Therapeutic strategies for uncomplicated cystitis in women.

Uncomplicated cystitis is affecting many women of all ages and has a great impact on the quality of life, especially in women suffering from recurrent, uncomplicated cystitis. By far the most frequent uropathogen, E. coli, may have acquired increasing resistance against a variety of oral antibiotics, which may differ between countries and regions. Therefore, local resistance data are important to be considered. On the other hand, non-antibiotic therapy has also become an option which should be discussed and offered to the patient. In patients suffering from recurrent uncomplicated cystitis, individual risk factors and possible behavioral changes should first be taken into account. Non-antimicrobial prophylactic strategies shown to be successful in well-designed clinical studies are the next options. Long term antibiotic prophylaxis, however, should only be considered as a last option. For some of those patients self-diagnosis and self-treatment may be suitable, e.g. by using a recognized questionnaire.

Linguistic and Clinical Validation of the Tajik Acute Cystitis Symptom Score for Diagnosis and Patient-Reported Outcome in Acute Uncomplicated Cystitis.

Background and Objectives: Acute Cystitis Symptom Score (ACSS) is a self-reporting questionnaire for clinical diagnosis and follow-up of acute uncomplicated cystitis (AC) in women. The ACSS, originally developed in Uzbek and Russian, both considered original languages, is now available in several other languages. This study aimed to translate and validate the ACSS in the Tajik language. Material and Methods: Linguistic validation was carried out according to the Linguistic Validation Manual for Patient-Reported Outcomes Instruments guidelines. Clinical validation was performed by enrolling fifty-four Tajik-speaking women. All women included in this study were first interviewed about the understandability of all questions and statements in the final Tajik ACSS and were asked to fill in form A at the first visit (diagnostics) and form B at any follow-up visit (patient-reported outcome). Results: Thirty-three women, median (range) age of 35 (18-77), were diagnosed with AC (patient group), while twenty-one women, median (range) age of 34 (20-61) (p = 0.109), were enrolled as the control group without any other urological disease. For the diagnostics of AC, a summary score of the six typical symptoms ("Typical" domain) showed the best balance between sensitivity (0.73) and specificity (0.71) at 5 and above. Cronbach's alpha [95% CI] and split-half reliability [95%] were 0.82 [0.76; 0.98] and 0.84 [0.77; 0.87], respectively. At the follow-up visit, the patients reported a significant reduction in the "Typical" domain and an improvement in the "Quality of Life" domain. Conclusion: The Tajik ACSS showed good reliability and diagnostic values and may be used as a reliable tool for the diagnosis and patient-reported outcome in women with AC in clinical and epidemiological studies and for daily practice.

Phytotherapy (BNO 1045) of Acute Lower Uncomplicated Urinary Tract Infection in Women Normalizes Local Host Responses.

INTRODUCTION: Acute lower uncomplicated urinary tract infection (uUTI) affects a large proportion of women. Increased antimicrobial resistance has created an urgent need for novel therapeutics and the phytotherapeutic drug BNO 1045 (Canephron® N) has previously been shown to be noninferior to standard antimicrobial stewardship. This sub-analysis from a randomized, double-blind, controlled phase III noninferiority clinical trial using BNO 1045 versus fosfomycin to treat uUTI aimed to determine how urine cytokine levels are altered by the two different treatments. METHODS: Urine samples from a predefined subset of women diagnosed with uUTI (18-70 years) and treated with BNO 1045 (n = 58) or fosfomycin (n = 69) were analyzed for urine levels of IL-6 and IL-8, using analyte-to-creatinine ratios. RESULTS: BNO 1045 treatment showed similar effects to fosfomycin treatment in reducing both urine IL-6 and IL-8 levels. Mean IL-6 and IL-8 levels were markedly reduced in all patients regardless of treatment. BNO 1045 treatment decreased urine IL-8 significantly (p = 0.0142) and showed a trend toward reduction of urine IL-6 (p = 0.0551). Fosfomycin treatment reduced both IL-6 and IL-8 levels significantly (p = 0.0038, <0.0001 respectively). CONCLUSION: BNO 1045 is, in addition to reducing symptoms, comparable to fosfomycin treatment in reducing the local inflammatory response associated with uUTI.

[Therapy of cystitis with nitroxoline-NitroxWin : Prospective, multicenter, non-interventional study and microbiological resistance surveillance]. / Therapie der Zystitis mit Nitroxolin ­ NitroxWin : Prospektive, multizentrische, nicht-interventionelle Studie und mikrobiologische Untersuchungen zur Resistenzsituation.

