In vitro activity of N-acetylcysteine against Stenotrophomonas maltophilia and Burkholderia cepacia complex grown in planktonic phase and biofilm

• Published in: PloS one 2018-10, Vol.13 (10), p.e0203941-e0203941
• Main Authors: Pollini, Simona, Di Pilato, Vincenzo, Landini, Giulia, Di Maggio, Tiziana, Cannatelli, Antonio, Sottotetti, Samantha, Cariani, Lisa, Aliberti, Stefano, Blasi, Francesco, Sergio, Francesco, Rossolini, Gian Maria, Pallecchi, Lucia
• Format: Article
• Language: English
• Subjects: Acetylcysteine; Anti-inflammatory agents; Antibiotics; Antiinfectives and antibacterials; Antimicrobial agents; Antioxidants; Biofilms; Biology and Life Sciences; Burkholderia cepacia; Causes of; Clinical medicine; Complications and side effects; Cystic fibrosis; Cysts; Dosage and administration; Drug resistance; Drug therapy; Genomes; Growth kinetics; Health aspects; Identification; Infections; Inflammation; Internal medicine; Kinetics; Laboratories; Medicine; Medicine and Health Sciences; Microbial drug resistance; Minimum inhibitory concentration; Multidrug resistance; Pathogens; Patients; Phenotypes; Physiological aspects; Stenotrophomonas maltophilia; Time dependence; Transplants & implants
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0203941

Stenotrophomonas maltophilia and Burkholderia cepacia complex (Bcc) have been increasingly recognized as relevant pathogens in hospitalized, immunocompromised and cystic fibrosis (CF) patients. As a result of complex mechanisms, including biofilm formation and multidrug resistance phenotype, S. maltophilia and Bcc respiratory infections are often refractory to therapy, and have been associated with a worse outcome in CF patients. Here we demonstrate for the first time that N-acetylcysteine (NAC), a mucolytic agent with antioxidant and anti-inflammatory properties, may exhibit antimicrobial and antibiofilm activity against these pathogens. The antimicrobial and antibiofilm activity of high NAC concentrations, potentially achievable by topical administration, was tested against a collection of S. maltophilia (n = 19) and Bcc (n = 19) strains, including strains from CF patients with acquired resistance traits. Minimum Inhibitory Concentrations (MICs) and Minimum Bactericidal Concentrations (MBCs) ranged from 16 to 32 mg/ml and from 32 to >32 mg/ml, respectively. Sub-MIC concentrations (i.e., 0.25 × MIC) slowed down the growth kinetics of most strains. In time-kill assays, 2-day-old biofilms were more affected than planktonic cultures, suggesting a specific antibiofilm activity of NAC against these pathogens. Indeed, a dose- and time-dependent antibiofilm activity of NAC against most of the S. maltophilia and Bcc strains tested was observed, with a sizable antibiofilm activity observed also at 0.5 and 1 × MIC NAC concentrations. Furthermore, at those concentrations, NAC was also shown to significantly inhibit biofilm formation with the great majority of tested strains.