Ciacci Nagaia, Boncompagni Selene, Valzano Felice, Cariani Lisa, Aliberti Stefano, Blasi Francesco, Pollini Simona, Rossolini Gian Maria, Pallecchi Lucia
Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy.
Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Cystic Fibrosis Microbiology Laboratory, 20122 Milan, Italy.
Antibiotics (Basel). 2019 Jul 25;8(3):101. doi: 10.3390/antibiotics8030101.
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 infections recalcitrant to treatment. Colistin is among the second-line options in case of difficult-to-treat 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 grown in planktonic phase and biofilm. Eighteen 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 ( = 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 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 respiratory infections and should be examined further.
是一种新兴的全球机会性病原体，可导致多种人类感染，包括呼吸道感染。其内在的多重耐药性和形成生物膜的倾向使感染难以治疗。对于难以治疗的感染，多粘菌素是二线治疗选择之一，其优势还在于可通过雾化给药。我们研究了多粘菌素与N - 乙酰半胱氨酸（NAC，一种具有抗氧化和抗炎特性的黏液溶解剂）联合使用对浮游菌和生物膜生长的潜在协同作用。纳入了18株临床分离株（包括3株来自囊性纤维化（CF）的分离株和2株耐甲氧苄啶 - 磺胺甲恶唑（SXT）菌株）。棋盘法试验显示，对于多粘菌素最低抑菌浓度（MIC）>2 μg/mL的菌株（n = 13），多粘菌素/NAC组合具有协同作用，这表明NAC可能拮抗多粘菌素耐药相关机制。尽管如此，时间杀菌试验表明，在多粘菌素MIC较低的情况下，NAC也可能增强其活性。在亚MIC浓度下，也清楚地观察到NAC对生物膜的多粘菌素活性具有剂量依赖性增强作用。多粘菌素/NAC组合在局部给药可能达到的浓度下，可能是治疗呼吸道感染的有效选择，应进一步研究。