BACKGROUND: According to German AWMF S3 guideline nitroxoline is recommended as one of the first-choice antibiotics for treatment of acute uncomplicated cystitis (UC) in women. Under real-world conditions the clinical efficacy of nitroxoline should be checked in a noninterventional, prospective and multicenter study (NIS) and the prevalence of nitroxoline resistance in E. coli be monitored. MATERIALS AND METHODS: Female patients with UC treated with nitroxoline (recommended dosage 250 mg tid for 5 days) were included by urologists, general practitioners (GPs), and internists in family medicine throughout Germany from April-December 2022 and followed for 21-28 days. The diagnosis and course of therapy were judged by the Acute Cystitis Symptom Score (ACSS) questionnaire and laboratory investigations (leukocyturia etc). Separately, a nationwide resistance surveillance was performed during 2019-2020 in collaboration with 23 laboratories to collect urinary E. coli isolates and test their susceptibility to nitroxoline. RESULTS: Of the 316 patients with mean (SD) age of 57.2 (±20.4 [median 62.5]) years who were included in the NIS, 193/248 (86.3%) in the per-protocol group and in 193/263 (81.44%) in the intention-to-treat group were clinically successful. Furthermore, 96% of the patients rated the tolerability of nitroxoline as "very good" or "good". All 272 E. coli isolates tested were susceptible to nitroxoline. CONCLUSIONS: Nitroxoline showed very good clinical results in the NIS, and 100% of the tested E. coli urine isolates were susceptible to nitroxoline. Nitroxoline can still be recommended as one of the first-choice antibiotics for treatment of UC in women.

Polish version of the Acute Cystitis Symptom Score for patients with acute uncomplicated cystitis.

Introduction: The Acute Cystitis Symptom Score (ACSS) is a self-reporting questionnaire to evaluate the symptoms and quality of life in women with uncomplicated acute cystitis (AC). The aim of the current study was the additional cognitive and clinical validation of the Polish version. Material and methods: Professional forward and backward translations from original Russian to Polish were performed by Mapi SAS. For cognitive assessment, women with different ages and educational levels were asked to comment on each item of the Polish ACSS to establish the final study version. The clinical validation was performed as a prospective, non-interventional cohort study. Women with AC (Patients) and those without (Controls) filled in the Polish ACSS during their visits to a physician's office and at a follow-up visit. Statistical analysis included ordinary descriptive values, calculation of reliability, validity, discriminative ability, responsiveness (sensitivity, specificity), and comparative analysis. Results: The cognitive assessment was performed in 60 women with a median (range) age of 44.5 (21-88) years and different educational levels: grade school (n = 8), high school (n = 25), college (n = 22), and postgraduate education (n = 5). Forty-three patients were recruited for the clinical validation study along with 34 controls. Statistical analyses resulted in excellent values of internal consistency, discriminative ability, and validity for diagnosis of AC. At a summary score of 6 and higher in the ´Typical´ domain, positive and negative predictive values were 97% and 79%, and sensitivity and specificity were 79% and 97%, respectively. Conclusions: The Polish version of the ACSS has demonstrated benefits for diagnosis and patient-reported outcome assessment. It is objective, fast, and cost-effective, and it may help to easily confirm the accurate diagnosis of AC. The Polish ASCSS can now be recommended for use in clinical and epidemiological studies, in clinical practice, or for self-diagnosis and patient-reported outcome in women with symptoms of AC.

Linguistic and clinical validation of the Turkish version of Acute Cystitis Symptom Score for the diagnosis and patient-reported outcome in acute uncomplicated cystitis.

PURPOSE: The Acute Cystitis Symptom Score (ACSS) was developed as a self-reporting questionnaire for diagnosing and monitoring acute uncomplicated cystitis (AC) in female patients. The study aims at the translation of the ACSS into Turkish from the original Uzbek including its linguistic, cognitive and clinical validation. MATERIALS AND METHODS: After forward and backward translation of the ACSS from Uzbek to Turkish and vice versa, the cognitive assessment of the Turkish ACSS was performed on 12 female subjects to achieve the final study version. RESULTS: The clinical validation was performed on a total of 120 female respondents including 64 Patients with AC and 56 controls without AC. For clinical diagnosis of AC, the predefined summary score of the typical symptoms of >6 showed high values (95% confidence interval) for sensitivity (0.88 [0.77-0.94]), specificity (0.98 [0.91-1.00]), and diagnostic accuracy (0.93 [0.86-0.97]). All patients were followed up between five to nine days after the baseline visit. Forty-four (68.75%) patients used antimicrobial treatment, whereas the rest (31.25%) preferred non-antimicrobial treatment. The severity scores of the typical symptoms and the quality of life were reduced significantly at follow-up. Using different (favored) thresholds for successful and non-successful treatment a clinical success rate between 54.7% and 64.1% (60.9%) was achieved. CONCLUSIONS: After translation from the original Uzbek and cognitive assessment, the Turkish ACSS showed similar good results for clinical diagnosis and patient-reported outcome as in other languages validated so far and could therefore now be used for clinical studies as well as in everyday practice.

