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An Approach to Measuring Colistin Plasma Levels Regarding the Treatment of Multidrug-Resistant Bacterial Infection
Article

In Vitro Synergism of Colistin and N-acetylcysteine against Stenotrophomonas maltophilia

1
Department of Medical Biotechnologies, University of Siena, 53100 Siena, Italy
2
Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Cystic Fibrosis Microbiology Laboratory, 20122 Milan, Italy
3
Department of Pathophysiology and Transplantation, University of Milan, 20122 Milan, Italy
4
Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Internal Medicine Department, Respiratory unit and Adult Cystic Fibrosis Center, 20122 Milan, Italy
5
Department of Experimental and Clinical Medicine, University of Florence, 50134 Florence, Italy
6
Microbiology and Virology Unit, Florence Careggi University Hospital, 50134 Florence, Italy
*
Author to whom correspondence should be addressed.
Received: 5 July 2019 / Revised: 20 July 2019 / Accepted: 23 July 2019 / Published: 25 July 2019
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. View Full-Text
Keywords: colistin; N-acetylcysteine; Stenotrophomonas maltophilia; biofilm colistin; N-acetylcysteine; Stenotrophomonas maltophilia; biofilm
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MDPI and ACS Style

Ciacci, N.; Boncompagni, S.; Valzano, F.; Cariani, L.; Aliberti, S.; Blasi, F.; Pollini, S.; Rossolini, G.M.; Pallecchi, L. In Vitro Synergism of Colistin and N-acetylcysteine against Stenotrophomonas maltophilia. Antibiotics 2019, 8, 101. https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics8030101

AMA Style

Ciacci N, Boncompagni S, Valzano F, Cariani L, Aliberti S, Blasi F, Pollini S, Rossolini GM, Pallecchi L. In Vitro Synergism of Colistin and N-acetylcysteine against Stenotrophomonas maltophilia. Antibiotics. 2019; 8(3):101. https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics8030101

Chicago/Turabian Style

Ciacci, Nagaia; Boncompagni, Selene; Valzano, Felice; Cariani, Lisa; Aliberti, Stefano; Blasi, Francesco; Pollini, Simona; Rossolini, Gian M.; Pallecchi, Lucia. 2019. "In Vitro Synergism of Colistin and N-acetylcysteine against Stenotrophomonas maltophilia" Antibiotics 8, no. 3: 101. https://0-doi-org.brum.beds.ac.uk/10.3390/antibiotics8030101

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