Kerato-konjunktivitis - zánět spojivek - rohovky
N-Chlorotaurine (Cl–HN–CH2–CH2–SO3H, NCT)
- Adenoviral keratoconjunctivitis
- N-Chlorotaurine (Cl–HN–CH2–CH2–SO3H, NCT) is the N-chloro derivative of the amino acid taurine
- Oxidant produced by human granulocytes and monocytes during inflammatory reactions
- NCT causes inactivation of several human adenovirus (HAdV) serotypes
A549 cells + HAdV serotypes 3, 4, 8, 19, and 37 were used.
- 50% cytotoxic concentration (CC50) of NCT for 7 days, and extracted adenoviral DNA was quantitatively measured by real-time PCR.
- A statistically significant (P < 0.05) dose-dependent inhibition was indicated for all serotypes except HAdV type 4 (HAdV4)
- Which was maximally inhibited by only ~50%
- NCT was particularly effective against HAdV8, HAdV19a, and HAdV37
- 50% effective concentration (EC50) obtained by real-time PCR of NCT ranged between 49 and 256 uM.
- EC50 of NCT against HAdV3 was slightly higher than that against serotypes of species D.
- The selective index (CC50/EC50) ranged between 41 and 60 except for HAdV4 (11.5).
- Results show that NCT has an antiviral effect against most serotypes of human HAdV inducing keratoconjunctivitis, indicating its possible therapeutic use.
N-chlorotaurine (NCT),
- Assess the tolerability and efficacy of N-chlorotaurine (NCT), an endogenous antimicrobial agent, in epidemic keratoconjunctivitis. In a prospective double- blind, randomized phase 2b study, the infected eyes were treated for 7 days with eye drops containing 1% aqueous solution of N-chlorotaurine (33 subjects) or gentamicin (27 subjects, control group). Adenovirus types 3, 4, 8, 19, and 37 were detected in 39 subjects (65%), enteroviruses in 8 (13.3%), and staphylococci in 5 (8.3%). Subjective and objective symptoms were scaled and added to a subjective and objective score, respectively, on day 1 (baseline), day 4, and day 8. Analyzing the whole study population, the subjective score on day 8 was lower in the NCT group (P = 0.016), whereas there were no differences in the objective score. However, in severe infections caused by adenovirus type 8 (n = 20) both the subjective and objective score were lower in the NCT group on day 4 (P = 0.003 and 0.015, respectively), which was also true for the subjective score on day 8 (P = 0.004) in this subgroup. The frequency of subepithelial infiltrates was similar in both groups. N-chlorotaurine was well-tolerated, shortened the duration of illness, and seems to be a useful causative therapeutic approach in severe epidemic keratoconjunctivitis.
May 2005Volume 46, Issue 13‹ISSUE›FREEARVO Annual Meeting Abstract | May 2005Topical N–Chlorotaurine (NCT), an Endogenous Microbicidal Oxidant, Inhibits Adenovirus Replication in the Ad5/NZW Rabbit Ocular ModelK.A. Yates; E.G. Romanowski; B. Teuchner; M. Nagl; W. Gottardi; Y.J. Gordonhttps://iovs.arvojournals.org/article.aspx?articleid=2400161
N–chlorotaurine (NCT), an endogenous microbicidal oxidant produced by stimulated human leukocytes, has broad spectrum antimicrobial activity against bacteria, virus, fungi and parasites. NCT demonstrated no ocular toxicity in Phase 1 clinical trials. NCT demonstrated concentration–dependent direct inactivation of multiple ocular adenovirus (Ad) serotypes in vitro (ARVO 2002). In the current in vivo study, we determined the antiviral effect of topical NCT on acute Ad replication in the Ad5/NZW rabbit ocular model. Methods: 50 NZW rabbits were topically inoculated in both eyes, following corneal scarification, with 1.5 x 106 pfu/eye of Ad5. On day 1, the rabbits were divided into 5 topical treatment groups containing 10 rabbits each: I – 2.5% NCT; II – 2.0% NCT; III – 1.0% NCT; IV – 0.5% Cidofovir (CDV); V – Control (saline). NCT and Control rabbits were treated in both eyes 10 times daily for 1 day and 5 times daily for 6 days, while CDV rabbits were treated in both eyes twice daily for 7 days. All eyes were cultured for virus on days 0, 1, 3, 4, 5, 7, 9, 11, and 14. Results: 2.5% NCT (74/159, 46.5%), 2.0% NCT (75/152, 49.3%), 1.0% NCT (82/152, 53.9%), and 0.5% CDV (67/160, 41.9%) demonstrated significantly fewer Positive Cultures per Total Days 1–14 compared with the Control (115/160, 71.9%) (p < 0.001, Chi–square). On a daily basis, 2.5% NCT (Days 1, 4, 5, 7), 2.0% NCT (Days 1, 4, 5), 1.0% NCT (Day 1, 4, 5), and 0.5% CDV (Day 4, 5, 7) all demonstrated significantly fewer Positive Cultures per Total compared with the Control (p < 0.035, Chi–square). Conclusions: Topical NCT appears to be a promising candidate as a broad spectrum topical antimicrobial. Additional studies to evaluate the antiviral properties of NCT in the experimental Ad5/NZW ocular model are indicated.
