InfectionsPrevention of Recurrent Urinary Tract Infections by Intravesical Administration of Hyaluronic Acid and Chondroitin Sulphate: A Placebo-Controlled Randomised Trial
Introduction
An estimated half of women will have at least one episode of urinary tract infection (UTI) requiring antibiotic therapy during their lifetime. Moreover, 25–35% of initial UTI episodes are followed by a recurrent infection within 3–6 mo [1], [2], [3].
Individual susceptibility to UTI is complex and depends on genetic, biologic, and behavioural factors. Among the recognised factors, the interaction between the bacteria and the epithelial cells lining the bladder wall is likely to play a major role [4], [5]. The glycosaminoglycan (GAG) layer lining the transitional epithelium of the human bladder is implicated in this process.
A damaged GAG layer may lead to direct exposure of epithelial cells to urine components, which increases the possibility of bacterial adherence and infection [6], [7]. Various approaches have been developed towards a reversal of the damage and a reconstruction of the GAG layer, including the use of heparin [8], oral pentosan polysulphate [9], and hyaluronic acid (HA) [10], [11], [12].
HA is a major mucopolysaccharide widely found in the connective, epithelial, and neural tissues. Chondroitin sulphate (CS) is also an important structural component for bladder mucosal integrity [13].
These substances have been administered orally, intravesically, or both, with the aim of restoring the integrity of the GAG layer in patients with interstitial cystitis [14]. The positive outcomes obtained in the management of interstitial cystitis suggest that a similar therapeutic approach might be beneficial for treating recurrent UTI.
We report the results of a prospective, randomised, double-blind, placebo-controlled trial aiming to investigate the efficacy and tolerability of intravesical administration of combined HA and CS in reducing the rate of UTI and improving the quality of life (QoL) in female patients with a history of recurrent UTI.
Section snippets
Synopsis
This single-centre randomised controlled trial was conducted in one tertiary reference centre (Policlinico Mater Domini, UMG, Catanzaro, Italy) and began in September 2009. The study was conducted in accordance with good clinical practice guidelines and the Declaration of Helsinki, and our local institutional review board approved the protocol. All subjects gave written informed consent before enrolment in the study. Efficacy and safety data were collected during the treatment period and
Population
A total of 57 women were randomised to sodium HA 1.6%/CS 2.0% solution (n = 28) or placebo (n = 29). Three patients were lost to follow-up during the study. Fifty-four women (mean age: 34.8 ± 11.1 yr) completed the study and were included in the analysis. Fig. 1 shows the study flowchart.
Table 1 lists baseline data gathered at the time of randomisation, which indicated no significant differences between the treatment groups in terms of age, number of UTIs per year recorded, symptoms, and QoL scores.
Urinary tract infections
Discussion
Recurrent UTIs in women are common, result in considerable morbidity and expense, and can be a management problem for physicians. On average, each episode of acute UTI in premenopausal women was shown to be associated with 6.1 d of symptoms, 2.4 d of restricted activity, 1.2 d in which they were not able to attend classes or work, and 0.4 d in bed [2]. Nonantimicrobial prevention strategies are desirable given the adverse effects associated with antimicrobials and the increasing problem with
Conclusions
Effective and safe strategies to prevent recurrent UTI that avoid the use of antimicrobials are highly desirable. Our findings show the efficacy of bladder instillation of combined HA-CS in preventing UTI in this study population. Larger open-label studies or a multicentre registry would be required to corroborate these encouraging results and to demonstrate the generalisability of this treatment option in patients with recurrent UTI.
References (18)
Epidemiology of urinary tract infections: incidence, morbidity and economic costs
Am J Med
(2002)The etiology of urinary tract infection: traditional and emerging pathogens
Am J Med
(2002)- et al.
Risk factors for second urinary tract infection among college women
Am J Epidemiol
(2000) - et al.
Dynamic interactions between host and pathogen during acute urinary tract infections
Urology
(2001) - et al.
Pathogenesis and management of recurrent urinary tract infections in women
World J Urol
(1999) - et al.
The bladder mucus (glycosaminoglycan) layer in interstitial cystitis
J Urol
(1993) Epithelial coating techniques in the treatment of interstitial cystitis
Urology
(1997)- et al.
Treatment of interstitial cystitis with intravesical heparin
Br J Urol
(1994) Analysis of long-term Elmiron therapy for interstitial cystitis
Urology
(1997)
Cited by (112)
Adherence to European Association of Urology Guidelines and State of the Art of Glycosaminoglycan Therapy for the Management of Urinary Tract Infections: A Narrative Review and Expert Meeting Report
2022, European Urology Open ScienceCitation Excerpt :Exogenous GAGs, especially in the combination of HA + CS and CaCl2 (Ialuril; IBSA, Lugano, Switzerland), were originally investigated for efficacy in patients with painful bladder syndrome and interstitial cystitis who had not benefited from other therapies [44]. More recent studies showed its efficacy in preventing rUTIs in patients with at least three episodes of bacterial cystitis in the previous year [45]. Early observational studies suggested that exogenous intravesical HA could reduce the frequency of episodes of rUTIs [46,47].
Recurrent Urinary Tract Infections: Diagnosis, Treatment, and Prevention
2021, Obstetrics and Gynecology Clinics of North AmericaMulticentre International Study for the Prevention with iAluRil of Radio-induced Cystitis (MISTIC): A Randomised Controlled Study
2021, European Urology Open ScienceBiological macromolecules as antimicrobial agents
2021, Biological Macromolecules: Bioactivity and Biomedical ApplicationsRecurrent urinary tract infections: from pathogenesis to prevention
2020, Medicina ClinicaThe efficacy of pentosan polysulfate monotherapy for preventing recurrent urinary tract infections in women: A multicenter open-label randomized controlled trial
2020, Journal of the Formosan Medical Association