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When lab tests are misleading: A mystery in antibiotic resistance

Most children with antibiotic-resistant urinary tract infections get better on less powerful antibiotics than lab tests say they need, says Stanford study.

Most children with antibiotic-resistant urinary tract infections get better when taking less powerful antibiotics than lab tests say they need, a new Stanford study has shown. The findings, published in Pediatrics, may change how doctors treat this common type of childhood infection.

Antibiotic resistance is a growing concern for treatment of pediatric UTIs, said the study's senior author, Stanford pediatrician Alan Schroeder, MD. Over the last two decades, doctors have had to switch from mild to medium-strength antibiotics to treat kids' UTIs, and there is evidence that the E. coli bacteria that cause UTIs are developing resistance to these drugs, too.

Schroeder wants to slow the bugs-vs-drugs arms race. If doctors prescribe unnecessarily powerful antibiotics, he said, over time, people will have harder-to-treat infections and there won't be any antibiotics to use for them.

The study looked at medical records from 316 generally healthy children who had come down with highly resistant UTIs and were treated at six large U.S. medical centers. When their UTIs were diagnosed, the children got started on standard treatment, usually cephalosporin antibiotics. A few days later, lab-test results came back that said these kids had cephalosporin-resistant infections. Typically, when this news arrives, patients are switched to an even more powerful drug, regardless of whether or not they are getting better.

But, intriguingly, the children in the study had done well on the "wrong" antibiotic. Only seven children of 316 needed escalation of care -- meaning they returned to the emergency room or were admitted to the hospital. And among the 230 kids whose clinical response was recorded in their medical records, almost three-quarters had improved symptoms after a few days on the wrong antibiotic.

"These antibiotics may work better than we think at the sites where infection is occurring," said the study's lead author, pediatrician Marie Wang, MD, noting that studies in other parts of the world, where highly resistant UTIs are more common, have shown a similar phenomenon. Why? No one is sure, but experts think the features of kidney function might explain the mystery.

"Some of these drugs are known to concentrate in the urine," Wang said. Kidneys filter the blood and pull out foreign compounds, including many drugs. "But when the lab creates criteria for how well drugs are supposed to work, they set the threshold for sites all over the body," Wang said.

There's another possible explanation, Schroeder added: Some patients might have recovered on their own, without antibiotics. "Because we've developed antibiotics, many of us have inherent assumptions that bacterial infections by definition require antibiotics to get better," he said. "But for some of the most common bacterial infections in children, such as ear infections and strep throat, the vast majority of patients get better on placebo, indicating that, by in large, our immune systems work. This may be true for UTIs as well."

The challenge now is coming up with a precise way to identify which patients really do need stronger antibiotics and which don't. Not only would targeted prescribing reduce antibiotic resistance in the long run, it would also lower treatment costs and spare children the side effects of stronger drugs.

"Ideally we'd use the narrowest-spectrum antibiotic possible, even if by our traditional measures the infection appeared to be drug-resistant," Schroeder said.

Scanning electron micrograph of E. coli bacteria by NIAID

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