Antibiotics may help people avoid surgery for appendicitis

- ADVERTISEMENT -

At first, Aubrey Gibson thought her daughter’s stomachache came from the pizza and candy canes she’d enjoyed at the town’s Christmas party. Gibson told Aria to lay down and rest. But when Aria, then 10 years old, woke up from her nap, her stomach hurt so much she couldn’t stand. And she was running a high fever.

Gibson rushed her daughter to the hospital, where, after an evaluation and an ultrasound, the doctors diagnosed Aria with appendicitis. Gibson and Aria were both devastated. Aria was scheduled to be in her school’s Christmas play just three days later, and her parents, unknown to her, had been saving for two years for a surprise Christmas trip to Disney World. An appendectomy meant no school play, and maybe no Disney.

But Gibson’s doctors at Nationwide Children’s Hospital near where they live in Reynoldsburg, Ohio, offered her another option: They could try treating Aria with antibiotics. She’d receive the drugs intravenously in the hospital, and if her symptoms improved, she could go home. Her only management would be a course of oral antibiotics afterward. Gibson didn’t hesitate.

“We were excited to try it,” she says. “It worked and we were able to go to Disney World and it was a wonderful surprise.”

Aria, who is now 21 and in nursing school, was one of the early patients enrolled in the first trial of whether antibiotics are an effective first-line treatment for appendicitis, a painful infection of the appendix. It’s nearly always treated with surgical removal of the appendix, making it the most common cause of emergency surgery in children. But evidence has started to accumulate that for those who want to avoid surgery, a course of antibiotics may be a valid alternative.

“It is good enough and safe enough and effective enough that we owe people the choice,” says Peter Minneci, who ran the study in which Aria was enrolled and is now chair of surgery at Nemours Children’s Health in Delaware.

Though appendectomies have been the gold standard of care since before the turn of the 20th century, doctors have been treating appendicitis with antibiotics since the 1950s, as soon as they became available – a “dark secret” in the surgery world, says David R. Flum, professor of surgery and director of the Surgical Outcomes Research Center at the University of Washington. A 1959 paper detailed the use of antibiotics to treat nearly 500 people (a mix of adults and children) with appendicitis. They were – and still are – often used in people whose appendicitis is so advanced that surgery risks spreading the infection further. The military relied on antibiotics for service members who got appendicitis while in inaccessible locations, like submarines.

But the treatment didn’t get wider attention until the late 1990s and early 2000s, Flum says, when researchers began to collect data on how often antibiotics don’t work and found that failure was not as common as they thought.

Then came two large, randomized trials in adults. In the first, published in 2015, 257 adults received an antibiotic treatment. Seventy of those patients, or 27 percent, had to have an appendectomy within one year. But the rest were fine.

A second, larger study of 1,552 adults had similar results: Twenty-nine percent of the 776 people who received antibiotics underwent surgery within 90 days; 4 percent of people in the antibiotics group had serious adverse events, compared with 3 percent in the appendectomy group. The New England Journal of Medicine published the results in 2020. The same year, the American College of Surgeons added nonoperative management as an option in its guidelines for treating appendicitis.

It wasn’t a slam dunk, but the studies showed that antibiotics could be a good choice.

“There are two treatments now for appendicitis, for sure,” says Flum, the principal investigator in the second larger study. “And they both work.”

Collecting data has proved more difficult in kids, largely because parents are – understandably – hesitant to test treatments on their children. As Minneci was starting his trial in 2015, he asked an audience of 150 hospital staff on his grand rounds – pediatricians, surgeons, nurses – how many would be open to randomized treatment for their own appendicitis. About half raised their hands, he recalls. But when he asked how many would make that same choice for their child? “Crickets,” Minneci says.

Minneci worked around that by designing a trial that allowed parents to choose their child’s treatment. (He was also careful to enroll only kids who met certain criteria indicating their appendicitis wasn’t severe or the organ hadn’t ruptured.) Ultimately, he and his colleagues across 10 children’s hospitals enrolled 1,068 children with appendicitis, 370 – 35 percent – of whom chose antibiotics for their condition. One year later, 33 percent of those children had had an appendectomy, according to results published in JAMA in 2020; 53 of them had surgery before leaving the hospital, either because their symptoms failed to improve or their caregiver changed their mind about treatment.

At the same time, another large trial was running at centers across the United States and in Europe. Known as APPY, the study compared appendectomy to antibiotics in 978 children ages 5 to 16. It was the first large study that randomized families to their treatment option, ensuring that results weren’t biased due to parents of children with less severe illness being more willing to forgo surgery, says Shawn D. St. Peter, surgeon in chief at Children’s Mercy Hospital in Kansas City, Mo., and APPY’s principal investigator.

Within a year, 33.8 percent of the children treated with antibiotics got surgery to remove their appendix, St. Peter says – either they never improved, or they went home only to get appendicitis again sometime in the months after. St. Peter expects the full results to be published by the end of the summer.

“What is important is what mom thinks of 33 percent,” St. Peter says. “To some moms, that sounds like a ridiculously high number. And to some that sounds totally reasonable if we’re avoiding an operation today.”

Both approaches carry benefits and risks, surgeons say. Unlike antibiotics, surgery eliminates the chance of ever having appendicitis again. In rare cases, surgeons discover a precancerous or cancerous growth on the appendix, which could later become a bigger health threat. Some people have bad reactions to antibiotics, such as diarrhea or nausea – although, as Minecci points out, most people receiving surgery will get similar antibiotics.

Though appendectomies are considered one of the safest surgical procedures, surgery is still surgery and carries risks. Anesthesia always carries risks. And appendectomy is undoubtedly a more expensive treatment than antibiotics.

As the data has become clearer – antibiotics work, a decent amount of the time – the decision has, in some ways, become murkier. For many families, it will depend largely on how important they believe it is to avoid surgery, as well as which surgeon they happen to see.

“It does seem like we are going to have this gray zone for what is the best way to treat this that’s subject to interpretation,” says Thomas Inge, surgeon in chief at Lurie Children’s Hospital of Chicago, who has not been involved in any of the trials.

For Inge, the existing data justifies presenting both options to families. But when parents ask him what he recommends – what he would do if it were his child – Inge tends to say surgery. In his experience, most families aren’t open to a 30 percent chance of landing back in the emergency room.

His recommendation may change if long-term data ever shows that fewer than 10 percent of people have a recurrence of appendicitis in five years, Inge says.

Children have a longer period of time left, than, say, a 60-year-old, in which their appendix may act up again. And because removing the appendix has been the go-to treatment for a first bout of appendicitis, there’s no long-term data on whether having it once increases the odds of getting it again.

“We really don’t know the 10- and 15- and 20-year follow-up,” says Meera Kotagal, a pediatric surgeon at Cincinnati Children’s Hospital.

In the meantime, surgeons are eyeing ways to improve both treatments. Many children who receive appendectomies can go home the same day. It’s possible that kids could be treated with IV antibiotics in the emergency room and get sent home with oral medication as soon as their symptoms improve, without ever being admitted. (The 2015 trial in adults even has data showing appendicitis can resolve with no treatment at all, though that’s likely an impossible sell for kids, Minneci says.)

And with more time, both surgeons and parents may get more comfortable with the idea that appendicitis doesn’t equal appendectomy.

“It’s 130 years of that story being out there,” Flum says. “To reverse that story is going to take some time.”