{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T23:31:43Z","timestamp":1781652703001,"version":"3.54.5"},"reference-count":28,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2021,2,10]],"date-time":"2021-02-10T00:00:00Z","timestamp":1612915200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Infections caused by multidrug-resistant Gram-negative bacteria increase hospitalizations and mortality rates; antibiotic pressure increases resistance rates. We evaluated the impact of the antibiotics stewardship program (ASP) on Escherichia coli resistance rates, evaluating all antibiotic use and patients with positive cultures hospitalized between 2011 and 2018. Data on antibiotics were collected quarterly as the defined daily dose (DDD)\/100 days hospitalization. In 2014, an intervention was introduced, targeting the reduction of overall antibiotic use as well as specifically targeting quinolones and other broad-spectrum antibiotics. Using interrupted time series analysis (ITS), we compared the rates and trends of antibiotic use and resistant E. coli. We included 6001 patients, 3182 pre-ASP and 2819 post-ASP. We observed significant changes in absolute numbers as well as in trends for use of DDD\/100 days of all antibiotics by 31% from 76 to 52, and by 52% from 10.4 to 4.9 for quinolones. ITS demonstrated that before the ASP intervention, there was a slope pattern for increased E. coli resistance to antibiotics. This slope was reversed following the intervention for quinolones \u22121.52, aminoglycosides \u22122.04, and amoxicillin clavulanate (amox\/clav) \u22121.76; the effect of the intervention was observed as early as three months after the intervention and continued to decrease over time until the end of the study, at 48 months. We conclude that the ASP can positively impact the resistance rate of Gram-negative infections over time, regardless of the targeted combination of antibiotics, if the overall use is reduced.<\/jats:p>","DOI":"10.3390\/antibiotics10020179","type":"journal-article","created":{"date-parts":[[2021,2,12]],"date-time":"2021-02-12T00:49:26Z","timestamp":1613090966000},"page":"179","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Impact of an Antibiotic Stewardship Program on the Incidence of Resistant Escherichia coli: A Quasi-Experimental Study"],"prefix":"10.3390","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5340-2834","authenticated-orcid":false,"given":"Elad","family":"Ziv-On","sequence":"first","affiliation":[{"name":"Goldman Medical School, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel"},{"name":"Department of Public Health, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D","family":"Friger","sequence":"additional","affiliation":[{"name":"Department of Public Health, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa","family":"Saidel-Odes","sequence":"additional","affiliation":[{"name":"Goldman Medical School, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel"},{"name":"Infectious Disease Institute, Soroka University Medical Center, Beer Sheva 84101, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abraham","family":"Borer","sequence":"additional","affiliation":[{"name":"Goldman Medical School, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel"},{"name":"Infectious Disease Institute, Soroka University Medical Center, Beer Sheva 84101, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Orly","family":"Shimoni","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Soroka University Medical Center, Beer Sheva 84101, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Nikonov","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Soroka University Medical Center, Beer Sheva 84101, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1230-0428","authenticated-orcid":false,"given":"Lior","family":"Nesher","sequence":"additional","affiliation":[{"name":"Goldman Medical School, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer Sheva 84105, Israel"},{"name":"Infectious Disease Institute, Soroka University Medical Center, Beer Sheva 84101, Israel"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,2,10]]},"reference":[{"key":"ref_1","unstructured":"Centers for Disease Control and Prevention (2020, August 08). Antibiotic Resistance Threats in the United States 2019, Available online: https:\/\/www.cdc.gov\/drugresistance\/pdf\/threats-report\/2019-ar-threats-report-508.pdf."