Azithromycin Avoidance in Pediatric Patients with Sickle Cell Disease and Respiratory Infections

Introduction: The use of azithromycin, a macrolide antibiotic, can be measured using Standardized Antibiotic Administration Ratio (SAAR). In response to higher than predicted usage, we conducted a retrospective medication-use evaluation of patients who received azithromycin in the pediatric medical-surgical ward (Ward) from August 2021 through January 2022. The evaluation showed that the most common indication for azithromycin was sickle cell disease (SCD) with acute chest syndrome (ACS). During this time period, the average SAAR rates for azithromycin in our Ward and pediatric medical-surgical intensive care unit (PICU) were, respectively, 3.5 and 1.3 times above the national average published in the 2020 National Healthcare Safety Network (NHSN) Antimicrobial Use Option Report. Historically, all patients with SCD and suspicion for ACS received empiric azithromycin because Chlamydia pneumoniae and Mycoplasma pneumoniae were considered the most common pathogens. Studies of PCR-based multiplex nucleic acid (mPCR) testing via nasopharyngeal swab, such as BioFire Respiratory Panel 2.1 (RP2.1), which identifies 18 viruses and 4 bacteria, demonstrated that screening for C. pneumoniae and M. pneumoniae could reduce unnecessary exposure to azithromycin. Methods: The primary objective of this prospective quality improvement study was to decrease the average azithromycin SAAR to below the national average using a RP2.1 testing protocol in pediatric patients with SCD presenting with respiratory infection within 1 year. The secondary objective was to evaluate if avoidance of azithromycin would lead to harm such as clinical deterioration (e.g. need for oxygen or ventilator support), escalation of care (e.g. transfer to ICU), or increased readmission rates. Pediatric patients with SCD admitted with respiratory infection underwent RP2.1 testing; azithromycin was initiated if results were positive for C. pneumoniae, M. pneumoniae, or Bordatella spp. Patients were excluded if admitted to a location other than the Ward or PICU, if they had a diagnosis of sickle cell anemia, or if they did not receive RP2.1 testing. Additionally, all patients who received azithromycin were tracked, irrespective of inclusion in the primary analysis. Results: Between May 17, 2023 and May 31, 2024, 61 patients with SCD and respiratory tract infection were included in the primary analysis; 49% patients were female, 80% Black/African American, 18% were 4 years of age or younger, 28% were 5-9 years of age, and 54% were 10 years of age or older. All patients had negative RP2.1 test results for C. pneumoniae and M. pneumoniae. Azithromycin was successfully avoided in 52 patients (85%). Azithromycin was initiated in 9 patients (15%); 5 had azithromycin discontinued by the study team because RP2.1 results were negative and 4 completed a 5-day course of azithromycin. One of these 4 patients tested negative for both C. pneumoniae and M. pneumoniae; however, the study team missed the opportunity to stop the azithromycin during transition to new electronic health record. A second patient tested positive for Coronavirus OC43 and azithromycin was stopped after 1 dose. The remaining 2 patients received azithromycin appropriately to treat respiratory infection caused by Bordetella parapertussis. In the secondary analysis, 12 patients without SCD received azithromycin; 5 had M. pneumoniae, 1 had cat scratch disease, and the remaining 7 had azithromycin discontinued based on RP2.1 test results. The average azithromycin SAAR decreased from 1.691 to 0.178 in the Ward and 0.486 to 0.454 in the PICU. Usage in both locations decreased to below the national average published in the 2022 NHSN Antimicrobial Use Option Report of 0.486 and 0.59, respectively. Avoidance of azithromycin did not appear to impact the number of patients who were receiving supplemental oxygen, transferred to PICU, or readmitted within 30 days for an upper respiratory infection. Conclusion: Use of a PCR-based multiplex nucleic acid test protocol in pediatric patients with sickle cell disease presenting with respiratory infection demonstrated that screening for C. pneumoniae and M. pneumoniae successfully reduced unnecessary exposure to azithromycin.