with infection. A composite risk score was created using retained factors in stepwise multivariab... more with infection. A composite risk score was created using retained factors in stepwise multivariable logistic regression modeling. RESULTS: A cohort of 74 patients was identified with obstructive urolithiasis evaluated for decompression due to concern for UTI of whom only 37 (50%) had a true UTI. The standard model of serum WBC > 15 or temperature > 38 C had an AUC of only 0.68 to predict true UTI. Conversely, a data-derived 5-point risk score (1-point for each of the following: positive gram stain, >50 WBCs/hpf on urine microscopy, perinephric fat stranding on CT, serum C-reactive protein (CRP) > 21.95, and serum procalcitonin (PCT) > 0.36) had an AUC of 0.92 (Figure). The chances of a true UTI increased from 5% to 60% to 93% among patients with risk scores of 0-1, 2, and 3-5, respectively (p<0.001). CONCLUSIONS: Currently, only 50% of patients with a suspected UTI and an obstructing stone are ultimately found to have a true UTI. A risk score (consisting of gram stain, pyuria, perinephric fat stranding, CRP, and PCT) outperformed standard clinical variables in predicting a true UTI in patients with obstructing urolithiasis. We are currently validating this score to help elucidate which patients with obstruction and clinical suspicion for infection require decompression.
<strong><em>Objective:</em></strong> Development and validation of a simp... more <strong><em>Objective:</em></strong> Development and validation of a simple and standardized self-reporting questionnaire for acute uncomplicated cystitis (AUC) assessing typical and differential symptoms, quality of life and possible changes after therapy in female patients with AUC. <b><i>Materials and Methods:</i></b> Literature research, development and evaluation of the Acute Cystitis Symptom Score (ACSS), an 18-item self-reporting questionnaire including (a) six questions about 'typical' symptoms of AUC, (b) four questions regarding differential diagnoses, (c) three questions on quality of life and (d) five questions on additional conditions which may affect therapy. The ACSS was evaluated in 286 women (mean age 32.3 ± 12.3 years) in the Russian and Uzbek language. Measurements of reliability, validity, predictive ability and responsiveness were performed. <b><i>Results:</i></b> Cronbach's alpha for the ACSS was 0.89, split-half reliability was 0.92 and correlation between halves was 0.85. Mann-Whitney test revealed significant difference scores of the 'typical' domain between patients and controls (10.75 vs. 2.02, p &lt; 0.001). The optimal threshold score was 6 points, with a 94% sensitivity and 90% specificity to predict AUC. The symptom score decreased significantly when comparing before and after therapy (10.7 vs. 2.1, p &lt; 0.001). <b><i>Conclusion:</i></b> The new validated ACSS is accurate enough and can be recommended for clinical studies and practice for initial diagnosis and monitoring treatment of AUC. Evaluation in other languages is in progress.
Purpose: The Acute Cystitis Symptom Score (ACSS) was developed as a self-reporting questionnaire ... more 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.
The acute uncomplicated cystitis in women is one of the most frequently diagnosed bacterial infec... more The acute uncomplicated cystitis in women is one of the most frequently diagnosed bacterial infection. A clinically symptomatic urinary tract infection must be differentiated from the asymptomatic bacteriuria, which is not considered an infection but rather a colonization which should not be treated. For the antimicrobial therapy according to the European guidelines the old oral antibiotics (fosfomycin trometamol, nitrofurantoin, pivmecillinam) should be prescribed, against which E. coli is still susceptible in over 90%. With new therapeutic concepts not mainly the elimination of bacteria but rather the treatment of the inflammatory (over)reaction of the host is highlighted. To establish the significance of these therapeutic options as compared to the standard antibiotic therapy, the results of the ongoing and planned phase 3 studies need to be awaited. Thus reliable clinical measuring parameters for diagnostics and outcome are needed. The acute cystitis symptom score (ACSS) was developed and validated in Russian and Uzbec languages. Because of its high reliability, validity and predictive value it can be used not only in daily practice but also for clinical studies for the diagnosis of an acute uncomplicated cystitis in women.
