Stesura Seveso INTRODUCTION The bacterial adhesiveness to the bladder walls is impor- tant virulence factor in the pathogenesis of urinary tract infections. The development of a biofilm that prevents bacterial adhesion plays an important role in prophylax- is of recurrent urinary tract infections (UTIr). Aim of this study is to evaluate the efficacy of a phytotherapic which includes Solidago, Orthosiphon and Birch extract (Cistimev®) in association with the antibiotic prophylaxis in female patients affected by (UTIr) MATERIALS AND METHODS All the female patients affected by UTIr who referred to our urogynaecological unit between September 2010 and 197Archivio Italiano di Urologia e Andrologia 2013; 85, 4 ORIGINAL PAPER Role of phytotherapy associated with antibiotic prophylaxis in female patients with recurrent urinary tract infections Emanuela Frumenzio, Daniele Maglia, Eleonora Salvini, Silvia Giovannozzi, Manuel Di Biase, Vittorio Bini, Elisabetta Costantini Clinica Urologica e Andrologica di Perugia, Università degli Studi di Perugia, Italy Objective: Aim of this study is to evaluate the efficacy of a phytotherapic which includes Solidago, Orthosiphon and Birch extract (Cistimev®) in association with antibiotic pro- phylaxis in female patients affected by recurrent urinary tract infections (UTIr). Materials and methods: Patients affected by UTIr older than 18 years started a 3-months antibiotic prophylaxis (Prulifloxacin 600 mg, 1 cps/week or Phosphomicyn 1 cachet/week) according to antibiogram after urine culture. The patients were divided in 2 groups: Group A: antibiotic prophylaxis plus phytotherapy (1 cps/die for 3 months) and Group B: antibiotic prophy- laxis alone. Results: 164 consecutive patients were studied: 107 were included in group A (mean age 59 ± 17.3 years) and 57 (mean age 61 ± 15.7) in group B. During the treatment period the relapse fre- quencies between the two groups were not significantly different (p = 0.854): 12/107 (11.21%) patients interrupted the treatment for UTIr in group A and 6/57 (10.52%) in group B. In the long term follow-up the relapse UTI risk was significant different in the two groups with a relapse risk 2.5 greater in group B than in group A (p < 0.0001). Conclusion: Our study demonstrated that in female patients affected by recurrent UTI, the associ- ation between antibiotic prophylaxis and of a phytotherapic which includes Solidago, Orthosiphon and Birch extract reduced the number of UTI in the 12 months following the end of prophylaxis and obtained a longer relapsing time, greatly improving the quality of life of the patients. KEY WORDS: Recurrent urinary infection; Phytotherapy; Antibiotc prophylaxis. Submitted 28 February 2013; Accepted 30 April 2013 No conflict of interest declared Summary January 2012 were included in a retrospective study com- paring antibiotic prophylaxis alone or combined with Solidago, Birch e Ortosiphon (Cistimev®). UTIr was defined as at least three episodes of uncompli- cated infection documented by urine culture (EAU guidelines) (1). Paatients affected by UTIr older than 18 years started a 3-months antibiotic prophylaxis (Prulifloxacin 600 mg, 1 cps/week or Phosphomicyn 1 cachet /week) according to antibiogram after urine culture. The patients were divided in 2 groups: Group A: antibiotic prophylaxis plus phytotherapy (1 cps/die for 3 months) and Group B: antibiotic prophylaxis alone. Exclusion criteria were patients with less than three DOI: 10.4081/aiua.2013.4.197 Archivio Italiano di Urologia e Andrologia 2013; 85, 4 E. Frumenzio, D. Maglia, E. Salvini, S. Giovannozzi, M. Di Biase, V. Bini, E. Costantini 198 uncomplicated UTIs in the previous year; significant (> 50 ml) residual urine; pregnancy; intolerance or allergy to drug compounds, Pelvic Organ Prolapse more than stage II (POP-q quantification). All patients were assessed by history, clinical examination, urine culture, uroflowmetry parameters and postvoid residual volume evaluation. The patients in both groups were followed-up with urine analysis and urine culture during the treatment every month and after the end of therapy at 3, 6 and 12 months. Primary outcome was the efficacy in preventing infection recurrences during the treatments and the evaluation of UTI relapse risk in the year after the end of therapy in both groups. Statistical analysis: