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Comparative Study
. 2021 Jun;174(6):737-746.
doi: 10.7326/M20-6315. Epub 2021 Feb 23.

Comparative Effectiveness and Harms of Antibiotics for Outpatient Diverticulitis : Two Nationwide Cohort Studies

Charles E Gaber  1 , Alan C Kinlaw  2 , Jessie K Edwards  3 , Jennifer L Lund  3 , Til Stürmer  4 , Sharon Peacock Hinton  3 , Virginia Pate  3 , Luther A Bartelt  5 , Robert S Sandler  5 , Anne F Peery  5
Affiliations
Comparative Study

Comparative Effectiveness and Harms of Antibiotics for Outpatient Diverticulitis : Two Nationwide Cohort Studies

Charles E Gaber et al. Ann Intern Med. 2021 Jun.

Abstract

Background: Outpatient diverticulitis is commonly treated with either a combination of metronidazole and a fluoroquinolone (metronidazole-with-fluoroquinolone) or amoxicillin-clavulanate alone. The U.S. Food and Drug Administration advised that fluoroquinolones be reserved for conditions with no alternative treatment options. The comparative effectiveness of metronidazole-with-fluoroquinolone versus amoxicillin-clavulanate for diverticulitis is uncertain.

Objective: To determine the effectiveness and harms of metronidazole-with-fluoroquinolone versus amoxicillin-clavulanate for outpatient diverticulitis.

Design: Active-comparator, new-user, retrospective cohort studies.

Setting: Nationwide population-based claims data on U.S. residents aged 18 to 64 years with private employer-sponsored insurance (2000 to 2018) or those aged 65 years or older with Medicare (2006 to 2015).

Participants: Immunocompetent adults with diverticulitis in the outpatient setting.

Intervention: Metronidazole-with-fluoroquinolone or amoxicillin-clavulanate.

Measurements: 1-year risks for inpatient admission, urgent surgery, and Clostridioides difficile infection (CDI) and 3-year risk for elective surgery.

Results: In MarketScan (IBM Watson Health), new users of metronidazole-with-fluoroquinolone (n = 106 361) and amoxicillin-clavulanate (n = 13 160) were identified. There were no differences in 1-year admission risk (risk difference, 0.1 percentage points [95% CI, -0.3 to 0.6]), 1-year urgent surgery risk (risk difference, 0.0 percentage points [CI, -0.1 to 0.1]), 3-year elective surgery risk (risk difference, 0.2 percentage points [CI, -0.3 to 0.7]), or 1-year CDI risk (risk difference, 0.0 percentage points [CI, -0.1 to 0.1]) between groups. In Medicare, new users of metronidazole-with-fluoroquinolone (n = 17 639) and amoxicillin-clavulanate (n = 2709) were identified. There were no differences in 1-year admission risk (risk difference, 0.1 percentage points [CI, -0.7 to 0.9]), 1-year urgent surgery risk (risk difference, -0.2 percentage points [CI, -0.6 to 0.1]), or 3-year elective surgery risk (risk difference, -0.3 percentage points [CI, -1.1 to 0.4]) between groups. The 1-year CDI risk was higher for metronidazole-with-fluoroquinolone than for amoxicillin-clavulanate (risk difference, 0.6 percentage points [CI, 0.2 to 1.0]).

Limitation: Residual confounding is possible, and not all harms associated with these antibiotics, most notably drug-induced liver injury, could be assessed.

Conclusion: Treating diverticulitis in the outpatient setting with amoxicillin-clavulanate may reduce the risk for fluoroquinolone-related harms without adversely affecting diverticulitis-specific outcomes.

Primary funding source: National Institutes of Health.

