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

Abstract

BackgroundThe recommended treatment for acute bacterial sinusitis in adults, amoxicillin with clavulanate, provides only modest benefit.ObjectiveTo see if a higher dose of amoxicillin will lead to more rapid improvement.Design, setting, and participantsDouble-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.InterventionsStandard-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 measureThe 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 resultsMajor 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).ConclusionsAdults 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 registrationClinicalTrials.gov Identifier: NCT02340000.

High-Dose vs Standard-Dose Amoxicillin Plus Clavulanate for Adults With Acute Sinusitis

“…power to detect an increase of 18 percentage points in the GRI among those in the high-dose group (ie, an increase to 52%, as reported previously 5 ) with an α of .05 for a 2-sided test. We aimed, therefore, to enroll 240 patients (anticipating 10 dropouts before day 3).…”

“…A double-blind, placebo-controlled trial was performed from 2014 to 2017 comparing high-dose and standard-dose amoxicillin with clavulanate for adults with clinically diagnosed acute bacterial sinusitis. 5 That study confirmed that very few individuals carried resistant bacteria. The primary outcome was the participants’ subjective rating of improvement after 3 days of treatment, knowing that most people get better by 2 weeks but value rapid relief and that the benefit of other common treatments—eg, for streptococcal pharyngitis 6 and influenza 7 —is largely a quicker improvement.…”

“…The previous study 5 found that 34% of the participants in the standard-dose group reported a GRI of 5 or 6 at the end of 3 days. We estimated that a sample size of 115 in each group would give us 80%…”

“…2 This outcome is also surprising in light of the promising results of the previous trial. 5 Why would we get such very different results? First, the current trial suffered from an incomplete collection of data (although mostly for the secondary outcomes).…”

Amoxicillin induced erythematous maculopapular rashes: a case report

“…1 Amoxicillin is used as an effective and safe therapy for sinusitis, otitis media, acute exacerbations of chronic bronchitis, epiglottitis, urinary tract infections, meningitis, and salmonella infections. [2][3][4] In India, a previous study reported that 1.78% of adverse reactions reported due to amoxicillin + clavulanate of 4.99% of total ADRs among pediatric patients, the ADRs include hypersensitivity reactions: angioedema, anaphylaxis, mild fever, rash, purpura, lymphadenopathy, generalized oedema, albuminuria, and hematuria. 5 Cutaneous adverse reactions like skin rashes, urticaria, itching, fixed drug eruption, angioedema are the common among the various adverse drug reactions (ADR).…”