Extended Versus Standard Antibiotic Course Duration in Children <5 Years of Age Hospitalized With Community-acquired Pneumonia in High-risk Settings: Four-week Outcomes of a Multicenter, Double-blind, Parallel, Superiority Randomized Controlled Trial

Abstract

Background: High-level evidence is limited for antibiotic duration in children hospitalized with community-acquired pneumonia (CAP) from First Nations and other at-risk populations of chronic respiratory disorders. As part of a larger study, we determined whether an extended antibiotic course is superior to a standard course for achieving clinical cure at 4 weeks in children 3 months to ≤5 years old hospitalized with CAP. Methods: In our multinational (Australia, New Zealand, Malaysia), double-blind, superiority randomized controlled trial, children hospitalized with uncomplicated, radiographic-confirmed, CAP received 1–3 days of intravenous antibiotics followed by 3 days of oral amoxicillin-clavulanate (80 mg/kg, amoxicillin component, divided twice daily) and then randomized to extended (13–14 days duration) or standard (5–6 days) antibiotics. The primary outcome was clinical cure (complete resolution of respiratory symptoms/signs) 4 weeks postenrollment. Secondary outcomes included adverse events, nasopharyngeal bacterial pathogens and antimicrobial resistance at 4 weeks. Results: Of 372 children enrolled, 324 fulfilled the inclusion criteria and were randomized. Using intention-to-treat analysis, between-group clinical cure rates were similar (extended course: n = 127/163, 77.9%; standard course: n = 131/161, 81.3%; relative risk = 0.96, 95% confidence interval = 0.86–1.07). There were no significant between-group differences for adverse events (extended course: n = 43/163, 26.4%; standard course, n = 32/161, 19.9%) or nasopharyngeal carriage of Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Staphylococcus aureus or antimicrobial resistance. Conclusions: Among children hospitalized with pneumonia and at-risk of chronic respiratory illnesses, an extended antibiotic course was not superior to a standard course at achieving clinical cure at 4 weeks. Additional research will identify if an extended course provides longer-term benefits.

Defining effective durations of antibiotic therapy for community-acquired pneumonia and urinary tract infections in hospitalized children

“…In 2022, the findings from the first clinical trial evaluating the duration of therapy for children hospitalized with CAP were reported [39 ▪▪ ]. McCallum et al performed a double-blind RCT assigning hospitalized children from Australia, New Zealand, and Malaysia with uncomplicated, radiographically confirmed CAP to approximately 5–6 days of antibiotics vs. 13–14 days of antibiotics.…”

Comparison between Short Therapy and Standard Therapy in Pediatric Patients Hospitalized with Urinary Tract Infection: A Single Center Retrospective Analysis

“…Importantly, our findings and the other mentioned studies seem to be in line with new evidence about the safety of short therapy in pediatric infectious diseases, such as pneumonia [ 10 ]: a recent review considered four clinical trials [ 23 , 24 , 25 , 26 ] aimed at analyzing the optimal duration of antibiotic therapy in children affected by non-hospitalized pneumonia, the conclusions of which are the same and indicate that in uncomplicated forms 5 days of antibiotic therapy are sufficient in the eradication of the infection. A similar conclusion can be applied to hospitalized patients [ 27 ] from a large multicenter study conducted in 2022, which showed that, in uncomplicated pneumonia cases, a 13–14-day cycle (defined as extended) does not exceed a standard 5–6-day cycle in healing at one month (extended course: n = 127/163, 77.9%; standard course: n = 131/161, 81%). In conclusion, fixed antibiotic durations provide straightforward guidance but do not take into account children’s characteristics or treatment response; a possible approach would be to individualize antibiotic durations via biomarker-assisted guidance such as C-reactive protein or procalcitonin, although these are non-specific indexes for bacterial infections [ 28 ].…”

Evaluation of a Pediatric Community-Acquired Pneumonia Antimicrobial Stewardship Intervention at an Academic Medical Center

“…Their results showed that 82.8% of outpatient antibiotic prescriptions for children with CAP were written for a duration of 10 days, whereas only 10.5% were written for a shorter duration [ 15 ]. However, multiple randomized control trials supporting shorter durations have since been published [ 3 , 4 , 5 , 6 ]. Pernica and colleagues published the SAFER trial in 2021, which compared five- and ten-day courses of high-dose amoxicillin for pediatric patients diagnosed with CAP in the emergency department (ED) [ 3 ].…”

“…The above studies provide data supporting short antibiotic durations for pediatric CAP treatment, but their application for hospitalized children with CAP may be limited since they were primarily completed in an outpatient setting. Another randomized control trial performed by McCallum and colleagues aimed to determine whether an extended antibiotic course was superior to a standard course of antibiotics for children hospitalized with uncomplicated CAP [ 6 ]. Patients received one to three days of intravenous (IV) antibiotics followed by oral amoxicillin/clavulanate (80 mg/kg/day amoxicillin) for a total of 13 to 14 days (extended group) or 5 to 6 days (standard group).…”

“…The guidelines support the transition to oral step-down therapy and suggest a total antibiotic treatment duration of ten days [ 2 ]. However, multiple randomized control trials have since been published, supporting shorter durations of approximately five days for children with CAP [ 3 , 4 , 5 , 6 ].…”