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.

Comparative studies on the effect of noxythiolin and other thioureas on the thyroid using in vitro and in vivo models of thyroid function.

Noxythiolin (Noxyflex-S) inhibited iodide organification (thyroid hormone synthesis) by cultured porcine thyrocytes in vitro after 5 hr (IC50 approx. 9.0 microM). The positive control, the anti-thyroid thiourea methimazole, was about 15 times more potent an inhibitor of iodide organification (IC50 approx. 0.6 microM) under the same incubation conditions. In an in vivo assessment of follicular organification capacity using the perchlorate discharge test, 14 days of ip treatment of male Charles River rats with noxythiolin (50 mg/kg body weight) produced no inhibition of iodide organification when tested 24 hr after the last administration of noxythiolin whereas the positive control, propylthiouracil, was a highly potent inhibitor.

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.

[Noxythiolin VUFB as part of antimicrobial prophylaxis and therapy in inflammatory intraabdominal complications in surgery]. / Noxythiolin VUFB jako soucást antimikrobní profylaxe a terapie nitrobrisních zánetlivých komplikací u chirurgických nemocných.

The author investigated the antimicrobial action of noxythioline, prepared by the Research Institute for Pharmacy and Biochemistry in Prague, in laboratory work as well as under clinical conditions. In the laboratory investigation the author assessed the minimal inhibitory concentration against aerobic and anaerobic bacteria within the range of 512-2048 mg/l, which is sufficient from the aspect of the noxythioline concentration (2.5%) used in clinical work. In the clinical part of the investigation noxythioline was administered to 58 patients hospitalized at the surgical clinic of the Medical Faculty of Hygiene in Prague in 1988-1989. In 13 patients it was used prophylactically in planned or acute intraabdominal operations. Therapeutically it was used in 45 patients operated mostly on account of intraabdominal diseases complicated by peritonitis or an abscess. Preliminary results confirmed the satisfactory effect of noxythioline VUFB which is comparable with Noxyflex S of Geistlich Co.

The management of empyema thoracis by thoracoscopy and irrigation.

A technique of irrigation for the management of empyema thoracis is described. Initial thoracoscopy using a laparoscope under general anaesthesia enabled adequate debridement and breakdown of loculi within the empyema cavity under direct vision. Following this procedure irrigation of the cavity with two tubes was started and continued until three consecutive cultures of drained irrigation fluid became sterile. The procedure was then discontinued. The results in 14 patients are presented using this method, irrigation was required for an average of 14 days. Patients remained in hospital for an average of 4.8 weeks. Tuberculous empyema was not found to be a contra-indication to the irrigation technique.

Bladder irrigation or irritation?

Exfoliation rates of urothelial cells following bladder irrigation were studied in patients with long-term indwelling catheters and chronic urinary tract infections (UTI). The irrigations were associated with an increased shedding of urothelial cells. Ultrastructural studies of these cells demonstrated increased disruption when compared with those obtained from normal subjects without catheters or chronic infection. The findings suggest that bladder irrigation further damages the already disrupted urothelium, which may in turn increase the predisposition of the bladder to the recurrent infections, commonly associated with patients who have indwelling urinary catheters. Bladder irrigation methods and the indications for their use require reassessment.

[Adjuvant treatment of tubal surgery. Randomized prospective study of systemically administered corticoids and noxythiolin]. / Traitement adjuvant des plasties tubaires. Etude prospective randomisée des corticoïdes par voie générale et de la noxytioline.

The effectiveness of systemic corticosteroids in the prevention of adhesion formation and reformation has been recently questioned, on the grounds of non randomized studies. Noxythiolin has been tried in animal experiments, but never in the human. In this paper, a randomized study of the effect of dexamethasone and/or noxythiolin versus no treatment has been conducted by the Group d'Etude des Adhérences Pelviennes. 126 patients have been operated upon by microsurgery (salpingectomy and/or salpingolysis). Adhesions have been assessed by a score derived from the American Fertility Society endometriosis classification, before operation and by laparoscopy 3 to 6 months later. The mean improvement on adhesion score was 23.2 in the corticosteroid treated group, 19.3 in the noxythiolin group, 15.7 in the noxythiolin and corticosteroid group, 10.2 in the control group. 40% of patients (13 out of 32) in the corticosteroid group, versus 26% (5 out of 29) in the noxythiolin and corticosteroid group and 19% (6 out of 31) in the control group (p less than 0.02) became pregnant. No adverse effect has been noted. These results support the use of corticosteroids in infertility surgery.

The use of noxythiolin (Noxyflex 'S') as an antiseptic irrigant in upper urinary tract drainage following percutaneous nephrolithotomy.

Percutaneous nephrostomy drainage for the relief of obstruction or stone removal has become a common procedure. Despite the routine use of prophylactic antibiotics, nephrostomy urine frequently becomes infected (approximately 30% of cases). Noxythiolin irrigation has been used to prevent and treat bladder infections. A double-blind, placebo controlled study was carried out in 20 patients undergoing a single-stage percutaneous nephrolithotomy to evaluate the use of noxythiolin as an upper urinary tract antiseptic. In the patients whose nephrostomy tubes were irrigated with a 2.5% solution of noxythiolin, significant bacterial infection was eliminated from the nephrostomy urine and colonisation of the catheter tip was markedly reduced. Noxythiolin also rendered pre-operative infected bladder urine sterile. There were no untoward local or systemic sequelae in either group of patients. This study indicates that irrigation of the upper urinary tract with noxythiolin solution is safe and may be a useful adjunct to reduce the risk of sepsis in patients undergoing percutaneous drainage procedures.

Controlled trial of intravesical noxythiolin in the prevention of infection following outflow tract surgery.

A randomised control trial was undertaken in 100 consecutive patients undergoing endoscopic surgery for outflow tract obstruction to assess the efficacy of noxythiolin in preventing post-operative bacteriuria; 1% noxythiolin or sterile water was instilled at the time of catheter removal. The incidence of bacteriuria in the treated group (7/50) was significantly lower than in the control group (19/50). This was statistically significant. This difference was more marked in patients who had been catheterised for retention of urine. There was no difference in the complication rate despite a reduction of infection in the treated group.

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.

Determination of in vivo concentration-time profiles of chlorhexidine and noxythiolin bladder irrigations.

The in vivo concentration-time profiles of chlorhexidine and noxythiolin bladder irrigations were determined by utilizing high-performance liquid chromatography techniques following a once daily irrigation. A total of 14 chlorhexidine irrigations established a mean concentration of 0.006% w/v, 2-3 h post irrigation. A total of 12 noxythiolin irrigations established a mean concentration of 0.266% w/v, 2-3 h post irrigation, which correlated to a mean formaldehyde concentration of 0.0119% w/v at 2-3 h, as estimated from N-methylthiourea. For both solutions the minimum inhibitory concentration was exceeded for up to 5 h post irrigation, which is sufficient contact time to establish a total kill, thus indicating the possibility that a once daily irrigation may be appropriate in asymptomatic bacteriuria which utilizes either chlorhexidine or 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.

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.