Effect of Amoxicillin Dose and Treatment Duration on the Need for Antibiotic Re-treatment in Children With Community-Acquired Pneumonia: The CAP-IT Randomized Clinical Trial

Bethie Seay — Sun, 07 Nov 2021 05:00:00 +0000

Date Added:

November 7, 2021

Journal/Publication:

JAMA

Publication Date:

November 2, 2021

Issue:

Volume:

326

Pages:

1713-1724

Type:

Clinical Research Results

DOI (1):

10.1001/jama.2021.17843

3 days of standard dose amoxicillin was as effective as 7 days of high-dose amoxicillin for treatment of CAP in children discharged from an ED. In both cases, additional antibiotic treatment was required subsequently in around 12.5% of kids.

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Importance
The optimal dose and duration of oral amoxicillin for children with community-acquired pneumonia (CAP) are unclear.

Objective
To determine whether lower-dose amoxicillin is noninferior to higher dose and whether 3-day treatment is noninferior to 7 days.

Design, Setting, and Participants
Multicenter, randomized, 2 × 2 factorial noninferiority trial enrolling 824 children, aged 6 months and older, with clinically diagnosed CAP, treated with amoxicillin on discharge from emergency departments and inpatient wards of 28 hospitals in the UK and 1 in Ireland between February 2017 and April 2019, with last trial visit on May 21, 2019.

Interventions
Children were randomized 1:1 to receive oral amoxicillin at a lower dose (35-50 mg/kg/d; n = 410) or higher dose (70-90 mg/kg/d; n = 404), for a shorter duration (3 days; n = 413) or a longer duration (7 days; n = 401).

Main Outcomes and Measures
The primary outcome was clinically indicated antibiotic re-treatment for respiratory infection within 28 days after randomization. The noninferiority margin was 8%. Secondary outcomes included severity/duration of 9 parent-reported CAP symptoms, 3 antibiotic-related adverse events, and phenotypic resistance in colonizing Streptococcus pneumoniae isolates.

Results
Of 824 participants randomized into 1 of the 4 groups, 814 received at least 1 dose of trial medication (median [IQR] age, 2.5 years [1.6-2.7]; 421 [52%] males and 393 [48%] females), and the primary outcome was available for 789 (97%). For lower vs higher dose, the primary outcome occurred in 12.6% with lower dose vs 12.4% with higher dose (difference, 0.2% [1-sided 95% CI –∞ to 4.0%]), and in 12.5% with 3-day treatment vs 12.5% with 7-day treatment (difference, 0.1% [1-sided 95% CI –∞ to 3.9]). Both groups demonstrated noninferiority with no significant interaction between dose and duration (P = .63). Of the 14 prespecified secondary end points, the only significant differences were 3-day vs 7-day treatment for cough duration (median 12 days vs 10 days; hazard ratio [HR], 1.2 [95% CI, 1.0 to 1.4]; P = .04) and sleep disturbed by cough (median, 4 days vs 4 days; HR, 1.2 [95% CI, 1.0 to 1.4]; P = .03). Among the subgroup of children with severe CAP, the primary end point occurred in 17.3% of lower-dose recipients vs 13.5% of higher-dose recipients (difference, 3.8% [1-sided 95% CI, –∞ to10%]; P value for interaction = .18) and in 16.0% with 3-day treatment vs 14.8% with 7-day treatment (difference, 1.2% [1-sided 95% CI, –∞ to 7.4%]; P value for interaction = .73).

Conclusions and Relevance
Among children with CAP discharged from an emergency department or hospital ward (within 48 hours), lower-dose outpatient oral amoxicillin was noninferior to higher dose, and 3-day duration was noninferior to 7 days, with regard to need for antibiotic re-treatment. However, disease severity, treatment setting, prior antibiotics received, and acceptability of the noninferiority margin require consideration when interpreting the findings.

Trial Registration
ISRCTN Identifier: ISRCTN76888927

Author/s:

Bielicki, J. A., Stöhr, W., Barratt, S., Dunn, D., Naufal, N., Roland, D., Sturgeon, K., Finn, A., Rodriguez-Ruiz, J. P., Malhotra-Kumar, S., Powell, C., Faust, S. N., Alcock, A. E., Hall, D., Robinson, G., Hawcutt, D. B., Lyttle, M. D., Gibb, D. M., Sharland, M.

Genome sequencing as a diagnostic test

Bethie Seay — Tue, 26 Oct 2021 05:00:00 +0000

Date Added:

October 26, 2021

Journal/Publication:

CMAJ

Publication Date:

October 25, 2021

Issue:

Volume:

193

Pages:

E1626-E1629

Type:

Meta-analyses, Reviews, and Guidelines

DOI (1):

10.1503/cmaj.210549

MeSH

High-throughput nucleotide sequencing

delivery of health care

microarray analysis

hospitals

United Kingdom

Get ready for genomic medicine, and good luck.

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KEY POINTS
Genome sequencing is a comprehensive genetic test that is being integrated into health care systems internationally.

Test indications include suspected genetic disorders in children and adults for whom a targeted genetic testing approach is likely to be low yield or has already failed.

Analytic validity, diagnostic yield and clinical utility are similar or superior to other clinical genetic tests, such as exome sequencing, chromosomal microarray analysis and next-generation sequencing gene panel tests.

Appropriate adoption of genome sequencing as a molecular diagnostic test in Canada would be facilitated by a cohesive national strategy for genomic medicine.

Genetic testing of patient constitutional DNA (i.e., their genome) is increasingly performed in medical practice. 1–3 Sequencing an entire human genome (about 3.2 billion nucleotides) is now possible to complete in days to weeks, and at a similar cost to some advanced imaging tests or to a brief admission to hospital.3,4 Genome sequencing is being integrated into health care systems internationally, most notably in the United Kingdom.5 Starting in 2021, genome sequencing is being performed as a clinical genetic test in Ontario, Canada.

Author/s:

Costain, G., Cohn, R. D., Scherer, S. W., Marshall, C. R.