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

ABSTRACT: The recommended treatment for acute bacterial sinusitis in adults, amoxicillin with clavulanate, provides only modest benefit.To see if a higher dose of amoxicillin will lead to more rapid improvement.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.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).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.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).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.ClinicalTrials.gov Identifier: NCT02340000.

SUBMITTER: Matho A

PROVIDER: S-EPMC5940197 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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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:BackgroundBuruli ulcer (BU) is a skin neglected tropical disease (NTD) caused by Mycobacterium ulcerans. WHO-recommended treatment requires 8-weeks of daily rifampicin (RIF) and clarithromycin (CLA) with wound care. Treatment compliance may be challenging due to socioeconomic determinants. Previous minimum Inhibitory Concentration and checkerboard assays showed that amoxicillin/clavulanate (AMX/CLV) combined with RIF+CLA were synergistic against M. ulcerans. However, in vitro time kill assays (TKA) are a better approach to understand the antimicrobial activity of a drug over time. Colony forming units (CFU) enumeration is the in vitro reference method to measure bacterial load, although this is a time-consuming method due to the slow growth of M. ulcerans. The aim of this study was to assess the in vitro activity of RIF, CLA and AMX/CLV combinations against M. ulcerans clinical isolates by TKA, while comparing four methodologies: CFU enumeration, luminescence by relative light unit (RLU) and optical density (at 600 nm) measurements, and 16S rRNA/IS2404 genes quantification.Methodology/principal findingsTKA of RIF, CLA and AMX/CLV alone and in combination were performed against different M. ulcerans clinical isolates. Bacterial loads were quantified with different methodologies after 1, 3, 7, 10, 14, 21 and 28 days of treatment. RIF+AMX/CLV and the triple RIF+CLA+AMX/CLV combinations were bactericidal and more effective in vitro than the currently used RIF+CLA combination to treat BU. All methodologies except IS2404 quantitative PCR provided similar results with a good correlation with CFU enumeration. Measuring luminescence (RLU) was the most cost-effective methodology to quantify M. ulcerans bacterial loads in in vitro TKA.Conclusions/significanceOur study suggests that alternative and faster TKA methodologies can be used in BU research instead of the cumbersome CFU quantification method. These results provide an in vitro microbiological support to of the BLMs4BU clinical trial (NCT05169554, PACTR202209521256638) to shorten BU treatment.

Dataset Information

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

Publications

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

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