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The stable N-bromotaurine analogs (N-dibromo-dimethyl taurine, N-monobromo-dimethyl taurine), and bromamine T (BAT) show anti-inflammatory and microbicidal properties. These bromamines are good candidates for a treatment of skin infectious/inflammatory diseases as local antiseptics. Ibuprofen, a non-steroidal anti-inflammatory drug (NSAID), is commonly used in various infectious/inflammatory diseases due to its analgesic and antipyretic therapeutic effects. However, systemic administration of ibuprofen may also result in adverse side effects. It has been reported that ibuprofen enhances serum levels of TNF-α and worsens secondary skin infections caused by invasive streptococci (S. pyogenes). Recently we have demonstrated that bromamines inhibit the stimulatory effect of ibuprofen on the production of inflammatory cytokines (TNF-α, IL-6). The aim of this study was to examine the combined antibacterial actions of ibuprofen and bromamines against S. pyogenes and their joint effect on the generation of reactive oxygen species (ROS) by activated neutrophils and macrophages. We have shown that the microbicidal activity of bromamines against S. pyogenes was not altered by ibuprofen. On the other hand, co-administration of ibuprofen and bromamines markedly decreased the generation of ROS by activated neutrophils and macrophages. Finally, we discuss how the antioxidant combined effect of bromamines and ibuprofen may affect a local defense system.

Taurine haloamines (N-chlorotaurine, N-bromotaurine) due to their strong antiseptic and anti-inflammatory properties are good candidates for topical application in treatment of skin inflammatory/infectious disorders. Recently, we have demonstrated that more stable N-bromotaurine analogs (N-dibromo-dimethyl taurine, N-monobromo-dimethyl taurine) and bromamine T show strong microbicidal and anti-inflammatory properties at concentrations well tolerated by human cells and tissue. Non-steroidal anti-inflammatory drugs (NSAIDs) with cyclooxygenase (COX) inhibitory activity are commonly used in various inflammatory diseases. However, systemic administration of NSAIDs may result in adverse side effects. For example, the use of ibuprofen in children with varicella is associated with enhanced serum levels of TNF-α and with increased risk of necrotizing soft tissue infections and secondary skin infections caused by invasive streptococci. The aim of this study was to examine combined immunomodulatory effects of bromamines and ibuprofen on J774.A1 macrophages. We have shown that the primary activity of ibuprofen, the inhibition of PGE2 production by activated macrophages was intensified in the presence of bromamines. Most importantly, the stimulatory effect of ibuprofen on production of inflammatory cytokines (TNF-α, IL-6) was inhibited by all tested bromamines. These observations indicate that bromamines may neutralize massive production of TNF-α at sites of inflammation, a side effect of ibuprofen. Therefore, we suggest that systemic administration of ibuprofen (NSAIDs) in treatment of inflammatory/infectious skin diseases should be supported by topical application of bromamines as an adjunctive therapy.

Formation of bacterial biofilm on dental surfaces is characteristic for existence of oral microbiota. It was also proved that uncontrolled biofilms on dental surfaces, as well as on biomaterials used in dentistry, are the main cause of oral cavity diseases such as dental caries and periodontitis. For years chlorhexidine (CHX) has been known as an excellent antiseptic and anti-biofilm agent. However, due to some of its unwanted adverse effects novel antiseptics are currently being tested by many laboratories. Our preliminary data have suggested that taurine bromamine (TauBr), a strong antiseptic against planktonic form of various bacteria and an anti-inflammatory agent, may also be a good candidate for treatment of biofilm-associated infections. Nevertheless, beneficial therapeutic effect of TauBr in the treatment of inflammatory acne lesions was not fully supported in vitro in the experimental model of Pseudomonas aeruginosa biofilm. Such discrepancies may be explained by distinct antiseptic resistance of biofilms generated by different microbial species. In this study we have extended the investigations of anti-biofilm properties of TauBr using novel in vitro models of Streptoccocus mutans and Candida albicans biofilms formed on orthodontic appliances. The ability of TauBr to kill the experimental pathogens hidden in a mature biofilm was compared with that of CHX.

Formation of biofilm is observed in a majority of chronic bacterial skin infections such as non-healing wounds. These infections are persistent as they show increased resistance to antibiotics. Moreover, bacteria hidden in biofilm are protected from the host defence system. It raises serious therapeutic problems in human and veterinary medicine. Therefore, novel anti-biofilm therapeutic strategies should be used. It has been shown in vitro that taurine bromamine (TauBr), the product of reaction between taurine and hypobromous acid (HOBr), exerts anti-microbial properties against planktonic form of various bacteria. Moreover, clinical studies have shown that TauBr is effective in the local treatment of skin and mucosa chronic infections. Nevertheless, it is still not clear whether it can kill bacteria hidden in a biofilm or destroy biofilm and enhance the effect of antibiotics. In this study we have investigated the capacity of TauBr to inhibit in vitro the formation of P. aeruginosa biofilm. Preformed biofilm was treated with TauBr alone or TauBr and ciprofloxacin, the antibiotic commonly used in skin infections. Efficacy of TauBr was compared with that of chlorhexidine (CHX), the most effective anti-biofilm agent that has been developed to date. Our results show that TauBr and CHX are able to inhibit the formation of P. aeruginosa biofilm in vitro but only CHX destroys the mature biofilm and effectively kills hidden bacteria. In contrast, only TauBr shows antioxidant properties. It therefore suggests that CHX and TauBr could be combined in treatment of chronic infections associated with biofilm formation and generation of oxidative stress.

antibiotic resistance is a common problem accompanying biofilm-associated chronic infections. new therapeutic strategies are based on a combined application of antiseptics with anti-biofilm agents. Taurine haloamines, taurine chloramine (Taucl) and taurine bromamine (TauBr), show antimicrobial and anti-inflammatory properties, which have been examined in a variety of local infections, including biofilm-associated infections. in contrast to beneficial antimicrobial effects of taurine haloamines against the planktonic form of bacteria, their efficacy against bacteria hidden in biofilm need to be enhanced. one possibility is to use them together with agents capable of destroying components of biofilm matrix. in this study we ask a question whether Taucl or TauBr are effective in killing streptococcus mutans and Porphyromonas gingivalis, major oral bacteria responsible for the development of dental plaque and pathogenesis of periodontal diseases. Moreover, we have examined TauBr and Taucl stability in the presence of n -acetylcysteine ( nac ) and dn ase, agents with known anti-biofilm activity. We have found that TauBr was much stronger than Taucl microbicidal agent against both tested bacterial strains. however, TauBr was less stable than Taucl. nac readily decomposed TauBr but not Taucl. in addition, TauBr inhibited dnase activity, when used in excess. This preliminary study confirms previous opinions that taurine haloamines have great potential in killing oral bacteria. however, further studies are necessary to find anti-biofilm agent(s) which together with Taucl/TauBr will give at least an additive therapeutic effect in the treatment of chronic infections, to support or replace ineffective antibiotic therapy.