De-Escalation of Broad-Spectrum and Last-Resort Antibiotics in Critically Ill Adults with Gram-Negative Infections: A Scoping Review and Evidence-Informed Framework for Tertiary-Care ICUs

Background: Early broad-spectrum empirical therapy is life-saving in critical illness, but its unnecessary continuation drives resistance, toxicity, and cost; antibiotic de-escalation is the principal stewardship strategy for resolving this tension, yet its evidence base is fragmented and its practice inconsistent. This scoping review mapped the evidence on the definitions, timing, eligibility, implementation, safety, and clinical, microbiological, and resistance outcomes of de-escalating cephalosporins, carbapenems, colistin, and tigecycline in critically ill adults with suspected or confirmed Gram-negative infection. It translated this into a framework for a tertiary-care intensive care unit (ICU). Methods: We conducted a focused scoping review informed by JBI methodological guidance and reported according to PRISMA-ScR. The Web of Science Core Collection was searched for English-language publications from 1 January 2016 to 4 August 2026. Following deduplication, two reviewers independently screened titles and abstracts, and subsequently assessed potentially eligible full texts. Disagreements were resolved through discussion or consultation with a third reviewer. The review was designed to map the characteristics and range of the identified evidence rather than to provide an exhaustive systematic assessment or quantitative synthesis of intervention effects. (PROSPERO CRD420261478424). Results: We included 51 publications (35 empirical studies; 16 reviews, editorials, or consensus statements), with the empirical evidence being predominantly observational, including a single randomized trial. The definitions were heterogeneous, and the spectrum-ranking systems were non-uniform; reassessment typically occurred at 48–72 h. The reported de-escalation proportions ranged from approximately 10% in broadly defined treated populations to 71% in a selected, extractable ICU subgroup. These values were not directly comparable because studies used different definitions, eligibility criteria, time points, and denominators, including all patients treated with antibiotics, empirical-treatment episodes, microbiologically documented infections, and patients considered clinically eligible for de-escalation. Direct comparative studies did not identify a consistent increase in mortality following de-escalation; however, the predominantly observational evidence was vulnerable to confounding by indication, survivor bias, and treatment-selection bias, and did not establish equivalence, non-inferiority, or a survival benefit. Conclusions: De-escalation appears safe but rests on low-certainty, heterogeneous evidence. We propose an evidence-informed framework, a structured 48–72 h time-out, an eligible-patient denominator and a minimum monitoring dataset for tertiary ICUs, and identify standardized definitions and resistance-focused trials as research priorities. These components represent an evidence-informed implementation proposal developed by the authors and require prospective local validation.