Background and Objectives: Acute uncomplicated cystitis (AC) is common among women. Acute onset o... more Background and Objectives: Acute uncomplicated cystitis (AC) is common among women. Acute onset of specific typical symptoms may serve as reliable criteria for developing a cost-effective strategy to make an accurate diagnosis of AC. We aimed to evaluate the diagnostic values of most common symptoms and signs of AC depending on their presence and severity. Methods: The current trial was designed as a case-control study. Data derived from the Acute Cystitis Symptom Score (ACSS) database were analyzed. Diagnostic values of the symptoms and their severity were assessed via the calculations of the sensitivity and specificity, odds ratio, positive and negative likelihood ratios. The strength of associations was estimated by the coefficient of correlation (Pearson’s R). Results: Data from 819 female subjects (423 Patients, 396 controls) with the mean age of 37.1 ± 15.3 were analyzed. Highest diagnostic values for AC in this study belonged to dysuria, urgency, and frequency. Interestingly, complaints of vaginal discharge was not found to decrease the odds for having AC in the study population. Conclusions: The severity of the symptom is even more essential than just its presence for an accurate diagnosis. The ACSS is an accurate tool and may be recommended for clinical practice and studies for diagnosis of AC in women. Further studies and unification of terms are need.
Real-world data were collected to examine antimicrobial resistance (AMR) prevalence, treatment pa... more Real-world data were collected to examine antimicrobial resistance (AMR) prevalence, treatment patterns, and clinical outcomes among female patients with uncomplicated urinary tract infection (uUTI) in Germany. Data were from a retrospective physician-based chart review completed by physicians treating patients with uUTI. Non-pregnant women aged ≥ 12 years, with a uUTI diagnosis, an E. coli-positive urine culture between January 2017–December 2019, and susceptibility test results for ≥ 4 drug classes were eligible. Patients were stratified into three cohorts by drug class susceptibility: susceptible to all (SUS), resistant to one or two drug classes (DR1/2), and resistant to ≥ 3 (MDR) drug classes tested. Among 386 eligible patients [SUS (67.1%); DR1/2 (29.0%); MDR (3.9%)], AMR prevalence was highest for FMIs (18.3%) and lowest for fluoroquinolones (5.2%). The most prescribed drugs were fosfomycin in SUS (44.0%), DR1/2 (41.4%), and fluoroquinolones in MDR (40.0%). Treatment for uUTI...
Background: the nature of alpha-D-mannose - natural aldohexose sugar, C-2 glucose epimer, whose i... more Background: the nature of alpha-D-mannose - natural aldohexose sugar, C-2 glucose epimer, whose intended use is for preventing urinary tract infections - in the interaction with E. coli is addressed in order to drive the issue of its regulatory classification as a medicinal product or medical device. Methods: PRISMA systematic review approach was applied; Delphi Panel method used to target consensus on statements retrieved from evidence. Results: Based of regulatory definitions and research evidences, the mechanism of D-mannose does not involve a metabolic or immunological action while there is an uncertainty regarding the pharmacological action. Specific interaction between the product and the bacteria within the body occurs, but its nature is inert: it does not induce a direct response activating or inhibiting body processes. Moreover, the action of D-mannose takes place, even if inside the bladder, outside the epithelium on bacteria that have not yet invaded the urothelial tissue...
Background: A catheter allowing a release of antibacterial substances such as antiseptics into th... more Background: A catheter allowing a release of antibacterial substances such as antiseptics into the bladder could be a new way of preventing biofilm formation and subsequent catheter-associated urinary tract infections. Methods: Minimal inhibitory and bactericidal concentration (MIC/MBC) determinations in cation-adjusted Mueller-Hinton broth and artificial urine were performed for 4 antiseptics against 3 uropathogenic biofilm producers, Escherichia coli, Pseudomonas aeruginosa, and Proteus mirabilis. Furthermore, effects of octenidine and polyhexanide against catheter biofilm formation were determined by quantification of biofilm-producing bacteria. Results: Sodium hypochlorite showed MIC/MBC values between 200 and 800 mg/L for all strains tested. Triclosan was efficient against E. coli and P. mirabilis (MIC ≤2.98 mg/L) but ineffective against P. aeruginosa. Octenidine and polyhexanide showed antibacterial activity against all 3 species tested (MIC 1.95–7.8 and 3.9–31.25 mg/L). Both ...
