Comparison of sublingual therapeutic vaccine with antibiotics for the prophylaxis of recurrent urinary tract infections

María F Lorenzo-Gómez, Bárbara Padilla-Fernández, María B García-Cenador, Álvaro J Virseda-Rodríguez, Isidoro Martín-García, Alfonso Sánchez-Escudero, Manuel J Vicente-Arroyo, José A Mirón-Canelo, María F Lorenzo-Gómez, Bárbara Padilla-Fernández, María B García-Cenador, Álvaro J Virseda-Rodríguez, Isidoro Martín-García, Alfonso Sánchez-Escudero, Manuel J Vicente-Arroyo, José A Mirón-Canelo

Abstract

Objective: To compare the clinical impact of a prophylactic treatment with sublingual immunostimulation in the prevention of recurrent urinary tract infections (rUTIs) with the use of antibiotics.

Material and methods: Retrospective cohort study evaluating the medical records of 669 women with rUTIs; 339 had a 6-month prophylaxis with antibiotics and 360 a 3-month prophylaxis with a sublingual bacterial preparation (MV 140-Uromune®). The time frame after the prophylaxis-period until the appearance of a new infection (assessed by uroculture) was scored and followed during 1 year. The absolute risk reduction (ARR) and number needed to treat (NNT) were also calculated.

Results: All patients treated with antibiotics experienced a new UTI during the scoring period of 12 months, being 19 days the median number of days free of UTIs (range 5-300). In the group treated with the bacterial preparation, 35 (9.7%) patients experienced an UTI in the same period. Kaplan-Meier curves comparing the accumulated survival (disease-free time) between both groups were significant different (P < 0.0001). The absolute risk reduction (ARR) was 90.28% (87.18-93.38) and the number needed to treat (NNT) 1.1 (1.1-1.1).

Conclusions: These results suggest that the treatment with this bacterial preparation significantly reduces the incidence of rUTIs, arising as an effective strategy to reduce the frequency of rUTIs. It reduces antibiotic consumption, matching the current recommendations due to the raise of antimicrobial resistance. Randomized, double-blind and placebo-controlled, clinical trials are needed to establish, more accurately, the clinical impact of this bacterial preparation in patients with rUTIs.

Keywords: Uromune (MV 140); bacterial vaccine; recurrent urinary infections.

Figures

Figure 1
Figure 1
Flow chart of the study.
Figure 2
Figure 2
Evolution of percent of women remaining free of UTI.

