Level 1a Evidence Comparing Use of Antibiotics Versus No Antibiotics in Management of Acute Left-Sided Uncomplicated Diverticulitis.

BACKGROUND: Acute uncomplicated diverticulitis (AUD) is a common cause of acute abdominal pain. Recent guidelines advise selective use of antibiotics in AUD patients. This meta-analysis aimed to compare the effectiveness of no antibiotics vs antibiotics in AUD patients. METHODS: This review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses to identify randomized controlled trials (RCTs) involving AUD patients which compared the use of antibiotics with no antibiotics. Pooled outcome data was calculated using random effects modeling with 95% confidence intervals (CIs). RESULTS: 5 RCTs with 1934 AUD patients were included. 979 patients were managed without antibiotics (50.6%). Patients in the no antibiotic and antibiotic groups had comparable demographics (age, sex, and body mass index) and presenting features (temperature, pain score, and C-reactive protein levels). There was no significant difference in rates of complicated diverticulitis (OR: .61, 95% CI: 0.27-1.36, P = .23), abscess (OR: .51, 95% CI: .08-3.25, P = .47) or fistula (OR: .33, 95% CI: .03-3.15, P = .33) formation, perforation (OR: .98, 95% CI: .32-3.07, P = .98), recurrence (OR: .96, 95% CI: .66-1.41, P = .85), need for surgery (OR: 1.36, 95% CI: .47-3.95, P = .37), mortality (OR: 1.27, 95% CI: .14-11.76, P = .82), or length of stay (MD: .215, 95% CI: -.43-.73, P = .61) between the 2 groups. However, the likelihood of readmission was higher in the antibiotics group (OR: 2.13, 95% CI: 1.43-3.18, P = .0002). CONCLUSION: There is no significant difference in baseline characteristics, clinical presentation, and adverse health outcomes between AUD patients treated without antibiotics compared to with antibiotics.

Effectiveness of Antibiotics for Uncomplicated Diverticulitis: A Retrospective Investigation Using a Nationwide Database in Japan.

INTRODUCTION: The efficacy of antibiotics for diverticulitis without abscess or peritonitis (uncomplicated diverticulitis) is controversial. We aimed to investigate the effectiveness of antibiotics for uncomplicated diverticulitis. METHODS: We collected admission data for patients with acute uncomplicated diverticulitis using a nationwide database. We divided eligible admissions into two groups according to antibiotic initiation within 2 days after admission (antibiotic group vs. nonantibiotic group). We conducted propensity score matching and compared the rates of surgery (intestinal resection and stoma creation), in-hospital death, and medical costs between the groups. We also performed multivariate analysis to identify the clinical factors that affect surgery. RESULTS: We enrolled 131,936 admissions; among these, we obtained 6,061 pairs after propensity score matching. Rates of both intestinal resection and stoma creation in the antibiotic group were lower than those in the nonantibiotic group (0.61 vs. 3.09%, p < 0.0001, and 0.08 vs. 0.26%, p = 0.027, respectively). Median costs in the antibiotic group were higher than those in the nonantibiotic group (315,820 JPY vs. 300,175 JPY, p < 0.0001, respectively). Multivariate analysis showed that non-initiation of antibiotics within 2 days after admission was a clinical factor that increased the risk of intestinal resection (odds ratio [OR] = 5.19, 95% confidence interval [CI]: 4.38-6.16, p < 0.0001) and stoma creation (OR = 2.68, 95% CI: 1.53-4.70, p = 0.0006). CONCLUSION: Our results indicated that antibiotics for uncomplicated diverticulitis expected to have moderate to severe disease activity may reduce the risk of intestinal resection and stoma creation. Further investigations are warranted.

Treatment for acute uncomplicated diverticulitis without antibiotherapy: systematic review and meta-analysis of randomized clinical trials.