Validation of the Spanish Acute Cystitis Symptoms Score (ACSS) in native Spanish-speaking women of Europe and Latin America.

INTRODUCTION AND OBJECTIVES: The Acute Cystitis Symptom Score (ACSS) is a patient self-reporting questionnaire for clinical diagnostics and patient-reported outcome (PRO), which may assess the symptoms and the effect on the quality of life in women with acute cystitis (AC). The current study aimed to create a validated Spanish version of the ACSS questionnaire. MATERIAL AND METHODS: The process of linguistic validation of the Spanish version of the ACSS consisted of the independent forward and backward translations, revision and reconciliation, and cognitive assessment. Clinical evaluation of the study version of the ACSS was carried out in clinics in Spain and Latin America. Statistical tests included the calculation of Cronbach's α, split-half reliability, specificity, sensitivity, diagnostic odds ratio, positive and negative likelihood ratio, and area under the receiver-operating characteristic curve (AUC). RESULTS: The study was performed on 132 patients [age (mean;SD) 45.0;17.8 years] with AC and 55 controls (44.5;12.2 years). Cronbach's α of the ACSS was 0.86, and the split-half reliability was 0.82. The summary scores of the ACSS domains were significantly higher in patients than in controls, 16.0 and 2.0 (p < 0.001), respectively. The predefined cut-off point of ≥6 for a summary score of the "Typical" domain resulted in a specificity of 83.6% and a sensitivity of 99.2% for the Spanish version of the ACSS. AUC was 0.91 [0.85; 0.97]. CONCLUSIONS: The validated Spanish ACSS questionnaire evaluates the symptoms and clinical outcomes of patients with AC. It can be used as a patient's self-diagnosis of AC, as a PRO measure tool, and help to rule out other pathologies in patients with voiding syndrome.

Diagnosis of acute cystitis in primary care: symptom-based versus urinalysis-based diagnosis.

AIM: This study aimed to provide insight into the congruity of acute cystitis (AC) diagnosis in women, measured both by the Acute Cystitis Symptom Score (ACSS) questionnaire and urine test(s). BACKGROUND: The ACSS questionnaire was developed as a self-administering tool for assessing urinary symptoms, quality of life (QoL) and treatment outcomes in healthy, nonpregnant female patients. METHODS: This prospective observational cohort study compared AC diagnosis based on the questionnaire with a GP diagnosis based on dipstick/dipslide test(s). ACSS questionnaire form A (typical and differential symptoms, QoL and relevant conditions) was filled in by the patient group, women suspected for AC visiting a GP practice with a urine sample, and the reference group, women visiting a community pharmacy for any medication. Analyses were performed assuming that the GP diagnosis based on urine test(s) was correct. Divergent result(s) of urine test(s) and ACSS questionnaire were analysed for scores of all individual questionnaire domains. Statistical analyses included descriptive statistics and the positive predictive value (PPV) and the negative predictive value (NPV) of the ACSS questionnaire and the urine test(s). FINDINGS: In the patient group, 59 women were included, 38 of whom a GP positively diagnosed for AC. The reference group included 70 women. The PPV of the ACSS questionnaire was 77.3%, and the NPV was 73.3%. Analysis of patient data for divergent results showed that differential symptoms, QoL and relevant conditions explained false-positive and false-negative results. Revised results (most probable diagnosis) based on this analysis showed a PPV and NPV of 88.6% and 73.3% for the ACSS questionnaire and 100% and 76.2% for the urine test(s). For use in primary care, a reduction in false-positive and false-negative results can be achieved by including scores for differential symptoms, QoL and relevant conditions, alongside a total typical symptoms score of 6 or higher.

Translation and validation of the Korean version of acute cystitis symptom score.