},{"key":"ref_2","unstructured":"WHO (2020, August 08). Global Antimicrobial Resistance and Use Surveillance System (GLASS) Report, Available online: https:\/\/apps.who.int\/iris\/bitstream\/handle\/10665\/332081\/9789240005587-eng.pdf?ua=1."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"254","DOI":"10.1016\/j.jinf.2007.04.007","article-title":"Mortality following bacteraemic infection caused by extended spectrum beta-lactamase (ESBL) producing E. coli compared to non-ESBL producing E. coli","volume":"55","author":"Melzer","year":"2007","journal-title":"J. Infect."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1093\/jac\/dkm318","article-title":"Mortality and delay in effective therapy associated with extended-spectrum \u03b2-lactamase production in Enterobacteriaceae bacteraemia: A systematic review and meta-analysis","volume":"60","author":"Schwaber","year":"2007","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1086\/510393","article-title":"Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America guidelines for developing an institutional program to enhance antimicrobial stewardship","volume":"44","author":"Dellit","year":"2007","journal-title":"Clin. Infect. Dis."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"544","DOI":"10.1126\/science.aad9358","article-title":"Antibiotic use and its consequences for the normal microbiome","volume":"352","author":"Blaser","year":"2016","journal-title":"Science"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/cid\/ciz089","article-title":"The Infectious Diseases Society of America\u2019s 10 \u00d7 \u201920 Initiative (Ten New Systemic Antibacterial Agents FDA-approved by 2020): Is 20 \u00d7 \u201920 a Possibility?","volume":"69","author":"Talbot","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"S97","DOI":"10.1093\/cid\/ciu542","article-title":"Core Elements of Hospital Antibiotic Stewardship Programs from the Centers for Disease Control and Prevention","volume":"59","author":"Pollack","year":"2014","journal-title":"Clin. Infect. Dis."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e51","DOI":"10.1093\/cid\/ciw118","article-title":"Implementing an antibiotic stewardship program: Guidelines by the Infectious Diseases Society of America and the Society for Healthcare Epidemiology of America","volume":"62","author":"Barlam","year":"2016","journal-title":"Clin. Infect. Dis."},{"key":"ref_10","first-page":"403","article-title":"The search for good antimicrobial stewardship","volume":"27","author":"Gerding","year":"2001","journal-title":"Jt. Comm. J. Qual. Improv."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"338","DOI":"10.1086\/664909","article-title":"Antimicrobial Stewardship at a Large Tertiary Care Academic Medical Center: Cost Analysis Before, During, and After a 7-Year Program","volume":"33","author":"Standiford","year":"2012","journal-title":"Infect. Control Hosp. Epidemiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"847","DOI":"10.1016\/S1473-3099(16)00065-7","article-title":"Current evidence on hospital antimicrobial stewardship objectives: A systematic review and meta-analysis","volume":"16","author":"Schuts","year":"2016","journal-title":"Lancet Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"990","DOI":"10.1016\/S1473-3099(17)30325-0","article-title":"Effect of antibiotic stewardship on the incidence of infection and colonisation with antibiotic-resistant bacteria and Clostridium difficile infection: A systematic review and meta-analysis","volume":"17","author":"Baur","year":"2017","journal-title":"Lancet Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1007\/s40506-016-0076-6","article-title":"The Legislative Momentum of Antimicrobial Stewardship: The US Perspective","volume":"8","author":"Johnson","year":"2016","journal-title":"Curr. Treat. Options Infect. Dis."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"348","DOI":"10.1086\/380964","article-title":"Long-Term Antibiotic Cost Savings from a Comprehensive Intervention Program in a Medical Department of a University-Affiliated Teaching Hospital","volume":"38","author":"Keck","year":"2004","journal-title":"Clin. Infect. Dis."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2897","DOI":"10.1093\/cid\/ciz1183","article-title":"Impact of a Comprehensive Antimicrobial Stewardship Program on Institutional Burden of Antimicrobial Resistance: A 14-Year Controlled Interrupted Time-series Study","volume":"71","author":"Peragine","year":"2019","journal-title":"Clin. Infect. Dis."