Background Health care associated urinary tract infections (HAUTI) is a common complicating facto... more Background Health care associated urinary tract infections (HAUTI) is a common complicating factor of urological practice. It is unclear what the appropriate empirical antibiotic choices are and how infection control policies (ICP) influence this. The aim of this study is to use probabilistic approaches towards the problem. That is to determine the chances of coverage of empirical antibiotic choices in HAUTIs and their annual trends in Europe. In addition, the impact of departmental self-reported compliance with catheter management and regulated usage of prophylactic antibiotics policies was tested. The estimated chances of coverage of antibiotics and further probabilistic calculations are carried out using the Global Prevalence of Infections in Urology (GPIU) annual surveillance study European data.
Background Health care-associated urinary tract infection (HAUTI) consists of unique conditions (... more Background Health care-associated urinary tract infection (HAUTI) consists of unique conditions (cystitis, pyelonephritis and urosepsis). These conditions could have different pathogen diversity and antibiotic resistance impacting on the empirical antibiotic choices. The aim of this study is to compare the estimated chances of coverage of empirical antibiotics between conditions (cystitis, pyelonephritis and urosepsis) in urology departments from Europe. Methods A mathematical modelling based on antibiotic susceptibility data from a point prevalence study was carried. Data were obtained for HAUTI patients from multiple urology departments in Europe from 2006 to 2017. The primary outcome of the study is the Bayesian weighted incidence syndromic antibiogram (WISCA) and Bayesian factor. Bayesian WISCA is the estimated chance of an antibiotic to cover the causative pathogens when used for first-line empirical treatment. Bayesian factor is used to compare if HAUTI conditions did or did n...
The broad-spectrum C-8-cyano-fluoroquinolone finafloxacin displays enhanced activity under acidic... more The broad-spectrum C-8-cyano-fluoroquinolone finafloxacin displays enhanced activity under acidic conditions. This phase II clinical study compared the efficacies and safeties of finafloxacin and ciprofloxacin in patients with complicated urinary tract infection and/or pyelonephritis. A 5-day regimen with 800 mg finafloxacin once a day (q.d.) (FINA05) had results similar to those of a 10-day regimen with 800 mg finafloxacin q.d. (FINA10). Combined microbiological and clinical responses at the test-of-cure (TOC) visit were 70% for FINA05, 68% for FINA10, and 57% for a 10-day ciprofloxacin regimen (CIPRO10) in 193 patients (64 for FINA05, 68 for FINA10, and 61 for CIPRO10) of the microbiological intent-to-treat (mITT) population. Additionally, the clinical effects of ciprofloxacin on patients with an acidic urine pH (80% of patients) were reduced, whereas the effects of finafloxacin were unchanged. Finafloxacin was safe and well tolerated. Overall, 43.4% of the patients in the FINA05 ...
Urinary tract infections are the most common bacterial infections encountered in ambulatory and l... more Urinary tract infections are the most common bacterial infections encountered in ambulatory and long-term care settings in the United States. Urine samples are the largest single category of specimens received by most microbiology laboratories and many such cultures are collected from patients who have no or questionable urinary symptoms. Unfortunately, antimicrobials are often prescribed inappropriately in such patients. Antimicrobial use, whether appropriate or inappropriate, is associated with the selection for antimicrobial-resistant organisms colonizing or infecting the urinary tract. Infections caused by antimicrobial-resistant organisms are associated with higher rates of treatment failures, prolonged hospitalizations, increased costs and mortality. Antimicrobial stewardship consists of avoidance of antimicrobials when appropriate and, when antimicrobials are indicated, use of strategies to optimize the selection, dosing, route of administration, duration and timing of antimicrobial therapy to maximize clinical cure while limiting the unintended consequences of antimicrobial use, including toxicity and selection of resistant microorganisms. This article reviews successful antimicrobial stewardship strategies in the diagnosis and treatment of urinary tract infections.