PURPOSE: Acute Cystitis Symptom Score (ACSS) is a simple self-reporting questionnaire initially developed in Uzbek language to help diagnose acute uncomplicated cystitis (AUC). The purpose of this study was to translate the ACSS to Korean and validate the Korean version of ACSS using Korean-speaking women. MATERIALS AND METHODS: The original version of ACSS in Uzbek was translated into the target (Korean) version according to internationally accepted guidelines for the translation and cultural adaptation. Cognitive interviews were then conducted for five women with symptoms of AUC and five women without AUC who were native speakers of the Korean language to investigate the clarity, understandability, and acceptability of the translation. The final Korean version of the ACSS was tested in 50 women (31 AUC patients and 19 controls) for clinical validation. RESULTS: Reliability test for 9 questions (6 questions about typical symptoms of AUC, and 3 questions on quality of life) showed high values (Cronbach's alpha=0.853). The sum score of typical symptoms showed the highest balance for diagnostic sensitivity and specificity (area under the ROC curve=0.935). Sensitivity and specificity to predict AUC were 90.3% and 89.5% at cut-off score 6 of the typical domain. CONCLUSIONS: The Korean version of the ACSS showed high levels of reliability and validity, similar to other validated versions in different languages. It will play an important role in practice and/or clinical research for diagnosis and treatment efficacy monitoring of Korean-speaking women suffering from AUC.

Clinical Validation of the Greek Version of the Acute Cystitis Symptom Score (ACSS)-Part II.

The Acute Cystitis Symptom Score (ACSS) is a patient self-reporting questionnaire for the clinical diagnosis and patient-reported outcome (PRO) in women with acute uncomplicated cystitis (AC). The aim of the current study (part II) is the clinical validation of the Greek ACSS questionnaire. After linguistic validation according to internationally accepted guidelines and cognitive assessment (part I), the clinical validation was performed by using the Greek ACSS study version in 92 evaluable female participants including 53 patients with symptoms suspicious of AC and 39 controls. The clinical outcome using the ACSS questionnaire at different points in time after the start of treatment was demonstrated as well. The age (mean ± SD) of the 53 patients (44.7 ± 17.0 years) and 39 controls (49.3 ± 15.9 years) and their additional conditions at baseline visits, such as menstruation, premenstrual syndrome, pregnancy, menopause, diabetes mellitus, were comparable. There was, however, a significant difference (p < 0.001) between patients and controls at baseline visit regarding sum score of the ACSS domains, such as typical symptoms and quality of life. The clinical outcome of up to 7 days showed a fast reduction of the symptom scores and improvement of quality of life. The optimal thresholds for the patient-reported outcome of successful therapy could be established. The linguistically and clinically validated Greek ACSS questionnaire can now be used for clinical or epidemiological studies and also for patients' self-diagnosis of AC and as a PRO measure tool.

Treatment of Urinary Tract Infections with Canephron® in Germany: A Retrospective Database Analysis.

Objective: The goal of the present study was to evaluate treatment with Canephron® compared to standard antibiotic treatment after diagnosis of acute cystitis or urinary tract infection (UTI), with regard to the risk of sporadic recurrent UTIs, frequent recurrent UTIs, UTI-related sick leave, additional antibiotic prescriptions, and renal complications (pyelonephritis). Methods: This retrospective cohort study was based on data from the IMS® Disease Analyzer database (IQVIA), and included outpatients in Germany with at least one diagnosis of acute cystitis or UTI with a prescription of either Canephron® or standard antibiotics between January 2016 and June 2019 and treated in general practitioner (GP), gynecologist, or urologist practices, from which the data were obtained. Multivariable regression models were used to investigate the association between Canephron® prescription and the amount of sporadic or frequent recurrent UTIs, as well as the duration of UTI-related sick leave, the number of additional antibiotic prescriptions, and cases of pyelonephritis. The effects of Canephron® were adjusted for age, sex, insurance status, and Charlson comorbidity score (CCI). Results: 2320 Canephron® patients and 158,592 antibiotic patients were available for analysis. Compared to antibiotic prescription, Canephron® prescription was significantly associated with fewer sporadic recurrences of UTI infections 30-365 days after the index date (odds ratio (OR): 0.66; 95%, confidence interval (CI): 0.58-0.72), as well as less frequent recurrences of UTI infections (OR: 0.61; 95% CI: 0.49-0.88), and also with reduced additional antibiotic prescription within 31-365 days (OR: 0.57; 95% CI: 0.52-0.63). No significant differences were observed between the Canephron® and antibiotic cohorts with regard to the likelihood of sick leave (OR: 0.99; 95% CI: 0.86-1.14), new antibiotic prescription within 1-30 days (OR: 1.01; 95% CI: 0.87-1.16), or occurrence of pyelonephritis (Hazard Ratio (HR): 1.00; 95% CI: 0.67-1.48). Conclusion: These real-world data show that Canephron® is an effective, safe symptomatic treatment for acute cystitis or UTI. It should be considered as an alternative treatment, particularly to also strengthen antimicrobial stewardship strategies.

