Temporal association between aerosolized colistin use and colistin resistance in the ICU: a time-series analysis

BACKGROUND: Aerosolized colistin has been increasingly used to treat multidrug-resistant gram-negative infections, particularly in the intensive care unit (ICU), as an alternative to intravenous colistin, which is limited by nephrotoxicity and poor pulmonary penetration. Systemic colistin use has been linked to the emergence of resistance, but the impact of inhaled colistin on resistance development remains unclear. METHODS: We conducted a time-series analysis using monthly data from April 2014 to December 2023 in the ICUs of a 2700-bed tertiary-care hospital comprising 108 adult ICU beds. Monthly antibiotic use and the incidence of colistin-resistant Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa and Acinetobacter baumannii from respiratory specimens were analysed using vector autoregressive (VAR) or vector error correction models (VECMs), depending on the presence of stationarity and cointegration. RESULTS: In bivariate VAR analyses, aerosolized colistin use was positively associated with subsequent increases in colistin-resistant K. pneumoniae and A. baumannii, with significant effects observed across multiple lags. In multivariate VAR models including other antibiotic classes, the temporal association persisted for K. pneumoniae. Sensitivity analyses using VECM also showed significant associations for E. coli, K. pneumoniae, P. aeruginosa and A. baumannii. In an additional analysis of non-respiratory specimens, aerosolized colistin was also significantly associated with colistin-resistant A. baumannii. CONCLUSIONS: Aerosolized colistin use was temporally associated with increased resistance in major gram-negative pathogens, particularly K. pneumoniae and A. baumannii. These findings highlight the need for cautious use of inhaled colistin and support its inclusion in targeted antimicrobial stewardship efforts, given its potential contribution to the emergence of resistance.