title: Bactericidal and Fungicidal Activity ofN-Chlorotaurine Is Enhanced in Cystic Fibrosis Sputum Medium.
abstract: Lung infections with multiresistant pathogens are a major problem among patients suffering from cystic fibrosis (CF).N-Chlorotaurine (NCT), a microbicidal active chlorine compound with no development of resistance, is well tolerated upon inhalation. The aim of this study was to investigate thein vitrobactericidal and fungicidal activity of NCT in artificial sputum medium (ASM), which mimics the composition of CF mucus. The medium was inoculated with bacteria (Staphylococcus aureus, including some methicillin-resistantS. aureus[MRSA] strains,Pseudomonas aeruginosa, andEscherichia coli) or spores of fungi (Aspergillus fumigatus,Aspergillus terreus,Candida albicans,Scedosporium apiospermum,Scedosporium boydii,Lomentospora prolificans,Scedosporium aurantiacum,Scedosporium minutisporum,Exophiala dermatitidis, andGeotrichumsp.), to final concentrations of 107to 108CFU/ml. NCT was added at 37°C, and time-kill assays were performed. At a concentration of 1% (10 mg/ml, 55 mM) NCT, bacteria and spores were killed within 10 min and 15 min, respectively, to the detection limit of 102CFU/ml (reduction of 5 to 6 log10units). Reductions of 2 log10units were still achieved with 0.1% (bacteria) and 0.3% (fungi) NCT, largely within 10 to 30 min. Measurements by means of iodometric titration showed oxidizing activity for 1, 30, 60, and >60 min at concentrations of 0.1%, 0.3%, 0.5%, and 1.0% NCT, respectively, which matches the killing test results. NCT demonstrated broad-spectrum microbicidal activity in the milieu of CF mucus at concentrations ideal for clinical use. The microbicidal activity of NCT in ASM was even stronger than that in buffer solution; this was particularly pronounced for fungi. This finding can be explained largely by the formation, through transhalogenation, of monochloramine, which rapidly penetrates pathogens.
authors.affiliation: Division of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Martina
authors.initials: M
authors.lastname: Gruber
authors.affiliation: Division of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Ivan
authors.initials: I
authors.lastname: Moser
authors.affiliation: Division of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria.
authors.forename: Markus
authors.initials: M
authors.lastname: Nagl
authors.affiliation: Division of Hygiene and Medical Microbiology, Medical University of Innsbruck, Innsbruck, Austria michaela.lackner@i-med.ac.at.
authors.forename: Michaela
authors.initials: M
authors.lastname: Lackner
mesh_terms: D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000935:Antifungal Agents / Q000494:pharmacology*; D003550:Cystic Fibrosis / Q000382:microbiology; D004926:Escherichia coli / Q000187:drug effects*; D005658:Fungi / Q000187:drug effects*; D006801:Humans; D008172:Lung Diseases, Fungal / Q000188:drug therapy / Q000382:microbiology; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D013171:Spores, Bacterial / Q000187:drug effects; D013172:Spores, Fungal / Q000187:drug effects; D013183:Sputum / Q000382:microbiology*; D013654:Taurine / Q000031:analogs & derivatives* / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D000935:Antifungal Agents; D013654:Taurine; C043410:N-chlorotaurine
keywords: N-chlorotaurine; anti-infective; antimicrobial; antiseptic; cystic fibrosis; lung