Inappropriate antibiotics for children linked to adverse events, higher costs

New research suggests that the negative consequences of inappropriately prescribing antibiotics in children with common infections are not limited to antibiotic resistance.

The studypublished yesterday in Open JAMA Networkfound that children who received inappropriate or non-recommended antibiotics for common viral and bacterial infections had an increased risk of adverse side effects such as Clostridioides difficile infection, severe allergic reactions and skin rashes. The additional medical care needed to deal with these adverse events resulted in excess healthcare costs of approximately $74 million in 2017.

And that number could be significantly higher, given that the study only included children covered by private health insurance.

The study authors say the findings provide further evidence for the need for judicious use of antibiotics, especially in children.

“Our study shows that there is an increased risk of adverse events when children receive unnecessary antibiotics or the wrong type of antibiotics, and there is a huge economic cost associated with children’s health care use. who are receiving inappropriate antibiotics,” David Hyun, MD, study co-author and director of the Antibiotic Resistance Project at the Pew Charitable Trusts, told CIDRAP News.

Defining patient risk

For the study, researchers from Pew and Washington University School of Medicine in St. Louis analyzed a large database of outpatient insurance claims and outpatient pharmacy-dispensed medications. with commercial insurance. Their aim was to quantify the downstream consequences of children receiving inappropriate antibiotic prescriptions for common childhood infections such as ear and sinus infections, beyond the well-established public health threat of antibiotic resistance. .

Previous research by Pew and others suggests that approximately 30% of outpatient antibiotic prescriptions that American children receive are inappropriate, either because the infection is caused by a virus and does not require antibiotic therapy, or because the child has not received the recommended guidelines. antibiotic. This inappropriate use of antibiotics can create selective pressure for resistant bacteria.

But while increasing antibiotic resistance is seen more as a collective threat to public health, Hyun said, he and his colleagues felt that an assessment of the potential threat posed to individual patients by inappropriate antibiotics was needed to help “recalibrate” the benefit/risk ratio.

“We wanted to dig deeper into more tangible results at the individual patient level,” he said. “We’re talking about potential side effects, and sometimes very serious side effects, which in some cases, like C diff, can kill the patient. And that’s a risk that’s assigned to each patient.”

Although the potential risks of antibiotic use are known, the study’s first author, Anne Mobley Butler, PhD, of the University of Washington School of Medicine, said the evidence on the risks associated inappropriate use of antibiotics and the costs associated with these risks are limited.

“There is already literature suggesting that inappropriate agents lead to adverse events, but we wanted to investigate it more fully,” Butler said. “We also wanted to consider the negative financial consequences, which would include the treatment of adverse events and the additional medical encounters and prescriptions these adverse events cause.”

High risk of adverse events

To do this, the researchers analyzed the records of more than 2.8 million American children aged 6 months to 17 years who were diagnosed with one of seven common bacterial and viral infections (suppurative otitis media [ear infection with discharge]pharyngitis, sinusitis, influenza, viral upper respiratory infection, bronchiolitis and bronchitis) from April 2016 to September 2018.

They then compared adverse events, such as it’s hard infection, no–it’s hard diarrhoea, anaphylaxis (severe allergic reaction), nausea/vomiting/abdominal pain and rash – in children who received inappropriate antibiotics with those who received appropriate antibiotics.

Antibiotics were considered inappropriate if prescribed for a viral infection or if the agent prescribed for a bacterial infection was not the agent recommended by the guidelines. The researchers used this expanded definition of inappropriate prescribing because previous research has shown that even when children are correctly given an antibiotic for a bacterial infection, the agent selected is not always the recommended first-line antibiotic. In some cases, non-recommended antibiotics are broader-spectrum agents that promote the development of resistance and may have an increased risk of adverse effects.

Looking at antibiotic prescriptions by diagnosis, the analysis found that 36% of children with sinusitis, 34% of children with pharyngitis, and 31% of children with suppurative otitis media received an inappropriate antibiotic. For children with viral infections, the proportion who received an inappropriate antibiotic ranged from 4% for those with influenza to 70% for children with bronchitis.

Analysis of adverse events revealed that, in children with bacterial infections, the increased risk of an adverse event associated with inappropriate antibiotic prescription was significant.

For example, inappropriate selection of antibiotics for pharyngitis was associated with a more than eight-fold increased risk of it’s hard infection (relative risk [HR], 8.42; 95% confidence interval [CI], 3.09 to 23.0). Children who received the antibiotic not recommended by the guidelines for suppurative otitis media had a fourfold risk of a serious allergic reaction (RR, 4.14; 95% CI, 2.48 to 6.92).

For children with viral infections, unnecessary antibiotics were associated with a higher risk of rash or hives (hives). In general, serious adverse events such as it’s hard infection and anaphylaxis were rare, while rash, nausea/vomiting/abdominal pain and no–it’s hard diarrhea was more frequent.

High cost of adverse events

The increased risk of adverse events was costly. When the researchers looked at the additional costs attributed to these inappropriate prescriptions, including follow-up clinician visits and additional medications prescribed for the adverse event within 30 days of initial diagnosis, they found that the additional cost per patient for children who received inappropriate medication antibiotics cost $21 for sinusitis, $42 for pharyngitis and $56 for otitis media.

Nationally, this translated to an additional cost of $7.1 million, $21.3 million and $25.3 million for the three infections. Unnecessary antibiotics for viral upper respiratory infections and influenza increased health care costs by approximately $20.7 million.

Hyun said the findings, while not necessarily surprising given what is known about antibiotic-related adverse events, were eye-opening.

“We all sort of suspected that there would be an increase in adverse events associated with inappropriate use of antibiotics, and there could be increased costs, but actually seeing the numbers really crystallizes the urgency of this. problem,” he said. “It really drives home the need for antibiotic stewardship practices in outpatient settings.”

Involve insurers in stewardship efforts

For Hyun, one of the takeaways is that health care payers, whether private insurers, Medicare or Medicaid, are incentivized to play a bigger role in promoting stewardship. antibiotics.

They could help drive management efforts by using medical claims and prescription data to assess the antibiotic prescribing practices of clinicians in their network, give providers individual feedback and peer comparison, and incentivize providers to improve their prescribing habits, he said.

“Providers and practitioners need a lot of help to adopt effective antibiotic stewardship strategies,” Hyun said. “Health systems and payers are in an excellent position to provide these resources.”

Butler said the study also highlights the need for more education about the risks and benefits of antibiotics for children. She would like parents to have enough information to feel empowered to consider whether their child is being prescribed an antibiotic for a viral infection or an antibiotic for a bacterial infection that is not recommended by the guidelines.

“It’s very clear that inappropriate antibiotics are not benign, they cause side effects that lead to costly doctor visits and additional prescriptions,” she said. “The results we’re seeing…really underscore the need for ongoing clinician education and patient or family education on antibiotic therapy,” she said.