References

    1. Ahnn S., Anderson S. J. (1995). Sample size determination for comparing more than two survival distributions. Stat. Med. 14, 2273–2282. 10.1002/sim.4780142010
    1. Alecsandru D., Valor L., Sanchez-Ramon S., Gil J., Carbone J., Navarro J., et al. . (2011). Sublingual therapeutic immunization with a polyvalent bacterial preparation in patients with recurrent respiratory infections: immunomodulatory effect on antigen-specific memory CD4+ T cells and impact on clinical outcome. Clin. Exp. Immunol. 164, 100–107. 10.1111/j.1365-2249.2011.04320.x
    1. Andreu A., Planells I. (2008). [Etiology of community-acquired lower urinary infections and antimicrobial resistance of Escherichia coli: a national surveillance study]. Med. Clin. (Barc) 130, 481–486. 10.1157/13119488
    1. Bauer H. W., Alloussi S., Egger G., Blumlein H. M., Cozma G., Schulman C. C. (2005). A long-term, multicenter, double-blind study of an Escherichia coli extract (OM-89) in female patients with recurrent urinary tract infections. Eur. Urol. 47, 542–548. 10.1016/j.eururo.2004.12.009
    1. Bauer H. W., Rahlfs V. W., Lauener P. A., Blessmann G. S. (2002). Prevention of recurrent urinary tract infections with immuno-active E. coli fractions: a meta-analysis of five placebo-controlled double-blind studies. Int. J. Antimicrob. Agents 19, 451–456. 10.1016/S0924-8579(02)00106-1
    1. Blander J. M., Sander L. E. (2012). Beyond pattern recognition: five immune checkpoints for scaling the microbial threat. Nat. Rev. Immunol. 12, 215–225. 10.1038/nri3167
    1. Centers_for_Disease_Control_and_Prevention. (2011). Transatlantic Taskforce on Antimicrobial Resistance Recommendations: Recommendations for future collaboration between the U.S. and EU. Available online at:
    1. Cox C. E., Lacy S. S., Hinman F., Jr. (1968). The urethra and its relationship to urinary tract infection. II. The urethral flora of the female with recurrent urinary infection. J. Urol. 99, 632–638.
    1. Croxen M. A., Finlay B. B. (2010). Molecular mechanisms of Escherichia coli pathogenicity. Nat. Rev. Microbiol. 8, 26–38. 10.1038/nrmicro2265
    1. Çuburu N., Kweon M. N., Song J. H., Hervouet C., Luci C., Sun J. B., et al. . (2007). Sublingual immunization induces broad-based systemic and mucosal immune responses in mice. Vaccine 25, 8598–8610. 10.1016/j.vaccine.2007.09.073
    1. Eriksson K., Quiding-Jarbrink M., Osek J., Moller A., Bjork S., Holmgren J., et al. . (1998). Specific-antibody-secreting cells in the rectums and genital tracts of nonhuman primates following vaccination. Infect. Immun. 66, 5889–5896.
    1. European_Commission. (2010). Commission Staff Working Document. Demography Report 2010. Available online at:
    1. European_Medicines_Agency. (2011). CVMP Strategy on Antimicrobials 2011–2015. EMA/CVMP/287420/2010. Available online at:
    1. European_Medicines_Agency. (2014). Antimicrobial Resistance. Available online at:
    1. Food_and-Drug_Administratrion. (2011). Combating Antibiotic Resistance. Available online at:
    1. Food_and_Drug_Administration U. S. (2014). Antimicrobial Resistance. Available online at:
    1. Foxman B. (2002). Epidemiology of urinary tract infections: incidence, morbidity, and economic costs. Am. J. Med. 113(Suppl. 1A), 5S-13S. 10.1016/S0002-9343(02)01054-9
    1. Foxman B., Barlow R., D'Arcy H., Gillespie B., Sobel J. D. (2000). Urinary tract infection: self-reported incidence and associated costs. Ann. Epidemiol. 10, 509–515. 10.1016/S1047-2797(00)00072-7
    1. Grabe M., Bjerklund-Johansen T., Botto H., Çek M., Naber K., Pickard P., et al. (2013). Guidelines on Urological Infections. European Association of Urology Web site. Available online at:
    1. Grabe M., Bjerklund-Johansen T., Botto H., Naber K., Tenke P., Wagenlehner F. (2010). Guía Clínica Sobre las Infecciones Urológicas. Available online at:
    1. Holmgren J., Czerkinsky C. (2005). Mucosal immunity and vaccines. Nat. Med. 11(4 Suppl.), S45–S53. 10.1038/nm1213
    1. Hooton T. M. (2001). Recurrent urinary tract infection in women. Int. J. Antimicrob. Agents 17, 259–268. 10.1016/S0924-8579(00)00350-2
    1. Hopkins W. J., Elkahwaji J., Beierle L. M., Leverson G. E., Uehling D. T. (2007). Vaginal mucosal vaccine for recurrent urinary tract infections in women: results of a phase 2 clinical trial. J. Urol. 177, 1349–1353; quiz 591. 10.1016/j.juro.2006.11.093
    1. Howard S. J., Hopwood S., Davies S. C. (2014). Antimicrobial resistance: a global challenge. Sci. Trans. Med. 6, 236ed10. 10.1126/scitranslmed.3009315
    1. Johansen T. E., Botto H., Cek M., Grabe M., Tenke P., Wagenlehner F. M., et al. . (2011). Critical review of current definitions of urinary tract infections and proposal of an EAU/ESIU classification system. Int. J. Antimicrob. Agents 38(Suppl.), 64–70. 10.1016/j.ijantimicag.2011.09.009
