Acute Otitis Externa: Efficacy and Tolerability of N‐Chlorotaurine, a Novel Endogenous Antiseptic Agent

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Many orthopedic surgeons consider surgical irrigation and debridement with prosthesis retention as a treatment option for postoperative infections. Usually, saline solution with no added antimicrobial agent is used for irrigation. We investigated the activity of N-chlorotaurine (NCT) against various biofilm-forming bacteria in vitro and thereby gained significant information on its usability as a soluble and well-tolerated active chlorine compound in orthopedic surgery. Biofilms of Staphylococcus aureus were grown on metal alloy disks and in polystyrene dishes for 48 h. Subsequently, they were incubated for 15 min to 7 h in buffered solutions containing therapeutically applicable concentrations of NCT (1%, 0.5%, and 0.1%; 5.5 to 55 mM) at 37°C. NCT inactivated the biofilm in a time-and dose-dependent manner. Scanning electron microscopy revealed disturbance of the biofilm architecture by rupture of the extracellular matrix. Assays with reduction of carboxanilide (XTT) showed inhibition of the metabolism of the bacteria in biofilms. Quantitative cultures confirmed killing of S. aureus, Staphylococcus epidermidis, and Pseudomonas aeruginosa biofilms on metal alloy disks by NCT. Clinical isolates were slightly more resistant than ATCC type strains, but counts of CFU were reduced at least 10-fold by 1% NCT within 15 min in all cases. NCT showed microbicidal activity against various bacterial strains in biofilms. Whether this can be transferred to the clinical situation should be the aim of future studies.

Section: Discussionmentioning

confidence: 60%

“…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).…”

Section: Discussionmentioning

confidence: 99%

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

Coraça‐Huber

Ammann

Fille

et al. 2014

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“…The remarkable enhancement of the killing of molds (and of bacteria and protozoa) by the addition of NH 4 Cl to NCT known from previous studies (21,23,36) was also confirmed to a similar extent against Scedosporium. Due to the more rapid killing of microorganisms in body fluids and exudates, and due to the successful therapeutic application of NCT in humans and animals (14,15,21,23,37,38), we are convinced that this effect plays a role in vivo. It is explained by the formation of monochloramine (NH 2 Cl) in equilibrium with NCT (36,39).…”

Section: Discussionmentioning

confidence: 99%

“…Because of the oxidative mechanism of action, NCT has typical broad-spectrum microbicidal activity against bacteria, viruses, fungi, and protozoa (12). Phase II clinical studies in conjunctivitis (13), external otitis (14), crural ulcers (15), and in the oral cavity (16) have already demonstrated its tolerability and therapeutic efficacy, and further applications are being investigated, e.g., via inhalation (17,18).…”

mentioning

confidence: 99%

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

Lackner

Binder

Reindl

et al. 2015

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N-Chlorotaurine (NCT), a well-tolerated endogenous long-lived oxidant that can be applied topically as an antiseptic, was tested on its fungicidal activity against Scedosporium and Lomentospora, opportunistic fungi that cause severe infections with limited treatment options, mainly in immunocompromised patients. In quantitative killing assays, both hyphae and conidia of Scedosporium apiospermum, Scedosporium boydii, and Lomentospora prolificans (formerly Scedosporium prolificans) were killed by 55 mM (1.0%) NCT at pH 7.1 and 37°C, with a 1-to 4-log 10 reduction in CFU after 4 h and a 4-to >6-log 10 reduction after 24 h. The addition of ammonium chloride to NCT markedly increased this activity. LIVE/DEAD staining of conidia treated with 1.0% NCT for 0.5 to 3 h increased the permeability of the cell wall and membrane. Preincubation of the test fungi in 1.0% NCT for 10 to 60 min delayed the time to germination of conidia by 2 h to >12 h and reduced their germination rate by 10.0 to 100.0%. Larvae of Galleria mellonella infected with 1.0 ؋ 10 7 conidia of S. apiospermum and S. boydii died at a rate of 90.0 to 100% after 8 to 12 days. The mortality rate was reduced to 20 to 50.0% if conidia were preincubated in 1.0% NCT for 0.5 h or if heat-inactivated conidia were used. Our study demonstrates the fungicidal activity of NCT against different Scedosporium and Lomentospora species. A postantifungal effect connected with a loss of virulence occurs after sublethal incubation times. The augmenting effect of ammonium chloride can be explained by the formation of monochloramine.

“…HOCl solutions are still of interest, as can be derived from a recent study on the treatment of chronic venous leg ulcers (11). A completely new anti-infective concept was the introduction of a chloramine in the form of the natural compound N-chlorotaurine (NCT), which was successfully used in several clinical studies (12)(13)(14)(15)(16)(17)(18)(19)(20)(21). In a comparative trial on chronic leg ulcers, NCT showed the same efficacy as chloramine T but induced significantly less pain (17).…”

Section: Active Halogen Compoundsmentioning

confidence: 99%

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

Gottardi

Debabov

Nagl

2013

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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.