BACKGROUND: Use of antibiotics in selected cases of acute uncomplicated diverticulitis (AUD) has recently been questioned. OBJECTIVE: The aim of this study is to examine the safety and efficacy of treatment regimens without antibiotics compared with that of traditional treatments with antibiotics in selected patients with AUD. DATA SOURCES: PubMed, Medline, Embase, Web of Science, and the Cochrane Library. METHODS: A systematic review was performed according to PRISMA and AMSTAR guidelines by searching through Medline, Embase, Web of Science, and the Cochrane Library for randomized clinical trials (RCTs) published before December 2022. The outcomes assessed were the rates of readmission, change in strategy, emergency surgery, worsening, and persistent diverticulitis. STUDY SELECTION: RCTs on treating AUD without antibiotics published in English before December 2022 were included. INTERVENTION: Treatments without antibiotics were compared with treatments with antibiotics. MAIN OUTCOME MEASURES: The outcomes assessed were the rates of readmission, change in strategy, emergency surgery, worsening, and persistent diverticulitis. RESULTS: The search yielded 1163 studies. Four RCTs with 1809 patients were included in the review. Among these patients, 50.1% were treated conservatively without antibiotics. The meta-analysis showed no significant differences between nonantibiotic and antibiotic treatment groups with respect to rates of readmission [odds ratio (OR)=1.39; 95% CI: 0.93-2.06; P =0.11; I2 =0%], change in strategy (OR=1.03; 95% CI: 0.52-2,02; P =0.94; I2 =44%), emergency surgery (OR=0.43; 95% CI: 0.12-1.53; P =0.19; I2 =0%), worsening (OR=0.91; 95% CI: 0.48-1.73; P =0.78; I2 =0%), and persistent diverticulitis (OR=1.54; 95% CI: 0.63-3.26; P =0.26; I2 =0%). LIMITATIONS: Heterogeneity and a limited number of RCTs. CONCLUSIONS: Treatment for AUD without antibiotic therapy is safe and effective in selected patients. Further RTCs should confirm the present findings.

Infection or Inflammation: Are Uncomplicated Acute Appendicitis, Acute Cholecystitis, and Acute Diverticulitis Infectious Diseases?

Background: It is recognized increasingly that common surgical infections of the peritoneal cavity may be treated with antibiotic agents alone, or source control surgery with short-course antimicrobial therapy. By extension, testable hypotheses have emerged that such infections may not actually be infectious diseases, but rather represent inflammation that can be treated successfully with neither surgery nor antibiotic agents. The aim of this review is to examine extant data to determine which of uncomplicated acute appendicitis (uAA), uncomplicated acute calculous cholecystitis (uACC), or uncomplicated mild acute diverticulitis (umAD) might be amenable to management using supportive therapy alone, consistent with the principles of antimicrobial stewardship. Methods: Review of pertinent English-language literature and expert opinion. Results: Only two small trials have examined whether uAA can be managed with observation and supportive therapy alone, one of which is underpowered and was stopped prematurely because of challenging patient recruitment. Data are insufficient to determine the safety and efficacy of non-antibiotic therapy of uAA. Uncomplicated acute calculous cholecystitis is not primarily an infectious disease; infection is a secondary phenomenon. Even when bactibilia is present, there is no high-quality evidence to suggest that mild disease should be treated with antibiotic agents. There is evidence to indicate that antibiotic prophylaxis is indicated for urgent/emergency cholecystectomy for uACC, but not in the post-operative period. Uncomplicated mild acute diverticulitis, generally Hinchey 1a or 1b in current nomenclature, does not benefit from antimicrobial agents based on multiple clinical studies. The implication is that umAD is inflammatory and not an infectious disease. Non-antimicrobial management is reasonable. Conclusions: Among the considered disease entities, the evidence is strongest that umAD is not an infectious disease and can be treated without antibiotic agents, intermediate regarding uACC, and lacking for uAA. A plausible hypothesis is that these inflammatory conditions are related to disruption of the normal microbiome, resulting in dysbiosis, which is defined as an imbalance of the natural microflora, especially of the gut, that is believed to contribute to a range of conditions of ill health. As for restorative pre- or probiotic therapy to reconstitute the microbiome, no recommendation can be made in terms of treatment, but it is not recommended for prevention of primary or recurrent disease.

Evaluation of a treatment pathway for the management of uncomplicated diverticulitis.

