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This spring the Ontario Medical Association released a report on the growing problem of antibiotic resistance. And while hospital-acquired “superbugs” often make the news, drug resistant gonorrhea is spreading in the province. 

Writer Jenny Hall spoke to Dr. Tony Mazzulli, a professor in the 91�Թ�’s Department of Laboratory Medicine and Pathobiology and a microbiologist at Mount Sinai Hospital/University Health Network to help explain how antibiotic resistance works—and how big a threat it is.

How does antibiotic resistance happen?

Some bacteria are resistant to some antibiotics naturally. That’s why patients get different antibiotics to treat different infections depending on which bug they have. We’re not so worried about this because we know about it and it is an inherent property of different bacteria. What we’re worried about is bacteria that start out sensitive or susceptible to a given antibiotic and then over time become resistant to that antibiotic or antibiotics, a phenomenon referred to as acquired resistance.

How do bacteria actually become resistant to a given antibiotic?

One of the most common things that happens is that bacteria develop a mutation in their DNA, which makes them resistant. They may also pick up little pieces of genetic material from the environment around them or from other bacteria, which may confer resistance to an antibiotic or class of antibiotics that they were previously susceptible to.

Bacteria have been on this planet longer than humans or anything else. They are constantly evolving, just like every other species. They live in a harsh environment—they live in sewage, in dirt, on surfaces, so they have to adapt. They’re very good at it.

The antibiotic is just another harsh environment to which the bacteria adapt?

That’s right.

What causes antibiotic resistance?

There are three major causes. First, the overuse of antibiotics. When a patient has an illness like a sore throat or pneumonia, it’s difficult to know what’s causing it. It may be a virus, an allergy, smoking or air pollution and not due to a bacterial infection. However, clinically the symptoms are the same, so physicians sometimes prescribe antibiotics unnecessarily. The assumption, historically, was that you’re going to take it for a short time and there are minimal side effects. And if I as a clinician miss a true bacterial infection, that could be a disaster for the patient.

What happens when you take an antibiotic you don’t need?

An antibiotic introduces what we call a selection pressure. The bacteria that are sensitive to it will be killed or suppressed, and the ones that can adapt and resist the effects of the antibiotic will be left behind. These surviving bacteria can then pass on their resistance genes to other bacteria and/or to their offspring. When a patient subsequently gets a true infection, it will be caused by this resistant bacteria, and the antibiotic you normally would have used won’t work.

You mentioned three causes. What are the other two?

The second is the misuse of antibiotics. Even when an antibiotic is needed, the physician sometimes doesn’t prescribe the right dose or the right duration. If you get too little of the drug, it creates what we call a sub-inhibitory level. It’s not enough to kill the bacteria, but it’s enough to stimulate it to become resistant. Similarly, when you don’t take a drug long enough to get rid of all the bacteria, you leave a few lingering ones behind. These can then mutate and become resistant.

The third big reason is the use of antibiotics in animal feeds. Most of the antibiotics that are put in animal feed aren’t there because the animals are sick, but because antibiotics have properties which make them growth promoters. If you can fatten up your cows and pigs faster, they’re worth more. People used to argue that they use antibiotics in animal feed that we don’t use in humans. That’s true sometimes, but there are human analogs or sister drugs in the same class as the drugs being used. So although a particular drug used in animal feed may not be used in a human, it still creates resistant bacteria in the environment. Then, when a person gets infected with that resistant bacteria, they can’t use the sister drug that they normally would because the bacteria will be resistant to it, too.

So once a bug becomes resistant, people start spreading it? Is this why we hear so much about “superbugs” in hospitals?

Yes. If it only happened to the individual, that would be one thing. But it becomes a population problem. One person passes a resistant bug to the next, who passes it to the next and so on. For example, people with kids in day care get more infections, and they’re more likely to have resistant bacteria which they acquired from their children.

What are the consequences of antibiotic resistance?

It used to be that when you saw a patient, you knew the common bugs that caused things like sinus infections or chest infections. You’d give an antibiotic, and it would be effective. Nowadays, we have to use antibiotics that are stronger, more expensive and have more side effects. Secondly, some of these bacteria are what we call multi-drug resistant. It’s not that they’re resistant to one drug—if they were just resistant one category, you could use a drug from another. But as they become resistant to multiple categories, you start running out of choices. We have seen patients with bacteria that are resistant to all the currently-available antibiotics.

What do you do when you encounter such a patient?

For the individual patient, there’s nothing to treat them with. We have to go to investigational drugs that are not fully developed and licensed, so there are a lot of unknowns.

Can you tell us about the antibiotic-resistant gonorrhea that’s in Ontario now?

It’s resistant to all the common antibiotics we would have used before. It’s not completely resistant, but it’s getting there. So treatment of gonorrhea, which used to be a simple pill, now requires intravenous treatment or intramuscular injections in some cases.

Can we develop new antibiotics as bacteria become resistant to the ones we have?

Pharmaceutical companies are looking to make a drug they can sell. Most people take antibiotics for a week or two for an infection. It’s very hard to recoup the millions of dollars invested in developing a new antibiotic. Consider that versus a pill for high blood pressure that a patient takes every day essentially for the rest of their life. New antibiotics coming through from the pharmaceutical industry are dwindling. If we lose our current crop of antibiotics, we may run out.

Are we looking at a future where people die of what used to be simple infections? It sounds alarming.

At the moment we still have strategies. We can use combination antibiotics. We’re also going back to older antibiotics that we have not used for many years. Once you remove an antibiotic from the pool, the pressure for selecting for resistant bacteria goes away. If the bacteria has no reason to maintain those extra genes that make it resistant, some of them will revert back to being fully susceptible.

What about the public? What can we do?

Know that if the doctor doesn’t prescribe you an antibiotic, that’s not a bad thing—it’s actually a good thing in most cases.

Jenny Hall is a writer with the Office of the Vice-President, Research and Innovations.