N -Chloramines, a Promising Class of Well-Tolerated Topical Anti-Infectives

Abstract

Antibiotic resistance is a growing public health crisis. To address the development of bacterial resistance, the use of antibiotics has to be minimized for nonsystemic applications in humans, as well as in animals and plants. Possible substitutes with low potential for developing resistance are active chlorine compounds that have been in clinical use for over 180 years. These agents are characterized by pronounced differences in their chlorinating and/or oxidizing activity, with hypochlorous acid (HOCl) as the strongest and organic chloramines as the weakest members. Bacterial killing in clinical practice is often associated with unwanted side effects such as chlorine consumption, tissue irritation, and pain, increasing proportionally with the chlorinating/oxidizing potency. Since the chloramines are able to effectively kill pathogens (bacteria, fungi, viruses, protozoa), their application as anti-infectives is advisable, all the more so as they exhibit additional beneficial properties such as destruction of toxins, degradation of biofilms, and anticoagulative and anti-inflammatory activities. Within the ample field of chloramines, the stable N-chloro derivatives of ß-aminosulfonic acids are most therapeutically advanced. Being available as sodium salts, they distinguish themselves by good solubility and absence of smell. Important representatives are N-chlorotaurine, a natural compound occurring in the human immune system, and novel mono-and dichloro derivatives of dimethyltaurine, which feature improved stability.

Bactericidal Activity of N -Chlorotaurine against Biofilm-Forming Bacteria Grown on Metal Disks

“…NCT completely eradicated the biofilm in our study, so it can be concluded that it kills bacteria independently of protein production, cell cycle, or proliferation. This is in accordance with its oxidative mechanism of action (5,21) and with its efficacy in treatment of infections of different body sites in humans (for a review, see reference 5). For instance, successful application was demonstrated in purulently coated crural ulcerations and in external otitis in humans (22,23).…”

“…However, the mild activity and high tolerability of N-chloro amino acids, particularly NCT, enable application of high concentrations to human tissue, which warrants a sufficient reserve of oxidation capacity despite some reduction (20). This can be of advantage compared with highly reactive oxidants that cause side effects at higher dosages (21). Accordingly, NCT was shown to be effective in topical therapy of infections where biofilms play a role, for instance, purulently coated crural ulcerations and external otitis in humans (22,23) and joint infections in mice (7).…”

N -Chlorotaurine Exhibits Fungicidal Activity against Therapy-Refractory Scedosporium Species and Lomentospora prolificans

“…As a representative of the active chlorine compounds, NCT exerts broad-spectrum microbicidal activity against all kinds of pathogens (11,12), which is typical for this class of antiseptics. Due to its low reactivity, which is the reason for its good tolerability in sensitive body regions (12), its killing activity against microorganisms is slower than that with highly reactive compounds, like hypochlorous acid (11,34).…”

“…Due to its low reactivity, which is the reason for its good tolerability in sensitive body regions (12), its killing activity against microorganisms is slower than that with highly reactive compounds, like hypochlorous acid (11,34). In previous studies (20,21,35), killing of different Candida species and molds needed incubation times of one or only few hours, and in the present study, that against Scedosporium spp.…”

“…For topical treatment of Scedosporium and Lomentospora infections, the use of antiseptics of the class of chloramines is conceivable (11). In particular, N-chlorotaurine (NCT), an endogenous long-lived oxidant produced by activated granulocytes and monocytes, comes into question (12).…”