Dataset Information

High-dose versus standard-dose amoxicillin/clavulanate for clinically-diagnosed acute bacterial sinusitis: A randomized clinical trial.

ABSTRACT:

Background

The recommended treatment for acute bacterial sinusitis in adults, amoxicillin with clavulanate, provides only modest benefit.

Objective

To see if a higher dose of amoxicillin will lead to more rapid improvement.

Design, setting, and participants

Double-blind randomized trial in which, from November 2014 through February 2017, we enrolled 315 adult outpatients diagnosed with acute sinusitis in accordance with Infectious Disease Society of America guidelines.

Interventions

Standard-dose (SD) immediate-release (IR) amoxicillin/clavulanate 875 /125 mg (n = 159) vs. high-dose (HD) (n = 156). The original HD formulation, 2000 mg of extended-release (ER) amoxicillin with 125 mg of IR clavulanate twice a day, became unavailable half way through the study. The IRB then approved a revised protocol after patient 180 to provide 1750 mg of IR amoxicillin twice a day in the HD formulation and to compare Time Period 1 (ER) with Time Period 2 (IR).

Main measure

The primary outcome was the percentage in each group reporting a major improvement-defined as a global assessment of sinusitis symptoms as "a lot better" or "no symptoms"-after 3 days of treatment.

Key results

Major improvement after 3 days was reported during Period 1 by 38.8% of ER HD versus 37.9% of SD patients (P = 0.91) and during Period 2 by 52.4% of IR HD versus 34.4% of SD patients, an effect size of 18% (95% CI 0.75 to 35%, P = 0.04). No significant differences in efficacy were seen at Day 10. The major side effect, severe diarrhea at Day 3, was reported during Period 1 by 7.4% of HD and 5.7% of SD patients (P = 0.66) and during Period 2 by 15.8% of HD and 4.8% of SD patients (P = 0.048).

Conclusions

Adults with clinically diagnosed acute bacterial sinusitis were more likely to improve rapidly when treated with IR HD than with SD but not when treated with ER HD. They were also more likely to suffer severe diarrhea. Further study is needed to confirm these findings.

Trial registration

ClinicalTrials.gov Identifier: NCT02340000.

SUBMITTER: Matho A

PROVIDER: S-EPMC5940197 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

High-dose versus standard-dose amoxicillin/clavulanate for clinically-diagnosed acute bacterial sinusitis: A randomized clinical trial.

Matho Andrea A Mulqueen Mary M Tanino Miyuki M Quidort Aaron A Cheung Jesse J Pollard Jennifer J Rodriguez Julieta J Swamy Supraja S Tayler Brittany B Garrison Gina G Ata Ashar A Sorum Paul P

PloS one 20180508 5

<h4>Background</h4>The recommended treatment for acute bacterial sinusitis in adults, amoxicillin with clavulanate, provides only modest benefit.<h4>Objective</h4>To see if a higher dose of amoxicillin will lead to more rapid improvement.<h4>Design, setting, and participants</h4>Double-blind randomized trial in which, from November 2014 through February 2017, we enrolled 315 adult outpatients diagnosed with acute sinusitis in accordance with Infectious Disease Society of America guidelines.<h4>I ...[more]

PMID: 29738561

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Project description:ImportanceAcute bacterial sinusitis is common, but currently recommended antibiotic treatment provides minimal benefit.ObjectiveTo confirm the previous finding that high-dose amoxicillin plus clavulanate (with double the amount of amoxicillin) may be superior to standard-dose amoxicillin plus clavulanate in adults.Design, setting, and participantsThis double-blind, comparative-effectiveness randomized clinical trial was conducted from February 26, 2018, through May 10, 2020, at the academic primary care internal medicine and pediatrics practice of Albany Medical Center, located in Cohoes, New York. Participants included adults aged 18 years or older who were prescribed amoxicillin plus clavulanate for acute bacterial sinusitis diagnosed in accordance with the Infectious Diseases Society of America guidelines.InterventionsAmoxicillin 875 mg with clavulanate 125 mg plus either placebo (standard dose) or amoxicillin 875 mg (high dose) twice a day for 7 days.Main outcomes and measuresThe primary efficacy outcome was a global rating of "a lot better" or "no symptoms" at the end of 3 days of treatment using a Global Rating of Improvement scale, with outcomes ranging from 1 (a lot worse) to 6 (no symptoms). The primary adverse effect outcome was severe diarrhea at 3 or 10 days after the start of treatment.ResultsAt an unplanned interim analysis prompted by COVID-19 restrictions, 157 of a projected 240 participants had been enrolled (mean age, 48.5 [range, 18.7-84.0] years; 117 women [74.5%]), with 79 randomized to the standard dose and 78 to the high dose; 9 and 12, respectively, withdrew or were lost to follow-up before the assessment of the primary outcome. At day 3, 31 of 70 participants (44.3%) in the standard-dose group reported a global rating of "a lot better" or "no symptoms," as did 24 of 66 (36.4%) in the high-dose group, for a difference of -7.9% (95% CI, -24.4% to 8.5%; P = .35). The study was, therefore, stopped for futility. Diarrhea was common in both groups by day 3, with any diarrhea reported in 29 of 71 participants (40.8%) receiving the standard dose and 28 of 65 (43.1%) receiving the high dose and severe diarrhea reported in 5 of 71 (7.0%) and 5 of 65 (7.7%), respectively.Conclusions and relevanceThe results of this randomized clinical trial suggest that adults treated for clinically diagnosed acute sinusitis did not appear to benefit from taking high-dose compared with standard-dose amoxicillin plus clavulanate.Trial registrationClinicalTrials.gov Identifier: NCT03431337.