Linguistic and clinical validation of the acute cystitis symptom score in German-speaking Swiss women with acute cystitis.

INTRODUCTION AND HYPOTHESIS: The Global Prevalence Study of Infections in Urinary tract in Community Setting (GPIU.COM) includes epidemiological aspects of acute cystitis (AC) in women in Germany and Switzerland. The primary study relates to the German version of the Acute Cystitis Symptom Score (ACSS), a self-reporting questionnaire for self-diagnosis and monitoring the symptomatic course of AC in women. The current study aimed to analyze the validity and reliability of the German ACSS in German-speaking female patients with AC in Switzerland. METHODS: Anonymized patient data were collected and analyzed from women with AC at the first visit (diagnosis) and follow-up visits as baseline and controls, respectively. Data from 97 patients with a median age of 41 years underwent analysis. Psychometric and diagnostic characteristics of the ACSS were measured and statistically analyzed. RESULTS: Average internal consistency of the ACSS resulted in a Cronbach's alpha (95% CI) of 0.86 (0.83; 0.89) and did not differ significantly between the Swiss and German cohorts. Diagnostic values of the ACSS for the Swiss cohort were relatively lower than for the German cohort, possible due to discrepancies between definitions of UTI in national guidelines. CONCLUSIONS: The analysis showed that the German version of the ACSS is also suitable for use in the German-speaking female population of Switzerland. Minor differences in definitions of AC between German and Swiss guidelines explain the observed discrepancies in diagnostic values of the ACSS between cohorts.

Validation of the American English Acute Cystitis Symptom Score.

The diagnosis of acute uncomplicated cystitis (UC) is usually based on clinical symptoms. The study aims to develop and validate the American-English Acute Cystitis Symptom Score (ACSS), a self-reporting questionnaire for diagnosis and patient-reported outcome in women with acute uncomplicated cystitis (UC). After certified translation into American-English and cognitive assessment, the clinical validation of the ACSS was performed embedded in a US phase-II trial. 167 female patients with typical symptoms of UC were included in the study following US Food and Drug Administration (FDA) guidance. At Day 1 (diagnosis), the mean (SD) sum score of the six ACSS typical symptoms reached 10.60 (2.51). Of 100 patients followed-up last time on Day 5 or 6 (End-of-treatment, EoT), 91 patients showed clinical success according to the favored ACSS criteria (sum score of typical symptoms 0.98 (1.94)). There was no correlation between the severity of symptoms on Day 1 or between clinical success rate at EoT and level of bacteriuria on Day 1. The American-English ACSS showed high predictive ability and responsiveness and excellent levels of reliability and validity. It can now be recommended as the new master version in clinical and epidemiological studies, in clinical practice, or for self-diagnosis of women with symptoms of UC.

Acute Cystitis Symptom Score questionnaire for measuring patient-reported outcomes in women with acute uncomplicated cystitis: Clinical validation as part of a phase III trial comparing antibiotic and nonantibiotic therapy.

PURPOSE: The Acute Cystitis Symptom Score (ACSS) used in a clinical trial comparing the phytodrug Canephron®N (BNO 1045) with an antibacterial agent (fosfomycin trometamol [FT]) in the treatment of acute uncomplicated cystitis (AC) in women was evaluated as a patient-reported outcome measure in a post hoc analysis. MATERIALS AND METHODS: This double-blind, randomized, multicenter, phase III noninferiority trial was performed in 51 centers in Europe. The ACSS questionnaire was used to assess severity and course of symptoms. RESULTS: The post hoc analysis included 325 patients treated with BNO 1045 and 332 patients treated with FT (total of 657 patients). The mean sum-scores of the ACSS-typical domain were comparable between groups on day 1 (BNO 1045: 10.2; FT: 10.1), and then decreased on day 4 (BNO 1045: 5.1; FT: 4.5), at end of treatment on day 8 (BNO 1045: 2.1; FT: 2.1), and at late follow-up on day 38 (BNO 1045: 0.8; FT: 0.9). Predefined thresholds using the scoring system of the ACSS could be established and validated to define "clinical cure." CONCLUSIONS: Evaluating not only antibacterial but also nonantibacterial agents indicated for the treatment of AC in women, clinical criteria for diagnostics, and measures of patient-reported outcomes are more important as main objectives than microbiological criteria. In this post hoc evaluation, we showed that the ACSS questionnaire, validated in several languages, has the potential to be used as a suitable instrument for diagnostics and patient-reported outcomes in well-designed, international, clinical studies investigating different treatment modalities of uncomplicated urinary tract infections.

