Vesna Šuljagić, Vojislava Nešković, Duško Maksimović, Ivo Udovičić, Danijela Đurić-Petković, Nenad Perisic, Ivan Leković, Đorđe Taušan, Bojan Rakonjac, Katarina Radisavljevic Vasiljevic, Nemanja Rančić
Background: 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. Methods: 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 Clostridioides difficile infection (HA-CDI) incidence density as well as changes in AMR rates were assessed. Direct expenditures for antibiotic therapy were also calculated. Results: 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 Klebsiella pneumoniae (K. pneumonia) demonstrated alarming trends. A strong correlation was observed between colistin use and colistin resistance in K. pneumoniae. Antibiotic expenditures peaked in 2023 at more than double pre-COVID levels, mainly driven by Reserve agents. Conclusions: 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.