},{"key":"ref_17","first-page":"199","article-title":"Long-term impact of an educational antimicrobial stewardship programme in primary care on infections caused by extended-spectrum \u03b2-lactamase-producing Escherichia coli in the community: An interrupted time-series analysis","volume":"20","author":"Turmo","year":"2019","journal-title":"Lancet Infect. Dis."},{"key":"ref_18","first-page":"538","article-title":"Ethnic diversity and increasing resistance patterns of hospitalized community-acquired urinary tract infections in Southern Israel: A prospective study","volume":"19","author":"Elnasasra","year":"2017","journal-title":"Isr. Med. Assoc. J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"2047","DOI":"10.1093\/jac\/dkw055","article-title":"Impact of antibiotic restriction on resistance levels of Escherichia coli: A controlled interrupted time series study of a hospital-wide antibiotic stewardship programme","volume":"71","author":"Boel","year":"2016","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2667","DOI":"10.1093\/jac\/dkt212","article-title":"Declining cephalosporin and fluoroquinolone non-susceptibility among bloodstream Enterobacteriaceae from the UK: Links to prescribing change?","volume":"68","author":"Livermore","year":"2013","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1007\/s11908-018-0615-z","article-title":"Fluoroquinolone Restriction as an Effective Antimicrobial Stewardship Intervention","volume":"20","author":"Claeys","year":"2018","journal-title":"Curr. Infect. Dis. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1007\/s12275-014-3420-x","article-title":"Diversity of extended-spectrum and plasmid-mediated AmpC \u03b2-lactamases in Enterobacteriaceae isolates from portuguese health care facilities","volume":"52","author":"Manageiro","year":"2014","journal-title":"J. Microbiol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Knudsen, J.D., and Andersen, S.E. (2014). A Multidisciplinary Intervention to Reduce Infections of ESBL- and AmpC-Producing, Gram-Negative Bacteria at a University Hospital. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0086457"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.jhin.2006.12.014","article-title":"Impact and cost of infection control measures to reduce nosocomial transmission of extended-spectrum \u03b2-lactamase-producing organisms in a non-outbreak setting","volume":"65","author":"Conterno","year":"2007","journal-title":"J. Hosp. Infect."},{"key":"ref_25","unstructured":"FDA Drug Safety and Availability (2020, August 18). FDA Drug Safety Communication: FDA Updates Warnings for Oral and Injectable Fluoroquinolone Antibiotics Due to Disabling Side Effects, Available online: https:\/\/www.fda.gov\/drugs\/drug-safety-and-availability\/fda-drug-safety-communication-fda-updates-warnings-oral-and-injectable-fluoroquinolone-antibiotics."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e010134","DOI":"10.1136\/bmjopen-2015-010134","article-title":"STROBE-AMS: Recommendations to optimise reporting of epidemiological studies on antimicrobial resistance and informing improvement in antimicrobial stewardship","volume":"6","author":"Tacconelli","year":"2016","journal-title":"BMJ Open"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1093\/ajcp\/45.4_ts.493","article-title":"Antibiotic susceptibility testing by a standardized single disk method","volume":"45","author":"Bauer","year":"1966","journal-title":"Am. J. Clin. Pathol."},{"key":"ref_28","unstructured":"CLSI (2019, May 14). Clinical and Laboratory Standards Institute Performance Standards for Antimicrobial Susceptibility Testing an informational Supplement for Global Application Developed through the Clinical and Laboratory Standards Institute Consensus Process. Available online: www.clsi.org."}],"container-title":["Antibiotics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2079-6382\/10\/2\/179\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:22:30Z","timestamp":1760160150000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2079-6382\/10\/2\/179"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,2,10]]},"references-count":28,"journal-issue":{"issue":"2","published-online":{"date-parts":[[2021,2]]}},"alternative-id":["antibiotics10020179"],"URL":"https:\/\/doi.org\/10.3390\/antibiotics10020179","relation":{},"ISSN":["2079-6382"],"issn-type":[{"value":"2079-6382","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,2,10]]}}}