{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T17:27:45Z","timestamp":1786123665347,"version":"build-2736575974"},"reference-count":21,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T00:00:00Z","timestamp":1786060800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Maccabi Healthcare Services"},{"id":[{"id":"https:\/\/ror.org\/04k1f6611","id-type":"ROR","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Background\/Objectives: The optimal antibiotic strategy for acute rhinosinusitis (ARS) in patients with comorbidities remains unclear. Guidelines often recommend amoxicillin-clavulanate (amx\/clv) for high-risk patients, despite limited comparative evidence. This study compared ARS outcomes of patients with comorbidities receiving amoxicillin and amx\/clv. Methods: This retrospective cohort study utilized electronic medical records from the Israeli community (2012\u20132023). Adults aged \u226518 years with \u22651 selected comorbidity and an ARS diagnosis were categorized according to the type of antibiotic prescribed. The primary outcome was treatment failure, defined as a follow-up ARS visit with an antibiotic prescription within 30 days of the initial visit. Secondary outcomes included ARS complications, emergency room referrals, chronic or subacute sinusitis diagnosis, and 90-day mortality rates. Adjusted odds ratios were estimated using multivariable logistic regression. Results: Of the 38,810 eligible patients, 4953 were prescribed amoxicillin, 7436 were prescribed amx\/clv, and 26,421 were not prescribed antibiotics. Treatment failure rates were not significantly different when comparing amoxicillin to amx\/clv or either antibiotic to no antibiotic therapy. Chronic or subacute sinusitis was more frequent with amx\/clv than with amoxicillin alone. No significant intergroup differences were observed in terms of complications, emergency room referrals, or mortality rates. These findings remained consistent in a sensitivity analysis of filled prescriptions and when analyzing the outcomes of individual comorbidities separately. Conclusions: Among adults with specified comorbidities diagnosed with ARS, the rates of treatment failure, complications, and ER referrals did not differ significantly between amoxicillin and amx\/clv, supporting narrow-spectrum therapy.<\/jats:p>","DOI":"10.3390\/antibiotics15080762","type":"journal-article","created":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T16:00:43Z","timestamp":1786118443000},"page":"762","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparative Outcomes of Amoxicillin and Amoxicillin-Clavulanate in the Treatment of Acute Rhinosinusitis in Adults with Comorbidities: A Retrospective Study"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-3261-6331","authenticated-orcid":false,"given":"Ran Yaacov","family":"Miron","sequence":"first","affiliation":[{"name":"Division of Health, Maccabi Healthcare Services, 27 Hamered St, Tel Aviv 6812509, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Revital","family":"Perlov Gavze","sequence":"additional","affiliation":[{"name":"Division of Health, Maccabi Healthcare Services, 27 Hamered St, Tel Aviv 6812509, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiraz","family":"Vered","sequence":"additional","affiliation":[{"name":"Division of Health, Maccabi Healthcare Services, 27 Hamered St, Tel Aviv 6812509, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shirley","family":"Shapiro Ben David","sequence":"additional","affiliation":[{"name":"Family Medicine Department, Gray\u2019s Faculty of Medical & Health Sciences, Tel Aviv University, Tel Aviv 6997801, Israel"},{"name":"Infectious Diseases Unit, Maccabi Healthcare Services, 27 Hamered St, Tel Aviv 6812509, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-1797-2496","authenticated-orcid":false,"given":"Ori","family":"Liran","sequence":"additional","affiliation":[{"name":"Division of Health, Maccabi Healthcare Services, 27 Hamered St, Tel Aviv 6812509, Israel"},{"name":"Family Medicine Department, Gray\u2019s Faculty of Medical & Health Sciences, Tel Aviv University, Tel Aviv 6997801, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,7]]},"reference":[{"key":"ref_1","first-page":"47","article-title":"Acute Rhinosinusitis: Rapid Evidence Review","volume":"111","author":"Butler","year":"2025","journal-title":"Am. Fam. Physician"},{"key":"ref_2","first-page":"S1","article-title":"Clinical Practice Guideline: Adult Sinusitis Update","volume":"173","author":"Payne","year":"2025","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"S17","DOI":"10.1016\/j.jaci.2006.09.005","article-title":"Rhinosinusitis: Developing guidance for clinical trials","volume":"118","author":"Meltzer","year":"2006","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"962","DOI":"10.1056\/NEJMcp1601749","article-title":"CLINICAL PRACTICE. Acute Sinusitis in Adults","volume":"375","author":"Rosenfeld","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Ahmed, O.A.F., Ghanem, A.S., M\u00f3r\u00e9, M., and Nagy, A.C. (2026). Respiratory and Related Comorbidities\u2019 Role in the Risk of Acute Sinusitis: A 15-Year Longitudinal Clinical Study. J. Clin. Med., 15.","DOI":"10.3390\/jcm15020660"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1598","DOI":"10.1016\/j.jaci.2020.01.023","article-title":"Clinical