{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,5,5]],"date-time":"2026-05-05T04:01:44Z","timestamp":1777953704915,"version":"3.51.4"},"posted":{"date-parts":[[2026,4,30]]},"group-title":"Infectious Diseases (except HIV\/AIDS)","reference-count":25,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T00:00:00Z","timestamp":1777507200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/publicdomain\/zero\/1.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,4,30]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>\n                    Implementation strategies are dynamic techniques used to apply evidence-based practices (EBPs) to diverse contexts. Despite their importance, context-specific selection and modification of implementation strategies remain underreported, limiting understanding of how to optimize strategy deployment across heterogeneous healthcare settings. We describe a systematic method to document and analyze modifications to implementation strategies using four diverse hospital sites from the Fluoroquinolone Restriction for the Prevention of\n                    <jats:italic>Clostridioides difficile<\/jats:italic>\n                    infection (FIRST) trial as case studies.\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>FIRST was a multisite fluoroquinolone pre-prescription restriction intervention delivered via the electronic health record. We partnered with multidisciplinary stakeholders at each site to co-design and adapt the intervention using pre-planned implementation strategies. Multiple data sources (interviews, meeting notes, implementation diaries) collected iteratively over two years were analyzed to identify strategy modifications. Strategies were coded using Expert Recommendations for Implementing Change (ERIC) conceptual clusters, and modifications were documented using the Framework for Reporting Adaptations and Modifications to Evidence-Based Implementation Strategies (FRAME-IS). Modified strategies were categorized as planned or unplanned and contextualized via thematic content analysis.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Across 458 total modifications, the most modified strategies focused on facilitating stakeholder engagement, adapting to local contexts, and using evaluative approaches to improve EBP uptake\/sustainment. Planned modifications (n=330, 72%) outnumbered unplanned modifications (n=157, 34%). Rural and community hospitals required more unplanned modifications (average 41 vs. 31 for academic centers), while sites with prior restrictive intervention experience had higher planned-to-unplanned ratios (3.1:1 vs. 1.6:1). Academic hospitals with trainee rotations required ongoing education and higher strategy modifications. All modifications maintained EBP core fidelity. Site-specific patterns organizational characteristics were linked to modification intensity and type, including absorptive capacity, prior experience, relational coordination, rurality, and educational requirements.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Conclusions<\/jats:title>\n                  <jats:p>Integrating ERIC and FRAME-IS enabled systematic documentation of implementation strategy modifications across diverse settings. Planned:unplanned modification ratios provided novel insights into organizational absorptive capacity and implementation preparedness. Standardized implementation approaches inadequately address critical organizational differences, requiring context-sensitive strategy selection and intensity calibration. This work advances implementation science methodology by demonstrating how systematic modification documentation can inform tailored implementation support.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Trial Registration<\/jats:title>\n                  <jats:p>\n                    ClinicalTrials.gov Identifier:\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT03848689\">NCT03848689<\/jats:ext-link>\n                  <\/jats:p>\n                <\/jats:sec>","DOI":"10.64898\/2026.04.28.26351921","type":"posted-content","created":{"date-parts":[[2026,4,30]],"date-time":"2026-04-30T17:25:21Z","timestamp":1777569921000},"source":"Crossref","is-referenced-by-count":0,"title":["Implementation strategy modifications: An applied multi-site comparison using ERIC and FRAME-IS for the \u201cFluoroquinolone Restriction for the Prevention of\n                  <i>Clostridioides difficile<\/i>\n                  infection Trial\u201d (FIRST)"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8787-4269","authenticated-orcid":false,"given":"Vishala","family":"Parmasad","sequence":"first","affiliation":[{"name":"Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Demetrius","family":"Solomon","sequence":"additional","affiliation":[{"name":"Department