Abstract
Stenotrophomonas maltophilia is an emerging global opportunistic pathogen, responsible for a wide range of human infections, including respiratory tract infections. Intrinsic multidrug resistance and propensity to form biofilms make S. maltophilia infections recalcitrant to treatment. Colistin is among the second-line options in case of difficult-to-treat S. maltophilia infections, with the advantage of being also administrable by nebulization. We investigated the potential synergism of colistin in combination with N-acetylcysteine (NAC) (a mucolytic agent with antioxidant and anti-inflammatory properties) against S. maltophilia grown in planktonic phase and biofilm. Eighteen S. maltophilia clinical isolates (comprising three isolates from cystic fibrosis (CF) and two trimethoprim-sulfamethoxazole (SXT)-resistant strains) were included. Checkerboard assays showed a synergism of colistin/NAC combinations against the strains with colistin Minimum Inhibitory Concentration (MIC) >2 µg/mL (n = 13), suggesting that NAC could antagonize the mechanisms involved in colistin resistance. Nonetheless, time–kill assays revealed that NAC might potentiate colistin activity also in case of lower colistin MICs. A dose-dependent potentiation of colistin activity by NAC was also clearly observed against S. maltophilia biofilms, also at sub-MIC concentrations. Colistin/NAC combinations, at concentrations likely achievable by topical administration, might represent a valid option for the treatment of S. maltophilia respiratory infections and should be examined further.
Highlights
Stenotrophomonas maltophilia is an emerging global opportunistic pathogen, responsible for a wide range of human infections, including chronic lung colonization and acute exacerbations in patients affected by chronic respiratory diseases, such as cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), and bronchiectasis [1]
Colistin Susceptibility of S. maltophilia Strains Included in the Study
The study was performed with 18 S. maltophilia clinical isolates, which had been previously investigated for NAC susceptibility [17]
Summary
Stenotrophomonas maltophilia is an emerging global opportunistic pathogen, responsible for a wide range of human infections, including chronic lung colonization and acute exacerbations in patients affected by chronic respiratory diseases, such as cystic fibrosis (CF), chronic obstructive pulmonary disease (COPD), and bronchiectasis [1]. As reported by the Italian Cystic Fibrosis Registry, S. maltophilia is the second most common non-fermenting Gram-negative respiratory pathogen, following Pseudomonas aeruginosa, in patients affected by CF, with a prevalence of chronic lung colonization of 4.6% and 4.7% in adult and pediatric patients, respectively [2]. Due to intrinsic and acquired multidrug resistance mechanisms and the propensity to grow as biofilm, S. maltophilia infections are difficult-to-treat and the therapeutic options are very limited [1,5,8,9,10,11]. In order to find new drugs and their combinations to improve outcomes of difficult-to-treat respiratory tract infections, a renewed interest has been recently focused on topical routes of administration (e.g., inhalation, nebulization, and aerosolization), which allow the achievement of high drug concentrations in the lungs with limited systemic toxicity [14,15]
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