factors associated with acute exacerbations of chronic rhinosinusitis","volume":"145","author":"Kwah","year":"2020","journal-title":"J. Allergy Clin. Immunol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1007\/s11882-015-0589-y","article-title":"Risk Factors and Comorbidities in Chronic Rhinosinusitis","volume":"16","author":"Tint","year":"2016","journal-title":"Curr. Allergy Asthma Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"e12181","DOI":"10.1002\/clt2.12181","article-title":"The relative proportion of comorbidities among rhinitis and rhinosinusitis patients and their impact on visit burden","volume":"12","author":"Nuutinen","year":"2022","journal-title":"Clin. Transl. Allergy"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Hoffmans, R., Wagemakers, A., van Drunen, C., Hellings, P., and Fokkens, W. (2018). Acute and chronic rhinosinusitis and allergic rhinitis in relation to comorbidity, ethnicity and environment. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0192330"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"e72","DOI":"10.1093\/cid\/cis370","article-title":"IDSA clinical practice guideline for acute bacterial rhinosinusitis in children and adults","volume":"54","author":"Chow","year":"2012","journal-title":"Clin. Infect. Dis."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1177\/0194599813510891","article-title":"No evidence for distinguishing bacterial from viral acute rhinosinusitis using fever and facial\/dental pain: A systematic review of the evidence base","volume":"150","author":"Hauer","year":"2014","journal-title":"Otolaryngol. Head Neck Surg."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"4382","DOI":"10.1128\/AAC.00971-07","article-title":"National and regional assessment of antimicrobial resistance among community-acquired respiratory tract pathogens identified in a 2005\u20132006 U.S. faropenem surveillance study","volume":"51","author":"Critchley","year":"2007","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e12465","DOI":"10.1002\/emp2.12465","article-title":"Comparative effectiveness of amoxicillin versus amoxicillin-clavulanate among adults with acute sinusitis in emergency department and urgent care settings","volume":"2","author":"Rovelsky","year":"2021","journal-title":"J. Am. Coll. Emerg. Physicians Open"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.1001\/jama.2025.26902","article-title":"Amoxicillin-Clavulanate vs Amoxicillin for Acute Sinusitis in Adults","volume":"335","author":"Savage","year":"2026","journal-title":"JAMA"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1064","DOI":"10.1001\/jama.2023.15503","article-title":"Treatment Failure and Adverse Events After Amoxicillin-Clavulanate vs Amoxicillin for Pediatric Acute Sinusitis","volume":"330","author":"Savage","year":"2023","journal-title":"JAMA"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Ammendolia, I., Mannucci, C., Esposito, E., Calapai, G., Curr\u00f2, M., Midiri, P., Cardia, L., and Calapai, F. (2025). Hepatotoxicity and Antimicrobial Resistance to Amoxicillin and Amoxicillin\/Clavulanic Acid: Data Analysis from EudraVigilance. Molecules, 30.","DOI":"10.20944\/preprints202508.0690.v1"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e212713","DOI":"10.1001\/jamanetworkopen.2021.2713","article-title":"High-Dose vs Standard-Dose Amoxicillin Plus Clavulanate for Adults with Acute Sinusitis: A Randomized Clinical Trial","volume":"4","author":"Gregory","year":"2021","journal-title":"JAMA Netw. Open"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Matho, A., Mulqueen, M., Tanino, M., Quidort, A., Cheung, J., Pollard, J., Rodriguez, J., Swamy, S., Tayler, B., and Garrison, G. (2018). High-dose versus standard-dose amoxicillin\/clavulanate for clinically-diagnosed acute bacterial sinusitis: A randomized clinical trial. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0196734"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1793","DOI":"10.1001\/archinte.163.15.1793","article-title":"Effect of amoxicillin-clavulanate in clinically diagnosed acute rhinosinusitis: A placebo-controlled, double-blind, randomized trial in general practice","volume":"163","author":"Bucher","year":"2003","journal-title":"Arch. Intern. Med."},{"key":"ref_20","first-page":"CD006089","article-title":"Antibiotics for clinically diagnosed acute rhinosinusitis in adults","volume":"Issue 10","author":"Lemiengre","year":"2012","journal-title":"Cochrane Database Syst. Rev."},{"key":"ref_21","unstructured":"Central Bureau of Statistics (2024, December 01). Characterization and Classification of Geographical Units by the Socio-Economic Level of the Population 2023. Publications and Media Releases, Available online: https:\/\/www.cbs.gov.il\/en\/publications\/Pages\/2023\/Statistical-Abstract-of-Israel-2023-No-74.aspx."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/15\/8\/762\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T16:10:52Z","timestamp":1786119052000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/15\/8\/762"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,7]]},"references-count":21,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["antibiotics15080762"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics15080762","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,7]]}}}