Project description:ObjectiveTo compare the effectiveness of amoxicillin-clavulanate versus amoxicillin for adults diagnosed with acute sinusitis (AS). A secondary objective compared antibiotic effectiveness in patients meeting risk criteria for treatment failure.MethodsA retrospective cohort study of adults diagnosed with AS prescribed amoxicillin ± clavulanate within Veterans Affairs emergency departments from 2012-2019 was conducted. The primary outcome was sinusitis-related return visits for amoxicillin versus amoxicillin-clavulanate. Secondary outcomes included 30-day infectious complications, gastrointestinal-related adverse events (AEs), and hospitalizations. Propensity-score matching and logistic regression models adjusted for potential confounders.ResultsA total of 89,627 AS patient visits were identified: 18,576 prescribed amoxicillin and 71,051 amoxicillin-clavulanate. Most patients were male (75,604; 84.4%) and afebrile (80,624; 91.7%). The propensity score-matched cohort comprised 17,929 amoxicillin and 42,294 amoxicillin-clavulanate patient visits. There was no difference in sinusitis-related return visits between amoxicillin (4.9%) and amoxicillin-clavulanate (5.1%) (adjusted odds ratio [OR], 0.96; 95% confidence interval [CI], 0.88, 1.04; P = 0.317). Infectious complications (amoxicillin [0.3%] vs amoxicillin-clavulanate [0.4%]); (adjusted OR, 0.78; 95% CI, 0.57, 1.07; P = 0.124) and hospitalization (amoxicillin [2.0%] vs amoxicillin-clavulanate [2.4%]); (adjusted OR, 0.92; 95% CI, 0.81, 1.04; P = 0.173) were not different. Gastrointestinal-related AEs were lower with amoxicillin (0.5%) relative to amoxicillin-clavulanate (0.7%); (adjusted OR, 0.67; 95% CI, 0.53, 0.86; P = 0.002). Comorbidity was the only guideline-recommended risk factor that was a significant predictor of infectious complications with respect to treatment (amoxicillin vs amoxicillin-clavulanate, OR, 0.63; 95% CI, 0.40 to 0.94; P = 0.022).ConclusionAmoxicillin demonstrated similar efficacy to amoxicillin-clavulanate for AS with fewer gastrointestinal-related AEs. Amoxicillin is a viable option in adults with AS meeting criteria for antibiotic therapy.

Project description:ImportanceAcute sinusitis is one of the most common indications for antibiotic prescribing in children, with an estimated 4.9 million such prescriptions in the US annually. Consensus does not exist regarding the optimal empirical antibiotic.ObjectiveTo compare amoxicillin-clavulanate vs amoxicillin for the treatment of acute sinusitis in outpatient children.Design, setting, and participantsCohort study of children and adolescents aged 17 years or younger with a new outpatient diagnosis of acute sinusitis and a same-day new prescription dispensation of amoxicillin-clavulanate or amoxicillin in a nationwide health care utilization database. Propensity score matching was used to mitigate confounding.ExposureA new prescription dispensation of amoxicillin-clavulanate or amoxicillin.Main outcomes and measuresTreatment failure, defined as an aggregate of a new antibiotic dispensation, emergency department or inpatient encounter for acute sinusitis, or inpatient encounter for a sinusitis complication, was assessed 1 to 14 days after cohort enrollment. Adverse events were evaluated, including gastrointestinal symptoms, hypersensitivity and skin reactions, acute kidney injury, and secondary infections.ResultsThe cohort included 320 141 patients. After propensity score matching, there were 198 942 patients (99 471 patients per group), including 100 340 (50.4%) who were female, 101 726 (51.1%) adolescents aged 12 to 17 years, 52 149 (26.2%) children aged 6 to 11 years, and 45 067 (22.7%) children aged 0 to 5 years. Treatment failure occurred in 1.7% overall; 0.01% had serious failure (an emergency department or inpatient encounter). There was no difference in the risk of treatment failure between the amoxicillin-clavulanate and amoxicillin groups (relative risk [RR], 0.98 [95% CI, 0.92-1.05]). The risk of gastrointestinal symptoms (RR, 1.15 [95% CI, 1.05-1.25]) and yeast infections (RR, 1.33 [95% CI, 1.16-1.54]) was higher with amoxicillin-clavulanate. After patients were stratified by age, the risk of treatment failure after amoxicillin-clavulanate was an RR of 0.98 (95% CI, 0.86-1.12) for ages 0 to 5 years; RR was 1.06 (95% CI, 0.92-1.21) for 6 to 11 years; and RR was 0.87 (95% CI, 0.79-0.95) for 12 to 17 years. The age-stratified risk of adverse events after amoxicillin-clavulanate was an RR of 1.23 (95% CI, 1.10-1.37) for ages 0 to 5 years; RR was 1.19 (95% CI, 1.04-1.35) for 6 to 11 years; and RR was 1.04 (95% CI, 0.95-1.14) for 12 to 17 years.Conclusions and relevanceIn children with acute sinusitis who were treated as outpatients, there was no difference in the risk of treatment failure between those who received amoxicillin-clavulanate compared with amoxicillin, but amoxicillin-clavulanate was associated with a higher risk of gastrointestinal symptoms and yeast infections. These findings may help inform decisions for empirical antibiotic selection in acute sinusitis.

Dataset Information

High-dose versus standard-dose amoxicillin/clavulanate for clinically-diagnosed acute bacterial sinusitis: A randomized clinical trial.

Background

Objective

Design, setting, and participants

Interventions

Main measure

Key results

Conclusions

Trial registration

Publications

High-dose versus standard-dose amoxicillin/clavulanate for clinically-diagnosed acute bacterial sinusitis: A randomized clinical trial.

Similar Datasets

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