    1. Kozlowski P. A., Cu-Uvin S., Neutra M. R., Flanigan T. P. (1997). Comparison of the oral, rectal, and vaginal immunization routes for induction of antibodies in rectal and genital tract secretions of women. Infect. Immun. 65, 1387–94.
    1. Lettgen B. (1996). Prevention of recurrent urinary tract infections in female children: OM-89 Immunotherapy compared with nitrofurantoin prophylaxis in a randomized pilot study. Curr. Ther. Res. 57, 464–475. 10.1016/S0011-393X(96)80055-5
    1. Lorenzo-Gómez M. F., Padilla-Fernández B., García-Criado F. J., Mirón-Canelo J. A., Gil-Vicente A., Nieto-Huertos A., et al. . (2013). Evaluation of a therapeutic vaccine for the prevention of recurrent urinary tract infections versus prophylactic treatment with antibiotics. Int. Urogynecol. J. 24, 127–134. 10.1007/s00192-012-1853-5
    1. Mayer T. R. (1980). UTI in the elderly: how to select treatment. Geriatrics 35, 67–77.
    1. Mulholland S. G. (1986). Controversies in management of urinary tract infection. Urology 27(2 Suppl.), 3–8.
    1. Naber K. G., Cho Y. H., Matsumoto T., Schaeffer A. J. (2009). Immunoactive prophylaxis of recurrent urinary tract infections: a meta-analysis. Int. J. Antimicrob. Agents 33, 111–119. 10.1016/j.ijantimicag.2008.08.011
    1. Negri D. R., Riccomi A., Pinto D., Vendetti S., Rossi A., Cicconi R., et al. . (2010). Persistence of mucosal and systemic immune responses following sublingual immunization. Vaccine 28, 4175–4180. 10.1016/j.vaccine.2010.04.013
    1. Nicolle L. E. (2005). Managing recurrent urinary tract infections in women. Women's Health 1, 39–50. 10.2217/17455057.1.1.39
    1. Nicolle L. E., Ronald A. R. (1987). Recurrent urinary tract infection in adult women: diagnosis and treatment. Infect. Dis. Clin. North Am. 1, 793–806.
    1. Pallett A., Hand K. (2010). Complicated urinary tract infections: practical solutions for the treatment of multiresistant Gram-negative bacteria. J. Antimicrob. Chemother. 65(Suppl. 3), iii25–iii 33. 10.1093/jac/dkq298
    1. Quiding M., Nordstrom I., Kilander A., Andersson G., Hanson L. A., Holmgren J., et al. . (1991). Intestinal immune responses in humans. Oral cholera vaccination induces strong intestinal antibody responses and interferon-gamma production and evokes local immunological memory. J. Clin. Invest. 88, 143–8. 10.1172/JCI115270
    1. Rahn D. D. (2008). Urinary tract infections: contemporary management. Urol. Nurs. 28, 333–341.
    1. Rosadini C. V., Kagan J. C. (2015). Microbial strategies for antagonizing Toll-like-receptor signal transduction. Curr. Opin. Immunol. 32c, 61–70. 10.1016/j.coi.2014.12.011
    1. Salvatore S., Salvatore S., Cattoni E., Siesto G., Serati M., Sorice P., et al. . (2011). Urinary tract infections in women. Eur. J. Obstet. Gynecol. Reprod. Biol. 156, 131–136. 10.1016/j.ejogrb.2011.01.028
    1. Sato S., Nomura F., Kawai T., Takeuchi O., Muhlradt P. F., Takeda K., et al. . (2000). Synergy and cross-tolerance between toll-like receptor (TLR) 2- and TLR4-mediated signaling pathways. J. Immunol. 165, 7096–101. 10.4049/jimmunol.165.12.7096
    1. Turck M., Stamm W. (1981). Nosocomial infection of the urinary tract. Am. J. Med. 70, 651–654. 10.1016/0002-9343(81)90590-8
    1. Ulett G. C., Totsika M., Schaale K., Carey A. J., Sweet M. J., Schembri M. A. (2013). Uropathogenic Escherichia coli virulence and innate immune responses during urinary tract infection. Curr. Opin. Microbiol. 16, 100–107. 10.1016/j.mib.2013.01.005
    1. Underhill D. M., Ozinsky A. (2002). Toll-like receptors: key mediators of microbe detection. Curr. Opin. Immunol. 14, 103–110. 10.1016/S0952-7915(01)00304-1
    1. U.S._Census_Bureau. (2008). U.S. Interim Projections by Age, Sex, Race, and Hispanic Origin. Available online at:
    1. Walsh F. (2014). Antibiotic Resistance: Cameron Warns of Medical ‘Dark Ages’. Available online at:
    1. Wiles T. J., Kulesus R. R., Mulvey M. A. (2008). Origins and virulence mechanisms of uropathogenic Escherichia coli. Exp. Mol. Pathol. 85, 11–19. 10.1016/j.yexmp.2008.03.007
    1. World-Economic-Forum. (2014). Global Risks 2014, Ninth Edn. Available online at:
    1. World-Health_Organization. (2014). Antimicrobial Resistance: Global Report on Surveillance. Available online at:
    1. World_Health_Organization. (2001). WHO Global Strategy for Containment of Antimicrobial Resistance. Available online at:
    1. Yu V. L., Hansen D. S., Ko W. C., Sagnimeni A., Klugman K. P., von Gottberg A., et al. . (2007). Virulence characteristics of Klebsiella and clinical manifestations of K. pneumoniae bloodstream infections. Emerg. Infect. Dis. 13, 986–993. 10.3201/eid1307.070187

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