The topical 0.66% PVP-I showed to be well tolerated, and it seemed to be effective especially in IKs of Gram-positive bacterial origin. At T1, eyes in this category showed significant improvement in both the ulcer and infiltrate areas and a reduction in ulcer depth. Actually, 38.5% of Gram-positive IK showed complete resolution and did not need to start any antibiotic therapy. On the other hand, while fungal IK showed little improvement in their infiltrate areas and ulcer depths, Gram-negative bacterial IK showed a slight increase in ulcer and infiltrate areas and ulcer depths.In this regard, it should be emphasized that all the eyes included in the fungal category and all of those with a Gram-negative infection were respectively infected by Candida albicans and Pseudomonas aeruginosa, two microorganisms with different pathogenetic mechanisms [5,25,26]. Pseudomonas aeruginosa is a very invasive bacterium; nevertheless, no statistically significant clinical worsening was found at T1. It should be related to the different time-to-result period required between fungi and bacteria: 48 h for Gram-negative bacteria and 6 days for fungal infections.Notably, the administration of PVP-I showed effectiveness in 36.0% of cases, 55.6% of which were in the Gram-positive and 11.1% in the fungal category. In the latter group, the empirical antibiotic could have actually worsened the patients’ condition due to the interference with the normal microbial competition [27].The apparent effectiveness of PVP-I on Gram-positive bacteria is encouraging. Despite being less virulent than Gram-negative bacteria, IK related to these microorganisms are one of the most common causes of ocular surface infections.A recent randomized controlled trial demonstrated that 1.25% PVP-I eye drops were as effective as topical antibiotics against both gram-negative and gram-positive bacteria [15]. It is conceivable that this concentration of PVP-I has greater efficacy against the Pseudomonas aeruginosa than the 0.66% one. However, in this study we utilized the 0.66% concentration because it is the only ophthalmic formulation available on the Italian market.At T1, three cultural tests displayed no growth, likely due to a low microbial load or to the presence of a sterile infiltrate. In such cases, the topical administration of 0.66% PVP-I represents a further reason to avoid an empirical therapy, which would have been unneeded and potentially detrimental.It is conceivable that the administration of PVP-I during the time-to-result period might have actually contributed to the relatively fast healing time (T1-TL) displayed in our study [10]. Indeed, while waiting for the cultural results to start the targeted therapy, thanks to its broad-spectrum activity, this antiseptic agent held back the IK of all origins.Despite the recent increased interest in low dosage Povidone-Iodine as a broad spectrum, low-cost, resistant-free antimicrobic agent [28], there is still limited strong evidence of its in vivo effectiveness in cases of IK [14,15,29,30,31], however, it suggests positive clinical outcomes. Herein, we present the first study to evaluate the role of 0.66% PVP-I during the time-to-results period of IK.There are several limitations to this study. First, since this was an exploratory study, we included a limited number of patients useful for a preliminary test of our hypothesis. Second, we excluded patients with protozoan cysts or fungal hyphae detected on in vivo confocal microscopy evaluation, and IK showing impending perforations. Therefore, our results cannot be applied to all types of IK.Further investigations including a larger number of patients in each of the four microbial categories will reduce the variability of the data we found in the present study.Nonetheless, the administration of topical PVP-I showed to be a safe strategy in patients with IK in order to avoid progression of the infection and is possibly effective against Gram-positive IK.https://www.mdpi.com/2077-0383/11/3/848
