{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T04:28:16Z","timestamp":1784694496136,"version":"3.55.0"},"reference-count":21,"publisher":"American Society for Microbiology","issue":"7","license":[{"start":{"date-parts":[[2017,7,1]],"date-time":"2017-07-01T00:00:00Z","timestamp":1498867200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.asm.org\/non-commercial-tdm-license"}],"content-domain":{"domain":["journals.asm.org"],"crossmark-restriction":true},"short-container-title":["Antimicrob Agents Chemother"],"published-print":{"date-parts":[[2017,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n          <jats:p>\n            Amoxicillin-clavulanate (A\/C) is currently the most effective oral antimicrobial in treating children with acute otitis media (AOM), but the standard dosage of 90 mg amoxicillin\/6.4 mg clavulanate\/kg of body weight\/day commonly causes diarrhea. We examined whether an A\/C formulation containing lower concentrations of clavulanate would result in less diarrhea while maintaining plasma levels of amoxicillin and clavulanate adequate to eradicate middle-ear pathogens and to achieve clinical success. We conducted an open-label study in children with AOM who were 6 to 23 months of age. In phase 1, we treated 40 children with a reduced-clavulanate A\/C formulation providing 90 mg amoxicillin\/3.2 mg clavulanate\/kg\/day for 10 days. In phase 2, we treated 72 children with the same formulation at a dosage of 80 mg amoxicillin\/2.85 mg clavulanate\/kg\/day for 10 days. We compared the rates of protocol-defined diarrhea (PDD), diaper dermatitis, and AOM clinical response in these children with rates we had reported in children who received the standard A\/C regimen, and we obtained plasma levels of amoxicillin and clavulanate at various time points. Outcomes in phase 1 children and in children who had received the standard regimen did not differ significantly. Rates of PDD in children receiving phase 2 and standard regimens were 17% and 26%, respectively (\n            <jats:italic>P<\/jats:italic>\n            = 0.10). The corresponding rates of diaper dermatitis were 21% and 33% (\n            <jats:italic>P<\/jats:italic>\n            = 0.04) and of AOM treatment failure were 12% and 16% (\n            <jats:italic>P<\/jats:italic>\n            = 0.44). Symptomatic responses did not differ significantly between regimens; both gave clavulanate levels sufficient to inhibit \u03b2-lactamase activity. In young children with AOM, clavulanate dosages lower than those currently used may be associated with fewer side effects without reducing clinical efficacy. (This study has been registered at ClinicalTrials.gov under registration no. NCT02630992.)\n          <\/jats:p>","DOI":"10.1128\/aac.00238-17","type":"journal-article","created":{"date-parts":[[2017,4,25]],"date-time":"2017-04-25T00:55:26Z","timestamp":1493081726000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":8,"title":["Reduced-Concentration Clavulanate for Young Children with Acute Otitis Media"],"prefix":"10.1128","volume":"61","author":[{"given":"Alejandro","family":"Hoberman","sequence":"first","affiliation":[{"name":"Department of Pediatrics, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jack L.","family":"Paradise","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Howard E.","family":"Rockette","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong-Hyeon","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diana H.","family":"Kearney","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonika","family":"Bhatnagar","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy R.","family":"Shope","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gysella","family":"Mu\u00f1iz","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith M.","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcia","family":"Kurs-Lasky","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MaryAnn","family":"Haralam","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcia A.","family":"Pope","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer P.","family":"Nagg","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenchen","family":"Zhao","sequence":"additional","affiliation":[{"name":"University of Pittsburgh School of Pharmacy, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mohammad Kowser","family":"Miah","sequence":"additional","affiliation":[{"name":"University of Pittsburgh School of Pharmacy, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jan","family":"Beumer","sequence":"additional","affiliation":[{"name":"University of Pittsburgh School of Pharmacy, Pittsburgh, Pennsylvania, USA"},{"name":"University of Pittsburgh Cancer Institute, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raman","family":"Venkataramanan","sequence":"additional","affiliation":[{"name":"University of Pittsburgh School of Pharmacy, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nader","family":"Shaikh","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, University of Pittsburgh School of Medicine, Children's Hospital of Pittsburgh of UPMC, Pittsburgh, Pennsylvania, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","first-page":"1","article-title":"Ambulatory medical care utilization estimates for 2007","volume":"2011","author":"Schappert SM","year":"2011","unstructured":"Schappert SM RechtsteinerEA. 2011. 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