Activity of disinfectants against Gram-negative bacilli isolated from patients undergoing lung transplantation for cystic fibrosis.

Lung transplant recipients with cystic fibrosis are frequently colonized with antibiotic-resistant bacteria. We evaluated the in vitro activity of 5 disinfectants frequently used in cardiac surgery against strains of Burkholderia cepacia and Pseudomonas aeruginosa isolated from patients undergoing sequential single lung transplantation. Our results suggest that the activity of Taurolin and Noxyflex is superior to conventional disinfectants.

The activity of locally applied cytotoxics to breast cancer cells in vitro.

The ability of commonly used operative lavage solutions to destroy breast cancer cells was investigated. The cytotoxicity of solutions of Savlon, noxythiolin, povidone iodine, hydrogen peroxide, bleomycin and water on two human breast cancer cell lines was measured in vitro. Viable cells were determined by ability to exclude trypan blue. Results have been analysed with standard non-parametric tests and demonstrate that all solutions tested significantly (P less than 0.01) reduced the number of viable cells recovered when compared with a control solution of phosphate buffered saline. Solutions of Savlon, 2.5% noxythiolin and povidone iodine were more effective than the other agents in reducing the number of recovered viable cells.

In-vitro antibacterial activity of noxythiolin and taurolidine.

The minimum inhibitory concentrations (MIC) of noxythiolin and taurolidine were determined for strains of Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa. Tests were performed in broth alone and in broth plus 25% v/v serum or 25% v/v urine. Inoculum density was either 10(3), 10(5) or 10(7) colony forming units per mL-1. Slight inoculum-dependent variation in the activity of both agents was observed for some, but not all, strains of P. aeruginosa and S. aureus. A more pronounced medium-dependent increase in activity was observed with both drugs, with up to 8-fold reduction of values for MIC when tested in the presence of serum or urine. These observations may help to clarify the disparity between the observed clinical efficacy of these agents and relatively poor in-vitro activity when tested using conventional methods in synthetic media.

Sustained anti-adherence activity of taurolidine (Taurolin) and noxythiolin (Noxyflex S) solutions.

Taurolidine (2% w/v) and noxythiolin (1% w/v and 2.5% w/v) solutions inhibit the adherence in-vitro of Escherichia coli and Staphylococcus aureus to human epithelial and fibroblast cells. This effect, demonstrable after 30 min exposure of cells to test drugs, persists after removal of the active compound. Significantly reduced adherence of bacteria is apparent for 5 h after taurolidine treatment and for 6 h after treatment with 2.5% noxythiolin. Anti-adherence activity of taurolidine and noxythiolin may contribute to the observed clinical efficacy of these agents.

The differential cytotoxicity of antiseptic agents.

The cytotoxicity of the antiseptic agents noxythiolin and chlorhexidine has been evaluated in-vitro using a range of tissue culture cell lines of differing degrees of neoplasticity. Noxythiolin appeared more cytotoxic than did chlorhexidine when tested against established neoplastic cell lines. By contrast, noxythiolin was not cytotoxic to normal control (non-neoplastic) cells. For chlorhexidine, the cytotoxic activity against control cells was similar to that observed for neoplastic cell lines. The results confirm an earlier observation of limited antitumour activity of noxythiolin solutions and, on the basis of differential cytotoxicity, confirm that noxythiolin is free from adverse effects against normal tissues and is safe for use as an antimicrobial agent applied to peritoneal surfaces and the healing wound.

Decrease in adherence of bacteria and yeasts to human mucosal epithelial cells by noxythiolin in vitro.

Adherence of buccal and vaginal isolates of Candida albicans to buccal epithelial cells and the adherence of urine isolates of Escherichia coli and Staphylococcus saprophyticus to uroepithelial cells was quantified by light microscopy. The antimicrobial agent noxythiolin reduced the adherence of these micro-organisms in both exponential and stationary growth phases. Adherence of both the blastospore and pseudohyphal forms of C. albicans was reduced. Treatment of epithelial cells and/or micro-organisms with noxythiolin resulted in decreased adherence. No anti-adherence effect was observed with formaldehyde and N-methylthiourea, the degradative products of noxythiolin.

Inhibition of hyphal development and kill of Candida albicans blastospores by noxythiolin in vitro.