INTRODUCTION: Recent clinical practice recommendations have radically modified the management of colonic diverticulitis. The goal of our study was to evaluate a treatment pathway for uncomplicated diverticulitis and to analyze the outcome (patient compliance, treatment failure and complications). PATIENTS AND METHODS: All patients who presented to the emergency department with the diagnosis of uncomplicated diverticulitis were prospectively included in this study. The treatment pathway included an outpatient clinical re-assessment by a gastrointestinal surgeon. In case of symptomatic treatment failure, oral antibiotics were prescribed. If developed clinical signs of severity developed, the patient was referred to the emergency department for new laboratory and imaging workup. RESULTS: Eighty-seven patients were included. The mean interval before re-assessment was 2.8 days. Fifty-nine patients (67.8%) had symptomatic treatment upon discharge from the emergency department and were reassessed as outpatients by the surgical team. Patient evolution was satisfactory for 45 (76.3%); 10 (16.9%) required oral antibiotics. One (1.7%) patient developed complicated diverticulitis. Thirty-four (39.1%) patients did not comply with the current recommendations. CONCLUSION: In our experience, uncomplicated diverticulitis can be treated effectively in an ambulatory setting followed by early re-assessment by a surgeon.

Impact of bowel preparation on elective colectomies for diverticulitis: analysis of the NSQIP database.

BACKGROUND: Recent data based on large databases show that bowel preparation (BP) is associated with improved outcomes in patients undergoing elective colorectal surgery. However, it remains unclear whether BP in elective colectomies would lead to similar results in patients with diverticulitis. The purpose of this study was to investigate whether bowel preparation affected the surgical site infections (SSI) and anastomotic leakage (AL) in patients with diverticulitis undergoing elective colectomies. STUDY DESIGN: We identified 16,380 diverticulitis patients who underwent elective colectomies from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) colectomy targeted database (2012-2017). Multivariate logistic regression models were employed to investigate the impact of different bowel preparation strategies on postoperative complications, including SSI and AL. RESULTS: In the identified population, a total of 2524 patients (15.4%) received no preparation (NP), 4715 (28.8%) mechanical bowel preparation (MBP) alone, 739 (4.5%) antibiotic bowel preparation (ABP) alone, and 8402 (51.3%) MBP + ABP. Compared to NP, patients who received any type of bowel preparations showed a significantly decreased risk of SSI and AL after adjustment for potential confounders (SSI: MBP [OR = 0.82, 95%CI: 0.70-0.96], ABP [0.69, 95%CI: 0.52-0.92]; AL: MBP [OR = 0.66, 95%CI: 0.51-0.86], ABP [0.56, 95%CI: 0.34-0.93]), where the combination type of MBP + ABP had the strongest effect (SSI:OR = 0.58, 95%CI:0.50-0.67; AL:OR = 0.46, 95%CI:0.36-0.59). The significantly decreased risk of 30-day mortality was observed in the bowel preparation of MBP + ABP only (OR = 0.32, 95%CI: 0.13-0.79). After the further stratification by surgery procedures, patients who received MBP + ABP showed consistently lower risk for both SSI and AL when undergoing open and laparoscopic surgeries (Open: SSI [OR = 0.51, 95%CI: 0.37-0.69], AL [OR = 0.47, 95%CI: 0.25-0.91]; Laparoscopic: SSI [OR = 0.58, 95%CI: 0.47-0.72, AL [OR = 0.49, 95%CI: 0.35-0.68]). CONCLUSIONS: MBP + ABP for diverticulitis patients undergoing elective open or laparoscopic colectomies was associated with decreased risk of SSI, AL, and 30-day mortality. Benefits of MBP + ABP for diverticulitis patients underwent robotic surgeries warrant further investigation.

Antibiotics for uncomplicated diverticulitis.

