Study: For kids with respiratory infections, broader isn't better

A new study in the Journal of the American Medical Association (JAMA) indicates that broad-spectrum antibiotics don't produce better clinical or patient-centered outcomes than narrow-spectrum antibiotics in children with acute respiratory infections, and the narrower-targeting drugs are linked to higher rates of adverse events.

Acute respiratory infections such as ear infections, sinus infections, and streptococcal pharyngitis (sore throat) account for most bacterial respiratory infections in children and are the primary drivers of pediatric antibiotic prescribing. But while narrow-spectrum antibiotics like penicillin or amoxicillin have traditionally been recommended as first line-treatment, recent studies have shown that broad-spectrum antibiotics—which cover more types of bacteria than the organism causing the infection—are increasingly being prescribed for these conditions and account for nearly half of all antibiotics prescribed for children.

Explanations for this trend include inconsistent guidance from pediatric medical societies. For example, while the American Academy of Pediatrics recommends amoxicillin with or without clavulanate for treating acute sinusitis (sinus infection), practice guidelines from the Infectious Diseases Society of America recommend amoxicillin-clavulanate over amoxicillin alone. But some experts suggest that there's a perception, among both patients and providers, that using drugs that cover more bacteria, especially in cases where the diagnosis is uncertain, makes it less likely that something could be missed.

"When the provider is not clear about the medical diagnosis they are making, and there are potentially multiple possibilities in their mind about what the true diagnosis could be, then the tendency is to not only prescribe antibiotics, but to also use a broader spectrum," David Hyun, MD, said in an interview. Hyun, a senior officer with the Pew Charitable Trusts antibiotic resistance project and former practicing physician who specialized in pediatric infectious diseases, was not involved in the study.

Hyun and other experts say that the unnecessary use of broad-spectrum antibiotics among both children and adults is one of the forces driving antibiotic resistance. "Studies have shown that broad-spectrum antibiotics carry a higher risk associated with the development of antibiotic resistance and antibiotic-resistant infections," said Hyun. "So whenever it's possible, when all things are equal, it is best to use narrow-spectrum antibiotics…to minimize the risk of antibiotic resistance."

Unique study design

To compare the effectiveness of broad-spectrum and narrow-spectrum antibiotics in children with acute respiratory infections, a team of investigators led by Jeffrey Gerber, MD, PhD, of Children's Hospital of Philadelphia, conducted 2 large cohort studies of children ages 6 months to 12 years in a network of 31 pediatric primary care practices.

One was a prospective study that evaluated quality of life and other patient-centered outcomes based on electronic health record data and structured interviews with parents and children. The other was a retrospective study that evaluated clinical outcomes using only electronic health records.  

The study design is unique because it goes beyond using traditional outcomes such as treatment failure to assess antibiotic therapy and looks at how antibiotic choice affects the lives of children and their parents. Measuring health-related quality of life takes into account factors that can affect families, such as missed school days (which can require parents to stay home or find additional childcare) and sleep disturbances. Evaluating the outcomes from the point of view of the patient and caregiver can reveal issues that may never show up on a medical chart.

"Clinical studies of different therapeutic approaches that rely exclusively on clinician-observed outcomes risk missing differential rates of symptom resolution and adverse events that are meaningful to families," Gerber and his co-authors wrote.

"Metrics like loss of sleep and missed school days and work days—these are things that are very important determinants of how patients or their parents feel their antibiotic therapy went," Hyun added.

Data support narrow-spectrum antibiotics

The results from both cohorts show that broad-spectrum antibiotics did not produce better clinical or patient-centered outcomes.

In the retrospective study, the investigators examined the clinical outcomes of 30,159 children treated with antibiotics for an acute respiratory infection (19,179 with acute otitis media, 6,746 with group A streptococcal pharyngitis, and 4,234 with acute sinusitis). Fourteen percent (4,307) were prescribed broad-spectrum antibiotics, including amoxicillin-clavulanate, cephalosporins, and macrolides.

Broad-spectrum antibiotics had a slightly higher rate of treatment failure after 14 days compared with narrow-spectrum drugs (3.4% versus 3.1%) and were not superior for any clinical outcomes, although a sub-analysis showed a lower rate of treatment failure in children with group A streptococcal pharyngitis. In addition, broad-spectrum drugs were associated with higher rate of adverse events (3.7% for broad-spectrum antibiotics vs. 2.7% for narrow-spectrum antibiotics).

In the prospective cohort, 2,472 children were enrolled (1,100 with acute otitis media, 705 with group A streptococcal pharyngitis, and 667 with acute sinusitis), and 865 (35%) received broad-spectrum antibiotics. Pediatric Quality of Life Inventory  scores, which were based on interviews with children and their parents or legal guardians, revealed that broad-spectrum antibiotics were associated with a slightly worse health-related quality of life for the child (score of 90.2 for broad-spectrum antibiotics vs. 91.5 for narrow-spectrum antibiotics) and a higher rate of adverse events (35.6% vs. 25.1%).

This last finding is noteworthy, Gerber and his colleagues noted, because it shows that the rates of adverse events associated with broad-spectrum antibiotics in the prospective, patient-centered cohort were almost 10 times higher than those identified in the medical records of the retrospective group. This suggests that a significant amount of adverse events, such as diarrhea, rashes, or vomiting, are going unreported.

"You have to reach a certain level of severity of symptoms for the parent or the patient to pick up the phone and call the doctor to report these adverse events," Hyun said. "But if it's something that they perceive to be more of an inconvenience or something that they can manage on their own, it may never register at the medical chart level."

Assessing these types of patient-centered outcomes, the authors said, could inform the risk-benefit analysis for antibiotic use in children.

The authors concluded that while the results don't suggest a clinically superior outcome for narrow-spectrum antibiotics, the data support use of narrow-spectrum antibiotics for most children with acute respiratory tract infections. Hyun believes this is an important conclusion.

"This study is very helpful because it really makes a very strong case that using broader-spectrum antibiotics for a lot of these bacterial respiratory infections does not provide any kind of advantage over narrow-spectrum antibiotics," Hyun said. "That's a very powerful and reassuring message, both for the providers as well as the patients."

See also:

Dec 19 JAMA study

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