From Crisis to Control: A Governance‑First Framework for CRAB

From Crisis to Control: A Governance‑First Framework for CRAB | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Research Article From Crisis to Control: A Governance‑First Framework for CRAB David Birchard This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7994582/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background: Carbapenem‑Resistant Acinetobacter baumannii (CRAB) combines OXA‑type carbapenemases and AmpC β‑lactamases with biofilm formation and environmental persistence, producing high morbidity and mortality in intensive care units (Watkins & Bonomo, 2023; Falcone, Tiseo, & Menichetti, 2022). Pharmacologic strategies that restore β‑lactam activity through enzyme inhibition, notably sulbactam paired with contemporary β‑lactamase inhibitors, have a mechanistic rationale and emerging clinical data supporting but depend on rapid detection and coordinated clinical workflows to affect outcomes (Pogue, Bonomo, & Patel, 2025; Infectious Diseases Society of America, 2024). Objective: To evaluate whether a governance‑first operational intervention genotype‑aware inhibitor alignment delivered through the electronic medical record (EMR), mandatory 24–48‑hour reassessment with pre‑authorized swap and rollback options, embedded renal and hepatic safety gates, and append‑only audit logging reduces detection‑to‑action latency and improves early clinical and unit‑level control measures for CRAB. Methods: This single‑site, prospective pragmatic pilot is designed for a high‑acuity adult ICU. Triggers include rapid molecular resistance flags or predefined clinical criteria combined with unit colonization pressure. The intervention surfaces single‑click order bundles with prepopulated dosing and organ‑function prompts, enforces pharmacist verification, permits provisional 24‑hour alignments when molecular confirmation is pending, and requires structured reassessments at 24 and 48 hours with pre‑authorized swaps or rollbacks. All actions are recorded in an immutable audit table. Primary operational endpoints are detection‑to‑action latency and the proportion of triggers aligned within 6 hours; primary clinical endpoints are 72‑hour clinical response and unit time to control, defined by a sustained, non‑increasing 7-day incident case trajectory. Safety endpoints include therapy‑related grade ≥2 renal, hepatic, or neurologic events, with predefined governance-stopping rules (Carenzo, Costantini, & Cecconi, 2024; Ben‑Chetrit, Smith, & Lee, 2018). Analysis: Descriptive summaries will report latency and response; pre‑post comparisons will use nonparametric and exact tests; interrupted time series and exponential decay models will estimate effects on incident case velocity and outbreak half‑life. Subgroup analyses will stratify by genotype, device burden, and backbone selection (Falcone et al., 2022; Pogue et al., 2025). Expected outcomes: The intervention is expected to shorten detection‑to‑action intervals, increase early clinical response in OXA/AmpC‑dominant infections, and reduce unit‑level propagation without increasing significant adverse events when operational safety gates function as designed (Infectious Diseases Society of America, 2024; Watkins & Bonomo, 2023). Conclusion: Embedding enzyme‑blocker strategies within an EMR‑enabled, governance‑driven control stack that prioritizes measurable time‑based operational metrics may improve early clinical response and unit containment for CRAB in ICU settings and provide a practical pathway for iterative, monitored scale‑up (Carenzo et al., 2024; Ben‑Chetrit et al., 2018). General Microbiology Infectious Diseases Critical Care & Emergency Medicine Clinical Pharmacology Full Text Additional Declarations The authors declare no competing interests. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Pharmacologic strategies that restore β‑lactam activity through enzyme inhibition, notably sulbactam paired with contemporary β‑lactamase inhibitors, have a mechanistic rationale and emerging clinical data supporting but depend on rapid detection and coordinated clinical workflows to affect outcomes (Pogue, Bonomo, \u0026amp; Patel, 2025; Infectious Diseases Society of America, 2024).\u003c/p\u003e\n\u003cp\u003eObjective: To evaluate whether a governance‑first operational intervention genotype‑aware inhibitor alignment delivered through the electronic medical record (EMR), mandatory 24–48‑hour reassessment with pre‑authorized swap and rollback options, embedded renal and hepatic safety gates, and append‑only audit logging reduces detection‑to‑action latency and improves early clinical and unit‑level control measures for CRAB.\u003c/p\u003e\n\u003cp\u003eMethods: This single‑site, prospective pragmatic pilot is designed for a high‑acuity adult ICU. 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Safety endpoints include therapy‑related grade ≥2 renal, hepatic, or neurologic events, with predefined governance-stopping rules (Carenzo, Costantini, \u0026amp; Cecconi, 2024; Ben‑Chetrit, Smith, \u0026amp; Lee, 2018).\u003c/p\u003e\n\u003cp\u003eAnalysis: Descriptive summaries will report latency and response; pre‑post comparisons will use nonparametric and exact tests; interrupted time series and exponential decay models will estimate effects on incident case velocity and outbreak half‑life. 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