BACKGROUND: Diverticulitis is a complication of the common condition, diverticulosis. Uncomplicated diverticulitis has traditionally been treated with antibiotics, as diverticulitis has been regarded as an infectious disease. Risk factors for diverticulitis, however, may suggest that the condition is inflammatory rather than infectious which makes the use of antibiotics questionable. OBJECTIVES: The objectives of this systematic review were to determine if antibiotic treatment of uncomplicated acute diverticulitis affects the risk of complications (immediate or late) or the need for emergency surgery. SEARCH METHODS: For this update, a comprehensive systematic literature search was conducted in Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, ClinicalTrials.gov and WHO International Clinical Trial Registry Platform on February 2021. SELECTION CRITERIA: Randomised controlled trials (RCTs), including all types of patients with a radiologically confirmed diagnosis of left-sided uncomplicated acute diverticulitis. Comparator and interventions included antibiotics compared to no antibiotics, placebo, or to any other antibiotic treatment (different regimens, routes of administration, dosage or duration of treatment). Primary outcome measures were complications and emergency surgery. Secondary outcomes were recurrence, late complications, elective colonic resections, length of hospital stay, length to recovery of symptoms, adverse events and mortality. DATA COLLECTION AND ANALYSIS: Two authors performed the searches, identification and assessment of RCTs and data extraction. Disagreements were resolved by discussion or involvement of the third author. Authors of trials were contacted to obtain additional data if needed or for preliminary results of ongoing trials. The Cochrane Collaboration's tool for assessing risk of bias was used to assess the methodological quality of the identified trials. The overall quality of evidence for outcomes was evaluated using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Effect estimates were extracted as risk ratios (RRs) with 95% confidence intervals. Random-effects meta-analyses were performed with the Mantel-Haenzel method. MAIN RESULTS: The authors included five studies. Three studies compared no antibiotics to antibiotics; all three were original RCTs of which two also published long-term follow-up information.  For the outcome of short-term complications there may be little or no difference between antibiotics and no antibiotics (RR 0.89; 95% CI 0.30 to 2.62; 3 studies, 1329 participants; low-certainty evidence). The rate of emergency surgery within 30 days may be lower with no antibiotics compared to antibiotics (RR 0.47; 95% CI 0.13, 1.71; 1329 participants; 3 studies; low-certainty evidence). However, there is considerable imprecision due to wide confidence intervals for this effect estimate causing uncertainty which means that there may also be a benefit with antibiotics. One of the two remaining trials compared single to double compound antibiotic therapy and, due to wide confidence intervals, the estimate was imprecise and indicated an uncertain clinical effect between these two antibiotic regimens (RR 0.70; 95% CI 0.11 to 4.58; 51 participants; 1 study; low-certainty evidence). The last trial compared short to long intravenous administration of antibiotics and did not report any events for our primary outcomes. Both trials included few participants and one had overall high risk of bias. Since the first publication of this systematic review, an increasing amount of evidence supporting the treatment of uncomplicated acute diverticulitis without antibiotics has been published, but the total body of evidence is still limited. AUTHORS' CONCLUSIONS: The evidence on antibiotic treatment for uncomplicated acute diverticulitis suggests that the effect of antibiotics is uncertain for complications, emergency surgery, recurrence, elective colonic resections, and long-term complications. The quality of the evidence is low. Only three RCTs on the need for antibiotics are currently available. More trials are needed to obtain more precise effect estimates.

Efficacy and Safety of a Strategy for Reviewing Intravenous Antibiotics for Hospitalized Japanese Patients with Uncomplicated Diverticulitis: A Single-center Observational Study.

Objective Treatment for uncomplicated diverticulitis (UD) is not well established. We evaluated the strategy of reviewing intravenous antibiotics for hospitalized Japanese patients with UD. Methods Treatment was based on the physician's choice until August 2018; the indications for hospitalization and treatment have been standardized since September 2018. In this study, we monitored the use of intravenous antibiotics administered to patients hospitalized for UD and then reviewed the need for them on hospital day 3. We compared patients' length of antibiotic use, hospital stay, health care cost, and complications via the review strategy from September 2018 to December 2020 and via the previous physicians' choice strategy from January 2016 to August 2018. Results Two hundred and forty-seven patients were admitted to our hospital because of acute colonic diverticulitis from January 2016 to December 2020. After excluding complicated cases, 106 individuals were enrolled during the period of physician's choice; 87 were enrolled when treatment review was employed. There were no significant differences in age, sex, inflammation site, or severity during the first hospital visit. The median duration of antibiotic use was significantly reduced from 5 to 4 days (p=0.0075), with no marked increase in rates of transfer to surgery, mortality, or readmission due to recurrence. A more significant proportion of patients completed 3-day antibiotic treatment with the review strategy than with the physician's choice strategy (6.6% vs. 25.3%, p=0.0004). However, the length of hospital stay and total medical costs did not decrease. Conclusion The strategy of reviewing treatment on day 3 after hospitalization for UD safety reduced the duration of antibiotic use, but the hospital stay and health care costs did not decrease.

