“…The additional strains of S. aureus (Smith diffuse and clinical isolates of MRSA) showed curves almost identical to that of MRSA strain 43300. The activity of 1% NCT, summing up the whole course of killing (i.e., bactericidal activity [BA] values [38]), is presented in Table 1; higher values indicate greater microbicidal activity.…”
Section: Resultsmentioning
confidence: 99%
“…The recently introduced BA values allow a very good survey and render such trends immediately visible (38). The broad-spectrum activity of NCT is unsurprising, taking into account the oxidizing mechanism of action, with numerous sites of attack (22,23).…”
Section: Discussionmentioning
confidence: 99%
“…*, P Ͻ 0.05; **, P Ͻ 0.01, versus control without NCT. versus time) into one value of bactericidal activity (BA) (38). Moreover, the method allows expanded statistical analysis, particularly between killing curves with small differences.…”
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 the in vitro bactericidal 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-resistant S. aureus [MRSA] strains, Pseudomonas aeruginosa, and Escherichia coli) or spores of fungi (Aspergillus fumigatus, Aspergillus terreus, Candida albicans, Scedosporium apiospermum, Scedosporium boydii, Lomentospora prolificans, Scedosporium aurantiacum, Scedosporium minutisporum, Exophiala dermatitidis, and Geotrichum sp.), to final concentrations of 10 7 to 10 8 CFU/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 10 2 CFU/ml (reduction of 5 to 6 log 10 units). Reductions of 2 log 10 units 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 Ͼ60 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.
“…The additional strains of S. aureus (Smith diffuse and clinical isolates of MRSA) showed curves almost identical to that of MRSA strain 43300. The activity of 1% NCT, summing up the whole course of killing (i.e., bactericidal activity [BA] values [38]), is presented in Table 1; higher values indicate greater microbicidal activity.…”
Section: Resultsmentioning
confidence: 99%
“…The recently introduced BA values allow a very good survey and render such trends immediately visible (38). The broad-spectrum activity of NCT is unsurprising, taking into account the oxidizing mechanism of action, with numerous sites of attack (22,23).…”
Section: Discussionmentioning
confidence: 99%
“…*, P Ͻ 0.05; **, P Ͻ 0.01, versus control without NCT. versus time) into one value of bactericidal activity (BA) (38). Moreover, the method allows expanded statistical analysis, particularly between killing curves with small differences.…”
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 the in vitro bactericidal 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-resistant S. aureus [MRSA] strains, Pseudomonas aeruginosa, and Escherichia coli) or spores of fungi (Aspergillus fumigatus, Aspergillus terreus, Candida albicans, Scedosporium apiospermum, Scedosporium boydii, Lomentospora prolificans, Scedosporium aurantiacum, Scedosporium minutisporum, Exophiala dermatitidis, and Geotrichum sp.), to final concentrations of 10 7 to 10 8 CFU/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 10 2 CFU/ml (reduction of 5 to 6 log 10 units). Reductions of 2 log 10 units 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 Ͼ60 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.
“…** P < 0.01 versus all other values. BA “bactericidal activity” [log 10 cfu/min] as a quantitative measure for the strength of killing calculated by the integral method for the whole killing curve according to (Gottardi et al 2015). The higher the value, the higher the microbicidal activityFig.…”
Section: Resultsmentioning
confidence: 99%
“…To gain an improved survey on the microbicidal activity of NCT against the different strains, the recently introduced Integral Method was used, which transforms the whole killing curve (log 10 cfu/ml versus time) into one value of “bactericidal activity (BA)” (Gottardi et al 2015). The higher the value, the stronger is the microbicidal activity.…”
N-chlorotaurine (NCT) and hydrogen peroxide are powerful endogenous antiseptics. In vivo, the reaction between hydrogen peroxide and metal ions leads to the formation of free hydroxyl radicals, which have an increased bactericidal activity. This study examined whether there is an additive antimicrobial effect of NCT combined with hydrogen peroxide. Additionally, it was tested if the additive effect is based on the formation of free radicals. We found by luminometry that, in the presence of H 2 O 2 , NCT caused a slow and long-lasting production of singlet oxygen in contrast to HOCl, where this burst occurred instantaneously. Both NCT and hydrogen peroxide (1.0 and 0.1%) demonstrated bactericidal and fungicidal activity. At pH 7.1 and 37 °C, hydrogen peroxide (1%, 294 mM) showed a stronger bactericidal and particularly fungicidal activity than NCT (1%, 55 mM), whereas at pH 4.0 and also in the presence of 5.0% peptone NCT revealed a stronger bactericidal activity. A combination of NCT and hydrogen peroxide led to an increased bactericidal but no increased fungicidal activity compared to both substances alone. The additive effect against bacteria was not removed in the presence of the radical scavengers NaN 3 , DMSO, or peptone. As a conclusion, NCT and hydrogen peroxide used concurrently interact additive against a range of microorganisms. However, the results of this study suggest that the additive effect of NCT combined with hydrogen peroxide is rather not based on the formation of free radicals.
N-Chlorotaurine (NCT) is a mild long-lived oxidant that can be applied to sensitive body regions as an endogenous antiseptic. Enhancement of its microbicidal activity in the presence of proteinaceous material because of transchlorination, a postantibiotic/postantifungal effect and antitoxic activity renders it interesting for treatment of fungal infections, too. This is confirmed by first case applications in skin and mucous membranes of different body sites. Recent findings of good tolerability of inhaled NCT suggest further investigations of this substance for treatment of bronchopulmonary diseases, where microorganisms play a role, particularly multi-resistant ones. The availability of a well-tolerated and effective inhaled antiseptic with anti-inflammatory properties could be a significant progress, in particular for chronic pulmonary diseases, such as chronic obstructive pulmonary disease or cystic fibrosis.
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