As concern about antibiotic resistance grows, physicians and researchers are taking a closer look at the use of the drugs.
Recently, researchers at Children's Hospital of Philadelphia analyzed more than 30,000 medical records of children with common infections and found that narrow-spectrum antibiotics, which target fewer kinds of germs, worked just as well as broad-spectrum antibiotics.
Plus, they were associated with fewer side effects and other problems.
The lead researcher was Jeffrey S. Gerber, an attending physician in the Division of Infectious Diseases at CHOP, and a senior scholar at the Penn Center for Clinical Epidemiology and Biostatistics. He spoke to us recently about antibiotics and children.
What prompted your research?
Antibiotics are the most commonly used prescription medications in children – about 70 million to 75 million prescriptions a year. That's about one prescription per child per year. Those numbers go higher when you look at children below age 2, where it's about two prescriptions per child per year.
There are just a few conditions that account for most of the antibiotic prescribing for kids: ear infections, sinus infections, and pharyngitis, where the target is strep throat. These three conditions together account for more than half of all antibiotic prescribing for kids.
We know from research that physicians use antibiotics variably. Maybe half the time, doctors prescribe broad-spectrum antibiotics, such as Augmentin and Omnicef, for these common conditions. The other half of the time, narrow-spectrum antibiotics, which would include penicillin and amoxicillin. So, which should we be using? There's a lot of interest from pediatricians and national organizations that write guidelines, such as the American Academy of Pediatrics.
All antibiotics aren't created equal. The principle is, how many germs can you kill with that antibiotic? How many do you target? The ideal is to target just the bug you want to.
Broad-spectrum antibiotics are sometimes appealing to prescribers because these drugs kill more germs, or because of the perception that they are more powerful against the same germs targeted by narrow-spectrum antibiotics. So it was important to test this idea.
The issue is that, because the broad-spectrum antibiotics can affect a wider range of bacteria, they can lead to more antibiotic resistance. That's a public-health problem. The next time you get an antibiotic, you want to make sure it works.
Broad-spectrum antibiotics also might kill off our beneficial colonizing bacteria. All of us have trillions of bacteria in and on us, most of it in our gut, which is referred to as the human microbiome. It's estimated that there are between five and 10 bacterial cells in and on your body for every one human cell. We used to think they were harmless, innocent bystanders. But studies suggest this microbiome might be important for human health, both in the short term and the long term.
Also, sometimes these broad-spectrum antibiotics might have more side effects, such as rashes, allergic reactions or diarrhea. One last thing – potentially a fringe benefit – narrow-spectrum antibiotics are usually cheaper.
What did you discover?
We did two studies. For the first, we analyzed electronic health records of more than 30,000 children. Comparing broad- to narrow-spectrum agents for those three common infections, we found no difference in the clinic cure rate. We also looked at side effects and found that patients who got broad-spectrum antibiotics experienced more side effects – 2 percent of cases with narrow-spectrum antibiotics, and 3 percent with broad-spectrum.
Next, we looked much more closely at a subset of 2,500 patients, calling the parent five days after the child's illness was diagnosed, and then 10 to 14 days after the illness was diagnosed. We asked a series of very specific questions to really get at outcomes. Plus, we didn't just paternalistically determine those questions. We actually interviewed families who were in waiting rooms with their kids and asked them what they were worried about most. Is my child suffering? How quickly are symptoms going to improve? Is my child sleeping? Do I have to stay home from work? Is my child going to miss school?
Once again, we found that clinical cure rates were no better with broad-spectrum antibiotics than with narrow-spectrum antibiotics. But the incidence of side effects was tenfold higher, although at roughly the same ratio – 25 percent for narrow-spectrum antibiotics, and 35 percent for broad. So if you really want to look at outcomes, you have to pay attention to what might be happening at home.
I participated in a study led by the Centers for Disease Control and Prevention that estimated about 50 percent of antibiotic prescriptions for outpatients are unnecessary. In kids, it's probably at least 30 percent. Someone might shrug and say, "What's the harm?" But, given the potential side effects, do you want a cold, or a cold with diarrhea?
Then there's the issue of antibiotic resistance. Antibiotic resistant infections have become increasingly common, causing more than two million illnesses and more than 23,000 deaths each year in the U.S. alone. And antibiotic resistance is caused by exposure to antibiotics, much of which is unnecessary.
You also may disrupt the balance of the ecosystem of bacteria that live in and on your body. You might turn it into a mix of bacteria that creates an unhealthy state. A lot of this is not absolutely proven, but a lot of research suggests it can lead to changes in how you metabolize food, leading to weight gain. The germs you have in your gut educate your immune system. And the influence of these germs on the immune system might dictate whether you become asthmatic, whether you have eczema.
When it comes down to it, getting an antibiotic, if you don't need it, can cause harm.
Another target we're working on is shortening the duration of antibiotic use. We're no longer advising 10 to 14 days for many of these common infections. In one study led by CHOP, and another we're participating in, we're comparing the outcomes of five days versus 10 days of antibiotics for kids with urinary tract infections and pneumonia.
Can you explain more about the difference between societal harm from antibiotic resistance and individual harm?
Let's say, for example, that you have a cold and you are prescribed an antibiotic. It won't help with the cold. But if you get an actual infection after that exposure, and the bacteria in your nose and throat have "seen" that antibiotic before, it's possible they've learned to deal with it and are not as susceptible to it. You are personally harboring antibiotic-resistant bacteria.
It becomes a societal problem because we spread bacteria from one person to another constantly. If one person is colonized with antibiotic-resistant bacteria, that person can spread it to others fairly easily.
What is your advice to parents?
When you take your child to the doctor, it's always good to know, even beyond antibiotics, what is the diagnosis that supports the medication being prescribed? And if you are getting an antibiotic, what's the bacterial infection that's being treated? It's also good to know if the physician has thought about just how long to give the antibiotic. I'm not telling parents not to listen to their doctors. It's just always good to have a conversation to make sure you understand exactly what the diagnosis is and what the medication is for.