D-mannose in the prophylaxis of recurrent urinary tract infections

Resistance of microorganisms to antimicrobially active substances, e.g. antibiotics, is an increasing problem in the medical care of infectious diseases. Two studies provide insight into the possibility of using D-mannose as an alternative therapy in the prophylaxis of recurrent urinary tract infections.

Uncomplicated urinary tract infection (UTI) is one of the most common bacterial infections. Mostly it occurs sporadically. Two or more episodes of illness in a six-month period or three or more in 12 months are referred to as recurrent UTIs, typically occurring in young sexually active or postmenopausal women. Recurrence of urinary tract infections is a fairly common problem in young otherwise healthy women. The incidence is 1-5% in this group of individuals [3]. Escherichia coli are responsible for most infections in this region, accounting for 75-95% [4]. However, these pathogens are showing increasingly pronounced resistance to the antibiotic agents commonly used. According to a Swiss study, 76-80% of E. coli are still sensitive to trimethoprim/sulfamethoxazole [5], one of the three drugs mentioned as the first choice for empiric therapy of outpatient women with acute uncomplicated cystitis in the guidelines of the Swiss Society of Infectious Diseases [6]. To reduce the use of antibiotics (and thus, if possible, the development of resistance), the guidelines mention prescribing antibiotic therapy in reserve or delayed prescribing as a possible approach after consultation with the patient [6]. Such considerations would be particularly important in the treatment of recurrent urinary tract infections or in the context of prophylaxis of the same.

Prophylaxis of recurrent HWIs.

In the case of recurrent urinary tract infections, the underlying causes should first be investigated and, if necessary, treated. If there are no abnormalities here, an attempt can be made to reduce the risk of infection with simple measures in the area of micturition, genital and sexual hygiene. Frequently recommended are: Micturition after sexual intercourse, refraining from excessive genital hygiene, drinking a sufficient amount of fluids, avoiding hypothermia (not all of these measures have a scientifically proven effect). Alternatively, antibiotic prophylaxis remains as permanent therapy in the low-dose range, postcoital single dose or self-therapy initiated by the patient. Due to side effects and the increasing resistance situation, alternative therapeutics are also attracting more and more attention in this field. Two studies provide information on a comparison between the efficacy of the mannoiside D-mannose and antibiotic prophylaxis.

Kranjcec et al. 2014 [7]: 308 women (with a history of recurrent UTIs) were divided into three groups after initial successful treatment of acute UTI with ciprofloxacin. The first received 2 g D-mannose powder 1x daily, the second 50 mg nitrofurantoin 1× daily, and the third received no prophylaxis. The treatment extended for six months. 14.6% of the women in the D-mannose group had a recurrent UTI episode during the observation period. This compares with 20.4% in the nitrofurantoin group and 60.8% in the untreated group. Thus, both the nitrofurantoin and D-mannose groups were significantly superior to the control group (p<0,001). The relative risk of recurrence during the treatment period was also significantly lower in the treatment groups than in the control group (nitrofurantoin RR 0.335; D-mannose RR 0.239; p<0.0001). Mild side effects were reported by 17.9% of subjects in the two treatment groups. With an RR of 0.276, women in the D-mannose group had a significantly lower risk (p<0.0001) of developing adverse events compared with those in the nitrofurantoin group. However, the authors point out that this difference is not crucial when nitrofurantoin is well tolerated clinically. Statistically, this showed a comparable result for the D-mannose and nitrofurantoin groups.

Porru et al. 2014 [8]: In this randomized cross-over study, 60 patients with status post recurrent UTIs in the past 12 months and a currently present acute UTI were divided into two groups. One received D-mannose 1 g three times daily for two weeks with subsequent reduction to 1 g twice daily for 22 weeks; the other received 2× daily. Trimethoprim/sulfamethoxazole for five days followed by a single dose of the antibiotic once daily every four weeks for one week for 23 weeks. After 24 weeks, the subjects switched to the other group. It took 200 days (mean) for UTI to recur in the D-mannose group and 52.7 days in the antibiotic group (p<0.0001). 8.3% of women in the antibiotic group and 80% of those in the D-mannose group remained relapse-free over the 24 weeks. It is possible that long-term use of the antibiotic negatively affected the vaginal flora. The authors concluded that D-mannose is safe and effective in the treatment of recurrent HWIs in adult women.

