Efficacy of adjunctive nebulized colistin in critically ill patients with nosocomial carbapenem-resistant Gram-negative bacterial pneumonia: a multi-centre observational study

Abstract

Objectives: To investigate the association between adjunctive nebulized colistin and treatment outcomes in critically ill patients with nosocomial carbapenem-resistant Gram-negative bacterial (CR-GNB) pneumonia. Methods: This retrospective, multi-centre, cohort study included individuals admitted to the intensive care unit with nosocomial pneumonia caused by colistin-susceptible CR-GNB. Enrolled patients were divided into groups with/without nebulized colistin as adjunct to at least one effective intravenous antibiotic. Propensity score matching was performed in the original cohort (model 1) and a time-window bias-adjusted cohort (model 2). The association between adjunctive nebulized colistin and treatment outcomes was analysed. Results: In total, 181 and 326 patients treated with and without nebulized colistin, respectively, were enrolled for analysis. The day 14 clinical failure rate and mortality rate were 41.4% (75/181) versus 46% (150/326), and 14.9% (27/181) versus 21.8% (71/326), respectively. In the propensity score-matching analysis, patients with nebulized colistin had lower day 14 clinical failure rates (model 1: 41% (68/ 166) versus 54.2% (90/166), p 0.016; model 2: 35.3% (41/116) versus 56.9% (66/116), p 0.001). On multivariate analysis, nebulized colistin was an independent factor associated with fewer day 14 clinical failures (model 1: adjusted odds ratio (aOR) 0.59, 95% CI 0.37e0.92; model 2: aOR 0.37, 95% CI 0.21 e0.65). Nebulized colistin was not associated independently with a lower 14-day mortality rate in the time-dependent analysis in both models 1 and 2.

Cefiderocol-Based Combination Therapy for “Difficult-to-Treat” Gram-Negative Severe Infections: Real-Life Case Series and Future Perspectives

“…Of note, VAP still remains a difficult-to-treat infection, particularly when the underlying cause are XDR pathogens; indeed, treatment strategies are controversial, often involving inhaled antibiotics [50], along with intravenous administration, although their role is not well established yet [51]. On the other hand, the higher efficacy of Cefiderocolbased regimens in the reported series can be possibly explained by its convenient PK/PD properties in lung tissues [52], along with its linear killing kinetics of resistant bacteria, including Enterobacterales, P. aeruginosa, A. baumannii and S. maltophilia [52].…”

Multi-drug resistant gram-negative bacterial pneumonia: etiology, risk factors, and drug resistance patterns

“…Colistin is a last resort therapy for infections caused by MDR-GNB, in particular P. aeruginosa , A. baumannii , and K. pneumoniae [ 110 ]. In critically ill patients with nosocomial pneumonia caused by MDR-GNB, including carbapenem-resistant strains, adjunctive nebulized colistin therapy provided non-inferior therapeutic efficacy to parenteral colistin therapy with lower clinical failure [ 111 , 112 ].…”

The necessity of a loading dose when prescribing intravenous colistin in critically ill patients with CRGNB-associated pneumonia: a multi-center observational study

“…This retrospective study was conducted in five medical centers in Taiwan and recruited ICU-admitted patients who had colistin-susceptible CRGNB-associated pneumonia from January 2016 to December 2016. Associated studies have been in preparation or published [ 19 , 20 ]. The flow diagram of this article for patient inclusion and exclusion is shown in Fig.…”