Community-acquired pneumonia is associated with approximately 740 000 hospitalizations and 41 000 deaths in the US annually. JAMA Review authors Scott A. Flanders, MD, and Valerie M. Vaughn, MD, MSc, discuss diagnosis and treatment of community-acquired pneumonia with JAMA Deputy Editor Mary McGrae McDermott, MD.
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
Background: This document provides evidence-based clinical practice guidelines on the management of adult patients with community-acquired pneumonia.
Methods: A multidisciplinary panel conducted pragmatic systematic reviews of the relevant research and applied Grading of Recommendations, Assessment, Development, and Evaluation methodology for clinical recommendations.
Results: The panel addressed 16 specific areas for recommendations spanning questions of diagnostic testing, determination of site of care, selection of initial empiric antibiotic therapy, and subsequent management decisions. Although some recommendations remain unchanged from the 2007 guideline, the availability of results from new therapeutic trials and epidemiological investigations led to revised recommendations for empiric treatment strategies and additional management decisions.
Conclusions: The panel formulated and provided the rationale for recommendations on selected diagnostic and treatment strategies for adult patients with community-acquired pneumonia.
The British Thoracic Society (BTS) Guidelines for the management of Community Acquired Pneumonia (CAP) in Adults was published in December 2001 and superseded Guidelines published in 1993. A web-based update of the 2001 Guidelines was published in 2004. The 2004 Guidelines assessed relevant evidence published up to August 2003.
This update represents a further assessment of published or available evidence from August 2003 to August 2008. An identical search strategy, assessment of relevance and appraisal of articles, and grading system was used.
The British Thoracic Society (BTS) Guidelines for the management of Community Acquired Pneumonia (CAP) in Adults was published in December 2001 and superseded Guidelines published in 1993. A web-based update of the 2001 Guidelines was published in 2004. The 2004 Guidelines assessed relevant evidence published up to August 2003.
This update represents a further assessment of published or available evidence from August 2003 to August 2008. An identical search strategy, assessment of relevance and appraisal of articles, and grading system was used.
