect because one slows bacterial growth while the other is trying to kill growing bugs. Definitely counterproductive.
Drug combinations for infections could be very useful since discovery of totally new agents is rare, and drug resistance a relentless and intractable problem. One possibility is using drugs approved for other maladies in combination with proven antibiotics. This cool idea was recently put to the test by a Canadian and Scottish research collaboration. About a thousand previously approved drugs (PADs) were tried in combination with minocycline against Pseudomonas, E. Coli, and Staph in culture. Surprisingly, about 15% of the PAD library was active in improving the action of minocycline, including against multi-drug resistant organisms.
The inquiring scientist will wonder how this effect works since the PADs do not have antibacterial activity on their own merit. The case of minocycline/loperamide (the latter an opiate used to treat diarrhea) was investigated in a bit more detail and found to result in a depolarization of the surface membrane. Thus, the minocycline probably still does the dirty work of inhibiting growth but accumulates more intensely inside the cell than in the absence of loperamide.
This is a nice result that opens the door to many new drug combos being discovered. Of course, what works in cultures doesn’t always translate to actual human patients, but the lead is surely worthwhile given the grave challenge of antimicrobial drug resistance.
Tom Tritton is President and CEO of CHF.
Bacteriamegoddon [Periodic Tabloid]
Drug Resistance and Clever Chemists [Periodic Tabloid]
Drugs Boost Antibiotic Function [The Scientist]