Antibiotic Consumption and Gram-Negative Resistance Dynamics in the ICU: A Five-Year Autoregressive Integrated Moving Average (ARIMA) Analysis

Aim: The aim of this study was to evaluate the impact of hospital antibiotic consumption on the rate of antimicrobial resistance (AMR) of gram-negative bacteria, specifically the Enterobacteriaceae family and the genus Acinetobacter, in the University Clinical Center (UCC) Tuzla, Bosnia and Herzegovina. Methods: A five-year retrospective, observational, pharmacoepidemiological study was conducted (2014 to 2018). Antibiotic consumption was calculated using the WHO Anatomical Therapeutic Chemical/defined daily dose (ATC/DDD) methodology and expressed as DDD per 100 bed-days (BD). Microbiological data were obtained for Klebsiella pneumoniae, Escherichia coli, Proteus mirabilis, and Acinetobacter species. The temporal associations between consumption and resistance were analyzed using linear regression and autoregressive integrated moving average (ARIMA) models. Results: The total antibiotic consumption at UCC Tuzla significantly increased from 61.35 to 73.51 DDD/100 BD (p=0.003). Consumption in intensive care units (ICUs) was significantly higher than the hospital-wide average (p<0.001), reaching up to 178.53 DDD/100 BD. ARIMA modeling confirmed significant positive correlations between the use of fluoroquinolones (J01MA) and resistance in Acinetobacter baumannii (beta = 7.678, p=0.006) and K. pneumoniae (beta = 18.368, p<0.001)9. A similar correlation was found for carbapenems (J01DD) and E. coli resistance (beta = 14.066, p=0.004). Conclusion: The study demonstrates a significant temporal association between the volume of broad-spectrum antibiotic consumption and the escalation of AMR. The high selective pressure in ICUs identifies these units as primary reservoirs for multidrug-resistant pathogens. These findings highlight the importance of multidisciplinary antimicrobial stewardship programs and restricted use of reserve antibiotics to preserve therapeutic efficacy.