This study describes the incidence of and antibiotic prescribing for pediatric CAP in outpatient settings nationally since the publication of national guideline recommendations. The rates of CAP diagnoses and antibiotic prescribing for CAP have been unchanged since the national guideline publication. Despite guideline recommendations to prescribe amoxicillin as the first-line antibiotic choice for children with CAP, there has been no significant increase in amoxicillin prescribing since publication, and azithromycin remains the predominant antibiotic prescribed for children of all ages with CAP. Older children and children residing in the Midwest and South are less likely to receive amoxicillin for CAP compared to younger children and children living in the Northeast. Children who visit EDs are more likely to receive azithromycin compared to children who visit a physician office.
Previous work that investigated antibiotic prescribing for children aged 1–6 years with CAP similarly found no differences in antibiotic prescribing overall or antibiotic class when comparing prescribing before and after guideline publication [3]. We found that younger children (aged 90 days–4 years) were prescribed azithromycin and amoxicillin at similar rates. However, when the entire population was expanded to all pediatric patients aged 90 days–18 years, we found that azithromycin was prescribed more frequently, and significantly more so in older children (aged 5–18 years) compared to younger children and when the visit occurred at an ED compared to an office setting. The majority of pediatric visits to EDs occur nationally at non-pediatric facilities, and previous work has shown that children are prescribed unnecessary antibiotics, particularly azithromycin, more frequently in non-pediatric EDs compared to pediatric EDs [9]. It is possible that children in this study received azithromycin more frequently in EDs due to lower prevalence of pediatric-trained physicians at the majority of EDs nationally. Additionally, although patients admitted to the hospital were excluded, patients could have presented to EDs with more concerning symptoms compared to physician offices, prompting physicians in EDs to treat for atypical pneumonia. However, the estimated rate of pediatric pneumonia from Mycoplasma pneumoniae is estimated to be as low at 8%, and we found that azithromycin was prescribed to nearly 50% of all CAP visits [10]. Other etiologies of atypical pneumonia, such as Chlamydia pneumoniae, are much less prevalent (< 1% of pediatric CAP hospitalizations) in the US [11].
Azithromycin is inappropriate treatment for the majority of pediatric ambulatory CAP diagnoses, as S. pneumoniae is much more likely to be resistant to azithromycin than to amoxicillin [10]. This study was not designed to assess clinical outcomes; therefore, we are unable to determine whether there was a difference in patient outcomes according to the antibiotic prescribed. However, the pathogenicity and clinical significance of M. pneumoniae is unclear and atypical pneumonia is often self-limited [10], which makes azithromycin treatment for atypical pneumonia of unclear benefit.
It is unknown why physicians favor azithromycin over amoxicillin for the treatment of CAP, and additional studies are needed to further explain this phenomenon. Factors that might contribute to the over-prescription of azithromycin include the convenience of azithromycin dosing and duration, over-estimation of the prevalence and morbidity of M. pneumoniae, and the over-diagnosis of penicillin allergy in children. The risk of over-prescribing azithromycin includes increasing resistance to S. pneumonia and S. pyogenes, the most common bacterial causes of acute respiratory tract infections in children. Other harmful effects of antibiotics include auto-immune diseases, other infectious diseases such as Clostridium difficile, and obesity [12].
It is possible the national guideline recommendations for the treatment of CAP have not been widely referenced or utilized because clinical practice is slow to change. It is estimated to take 17 years for scientific discovery to enter daily clinical practice [13]. However, inpatient settings have shown a significant increase in first-line guideline prescribing for hospitalized children with CAP since the publication of the national guideline recommendations [14]. Hospitals with individualized plans for guideline implementation were significantly more likely to prescribe first-line antibiotics to children with CAP [14], highlighting the importance of dedicated antibiotic stewardship (AS) efforts in guideline implementation.
Finally, previous work has found geographic variation in unnecessary antibiotic and azithromycin prescribing in outpatient settings [15]. This study adds to this work by showing similar geographic variability in first-line guideline-recommended antibiotic prescribing for CAP. Geographic variations in the rate of azithromycin prescribing could be partially explained by disease prevalence; however, cultural differences nationally surrounding antibiotic prescribing could be playing a significant role in prescribing trends. Future studies are needed to better understand why this geographic discordance exists in antibiotic prescribing.
This study has several limitations. First, patient allergies or antibiotics prescribed at previous visits, which can influence antibiotic prescribing, are unavailable. However, it is expected that a true penicillin allergy and previous medication failure would contribute to a small percentage of indicated azithromycin prescriptions [10]. Second, patient-level data including vital signs and physical exam findings are unavailable, limiting our ability to assess the severity of illness, which could influence prescribing practices. Third, visits for CAP were identified based on three diagnosis codes available in the NHAMCS dataset, which were not directly linked to medications mentioned in the visit. It is therefore possible that the indication of CAP for the antibiotic mentioned could be misclassified.