Short-Course Antimicrobial Therapy for Pediatric Community-Acquired Pneumonia: The SAFER Randomized Clinical Trial
Jeffrey M Pernica1,2, Stuart Harman2,3, April J Kam2,4
1Division of Infectious Diseases, Department of Pediatrics, McMaster University, Hamilton, Ontario, Canada.
Insights
Five days of high-dose amoxicillin is as effective as 10 days for treating childhood community-acquired pneumonia (CAP) in children not requiring hospitalization. This shorter course supports antimicrobial stewardship principles for pediatric pneumonia.
Area of Science:
- Pediatric infectious diseases
- Clinical pharmacology
- Evidence-based medicine
Background:
- Community-acquired pneumonia (CAP) is a frequent childhood illness, necessitating evidence-based treatment guidelines.
- Optimizing antibiotic duration is crucial for effective treatment and antimicrobial stewardship.
Purpose of the Study:
- To compare the clinical cure rates of 5-day versus 10-day high-dose amoxicillin regimens for pediatric CAP.
- To evaluate the noninferiority of a shorter antibiotic course in children with uncomplicated CAP.
Main Methods:
- A 2-center, blinded, noninferiority randomized clinical trial (SAFER study) involving 281 children aged 6 months to 10 years.
- Participants received either 5 days of high-dose amoxicillin followed by placebo, or 10 days of high-dose amoxicillin.
- Clinical cure was assessed 14 to 21 days post-treatment.
Main Results:
- Per-protocol analysis showed clinical cure rates of 88.6% for the 5-day group and 90.8% for the 10-day group.
- Intention-to-treat analysis revealed clinical cure rates of 85.7% for the 5-day group and 84.1% for the 10-day group.
- The 5-day regimen was noninferior to the 10-day regimen for clinical cure.
Conclusions:
- Short-course (5-day) amoxicillin therapy is comparable to standard 10-day treatment for pediatric CAP in previously healthy children.
- Clinical guidelines should consider shorter amoxicillin courses for pediatric pneumonia to align with antimicrobial stewardship.
- This approach can help reduce antibiotic exposure and promote responsible antibiotic use in children.
Importance:
Community-acquired pneumonia (CAP) is a common occurrence in childhood; consequently, evidence-based recommendations for its treatment are required.
Objective:
To determine whether 5 days of high-dose amoxicillin for CAP was associated with noninferior rates of clinical cure compared with 10 days of high-dose amoxicillin.
Design, Setting, And Participants:
The SAFER (Short-Course Antimicrobial Therapy for Pediatric Respiratory Infections) study was a 2-center, parallel-group, noninferiority randomized clinical trial consisting of a single-center pilot study from December 1, 2012, to March 31, 2014, and the follow-up main study from August 1, 2016, to December 31, 2019 at the emergency departments of McMaster Children's Hospital and the Children's Hospital of Eastern Ontario. Research staff, participants, and outcome assessors were blinded to treatment allocation. Eligible children were aged 6 months to 10 years and had fever within 48 hours, respiratory symptoms, chest radiography findings consistent with pneumonia as per the emergency department physician, and a primary diagnosis of pneumonia. Children were excluded if they required hospitalization, had comorbidities that would predispose them to severe disease and/or pneumonia of unusual origin, or had previous β-lactam antibiotic therapy. Data were analyzed from March 1 to July 8, 2020.
Interventions:
Five days of high-dose amoxicillin therapy followed by 5 days of placebo (intervention group) vs 5 days of high-dose amoxicillin followed by a different formulation of 5 days of high-dose amoxicillin (control group).
Main Outcomes And Measures:
Clinical cure at 14 to 21 days.
Results:
Among the 281 participants, the median age was 2.6 (interquartile range, 1.6-4.9) years (160 boys [57.7%] of 279 with sex listed). Clinical cure was observed in 101 of 114 children (88.6%) in the intervention group and in 99 of 109 (90.8%) in the control group in per-protocol analysis (risk difference, -0.016; 97.5% confidence limit, -0.087). Clinical cure at 14 to 21 days was observed in 108 of 126 (85.7%) in the intervention group and in 106 of 126 (84.1%) in the control group in the intention-to-treat analysis (risk difference, 0.023; 97.5% confidence limit, -0.061).
Conclusions And Relevance:
Short-course antibiotic therapy appeared to be comparable to standard care for the treatment of previously healthy children with CAP not requiring hospitalization. Clinical practice guidelines should consider recommending 5 days of amoxicillin for pediatric pneumonia management in accordance with antimicrobial stewardship principles.
Trial Registration:
ClinicalTrials.gov Identifier: NCT02380352.
More Related Videos
07:46Use of Artificial Sputum Medium to Test Antibiotic Efficacy Against Pseudomonas aeruginosa in Conditions More Relevant to the Cystic Fibrosis Lung
Published on: June 5, 2012
06:18Quantifying the Effects of Antimicrobials on In vitro Biofilm Architecture using COMSTAT Software
Published on: December 14, 2020
Related Concept Videos
01:26Pharmacokinetics in Pediatric Patients: Drug Excretion
01:23Pharmacokinetics in Pediatric Patients: Overview and Drug Absorption
01:24Pharmacokinetics in Pediatric Patients: Drug Metabolism
01:17Pharmacokinetics in Pediatric Patients: Drug Distribution
01:28Pneumonia IV: Management
Bacterial Pneumonia Treatment
For bacterial pneumonia, antibiotics serve as the cornerstone of therapy. Initial treatment often begins with empirical antibiotics, tailored to the anticipated causative organism and adjusted based on culture results. Key antibiotic choices include:
01:28Antimicrobial Effectiveness