Use of d‐mannose in prophylaxis of recurrent urinary tract infections (UTIs) in women

Abstract

Recurrent UTIs, defined as at least two UTIs in 6 months or three UTIs in 1 year, are a significant burden for the patient and result in high costs to the health system. There are several options for preventing recurrent UTIs, including antibiotic prophylaxis, methenamin prophylaxis and topical oestrogen. The two most commonly used strategies are long-term low-dose antibiotic prophylaxis and post-coital antibiotic prophylaxis for women who have UTI associated with sexual intercourse. Large reviews have shown that antibiotic prophylaxis lasting from 6 to 12 months (or even longer) significantly reduces the number of clinical recurrences in women with recurrent UTIs, but there is no consensus on when to start the prophylaxis, on how long it should last or at which dose and schedule the antibiotic should be taken. Several prophylactic antibiotic regimens can be used with the same efficiency. The most commonly prescribed regimens are trimethoprim-sulfamethoxazole (or trimethoprim alone), nitrofurantoin, cephalexin and the fluoroquinolones at a quarter of the usual daily dose for 6 months. The downsides of long-term antibiotic prophylaxis are possible adverse reactions (although rare), costs and increasing bacterial resistance to antibiotics; therefore, alternative prophylactic agents, such as cranberry juice and probiotics have been extensively studied. One such agent is D-mannose, which is normally present in human metabolism and has an important role, especially in the glycosylation of certain proteins. The supposed mechanism of action is inhibition of bacterial adherence to urothelial cells. In vitro experiments have shown that D-mannose binds and blocks FimH adhesin, which is positioned at the tip of the type 1 fimbria of enteric bacteria. During bacterial colonization, FimH binds to carbohydrate-containing glycoprotein receptors on the epithelium of the urinary tract. As it is similar in structure to the binding site of urothelial glycoprotein receptors, D-mannose acts as a competitive inhibitor of bacterial adherence; in sufficient concentration in urine D-mannose causes saturation of FimH adhesins and prevents the bacteria from binding to urothelial receptors. As well as in vitro, reduction of bacteriuria levels has also been confirmed in in vivo animal UTI models [1]. A similar anti-adhesive effect mechanism has been suggested for Tamm–Horsfall protein. The mannose-containing side chains of the protein bind bacteria and facilitate their elimination [2]. It is important to note that the anti-adhesive effect of mannose depends on the configuration of the molecule. Only D-isomer and α-anomer (α-D-mannose) can bind and block the FimH adhesin. Other carbohydrates have little or no anti-adhesive effect [3].