Acute Cystitis Symptom Score (ACSS): Clinical Validation of the Italian Version.

Acute Cystitis Symptom Score (ACSS) is an 18-item self-reporting questionnaire for clinical diagnosis and follow-up of acute uncomplicated cystitis (AUC) in women. The ACSS, originally developed in Uzbek and Russian languages, is now available in several languages. The purpose of the study was to validate the ACSS questionnaire in the Italian language. Linguistic validation was carried out according to Linguistic Validation Manual for Patient-Reported Outcomes Instruments guidelines. Clinical validation was carried out by enrolling one hundred Italian-speaking women. All women were asked to fill in the ACSS questionnaire during their medical visit. Fifty-four women, median age 36 (Inter Quartile Range 28-49), were diagnosed with AUC, while 46 women, median age 38 (IQR 29-45), were enrolled as the control group attending the hospital's fertility center for couples. The most frequently isolated pathogen in AUC was Escherichia coli (40; 74.0%) followed by Enterococcus faecalis (7; 13.0%) and Staphylococcus saprophyticus (3; 5.6%). Receiver operating characteristic (ROC) curve analysis performed at the first diagnostic visit on a typical symptoms domain cut-off score of 6 revealed a sensitivity of 92.5% and specificity of 97.8%. The Italian version of the ACSS has proved to be a reliable tool with a high accuracy in diagnosis and follow-up in women with AUC. The ACSS may also be useful for clinical and epidemiological studies.

Evaluation of the draft guidelines proposed by EMA and FDA for the clinical diagnosis of acute uncomplicated cystitis in women.

PURPOSE: To reassess the diagnostic values of the "draft" guidelines for the clinical diagnosis of acute uncomplicated cystitis (AC), recently proposed by US Food and Drug Administration (FDA) and European Medicines Agency (EMA). METHODS: The data of 517 female respondents (patients with acute cystitis and controls) derived from the e-USQOLAT database were analyzed and used for the validation of proposed "draft" guidelines of FDA and EMA, compared to the Acute Cystitis Symptom Score (ACSS) questionnaire. The diagnostic values of the proposals concerning signs, symptoms and their severity were assessed and compared. RESULTS: The six "typical" symptoms of the ACSS were strongly associated with the diagnosis of AC. The number of positive "typical" symptoms differed significantly between patients and controls: median 5 (IQR 4-6) vs 1 (IQR 0-3) respectively. Scored severity of "typical" symptoms also differed significantly between groups of patients and controls: median (IQR) 10 (7-13) vs 1 (0-4), respectively. The best balance between sensitivity and specificity is shown by the ACSS cut-off value of 6 scores and more of the "Typical" domain, followed by an approach proposed by FDA and EMA, justifying ACSS to be used as a diagnostic criterion for the clinical diagnosis of AC. CONCLUSIONS: Not only the presence but also the severity of the symptoms is important for an accurate diagnosis of AC. The ACSS, even without urinalysis is at least as favourable as the draft diagnostic proposals by FDA and EMA. The ACSS can be recommended for epidemiological and interventional studies, and allows women to establish self-diagnosis of AC, making the ACSS also cost-effective for healthcare.

Effect of a Herbal Therapy on Clinical Symptoms of Acute Lower Uncomplicated Urinary Tract Infections in Women: Secondary Analysis from a Randomized Controlled Trial.