of Industrial and Systems Engineering, University of Wisconsin-Madison, Madison, WI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Douglas","family":"Wiegmann","sequence":"additional","affiliation":[{"name":"Department of Industrial and Systems Engineering, University of Wisconsin-Madison, Madison, WI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marin","family":"Schweizer-Looby","sequence":"additional","affiliation":[{"name":"Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nasia","family":"Safdar","sequence":"additional","affiliation":[{"name":"Department of Medicine, School of Medicine and Public Health, University of Wisconsin-Madison, Madison, WI, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"issue":"1","key":"2026050409250705000_2026.04.28.26351921v1.1","first-page":"1","article-title":"A refined compilation of implementation strategies: results from the Expert Recommendations for Implementing Change (ERIC) project","volume":"10","year":"2015","journal-title":"Implementation Science"},{"key":"2026050409250705000_2026.04.28.26351921v1.2","doi-asserted-by":"crossref","unstructured":"Chambers DA , Glasgow RE , Stange KC . The dynamic sustainability framework: addressing the paradox of sustainment amid ongoing change. Implementation science : IS. 2013;8.","DOI":"10.1186\/1748-5908-8-117"},{"key":"2026050409250705000_2026.04.28.26351921v1.3","doi-asserted-by":"crossref","unstructured":"Aarons GA , Green AE , Palinkas LA , Self-Brown S , Whitaker DJ , Lutzker JR , et al. Dynamic adaptation process to implement an evidence-based child maltreatment intervention. Implementation science : IS. 2012;7.","DOI":"10.1186\/1748-5908-7-32"},{"key":"2026050409250705000_2026.04.28.26351921v1.4","doi-asserted-by":"crossref","unstructured":"Stirman SW , Kimberly J , Cook N , Calloway A , Castro F , Charns M . The sustainability of new programs and innovations: a review of the empirical literature and recommendations for future research. Implementation science : IS. 2012;7.","DOI":"10.1186\/1748-5908-7-17"},{"key":"2026050409250705000_2026.04.28.26351921v1.5","doi-asserted-by":"publisher","DOI":"10.1007\/s10488-010-0319-7"},{"key":"2026050409250705000_2026.04.28.26351921v1.6","doi-asserted-by":"crossref","unstructured":"Proctor E , Powell B , McMillen J . Implementation strategies: recommendations for specifying and reporting. Implementation science : IS. 2013;8.","DOI":"10.1186\/1748-5908-8-139"},{"key":"2026050409250705000_2026.04.28.26351921v1.7","doi-asserted-by":"crossref","unstructured":"Mody A , Filiatreau L , Goss C , Powell B , Geng E . Instrumental variables for implementation science: exploring context-dependent causal pathways between implementation strategies and evidence-based interventions. Implementation science communications. 2023;4(1).","DOI":"10.1186\/s43058-023-00536-x"},{"key":"2026050409250705000_2026.04.28.26351921v1.8","doi-asserted-by":"crossref","unstructured":"Escoffery C , Lebow-Skelley E , Haardoerfer R , Boing E , Udelson H , Wood R , et al. A systematic review of adaptations of evidence-based public health interventions globally. Implementation science : IS. 2018;13(1).","DOI":"10.1186\/s13012-018-0815-9"},{"key":"2026050409250705000_2026.04.28.26351921v1.9","doi-asserted-by":"crossref","unstructured":"Moore J , Mascarenhas A , Bain J , Straus S . Developing a comprehensive definition of sustainability. Implementation science : IS. 2017;12(1).","DOI":"10.1186\/s13012-017-0637-1"},{"issue":"1","key":"2026050409250705000_2026.04.28.26351921v1.10","first-page":"1","article-title":"Use of concept mapping to characterize relationships among implementation strategies and assess their feasibility and importance: results from the Expert Recommendations for Implementing Change (ERIC) study","volume":"10","year":"2015","journal-title":"Implementation Science"},{"key":"2026050409250705000_2026.04.28.26351921v1.11","doi-asserted-by":"crossref","unstructured":"Powell B , McMillen J , Proctor E , Carpenter C , Griffey R , Bunger A , et al. A compilation of strategies for implementing clinical innovations in health and mental health. Medical care research and review : MCRR. 2012;69(2).","DOI":"10.1177\/1077558711430690"},{"key":"2026050409250705000_2026.04.28.26351921v1.12","doi-asserted-by":"crossref","first-page":"1204138","DOI":"10.3389\/frhs.2023.1204138","article-title":"Advancing adaptation of evidence-based interventions through implementation science: progress and opportunities","volume":"3","year":"2023","journal-title":"Frontiers in Health Services"},{"key":"2026050409250705000_2026.04.28.26351921v1.13","doi-asserted-by":"crossref","unstructured":"Miller C , Barnett M , Baumann A , Gutner C , Wiltsey-Stirman S . The