Antibiotic Use, Healthcare-Associated Infections, and Antimicrobial Resistance in Intensive Care Unit of a Serbian Tertiary University Hospital, 2018–2024: An Ecological Analysis

<b>Background</b>: Healthcare-associated infections (HAIs), antimicrobial resistance (AMR), and antibiotic use (AU) remain critical challenges in intensive care units (ICUs). Reliable long-term surveillance is essential to inform stewardship programs and infection prevention. <b>Methods</b>: We conducted a seven-year ecological study (2018-2024) of adult patients admitted to the surgical ICU of a Serbian tertiary university hospital. Patients with ICU stays >48 h were included. Data on demographics, HAIs, AU expressed as 'days of therapy' (DOT) per 100 patient-days, and resistance profiles of key pathogens were collected. AU was classified by WHO Access, Watch and Reserve categories. Trends were analyzed, and correlations between AU and healthcare-associated <i>Clostridioides difficile</i> infection (HA-CDI) incidence density as well as changes in AMR rates were assessed. Direct expenditures for antibiotic therapy were also calculated. <b>Results:</b> Among 2055 patients, 511 (24.9%) developed at least one HAI. HA-CDI showed a marked upward trend. Overall, AU was stable, but Reserve antibiotics increased significantly (R² = 0.456), particularly linezolid, colistin, and ceftazidime-avibactam. Resistance to carbapenems and colistin in <i>Klebsiella pneumoniae</i> (<i>K. pneumonia</i>) demonstrated alarming trends. A strong correlation was observed between colistin use and colistin resistance in <i>K. pneumoniae</i>. Antibiotic expenditures peaked in 2023 at more than double pre-COVID levels, mainly driven by Reserve agents. <b>Conclusions:</b> This study reveals a concerning rise in multidrug-resistant pathogens, escalating Reserve antibiotic use, and substantial financial burden. Strengthened antimicrobial stewardship, optimization of Access, restriction of Reserve agents, and investment in infection prevention and surveillance are urgently needed.