The cidal activity of the antimicrobial agent, noxythiolin, was investigated against a laboratory strain and a fresh isolate of Candida albicans. The order of resistance to noxythiolin was hyphal form (isolate) greater than or equal to 25 degrees C-grown blastospores (isolate) greater than 37 degrees C-grown blastospores (isolate) greater than laboratory strain blastospores. Noxythiolin activity was superior to that of 'equivalent' formaldehyde concentrations. Mycelial transformation in C. albicans was examined by light and scanning electron microscopy and measured in terms of percentage germination and hyphal extension. Noxythiolin, 2.5%, in contact for 30 min prevented germination of the blastospore population whereas the decomposition products, formaldehyde and N-methylthiourea, showed no appreciable effect in the expected concentrations. The implications of these results are discussed in relation to the observed clinical efficacy of noxythiolin.

An investigation of the in vitro anti-bacterial activity of noxythiolin against 1,000 pathogenic bacterial isolates.

The susceptibility of 1,000 recent bacterial isolates to noxythiolin was determined by the disc susceptibility method. No Gram-positive strains were resistant to this method but 56 (5.6%) of Gram-negative strains gave zones of inhibition of 12 mm diameter or less. The minimum inhibitory concentration (MIC) of the latter were determined by the agar incorporation method. No strains had MIC values greater than 4096 mg/litre. Since concentrations of 50,000 mg/litre can be used for topical treatment, these organisms may be considered susceptible.

A comparison of the antimicrobial activities of noxythiolin and formaldehyde solutions.

The availability of a rapid and highly specific polarographic method of analysis for formaldehyde enabled investigation of the rate of formaldehyde release from noxythiolin solutions and actual concentrations of formaldehyde in solutions during clinical use and storage. The antimicrobial activity of noxythiolin solutions, equivalent pure formaldehyde solutions and N-methylthiourea individually or in combination was examined against standard bacteriological strains and clinical isolates. Several interesting observations were made. Clinical isolates were found to be relatively susceptible to noxythiolin in contrast to laboratory strains. The growth phase of the organism radically affects activity, early exponential phase cells being susceptible to 1.0% noxythiolin. Levels of formaldehyde detected in fresh noxythiolin solutions are extremely low and would not appear to be solely responsible for the antimicrobial activity observed.

A simple method for the evaluation of antiseptic and disinfectant virucidal activity.

A simple method for evaluating the virucidal activity of water-soluble antiseptic and disinfectant products using poliovirus type 1 (Sabin strain) is described. Using a commercial concentrator, kinetic studies of four products were carried out. It was shown that 2% glutaraldehyde and 5% povidone iodine are rapidly virucidal. 0.2% glutaraldehyde and 2.5% noxythiolin (37 degrees C) are considerably less effective. 0.05% chlorhexidine digluconate has no virucidal activity.

[Effect of various antiseptics on Chlamydia trachomatis]. / Action de différents antiseptiques sur Chlamydia trachomatis.

We compared the activity of different antiseptics (chlorhexidine, picloxidine dichlorhydrate, povidone-iodine, and noxythiolin) on Chlamydia trachomatis using two techniques. In the first, an antigenic preparation obtained from a Chlamydia trachomatis-infected cell culture was used. Different times of contact and different concentrations were studied. The antigen-antiseptic mixture was inoculated on healthy cell cultures and infected cells were counted 48 hours later. In the second technique, previously infected cells were incubated with antiseptics at different concentrations for 48 hours. Results are given as a percentage of infected cells. Chlorhexidine and picloxidine dichlorhydrate have a rapid action on Chlamydia trachomatis. Noxythiolin requires a longer period (2 hours) to be active. Povidone-iodine exhibits no activity on Chlamydia trachomatis.

Noxythiolln-resistant organisms in a district general hospital.

Twelve strains of Pseudomonas aeruginosa, three strains of Klebsiella aerogenes, and two strains of Escherichia coli were found to be resistant to noxythiolin. Some of the pseudomonads were isolated from patients in the same ward, not all of whom were on noxythiolin treatment. The strains from these patients were indistinguishable from each other on phage typing, which suggested cross-contamination. No Gram-positive organism was found to be resistant to noxythiolin. Noxythiolin should not be used before a disc diffusion sensitivity test has been performed to determine whether the organisms are sensitive to it. This is particularly important when pseudomonads are the offending organisms.

Microbiological studies on some bladder irrigation fluids.

A 1.5% glycine solution has recently been introduced as a bladder irrigation fluid. In this study, glycine solution was compared with two other recognised bladder irrigants (chlorhexidine and noxythiolin) for its inhibitory activity against common urinary tract pathogens. Glycine solution supported the growth of nearly 50% of the bacterial strains tested whereas chlorhexidine and noxythiolin were completely inhibitory. In quantitative studies with selected strains it was found that growth could be initiated from as few as 200 organisms/ml. It was concluded that glycine solution was capable of supporting bacterial growth and thus, from a microbiological viewpoint, was unsuitable as a bladder irrigant.