Background: Antimicrobial resistance (AMR) in Gram-negative bacteremia (GNB) poses a major threat to patient outcomes and challenges healthcare systems. Local resistance data are essential to guide effective stewardship strategies.

Methods: This retrospective study included patients aged ≥18 years with positive blood cultures for GNB at a 500-bed tertiary hospital in Taif, Saudi Arabia, from January 2023 to January 2024. Data included demographics, infection sources, microbial resistance, treatment, and outcomes.

Results: Among 151 patients, 41% had resistant Gram-negative bloodstream infections. Urinary tract and skin/soft tissue infections were the most common sources (28.5% each). The surgical ward had the highest infection rate (41.7%). ESBL-producing and carbapenem resistant Enterobacterales were the leading resistant strains. Median times to Gram stain and final identification were 12 and 72 hours, respectively. Delayed de-escalation (>24 hours post-culture) occurred in 37% of cases. Median hospital stay was 240 hours. Intensive Care Units (ICU) patients had significantly higher mortality (53% vs. 11.8%, p < 0.001). Intensive Care Unit (ICU) admission (OR = 4.67) and delayed therapy (OR = 3.25) were independent mortality predictors.

Conclusions: Resistant GNB infections are common and linked to high ICU mortality. Prompt de-escalation and strong infection control are essential. Multi-center studies are needed to inform broader strategies.