Antimicrobial and Anticoagulant Activities of
 N
 -Chlorotaurine,
 N
 ,
 N
 -Dichloro-2,2-Dimethyltaurine, and
 N
 -Monochloro-2,2-Dimethyltaurine in Human Blood

Martini, Camila de David Tessele; Hammerer-Lercher, Angelika; Zuck, Meghan; Jekle, Andreas; Debabov, Dmitri; Anderson, M. E.; Nagl, Markus

doi:10.1128/aac.05685-11

Cited by 20 publications

(16 citation statements)

References 26 publications

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“…NCT was investigated for nearly 15 years, and its anti-infective usefulness has been confirmed to date by numerous studies (reviewed in reference 49). DM-NCT and DM-NDCT, on the other hand, are new compounds, whose anti-infective properties are currently explored in detail, yielding promising results, which confirm them as equivalent to NCT (23,25,(50)(51)(52). Specifically, DM-NDCT (NVC-422) is active against a broad range of Gram-positive and Gram-negative bacteria, including drug-resistant pathogens (25), without generating resistance in multiplepassage studies (53).…”

Section: Choosing Suitable Candidates For Anti-infective Applicationmentioning

confidence: 96%

“…An impressive example concerns NCT and the very reactive hypochlorous acid (HOCl). While the consumption of HOCl is twice as high (45), the bactericidal effect, however, is approximately 10,000-fold higher (51,67,68). This astonishing result can be reduced to both the faster penetration of HOCl and its superior oxidizing activity (see above), which causes immediate inactivation of S-H and S-CH 3 functions of vitally essential enzymes.…”

Section: Nonmicrobicidal Effects Caused By Chloramine Compoundsmentioning

confidence: 99%

“…To manage these problems, two agents are necessary, a bactericidal one and an anticoagulant one, the latter, in general, heparin. Therefore, the discovery of the anticoagulant activity of active chlorine compounds (51,60,61) represented important progress because it suggests the use of a single agent for both jobs. On the grounds of their low oxidizing potency, N-chloramines are especially favored because, in the presence of up to 75% blood, they are not completely consumed at clinically applicable concentrations and are still active and because they do not interact with heparin, which may be used in combination with, e.g., NCT or DM-NDCT (51).…”

Section: Nonmicrobicidal Effects Caused By Chloramine Compoundsmentioning

confidence: 99%

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

Gottardi

Debabov

Nagl

2013

Antimicrob Agents Chemother

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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.

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Section: Choosing Suitable Candidates For Anti-infective Applicationmentioning

confidence: 96%

Section: Nonmicrobicidal Effects Caused By Chloramine Compoundsmentioning

confidence: 99%

Section: Nonmicrobicidal Effects Caused By Chloramine Compoundsmentioning

confidence: 99%

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

Gottardi

Debabov

Nagl

2013

Antimicrob Agents Chemother

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“…Its bactericidal activity against S. aureus and S. epidermidis in biofilm (reduction of CFU to the detection limit by 1% NCT needed about 30 to 60 min [ Fig. 3]) appears approximately 3 to 6 times slower than that against planktonic bacteria (10 min for a reduction to the detection limit [9,10]) but is still sufficient. Remarkably, viable counts of all tested bacteria in biofilm were reduced by at least 1 power of 10 after 15 min of incubation in 1% NCT, so that an impact on biofilm by irrigations with NCT can be conceived in vivo.…”

Section: Discussionmentioning

confidence: 99%

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

Coraça‐Huber

Ammann

Fille

et al. 2014

Antimicrob Agents Chemother

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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.

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“…The plates were incubated at 37 ± 1 °C for 24 h and the numbers of fungal CFU were counted and assessed, considering the duplicity and the dilution [6]. …”

mentioning

confidence: 99%

Biliary amphotericin B pharmacokinetics and pharmacodynamics in critically ill liver transplant recipients receiving treatment with amphotericin B lipid formulations

Welte¹,

Eschertzhuber²,

Weiler³

et al. 2015

International Journal of Antimicrobial Agents

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Fungal cholangitis is a potentially life-threatening condition. As amphotericin B (AmB) has a broad antimycotic spectrum, in this study its biliary penetration and activity was determined in two patients treated with liposomal AmB (L-AmB) and in one patient receiving AmB colloidal dispersion (ABCD). Biliary and plasma AmB levels were quantified by high-performance liquid chromatography after purification by solid-phase extraction. For assessment of biliary AmB activity, isolates of Candida albicans, Candida tropicalis, Candida glabrata and Candida krusei were incubated in porcine bile at AmB concentrations of 0.025-5.00 mg/L. In addition, patient bile samples retrieved for AmB quantification were inoculated with the same Candida strains. Biliary AmB concentrations were lower and displayed a slower rise and decline than plasma levels. The highest penetration ratio, as expressed by the ratio between the area under the AmB concentration-time curve in bile and plasma (liberated AmB) over the sampling period (AUC0-n bile/AUC0-n LI plasma), was 0.28. Proliferation of C. albicans and C. tropicalis in bile was similar to that in culture medium, whereas growth of C. glabrata was diminished and proliferation of C. krusei was absent in bile. In comparison with culture medium, AmB activity decreased in spiked porcine bile. In all but one patient bile sample, fungal growth was delayed or lacking even when AmB was not detectable. However, no fungicidal effect was observed in patient bile at AmB concentrations up to 1.28 mg/L. Thus, a reliable response of fungal cholangitis to treatment with L-AmB or ABCD cannot be anticipated. Biliary AMB concentrations were lower and displayed a slower rise and decline than plasma levels. The highest penetration ratio as expressed by the ratio between the area under the time-AMB-concentration curve in bile and plasma (liberated AMB) over the sampling period (AUC 0-n bile /AUC 0-n LI plasma ) amounted to 0.28. Proliferation of C. albicans and C. tropicalis in bile was similar to that in culture medium whereas growth of C. glabrata was diminished and proliferation of C. krusei was absent in bile. In comparison with medium, AMB activity decreased in spiked porcine bile. In all but one patient bile sample, fungal growth was delayed or lacking, even when AMB was not detectable. However, no fungicidal effect was observed in patient bile at AMB concentrations of up to 1.28 mg/L. Thus, a reliable response of fungal cholangitis to treatment with LAMB or ABCD cannot be anticipated.

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Antimicrobial and Anticoagulant Activities of N -Chlorotaurine, N , N -Dichloro-2,2-Dimethyltaurine, and N -Monochloro-2,2-Dimethyltaurine in Human Blood

Cited by 20 publications

References 26 publications

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

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

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

Biliary amphotericin B pharmacokinetics and pharmacodynamics in critically ill liver transplant recipients receiving treatment with amphotericin B lipid formulations

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