European Urology Today: June/July 2023

How to prevent repeat UTIs Predisposing factors, immunoprophylaxis, and immune-responsive strains

patients and males with MV140 and autovaccine according to the results of the urinary culture with a significant reduction of infections from five UTIs in females to 0.1-0.3 and from 3.5-4 to 0.1-0.3 in males. [6–11]. Other alternatives are Solco-urovac ® which is composed of 10 heat-inactivated uropathogens, including six serotypes of E. coli, Proteus vulgaris, Klebsiella pneumoniae, Morganella morganii and Enterococcus faecalis. It can be administered intramuscularly or vaginally. Vaginal suppositories are administered weekly for three weeks and then a monthly reminder for three months. It requires lying down for 15 minutes to prevent the expulsion of the product. The intramuscular regimen consists of a weekly injection for three weeks with a repeat injection after six months. Its mechanism of action is the production of immunoglobulin A (IgA) and immunoglobulin G (IgG) in the urogenital tract. [3] This vaccine has been evaluated in several studies, including by Hopkins WJ et al. which is entitled “Vaginal mucosal vaccine for recurrent urinary tract infections in women: results of phase 2 clinical trial”. It consists of a double-blind study with 75 women comparing the use of a placebo with Urovac ® without a booster and another group with a booster. A six-month follow-up shows that there is a greater benefit in sexually active women under 52 years of age and without hysterectomy, especially if a booster is used. [12] The ExPEC4V ® vaccine is composed of four bioconjugates containing E. coli O-antigens O1A, O2, O6A, and O25B, which are responsible for the evasive strategy of the bacterium. It is administered intramuscularly with a single 0.5 ml injection and its mechanism of action is through the production of specific antibodies. [3] Among the main studies evaluating its use is Huttner A, et al. which is entitled “Safety, immunogenicity, and preliminary clinical efficacy of a vaccine against extraintestinal pathogenic Escherichia coli in

is used by generally daily sublingual administration for three months. Several publications including 1,408 patients treated with Uromune ® for three months (formula MV140) show evidence of efficacy and safety. Two studies are retrospective including one group with antibiotic prophylaxis and the other three studies are uncontrolled comparing results before and after immunoactive treatment. Among patients treated with the vaccine, the UTI-free rate ranged from 33% to 90% in study periods lasting nine to 24 months. Moreover, a two- to six-fold reduction in UTI episodes was observed during the studies. The retrospective studies also showed that MV140 significantly delayed the onset of new episodes in those subjects suffering recurrences with a reduction of UTIs up to 77% at 15 months follow-up compared to the group with antibiotic prophylaxis. The prospective studies reported a 64.7% reduction of UTIs at 6 months follow-up compared to the pre-treatment period. Another prospective study demonstrated that MV140 effectiveness may be preserved for 24 months, as well as reported a significant decrease in the need for antibiotics. Side effects were reported in 1.5% of all subjects included, being mostly mild and local. “The first point of treatment is to control possible aetiological

preparations and food supplements, D-mannose, immunoprophylaxis, vaginal and oral lactobacillus, prophylactic antibiotic courses, endovesical therapy. [1,3] The use of immunoprophylaxis with oral, intravaginal or intramuscular administration of vaccines obtained from bacterial extracts of uropathogenic strains is a measure that has been evaluated in the management of UTIs. Among them, Uro-Vaxon ® (OM-89) is more efficient than placebo in several randomised studies and with a good safety profile. Thus, the clinical practice guidelines of the European Association of Urology conclude that it can be recommended for use as immunoprophylaxis in women with recurrent UTIs. [1] The rationale for the use of immune-responsive strains of Escherichia coli is based on the fact that it is the pathogen responsible for 52-77% of repeat UTIs. In addition, a large proportion of recurrent UTIs are attributed to specific serogroups. This is because the virulence factors present in uropathogenic variants of E. coli are mostly concentrated in a small group of O-serotypes, O1, O2, O4, O6, O7, O16, O18 and O75. Uro-Vaxon ® (OM-89) is a conjugate vaccine based on lysed bacteria that is used orally. It consists of one tablet per day for three months, with the possibility of adding a booster dose at 10-day intervals for six to nine months. Its mechanism of action is based on the stimulation of dendritic cells, and neutrophils and the stimulation of phagocytosis by macrophages. [4,5] Other alternatives are the sublingual formulation MV140 ® which acts by activating the dendritic cells and T-cell response. The MV140 formula consists of preparation with heat-inactivated whole bacteria with autovaccine or formula containing 25% Escherichia coli , 25% Klebsiella pneumoniae, 25% Enterococcus faecalis and 25% Proteus vulgaris . It

Dr. José Medina-Polo ESIU, Board Member Dept. of Urology Hospital Universitario 12 de Octubre Madrid (ES)


Urinary tract infections (UTIs) are the second most frequent reason why patients seek medical attention. It is estimated that more than half of all women will require medical treatment for acute cystitis. In addition, recurrent UTIs sometimes occur, which are not always easy to manage and will significantly affect the quality of life of patients . On the other hand, the extensive use of antibiotics in these conditions has led to the emergence of antibiotic resistance. More than half of all women are estimated to experience UTIs in their lifetime and 20% of women who have a UTI will have at least one new episode. Of the total number of patients with more than one UTI, 30% will meet the criteria for recurrent UTIs, which are generally very frequent infectious episodes. Overall, it is estimated that 2.4% of women will have recurrent UTIs. [1,2] The first step in the prevention of repeat UTIs is to try to identify possible predisposing factors for an aetiological approach. Hygiene measures, in general, have not been demonstrated to be effective, but are simple and inexpensive to implement. In addition to these measures, multiple strategies are employed in the prevention of recurrent UTIs, including the use of cranberry

factors leading to the development of UTIs.”

Recently a clinical trial comparing the MV140 formula during three months and six months with placebo reported that both immunoprophylaxis regimens are associated with a significant difference regarding fewer episodes of UTIs and a longer period free of infections. Immuno- prophylaxis has also been evaluated in older

EAU Section of Infections in Urology (ESIU)

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European Urology Today June/July 2023


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