Abstract
Background: Stenotrophomonas maltophilia infections treatment is complicated by intrinsic multidrug resistance and increasing trend of acquired-resistance to first-line treatment options. Colistin is in the second-line options and has nebulization route. We investigated colistin synergistic activity with N-acetylcysteine (NAC), mucolytic agent with antioxidant/anti-inflammatory properties, commonly co-administered with antibiotics for treating lower respiratory tract infections. Methods: 20 S.maltophilia clinical isolates were tested. Synergism colistin (0.25-256µg/ml) and NAC (0.5-32mg/ml) was investigated by classic checkerboard assays. Fraction inhibitory concentration indices (FICIs) were calculated, synergism was defined as FICI values Results: Colistin MICs ranged 0.5µg/ml-128µg/ml (MIC50:16µg/ml;MIC90:64µg/ml). NAC MIC was 16mg/ml for 9 isolates,>32mg/ml for 1 isolate, 32mg/ml for the remaining ones. Synergism NAC/colistin was observed in checkerboard assays with all tested isolates. Time-kill curves confirmed synergy observed by checkerboard assays, demonstrating NAC/colistin combination bactericidal effect at sub-MIC concentrations. Conclusions NAC via topical route shows in vitro synergy with colistin against S.maltophilia. The combination is a valid option to treat difficult-to-treat S.maltophilia respiratory infections.
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