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Results for “Noxythiolin”

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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.

Administration, Intravesical↗

Mechanisms of antibacterial formaldehyde delivery from noxythiolin and other 'masked-formaldehyde' compounds.

Formaldehyde release in aqueous solutions of noxythiolin (N-methyl-N'-hydroxymethyl thiourea) has been monitored by nuclear magnetic resonance (n.m.r.) spectroscopy. The results suggest that antibacterial activity in such solutions resides mainly in the free formaldehyde. N.m.r. spectroscopy also demonstrated slow C-N bond rotation in noxythiolin and N-methylthiourea, with delta G of ca 15 kcal mol-1 (63 kJ mol-1). N-Hydroxymethyl imidazole is marginally more effective than corresponding hydrated formaldehyde solutions, an effect which is attributed to more rapid turnover of unhydrated formaldehyde as detected by saturation transfer n.m.r. spectroscopy. These observations are combined with the known delivery of lethal iminium ions, R2N+ = CH2, by compounds of the form R2NCH2X (X = OH, NR2; R is alkyl) to suggest a single consistent explanation of the antibacterial properties of a wide range of masked formaldehyde compounds.

Biological Assay↗

Noxythiolin--high-performance liquid chromatographic assay and stability.

A rapid stability-indicating high-performance liquid chromatographic assay for noxythiolin has been developed and its application to the determination of the shelf-life of solid and solution forms is illustrated. Kinetic models which describe the degradation profile have been evaluated and concentrated solutions are modelled by a A B + C system whereas more dilute solutions approximate to the A B or limiting first-order case.

Chemical Phenomena↗

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.

Bacteria↗

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.

Drug Evaluation, Preclinical↗

[Results of noxythiolin use in acute peritonitis].

The authors present a series of 30 cases of acute supra- and inframesocolic peritonitis which, in addition to the treatment of their organic causes, benefitted from medical treatment by noxythioline, used as a peritoneal lavage, an irrigation with aspiration, or an instillation. A marked amelioration in the postoperative course was noted, particularly in those cases with infra-mesocolic peritonitis, with the absence of adhesions and suppurative collections on reintervention, and a rapid return to negativity of the positive bacteriological investigations performed systematically on the pe ritoneal fluid and on the drainage.

Acute Disease↗