Background: Antibiotics are commonly used as first-line treatment for acute lower uncomplicated urinary tract infections (uUTIs). However, antimicrobial resistance is a growing global problem and efficacious nonantibiotic treatment options are urgently needed. METHODS: A secondary analysis was conducted with data from a randomized, controlled, double-blind trial comparing a fixed combination of extracts of restharrow root, Java tea, and goldenrod herb (Aqualibra®) to placebo in 200 women with acute lower uUTI. Symptom scores reported in the original trial were reanalyzed and adjusted to the definitions of the Acute Cystitis Symptom Score (ACSS). RESULTS: Based on a subgroup of patients with evaluable microbiologic data (n = 122), the decrease of the mean sum-score of three typical ACSS-adjusted symptoms showed significant superiority of the herbal preparation over placebo already after one day of treatment (p = 0.0086); on Day 7, the average difference was -1.9 score points (p < 0.0001). The superior efficacy of the herbal preparation on Day 1 was mainly driven by a difference in response rates of the symptom 'dysuria' (group difference: -29.4%, p = 0.0042). Furthermore, significantly fewer patients in the verum group required antibiotic therapy (15.3% vs. 49.2%, p = 0.0001). These results were confirmed in the intention-to-treat (ITT) population (n = 200). CONCLUSIONS: A fixed combination of extracts of restharrow root, Java tea, and goldenrod herb was superior to placebo regarding symptom relief and prevention of antibiotic use in women with lower uUTI. TRIAL REGISTRATION: ClinicalTrials.gov: NCT04032574.

Prevention of recurrent urinary tract infections: bridging the gap between clinical practice and guidelines in Latin America.

The branches of the immune system work in concert to defend against pathogens and prevent tissue damage due to excessive inflammation. Uropathogens in general, and uropathogenic Escherichia coli (UPEC) in particular, have evolved a diverse range of virulence mechanisms to avoid detection and destruction by the mucosal immune system of the urinary tract. Research towards a vaccine active against UPEC continues but has yet to be successful. Orally administered immunomodulatory bacterial lysates both stimulate and modulate the immune response in the urinary tract via the integrated mucosal immune system. The 2018 European Association of Urology (EAU) guidelines on treating acute uncomplicated cystitis recommend aiming for rapid resolution of symptoms, reduction of morbidity, and prophylaxis against reinfection. Recommended short-term antibiotic therapy has the advantage of good compliance, low cost, few adverse events, and low impact on bacterial flora. Antibiotic treatment of asymptomatic bacteriuria is only indicated during pregnancy and before invasive interventions. For recurrent infection, prophylaxis using behavioral modification and counseling should be employed first, then nonantibiotic prophylaxis, and, finally, low-dose continuous or postcoital antibiotic prophylaxis. The 2018 EAU guidelines give a strong recommendation for the oral bacterial lysate immunomodulator OM-89. All other nonantibiotic prophylactic strategies require more data, except for topical estrogen for postmenopausal women. For last-resort antibiotic prophylaxis, nitrofurantoin or fosfomycin trometamol are recommended. Guidelines for Latin America are currently being drafted, taking into account the unique ethnicity, availability of medicines, prevalence of antibiotic resistance, and healthcare practices found throughout the region.

Multidisciplinary approach to prostatitis.

