Can recurrent UTIs in post-menopausal women be prevented with aspirin?

UTIs are the commonest bacterial infections. They range from cystitis to life-threatening urosepsis. Recurrent UTIs are also common, particularly in women. Recurrent UTIs are debilitating, leading to high usage of medical resources including frequent prescription of antibiotics. There is an increasing frequency of antibiotic resistance among recurrent UTI causative organisms that are unresponsive not only to the routine antibiotics used for UTI, but increasingly, to more potent antibiotics reserved for severe infections. Suppressive antibiotics for recurrent UTI are not totally effective, are associated with substantial toxicity and select resistant bacteria. The bacteria that cause UTI are predominantly gram-negative, most commonly E. coli. Uropathogenic E. coli strains produce type I fimbriae; ‘arms’ of the bacteria, that allow it to attach to the lining of the urinary tract. These and other fimbriae are also involved in biofilm formation that is required for infections of urinary catheters as well as recurrent UTI. These bacterial factors; type I fimbriae production and biofilm formation in E. coli and other uropathogens, are both reduced by salicylic acid, the biometabolite of aspirin, and this drug may be useful in prevention of recurrent UTIs. The minimum salicylic acid concentration required for Type I fimbrial suppression is 0.1-0.5mM. This is exceeded by 300mg doses of aspirin as 30% of the total dose is excreted in alkaline urine. The safety of the 300mg dose has been precisely determined in large-scale studies. The rate of major haemorrhage (requiring transfusion or hospitalisation) in patients taking greater than 200mg aspirin/day is 2.29%. This Is significantly higher than those on doses <100mg, but even here the rate of major haemorrhage (1.56%) remains substantial. These risks must be balanced against the morbidity of recurrent UTIs and the toxicity of prophylactic antibiotics like nitrofurantoin. We will trial both doses of aspirin and hope to show that 100mg is as effective as 300mg. This randomised controlled trial aims to examine the efficacy of Aspirin, 100 mg and 300 mg, compared with matching placebo in reducing the frequency of UTIs in post menopausal women with recurrent UTIs. The time to first breakthrough UTI will be another primary endpoint measured. The secondary endpoints will be the safety of low dose Aspirin in these subject. Another secondary microbiological end point is the effect of Aspirin on biofilm formation.