Jennifer Gregory1,2, Bichtram Huynh1, Brittany Tayler1, Chaitali Korgaonkar-Cherala3,4, Gina Garrison5, Ashar Ata6,7, Paul Sorum8,9. 1. Medicine and Pediatrics, Albany Medical Center Hospital, Cohoes, New York. 2. Englewood Health Medical Center, Englewood, New Jersey. 3. Albany Medical College, Albany, New York. 4. Department of Obstetrics-Gynecology, Stony Brook University Hospital, Stony Brook, New York. 5. Department of Pharmacy Practice, Albany College of Pharmacy and Health Sciences, Albany, New York. 6. Department of Surgery, Albany Medical College, Albany, New York. 7. Department of Emergency Medicine, Albany Medical College, Albany, New York. 8. Department of Internal Medicine, Albany Medical College, Albany, New York. 9. Department of Pediatrics, Albany Medical College, Albany, New York.
Abstract
Importance: Acute bacterial sinusitis is common, but currently recommended antibiotic treatment provides minimal benefit. Objective: To 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 Participants: This 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 prescribedamoxicillin plus clavulanatefor acute bacterial sinusitis diagnosed in accordance with the Infectious Diseases Society of America guidelines. Interventions: Amoxicillin 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 Measures: The 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. Results: At 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 Relevance: The 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 Registration: ClinicalTrials.gov Identifier: NCT03431337.
RCT Entities:
Importance: Acute bacterial sinusitis is common, but currently recommended antibiotic treatment provides minimal benefit. Objective: To 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 Participants: This 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. Interventions: Amoxicillin 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 Measures: The 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. Results: At 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 Relevance: The 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 Registration: ClinicalTrials.gov Identifier: NCT03431337.
Authors: Anthony W Chow; Michael S Benninger; Itzhak Brook; Jan L Brozek; Ellie J C Goldstein; Lauri A Hicks; George A Pankey; Mitchel Seleznick; Gregory Volturo; Ellen R Wald; Thomas M File Journal: Clin Infect Dis Date: 2012-03-20 Impact factor: 9.079
Authors: Drosos E Karageorgopoulos; Konstantina P Giannopoulou; Alexandros P Grammatikos; George Dimopoulos; Matthew E Falagas Journal: CMAJ Date: 2008-03-25 Impact factor: 8.262