Targeting drug-resistant infections

William Hanage-Big 3

November 25, 2015 — Last week, Chinese and British scientists reported finding a strain of E. coli resistant to a last-resort antibiotic called colistin—and that this resistance can be transferred to other bacteria. Harvard Chan School’s William Hanage, an infectious disease epidemiologist, discusses the growing problem of drug-resistant infections.

What is causing the increase in drug-resistant infections?

We’ve been using antibiotics inappropriately. These drugs don’t work against things like flu that are caused by viruses, and so you shouldn’t expect them if you go to see your doctor about those typical winter respiratory infections. Also, we should remember that enormous volumes of these drugs are used in agriculture, not only to keep animals healthy but as growth promoters to improve yields. Drug resistance is getting worse because every time we use an antibiotic, whether in humans or animals, we give an advantage to any bacteria that are resistant to it! So this means we have to be careful with how we use antibiotics, because they are precious.

What does the new discovery about colistin mean, and why is it worrying?

Colistin is one of the last lines of defense we have against drug-resistant infections. So if we can’t use colistin that means more people will die from infections, because we won’t be able to treat them. The gene for resistance is carried on a plasmid. These are little circles of DNA that bacteria can transfer among themselves, a bit like downloading an app. Other bacteria that ‘download’ the plasmid could become resistant themselves and spread the problem to other sorts of bacteria, leading to other infections.

Right now most antibiotics are ‘broad-spectrum,’ meaning they work against lots of different infections. This sounds good, but a broad spectrum means that lots of bacteria stand to benefit from a resistance gene, so any genes offering resistance can be downloaded quickly into lots of different species of bacteria. And by increasing the numbers of bacteria affected by the antibiotic, the numbers of opportunities for resistance to evolve are increased. In some cases broad-spectrum antibiotics can cause problems by wiping out far more bacteria than the dangerous ones, including ones that we need to stay healthy.

What are some of the most promising developments in drug-resistance research?

Right now, we often have to make an educated guess at what bacteria is causing disease, and then treat with a broad-spectrum antibiotic that will take it out—and much else besides. Narrow-spectrum antibiotics targeted at a small number of strains or species would be great, but we wouldn’t be able to risk a guess at what is causing disease. So this would need much quicker diagnostics, to tell us what is causing disease and what we can treat it with. One exciting possibility is making use of viruses that prey on bacteria, and another is using toxins that bacteria use when they are fighting with each other. But individual viruses and toxins are usually very specific in which bacteria they target. Looking forward, we hope to be able to do genetic testing in real time. So when you have a bacterial infection, your doctor will be able to check its genes, and select a made-to-order therapy that will specifically target the problem.

Karen Feldscher