PubMed Disclaimer

Conflict of interest statement

Conflict of Interest Disclosures: None

Figures

FIGURE 1.
FIGURE 1.
Risk of inpatient admission for diverticulitis, elective colectomy, urgent colectomy, and Clostridium Difficile infection in privately insured adults diagnosed with incident outpatient diverticulitis and treated with metronidazole-with-fluoroquinolone compared to amoxicillin-clavulanate, 2001-2018. A. Inpatient admission for diverticulitis, B. Elective colectomy, C. Urgent colectomy, D. Clostridium difficile infection Abbreviations: CI, confidence interval; MTZ, metronidazole; FQ, fluoroquinolone; Amox-clav, amoxicillin-clavulanate Risk ratios and risk differences were calculated at the end of follow-up. 95% CI calculated via nonparametric bootstrap of 1000 resamples.
FIGURE 1.
FIGURE 1.
Risk of inpatient admission for diverticulitis, elective colectomy, urgent colectomy, and Clostridium Difficile infection in privately insured adults diagnosed with incident outpatient diverticulitis and treated with metronidazole-with-fluoroquinolone compared to amoxicillin-clavulanate, 2001-2018. A. Inpatient admission for diverticulitis, B. Elective colectomy, C. Urgent colectomy, D. Clostridium difficile infection Abbreviations: CI, confidence interval; MTZ, metronidazole; FQ, fluoroquinolone; Amox-clav, amoxicillin-clavulanate Risk ratios and risk differences were calculated at the end of follow-up. 95% CI calculated via nonparametric bootstrap of 1000 resamples.
FIGURE 1.
FIGURE 1.
Risk of inpatient admission for diverticulitis, elective colectomy, urgent colectomy, and Clostridium Difficile infection in privately insured adults diagnosed with incident outpatient diverticulitis and treated with metronidazole-with-fluoroquinolone compared to amoxicillin-clavulanate, 2001-2018. A. Inpatient admission for diverticulitis, B. Elective colectomy, C. Urgent colectomy, D. Clostridium difficile infection Abbreviations: CI, confidence interval; MTZ, metronidazole; FQ, fluoroquinolone; Amox-clav, amoxicillin-clavulanate Risk ratios and risk differences were calculated at the end of follow-up. 95% CI calculated via nonparametric bootstrap of 1000 resamples.
FIGURE 1.
FIGURE 1.
Risk of inpatient admission for diverticulitis, elective colectomy, urgent colectomy, and Clostridium Difficile infection in privately insured adults diagnosed with incident outpatient diverticulitis and treated with metronidazole-with-fluoroquinolone compared to amoxicillin-clavulanate, 2001-2018. A. Inpatient admission for diverticulitis, B. Elective colectomy, C. Urgent colectomy, D. Clostridium difficile infection Abbreviations: CI, confidence interval; MTZ, metronidazole; FQ, fluoroquinolone; Amox-clav, amoxicillin-clavulanate Risk ratios and risk differences were calculated at the end of follow-up. 95% CI calculated via nonparametric bootstrap of 1000 resamples.
FIGURE 2.
FIGURE 2.
Risk of inpatient admission for diverticulitis, elective colectomy, urgent colectomy, and Clostridium Difficile infection in Medicare-insured adults diagnosed with incident outpatient diverticulitis and treated with metronidazole-with-fluoroquinolone compared to amoxicillin-clavulanate, 2007-2015. A. Inpatient admission for diverticulitis, B. Elective colectomy, C. Urgent colectomy ,D. Clostridium difficile infection Abbreviations: CI, confidence interval; MTZ, metronidazole; FQ, fluoroquinolone; Amox-clav, amoxicillin-clavulanate Risk ratios and risk differences were calculated at the end of follow-up. 95% CI calculated via nonparametric bootstrap of 1000 resamples.
FIGURE 2.
FIGURE 2.
Risk of inpatient admission for diverticulitis, elective colectomy, urgent colectomy, and Clostridium Difficile infection in Medicare-insured adults diagnosed with incident outpatient diverticulitis and treated with metronidazole-with-fluoroquinolone compared to amoxicillin-clavulanate, 2007-2015. A. Inpatient admission for diverticulitis, B. Elective colectomy, C. Urgent colectomy ,D. Clostridium difficile infection Abbreviations: CI, confidence interval; MTZ, metronidazole; FQ, fluoroquinolone; Amox-clav, amoxicillin-clavulanate Risk ratios and risk differences were calculated at the end of follow-up. 95% CI calculated via nonparametric bootstrap of 1000 resamples.
FIGURE 2.
FIGURE 2.
Risk of inpatient admission for diverticulitis, elective colectomy, urgent colectomy, and Clostridium Difficile infection in Medicare-insured adults diagnosed with incident outpatient diverticulitis and treated with metronidazole-with-fluoroquinolone compared to amoxicillin-clavulanate, 2007-2015. A. Inpatient admission for diverticulitis, B. Elective colectomy, C. Urgent colectomy ,D. Clostridium difficile infection Abbreviations: CI, confidence interval; MTZ, metronidazole; FQ, fluoroquinolone; Amox-clav, amoxicillin-clavulanate Risk ratios and risk differences were calculated at the end of follow-up. 95% CI calculated via nonparametric bootstrap of 1000 resamples.