FRAME-IS: a framework for documenting modifications to implementation strategies in healthcare. Implementation science : IS. 2021;16(1).","DOI":"10.1186\/s13012-021-01105-3"},{"key":"2026050409250705000_2026.04.28.26351921v1.14","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/s13012-019-0898-y","article-title":"The FRAME: an expanded framework for reporting adaptations and modifications to evidence-based interventions","volume":"14","year":"2019","journal-title":"Implementation Science : IS"},{"key":"2026050409250705000_2026.04.28.26351921v1.15","doi-asserted-by":"crossref","unstructured":"Garza RH , Jacobson N , Cohen A , Landeck J , Schumacher N , Lundwall R , et al. Using the Framework for Reporting Adaptations and Modifications to Evidence-Based Implementation Strategies (FRAME-IS) to Document Modifications to a Multilevel Deimplementation Strategy Aimed at Reducing Opioid Prescribing for Chronic Pain. Implementation Research and Practice. 2026;7:26334895251407338.","DOI":"10.1177\/26334895251407338"},{"key":"2026050409250705000_2026.04.28.26351921v1.16","doi-asserted-by":"crossref","unstructured":"Schoenthaler A , De La Calle F , De Leon E , Garcia M , Colella D , Nay J , et al. Application of the FRAME-IS to a multifaceted implementation strategy. BMC health services research. 2024;24(1).","DOI":"10.1186\/s12913-024-11139-0"},{"key":"2026050409250705000_2026.04.28.26351921v1.17","doi-asserted-by":"crossref","unstructured":"Bandal A , Hern\u00e1ndez S , Mustafa R , Choy K , Edwards N , Guarchaj M , et al. Methodology for adapting a co-created early childhood development intervention and implementation strategies for use by frontline workers in India and Guatemala: a systematic application of the FRAME-IS framework. Global health action. 2024;17(1).","DOI":"10.1080\/16549716.2024.2338324"},{"key":"2026050409250705000_2026.04.28.26351921v1.18","doi-asserted-by":"crossref","unstructured":"Safdar N , Parmasad V , Brown R , Carayon P , Lepak A , O\u2019Horo JC , et al. Decreasing ICU-associated Clostridioides difficile infection through fluoroquinolone restriction, the FIRST trial: a study protocol. BMJ Open. 2021;11.","DOI":"10.1136\/bmjopen-2020-046480"},{"key":"2026050409250705000_2026.04.28.26351921v1.19","doi-asserted-by":"crossref","unstructured":"Curran G , Bauer M , Mittman B , Pyne J , Stetler C . Effectiveness-implementation hybrid designs: combining elements of clinical effectiveness and implementation research to enhance public health impact. Medical care. 2012;50(3).","DOI":"10.1097\/MLR.0b013e3182408812"},{"key":"2026050409250705000_2026.04.28.26351921v1.20","doi-asserted-by":"crossref","unstructured":"Leffler D , Lamont J . Clostridium difficile infection. The New England journal of medicine. 2015;372(16).","DOI":"10.1056\/NEJMra1403772"},{"key":"2026050409250705000_2026.04.28.26351921v1.21","doi-asserted-by":"crossref","unstructured":"Hensgens M , Goorhuis A , Dekkers O , Kuijper E . Time interval of increased risk for Clostridium difficile infection after exposure to antibiotics. The Journal of antimicrobial chemotherapy. 2012;67(3).","DOI":"10.1093\/jac\/dkr508"},{"key":"2026050409250705000_2026.04.28.26351921v1.22","doi-asserted-by":"crossref","unstructured":"Deshpande A , Pasupuleti V , Thota P , Pant C , Rolston D , Hernandez A , et al. Risk factors for recurrent Clostridium difficile infection: a systematic review and meta-analysis. Infection control and hospital epidemiology. 2015;36(4).","DOI":"10.1017\/ice.2014.88"},{"key":"2026050409250705000_2026.04.28.26351921v1.23","doi-asserted-by":"crossref","unstructured":"Baur D , Gladstone B , Burkert F , Carrara E , Foschi F , D\u00f6bele S , et al. 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. The Lancet Infectious diseases. 2017;17(9).","DOI":"10.1016\/S1473-3099(17)30325-0"},{"key":"2026050409250705000_2026.04.28.26351921v1.24","doi-asserted-by":"publisher","DOI":"10.1111\/j.0887-378X.2004.00325.x"},{"key":"2026050409250705000_2026.04.28.26351921v1.25","first-page":"65","article-title":"Fidelity and acceptability of implementation strategies developed for adherence to a clinical pathway for screening, assessment and management of anxiety and depression in adults with cancer","volume":"82","year":"2026","journal-title":"Archives of Public Health"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.04.28.26351921","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T16:25:18Z","timestamp":1777911918000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.64898\/2026.04.28.26351921"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,4,30]]},"references-count":25,"URL":"https:\/\/doi.org\/10.64898\/2026.04.28.26351921","relation":{},"subject":[],"published":{"date-parts":[[2026,4,30]]},"subtype":"preprint"}}