Short-Course Antimicrobial Therapy for Pediatric Community-Acquired Pneumonia

Abstract

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.

Antibiotics for lower respiratory tract infection in children presenting in primary care in England (ARTIC PC): a double-blind, randomised, placebo-controlled trial

“…6 A placebo-controlled trial of antibiotic versus placebo for pneumonia in young children in an LMIC setting found low failure rates in both placebo (5%) and antibiotic (3%) groups, 44 and a 5-day course is equivalent to 10 days for communityacquired pneumonia. 45 Our results suggest that antibiotics do not provide a clinically important benefit on average for symptom reduction nor symptom severity. The question remains whether there are some children who receive a meaningful benefit, but the benefit is diluted by large numbers of children who receive no benefit.…”

Pediatricians’ Compliance to the Clinical Management Guidelines for Community-Acquired Pneumonia in Infants and Young Children in Pakistan

“…Yet, extended hospitalization for the IV antibiotics administration remains a general practice in the Asian region countries. By reducing needless hospitalization for IV antibiotics, major health expenses may be saved [26]; however, none of the study respondents confessed to generating revenue from prescribing antibiotics. In some countries, drug prescriptions normally increase a doctor's earnings, and the exclusion of these profitable inducements accompanied by improved regulation can significantly decrease the misuse [27].…”

Assessment of nasopharyngeal Streptococcus pneumoniae colonization does not permit discrimination between Canadian children with viral and bacterial respiratory infection: a matched-cohort cross-sectional study

“…Those with ventilator-associated pneumonia, cystic fibrosis, anatomic lung disease, bronchiectasis, congenital heart disease, history of repeated aspiration, malignancy, conditions requiring treatment with immune suppressants, or primary immunodeficiency were excluded. Group 3 consisted of previously healthy children aged 6 mos – 10 y who were diagnosed with community-acquired pneumonia in the MCH Emergency Department (ED) and were well enough to be managed as outpatients, as previously described, in a prospective randomized trial [ 22 ]. Participants were enrolled during Dec 2012-March 2014 (pilot phase) and Aug 2016-Dec 2019.…”

“…Group 3 consisted of previously healthy children aged 6 mos – 10 y who were diagnosed with community-acquired pneumonia in the MCH Emergency Department (ED) and were well enough to be managed as outpatients, as previously described, in a prospective randomized trial [ 22 ]. Participants were enrolled during Dec 2012-March 2014 (pilot phase) and Aug 2016-Dec 2019.…”

“…The study was approved by the Hamilton Integrated Research Ethics Board and informed consent was obtained from all participants (and from the parents/legal guardians for those aged less than 18 years) who were recruited and followed prospectively (ie. Group 2 and 3), some of whom were drawn from other studies [ 21 , 22 ]. All methods were performed in accordance with the Declaration of Helsinki.…”