FIGURE 2.
FIGURE 2.
Risk of inpatient admission for diverticulitis, elective colectomy, urgent colectomy, and Clostridium Difficile infection in Medicare-insured adults diagnosed with incident outpatient diverticulitis and treated with metronidazole-with-fluoroquinolone compared to amoxicillin-clavulanate, 2007-2015. A. Inpatient admission for diverticulitis, B. Elective colectomy, C. Urgent colectomy ,D. Clostridium difficile infection Abbreviations: CI, confidence interval; MTZ, metronidazole; FQ, fluoroquinolone; Amox-clav, amoxicillin-clavulanate Risk ratios and risk differences were calculated at the end of follow-up. 95% CI calculated via nonparametric bootstrap of 1000 resamples.
FIGURE 3.
FIGURE 3.
Cumulative burden of recurrent healthcare visits for diverticulitis in privately insured (2001-2018) and Medicare-insured (2007-2015) adults diagnosed with incident outpatient diverticulitis and treated with antibiotics. A. Emergency department visits, MarketScan, B. Emergency department visits, Medicare, C. Outpatient visits, MarketScan, D. Outpatient visits, Medicare, E. Inpatient visits, MarketScan, F. Inpatient visits, Medicare Abbreviations: CI, confidence interval Burden ratios and burden differences were calculated at the end of follow-up. 95% CI calculated via nonparametric bootstrap of 1000 resamples.
FIGURE 3.
FIGURE 3.
Cumulative burden of recurrent healthcare visits for diverticulitis in privately insured (2001-2018) and Medicare-insured (2007-2015) adults diagnosed with incident outpatient diverticulitis and treated with antibiotics. A. Emergency department visits, MarketScan, B. Emergency department visits, Medicare, C. Outpatient visits, MarketScan, D. Outpatient visits, Medicare, E. Inpatient visits, MarketScan, F. Inpatient visits, Medicare Abbreviations: CI, confidence interval Burden ratios and burden differences were calculated at the end of follow-up. 95% CI calculated via nonparametric bootstrap of 1000 resamples.
FIGURE 3.
FIGURE 3.
Cumulative burden of recurrent healthcare visits for diverticulitis in privately insured (2001-2018) and Medicare-insured (2007-2015) adults diagnosed with incident outpatient diverticulitis and treated with antibiotics. A. Emergency department visits, MarketScan, B. Emergency department visits, Medicare, C. Outpatient visits, MarketScan, D. Outpatient visits, Medicare, E. Inpatient visits, MarketScan, F. Inpatient visits, Medicare Abbreviations: CI, confidence interval Burden ratios and burden differences were calculated at the end of follow-up. 95% CI calculated via nonparametric bootstrap of 1000 resamples.
FIGURE 3.
FIGURE 3.
Cumulative burden of recurrent healthcare visits for diverticulitis in privately insured (2001-2018) and Medicare-insured (2007-2015) adults diagnosed with incident outpatient diverticulitis and treated with antibiotics. A. Emergency department visits, MarketScan, B. Emergency department visits, Medicare, C. Outpatient visits, MarketScan, D. Outpatient visits, Medicare, E. Inpatient visits, MarketScan, F. Inpatient visits, Medicare Abbreviations: CI, confidence interval Burden ratios and burden differences were calculated at the end of follow-up. 95% CI calculated via nonparametric bootstrap of 1000 resamples.
FIGURE 3.
FIGURE 3.
Cumulative burden of recurrent healthcare visits for diverticulitis in privately insured (2001-2018) and Medicare-insured (2007-2015) adults diagnosed with incident outpatient diverticulitis and treated with antibiotics. A. Emergency department visits, MarketScan, B. Emergency department visits, Medicare, C. Outpatient visits, MarketScan, D. Outpatient visits, Medicare, E. Inpatient visits, MarketScan, F. Inpatient visits, Medicare Abbreviations: CI, confidence interval Burden ratios and burden differences were calculated at the end of follow-up. 95% CI calculated via nonparametric bootstrap of 1000 resamples.
FIGURE 3.
FIGURE 3.
Cumulative burden of recurrent healthcare visits for diverticulitis in privately insured (2001-2018) and Medicare-insured (2007-2015) adults diagnosed with incident outpatient diverticulitis and treated with antibiotics. A. Emergency department visits, MarketScan, B. Emergency department visits, Medicare, C. Outpatient visits, MarketScan, D. Outpatient visits, Medicare, E. Inpatient visits, MarketScan, F. Inpatient visits, Medicare Abbreviations: CI, confidence interval Burden ratios and burden differences were calculated at the end of follow-up. 95% CI calculated via nonparametric bootstrap of 1000 resamples.
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