chi2 test was used for comparisons of categorical variables; Kaplan-Meier estimation with log- rank test was applied to compare the relapse-free sur- vival time in both groups. RESULTS 164 consecutive patients were stud- ied: 107 were included in group A (mean age 59 ± 17.3 years) and 57 (mean age 61 ± 15.7) in group B. Both groups were equivalent: there were no statistically significant dif- ference, as regards the type of antibiotic chosen (Prulifloxacin or Phospho micyn), menopausal status, sexual activity, urinary incontinence and residual urine (Table 1). No patients reported side effects in both groups. During the treatment the relapse fre- quencies between the two groups were not significantly different (p = 0.854): 12/107 (11.21%) patients interrupted the treatment for UTIr in group A and 6/57 (10.52%) in group B. In the long term follow-up the relapse UTI risk was significant different in the two groups with a relapse risk 2.5 greater in group B than in group A (p < 0.0001). The survival curves (Figure 1) demonstrated that 25% of patients that underwent the antibiotic prophylaxis plus Phytotherapy had no recurrence at 1 year, while all the patients in group B had at least one recurrence with- in 1 year. It is also evident that the time to recurrence is always longer in group A, in fact the mean survival time was 10.4 months in group A and 3.6 months in group B (log-rank test p < 0.0001) DISCUSSION A major problem today in public health economy is the increase in multi-resistant micro-organisms in patients with recurrent cystitis. New therapeutic and behavioural strategies are needed to prevent recurrences. Using drugs based on natural sub- stances which are free of side effects may have a place in the armentarium for these very hard to treat patients. Figure 1. Kaplan-Meier survival analysis. Table 1. Group A Group B p Antibiotic prophylaxis 55/107(51.4%) pts 52/107(48.6%) pts 29/57(50.9%) pts 28/57 (49.1%) pts Prulifloxacin Phosphomicyn Prulifloxacin Phosphomicyn < 0.540 Sexual activity 62/107(57.9%) pts 45(42.1%) pts 30/57 (52.6%) pts 27/57 (47.4%) pts sexual activity no sexual activity sexual activity no sexual activity <0.312 Menopause 72/107(67.3%) pts 35/107 (32.7%) pts 44/57(77.2%) pts 13/57 (22.8%) pts menopause no menopause menopause no menopause < 0.125 Incontinence 56/107(52.3%) pts 51/107 (47.7%) pts 36/57 (63.2%) pts 21/57 (36.8%) pts incontinence no incontinence incontinence no incontinence < 0.122 Survival Plot (PL estimates) Antibiotic prophylaxis has been reported to prevent recurrent episodes for as long as it is continued, with UTI usually recurring as soon as it is suspended (2). When antibiotics are combined with drugs that inhibit bacteri- al adhesion it appears that the dose can be reduced and recurrences are not as frequent. The present study demonstrates that long-term results are better with a drop in the number of recurrences after prophylaxis was suspended. CONCLUSIONS Our study demonstrated that in female patients affected by recurrent UTI, the association between antibiotic pro- phylaxis and Cistimev® reduced the number of UTI in the 12 months following the end of prophylaxis and obtained a longer relapsing time, greatly improving the quality of life of the patients. REFERENCES 1. Naber KG, Bergman B, Bishop MC, at all. EAU guidelines for the management of urinary and male genital tract infections. Urinary Tract Infection (UTI) Working Group of the Health Care Office (HCO) of the European Association of Urology (EAU); Urinary Tract Infection (UTI) Working Group of the Health Care Office (HCO) of the European Association of Urology (EAU). Eur Urol. 2001; 40:576-88. 2. Costantini E, Salvini E, Lazzeri M, et al. Prulifloxacin vs Phosphomycin: Prophylaxis in patients with recurrent UTI. Preliminary results of a randomized multi-centre study. Eur Urol 2011; (Suppl 10):480. 199Archivio Italiano di Urologia e Andrologia 2013; 85, 4 Role of phytotherapy associated with antibiotic prophylaxis in female patients with recurrent urinary tract infections Correspondence Emanuela Frumenzio, MD (Corresponding Author) emanuela.frumenzio@virgilio.it Daniele Maglia, MD Eleonora Salvini, MD Silvia Giovannozzi, MD Manuel Di Biase, MD Vittorio Bini, MD Elisabetta Costantini, MD Clinica Urologica e Andrologica di Perugia, Università degli Studi di Perugia, Perugia, Italy