D-Mannose

D-mannose is a naturally occurring simple sugar derived from corn. As a drug, it is in the form of a white powder that can be dissolved in water and has a sweet taste.

According to manufacturers, the use of D-mannose is based on the ability of the remedy to inhibit the adhesion of bacteria to the cells of the bladder epithelium [9,10]. It is thought to prevent the usual binding of FimH, a lectin of bacteria, with mannose-like structures, thus ensuring that the bacteria do not adhere but are excreted in the urine [11,12]. In the mouse model, the use of mannose-like molecules showed a twofold reduction in colony-forming units in urine and a fourfold reduction in the urinary bladder [12].

D-mannose appears to have good efficacy and tolerability in the prophylaxis of recurrent HWIs, so that depending on the findings, individual clinic and the patient’s wishes, its use in this situation may be considered, especially in view of the possible saving of an antibiotic.

Literature:

European Commission: EU Action on Antimicrobial Resistance. https://ec.europa.eu/health/amr/antimicrobial-resistance_en (as of 03/13/2018)
10-Point Plan of the Federal Ministry of Health from 03/2015: www.bundesgesundheitsministerium.de/fileadmin/Dateien/3_Downloads/A/Antibiotika-Resistenz-Strategie/10-Punkte_Antibiotika-Resistenzen.pdf (as of 03/14/2018).
Guidelines Program DGU: Interdisciplinary S3 Guideline: Epidemiology, Diagnosis, Therapy, Prevention, and Management of Uncomplicated, Bacterial, Community-Acquired Urinary Tract Infections in Adult Patients. Long version 1.1-2, 2017 AWMF Registry Number: 043/044, www.awmf.org/uploads/tx_szleitlinien/043-044l_S3_Harnwegsinfektionen_2017-05.pdf (accessed on: 03/15/2018).
Gupta K, et al: International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases. Clin Infect Dis 2011; 52(5): e103-20.
Kronenberg A, et al: Active surveillance of antibiotic resistance prevalence in urinary tract and skin infections in the outpatient setting. Clin Microbiol Infect 2011; 17(12): 1845-1851.
Swiss Society of Infectiology: Guidelines Urinary Tract Infections (UTI) – May 2014: Treatment of UTI in Switzerland. www.sginf.ch/files/behandlung_von_unkomplizierten_harnwegsinfektionen.pdf (as of 03/14/18)
Kranjčec B, Papeš D, Altarac S: D-mannose powder for prophylaxis of recurrent urinary tract infections in women: a randomized clinical trial. World J Urol 2014; 32(1): 79-84.
Porru D, et al: Oral D-mannose in recurrent urinary tract infections in women: A pilot study. Journal of Clinical Urology 2014; 7(3): 208-213.
Kim J, et al: Glyco-pseudopolyrotaxanes: carbohydrate wheels threaded on a polymer string and their inhibition of bacterial adhesion. Chemistry 2010; 16(40): 12168-12173.
Pak J, et al: Tamm-Horsfall protein binds to type 1 fimbriated Escherichia coli and prevents E. coli from binding to uroplakin Ia and Ib receptors. J Biol Chem 2001; 276(13): 9924-9930.
Manufacturer information Femannose. www.femannose.ch/Inhaltsstoff-d-mannose-Zucker-gegen-blasenentzuendung.html (as of 03/15/18)
Klein T, et al: FimH antagonists for the oral treatment of urinary tract infections: from design and synthesis to in vitro and in vivo evaluation. J Med Chem 2010; 53(24): 8627-8641.