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.

Interventions for hand eczema

Brian Desmarais — Wed, 05 Jun 2019 20:27:09 +0000

Date Added:

June 5, 2019

Journal/Publication:

Cochrane Systematic Review

Publication Date:

April 26, 2019

URL:

Interventions for hand eczema

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1002/14651858.CD004055.pub2.

Keywords

MeSH

Calcineurin Inhibitors/therapeutic use

Eczema/drug therapy

Emollients/therapeutic use

Immunosuppressive Agents/therapeutic use

Severity of Illness Index

Emollients

A Cochrane review of current RCT evidence regarding treatment of hand eczema. James W. Mold, MD, MPH

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Abstract

BACKGROUND:

Hand eczema is an inflammation of the skin of the hands that tends to run a chronic, relapsing course. This common condition is often associated with itch, social stigma, and impairment in employment. Many different interventions of unknown effectiveness are used to treat hand eczema.

OBJECTIVES:

To assess the effects of topical and systemic interventions for hand eczema in adults and children.

SEARCH METHODS:

We searched the following up to April 2018: Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase, AMED, LILACS, GREAT, and four trials registries. We checked the reference lists of included studies for further references to relevant trials.

SELECTION CRITERIA:

We included randomised controlled trials (RCTs) that compared interventions for hand eczema, regardless of handeczema type and other affected sites, versus no treatment, placebo, vehicle, or active treatments.

DATA COLLECTION AND ANALYSIS:

We used standard methodological procedures expected by Cochrane. Primary outcomes were participant- and investigator-rated good/excellent control of symptoms, and adverse events.

Author/s:

Christoffers, W.A., Coenraads, P.J., Svensson, Å., Diepgen, T.L., Dickinson-Blok, J.L., Williams, H.C., Xia, J.