Diagnostic Imaging and Medical Management of Acute Left-Sided Colonic Diverticulitis : A Systematic Review.

BACKGROUND: Clinicians need to better understand the value of computed tomography (CT) imaging and nonsurgical treatment options to manage acute left-sided colonic diverticulitis. PURPOSE: To evaluate CT imaging, outpatient treatment of uncomplicated diverticulitis, antibiotic treatment, and interventional radiology for patients with complicated diverticulitis. DATA SOURCES: MEDLINE, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Embase, CINAHL, and ClinicalTrials.gov from 1 January 1990 through 16 November 2020. STUDY SELECTION: Existing systematic reviews of CT imaging accuracy, as well as randomized trials and adjusted nonrandomized comparative studies reporting clinical or patient-centered outcomes. DATA EXTRACTION: 6 researchers extracted study data and risk of bias, which were verified by an independent researcher. The team assessed strength of evidence across studies. DATA SYNTHESIS: Based on moderate-strength evidence, CT imaging is highly accurate for diagnosing acute diverticulitis. For patients with uncomplicated acute diverticulitis, 6 studies provide low-strength evidence that initial outpatient and inpatient management have similar risks for recurrence or elective surgery, but they provide insufficient evidence regarding other outcomes. Also, for patients with uncomplicated acute diverticulitis, 5 studies comparing antibiotics versus no antibiotics provide low-strength evidence that does not support differences in risks for treatment failure, elective surgery, recurrence, posttreatment complications, and other outcomes. Evidence is insufficient to determine choice of antibiotic regimen (7 studies) or effect of percutaneous drainage (2 studies). LIMITATIONS: The evidence base is mostly of low strength. Studies did not adequately assess heterogeneity of treatment effect. CONCLUSION: Computed tomography imaging is accurate for diagnosing acute diverticulitis. For patients with uncomplicated diverticulitis, no differences in outcomes were found between outpatient and inpatient care. Avoidance of antibiotics for uncomplicated acute diverticulitis may be safe for most patients. The evidence is too sparse for other evaluated questions. PRIMARY FUNDING SOURCE: Agency for Healthcare Research and Quality and American College of Physicians. (PROSPERO: CRD42020151246).

[Management of simple acute diverticulitis : Towards a "less is more" approach]. / Prise en charge de la diverticulite aiguë simple : vers une approche plus « less is more ¼.

Acute diverticulitis is the most common complication of diverticular disease, increasing in industrialized countries and in young people under 45 years of age. The modified Hinchey classification remains the most widely used and includes simple diverticulitis, i.e. localized inflammation without sepsis, and complicated diverticulitis from pericolic abscess to stercoral peritonitis. Recent studies recommend conservative management of uncomplicated forms. This article summarizes the management of simple acute left-sided diverticulitis based on the new recommendations and focusing on antibiotic treatment, outpatient or inpatient management and indications for colonoscopy.

La diverticulite aiguë est la complication la plus fréquente de la maladie diverticulaire. Son incidence est en augmentation dans les pays industrialisés, notamment chez les jeunes de moins de 45 ans. La classification de Hinchey modifiée reste la plus utilisée et comprend la diverticulite simple, inflammation localisée sans sepsis, et la diverticulite compliquée, de l'abcès péricolique jusqu'à la péritonite stercorale. Les récentes études favorisent une prise en charge de plus en plus conservatrice des formes non compliquées. Cet article résume la prise en charge de la diverticulite aiguë gauche simple, en s'appuyant sur les nouvelles recommandations et en abordant principalement le traitement antibiotique, la prise en charge ambulatoire ou hospitalière et les indications à la coloscopie.

[Acute diverticulitis can be treated without antibiotics].

Diverticulitis is a complication to the common condition diverticulosis. Uncomplicated diverticulitis has traditionally been treated with antibiotics. Risk factors for diverticulitis, however, may suggest, that the condition is inflammatory rather than infectious. The evidence on antibiotic treatment for uncomplicated acute diverticulitis suggests, that antibiotics have no effect on complications, emergency surgery, recurrence, elective colonic resections and long-term complications. The evidence is based on three randomised clinical trials on the need for antibiotics, which is summarised in this review.