The modern clinical research on prostatitis started with the work of Stamey and coworkers who developed the basic principles we are still using. They established the segmented culture technique for localizing the infections in the males to the urethra, the bladder, or the prostate and to differentiate the main categories of prostatitis. Such categories with slight modifications are still used according to the NIH classification: acute bacterial prostatitis, chronic bacterial prostatitis, Chronic Pelvic Pain Syndrome (CPPS) and asymptomatic prostatitis. Prostatic inflammation is considered an important factor in influencing both prostatic growth and progression of symptoms of benign prostatic hyperplasia and prostatitis. Chronic inflammation/neuroinflammation is a result of a deregulated acute phase response of the innate immune system affecting surrounding neural tissue at molecular, structural and functional levels. Clinical observations suggest that chronic inflammation correlates with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) and benign prostatic hyperplasia (BPH) and an history of clinical chronic prostatitis significantly increases the odds for prostate cancer. The NIHNIDDK classification based on the use of the microbiological 4- glasses localization test or simplified 2-glasses test, is currently accepted worldwide. The UPOINT system identifies groups of clinicians with homogeneous clinical presentation and is used to recognize phenotypes to be submitted to specific treatments. The UPOINTS algorithm implemented the original UPOINT adding to the urinary domains (U), psycho-social (P), organspecific (O), infection (I), neurological (N), muscle tension and tenderness (T) a further domain related to sexuality (S). In fact sexual dysfunction (erectile, ejaculatory, libido loss) has been described in 46-92% of cases with a high impact on the quality of life of patients with CP/CPPS. Prostatic ultrasound represents the most popular imaging test in the work-up of either acute and chronic prostatitis although no specific hypo-hyperechoic pattern has been clearly associated with chronic bacterial prostatitis and CPPS. Use of a digital-processing software to calculate the extension of prostatic calcification area at ultrasound demonstrated a higher percentage of prostatic calcification in patients with chronic bacterial prostatitis. Multiparametric Magnetic Resonance Imaging (mpMRI) is the current state-of-the art imaging modality in the assessment of patients with prostate cancer although a variety of benign conditions, including inflammation, may mimic prostate cancer and act as confounding factors in the discrimination between neoplastic and non-neoplastic lesions. Bacteria can infect prostate gland by: ascending the urethra, reflux of urine into the prostatic ducts, direct inoculation of bacteria through inserted biopsy needles or hematogenous seeding. Enterobacteriaceae are the predominant pathogens in acute and chronic bacterial prostatitis, but an increasing role of Enterococci has been reported. Many strains of these uropathogens exhibit the ability to form biofilm and multidrug- resistance. Sexually Transmitted Infections (STI) agents, in particular Chlamydia trachomatis and Mycoplasma genitalium, have been also considered as causative pathogens of chronic bacterial prostatitis. On the contrary the effective role in genital diseases of other "genital mycoplasmas" is still a much debated issue. Sexually Transmitted Infections agents should be investigated by molecular methods in both patient and sexual partner. "Next generation" investigations, such as cytokine analysis, cytological typing of immune cells could help stratifying the immune response. Epigenetic dysregulation of inflammatory factors should be investigated according to systemic and compartment-specific signals. The search for biomarkers should also include evaluation of hormonal pathways, as measurement of estrogen levels in semen. Antimicrobials are the first line agents for the treatment of bacterial prostatitis. The success of antimicrobial treatment depends on the antibacterial activity and the pharmacokinetic characteristics of the drug which must reach high concentrations in prostate secretion and prostate tissue. Acute bacterial prostatitis can be a serious infection with a potential risk for urosepsis For iInitial treatment of severely ill patients, intravenous administration of high doses of bactericidal antimicrobials, such as broad-spectrum penicillins, third-generation cephalosporins or fluoroquinolones, is recommended in combination with an aminoglycoside. Use of piperacillin-tazobactam and meropenem is justified in presence of multiresistant gramnegative pathogens. The antibiotic treatment of chronic prostatitis is currently based on the use of fluoroquinolones that, given for 2 to 4 weeks, cured about 70% of men with chronic bacterial prostatitis. For the treatment of Chlamydial prostatitis macrolides were shown to be more effective than fluoroquinolones, whereas no differences were observed in microbiological and clinical efficacy between macrolides and tetracyclines for the treatment of infections caused by intracellular pathogens. Aminoglycosides and fosfomycin could be considered as a therapeutic alternative for the treatment of quinolone resistant prostatitis. Use of alpha-blockers in CP/CPPS patients with urinary symptoms and analgesics +/- non steroidal anti-inflammatory drugs (NSAID), in presence of pain demonstrated a reduction of symptoms reduction and an improvement of quality of life, although long term use of NSAID is limited by side effect profile. However, the multimodal therapeutic regimen by contemporary use of alphablockers, antibiotics and anti-inflammatory showed a better control of prostatitis symptoms than single drug treatment. Novel therapeutic substances for the treatment of pain, such as the cannabinoid anandamide would be highly interesting to test. An alternative for the treatment of chronic prostatitis/chronic pelvic pain syndrome is phytotherapy, as primary therapy or in association with other drugs. Quercetin, pollen extract, extract of Serenoa repens and other mixtures of herbal extracts showed a positive effect on symptoms and quality of life without side effects. The association of CP/CPPS with alterations of intestinal function has been described. Diet has its effects on inflammation by regulation of the composition of intestinal flora and direct action on the intestinal cells (sterile inflammation). Intestinal bacteria (microbiota) interacts with food influencing the metabolic, immune and inflammatory response of the organism. The intestinal microbiota has protective function against pathogenic bacteria, metabolic function by synthesis of vitamins, decomposition of bile acids and production of trophic factors (butyrate), and modulation of the intestinal immune system. The alteration of the microbiota is called "dysbiosis" causing invasive intestinal diseases pathologies (leaky gut syndrome and food intolerances, irritable bowel syndrome or chronic inflammatory bowel diseases) and correlating with numerous systemic diseases including acute and chronic prostatitis. Administration of live probiotics bacteria can be used to regulate the balance if intestinal flora. Sessions of hydrocolontherapy can represent an integration to this therapeutic approach. Finally, microbiological examination of sexual partners can offer supplementary information for treatment.