Changing Paradigms in the Management of Acute Uncomplicated Diverticulitis.

Left-sided colonic diverticulitis is a common condition with significant morbidity and health care costs in Western countries. Acute uncomplicated diverticulitis which is characterized by the absence of organ dysfunction, abscesses, fistula, or perforations accounts for around 80% of the cases. In the last decades, several traditional paradigms in the management of acute uncomplicated diverticulitis have been replaced by evidence-based routines. This review provides a comprehensive evidence-based and clinical-oriented overview of up-to-date diagnostics with computer tomography, non-antibiotic treatment, outpatient treatment, and surgical strategies as well as follow-up of patients with acute uncomplicated diverticulitis.

Antibiotics for acute uncomplicated diverticulitis in hospitalized patients. / Antibióticos para diverticulitis aguda no complicada en pacientes hospitalizados.

INTRODUCTION: Acute diverticulitis is one of the complications of diverticular disease. Nowadays, there is a paradigm shift regarding the use of antibiotics to manage acute uncomplicated diverticulitis in hospitalized patients, with controversial information about it. METHODS: A search was done in Epistemonikos, the most comprehensive health-related systematic review database, maintained by screening multiple information sources including MEDLINE/PubMed, EMBASE, Cochrane, among others. Data were extracted from the identified systematic reviews, data from primary studies were analyzed, which in this work considered only randomized clinical trials, a meta-analysis was done, and a summary table of results was created using GRADE methodology. RESULTS AND CONCLUSIONS: Eleven systematic reviews were identified that included seven primary studies in total, of which two were randomized control trials. We concluded that the use of antibiotics in acute uncomplicated diverticulitis could slightly increase complications and result in a minor or no difference in the risk of recurrence and need for urgent surgery. However, the certainty of the evidence is low. Regarding hospital stay and readmission, it was not possible to evaluate the effect due to a low certainty of evidence.

INTRODUCCIÓN: La diverticulitis aguda es una de las complicaciones de la enfermedad diverticular. En la actualidad, ha habido un cambio de paradigma sobre el uso de antibióticos en el manejo de la diverticulitis aguda no complicada en pacientes hospitalizados, existiendo evidencia controversial al respecto. MÉTODOS: Se realizó una búsqueda en Epistemonikos, la mayor base de datos de revisiones sistemáticas en salud, la cual es mantenida mediante el tamizaje de múltiples fuentes de información, incluyendo MEDLINE/PubMed, EMBASE, Cochrane, entre otras. Se extrajeron los datos desde las revisiones identificadas, se analizaron los datos de los estudios primarios, que en este trabajo consideraron solo ensayos clínicos aleatorizados, se realizó un metanálisis y se preparó una tabla de resumen de los resultados utilizando el método GRADE. RESULTADOS Y CONCLUSIONES: Se identificaron 11 revisiones sistemáticas que en conjunto incluyeron siete estudios primarios, de los cuales dos correspondieron a ensayos aleatorizados. Se concluyó que el uso de antibióticos en la diverticulitis aguda no complicada podría aumentar levemente las complicaciones y podría resultar en nula o poca diferencia en el riesgo de recurrencia y la necesidad de cirugía de urgencia. Sin embargo, la certeza de la evidencia es baja. Respecto a la estadía hospitalaria y la readmisión no se pudo evaluar un efecto claro de esta intervención, dado que la certeza de la evidencia fue evaluada como muy baja.

The role of procalcitonin in reducing antibiotics across the surgical pathway.

Procalcitonin (PCT) is widely considered as a highly sensitive biomarker of bacterial infection, offering general and emergency surgeons a key tool in the management of surgical infections. A multidisciplinary task force of experts met in Bologna, Italy, on April 4, 2019, to clarify the key issues in the use of PCT across the surgical pathway. The panelists presented the statements developed for each of the main questions regarding the use of PCT across the surgical pathway. An agreement on the statements was reached by the Delphi method, and this document reports the executive summary of the final recommendations approved by the expert panel.

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

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.