International Journal of Antimicrobial Agents, 2018
To examine the serum bactericidal activity of colistin-sulphate (CS) and azidothymidine (AZT) com... more To examine the serum bactericidal activity of colistin-sulphate (CS) and azidothymidine (AZT) combinations, time-kill curves were performed in native and heat-inactivated human serum with five colistin-resistant and four colistin-susceptible Gram-negative strains. The serum samples were spiked according to the median and minimum plasma peak concentrations measured in a phase 1 clinical study, in which seven healthy subjects received 3-times (q12) 1h-IV-infusions of 4, 2 and 2 million international units (MIU) colistin-methanesulfonate (CMS) co-administered with 200, 100 and 100 mg AZT, respectively. This trial was performed to assess the pharmacokinetics and safety of CMS/AZT-combination therapy. Minimal bactericidal concentrations of CS in native, but not heat-inactivated serum, were strongly reduced compared to Mueller-Hinton-Broth for all tested Enterobacteriaceae, except one colistin-resistant (serum-resistant) strain. For colistin-susceptible strains, the minimum CS concentration after 2 MIU CMS dosage was already bactericidal in native and heat-inactivated serum. Median, but not minimum, CS concentrations after 2 MIU CMS dosage were sufficient to kill the serum-resistant, colistin-resistant E.coli strain in native serum. In heat-inactivated serum, even the median CS concentration after 2 MIU CMS dosage was not bactericidal for all colistin-resistant strains. In general, combinations with AZT accelerated killing of colistin-resistant E.coli or showed bactericidal activity even if the substances alone were not bactericidal. Thus, the combination with AZT potentiates the bactericidal effect of colistin against colistin-resistant E.coli strains. Although the dosage of 2 MIU CMS plus AZT may be sufficient to treat infections with colistin-susceptible strains, for infections caused by colistin-resistant E.coli the dosing should be further optimized.
Aim. The aim of this observational study was to evaluate the effectiveness of a phytotherapic dru... more Aim. The aim of this observational study was to evaluate the effectiveness of a phytotherapic drug (Canephron N) in preventing urinary tract infection (UTI) in high-risk women undergoing urodynamic studies (UDS). Methods. The study protocol was approved by the local institutional ethical committee. Adult women with at least one risk factor for acquiring UTI (defined as: age over 70, elevated postvoid residual urine>100 ml, recurrent UTI, pelvic organ prolapse (POP) ≥II in POP-Q scale, and neurogenic bladder) had received after UDS either a single oral dose of fosfomycin trometamol (FT) (3 grams) or a phytodrug containing centaury herb, lovage root, and rosemary leaves (5 ml taken orally three times daily for one week). All patients included in the study had no pyuria according to urine dipstick (nitrite and/or blood and/or leukocyte esterase) and negative urine culture (CFU < 103/ml) before UDS. Urine samples were also tested 7 days after UDS. Results. Seventy-two high-risk pa...
The first note on urogenital TB was made by Porter in 1894 [2]. In 1937, Wildbolz [3] suggested t... more The first note on urogenital TB was made by Porter in 1894 [2]. In 1937, Wildbolz [3] suggested the term genitourinary TB. However, the term urogenital TB is more correct because kidney TB, which is usually primary, is diagnosed more often than genital TB.
The current European Association of Urology and European Section of Infection in Urology classifi... more The current European Association of Urology and European Section of Infection in Urology classification of urinary tract infections (UTIs) is a working instrument useful for daily patient assessment and clinical research. This new classification of UTI is based on clinical presentation, risk factors, and severity scale. Symptomatic UTIs are classified as cystitis, pyelonephritis, and urosepsis, considering that the urosepsis syndrome is the most severe form and that pyelonephritis is more severe than cystitis. The risk factors are phenotyped according to the ORENUC system: O indicates no known risk factors; R, risk of recurrent UTIs but without risk of a more severe outcome; E, extraurogenital risk factors; N, relevant nephropathic diseases; U, urologic resolvable (transient) risk factors; C, permanent external urinary catheter and unresolved urologic risk factors. Although clinical findings, culture tests, and microscopy remain the standard methods for diagnosing UTIs, improved detection of bacteria by novel diagnostic technologies, such as metagenomic sequencing (MGS), might change this paradigm in the future. Applying a culture-independent MGS technology allows detection of rich bacterial communities in urologic patients with ''sterile'' urine. However, the clinical relevance of detecting difficult-to-culture bacteria needs to be established by well-designed clinical studies. Patient summary: The current European Association of Urology Section of Infection in Urology classification of urinary tract infections (UTIs) is useful for patient assessment. Symptomatology and urine culture remain the standards for diagnosing UTIs. Novel technologies will further explore the interactions between the host and microorganisms in the urogenital tract.
What pathogens cause chronic prostatitis? There is an ongoing debate on which bacteria can be tak... more What pathogens cause chronic prostatitis? There is an ongoing debate on which bacteria can be taken as pathogens. In the most conservative approach
Background To develop and validate the American-English version of the self-reporting Acute Cysti... more Background To develop and validate the American-English version of the self-reporting Acute Cystitis Symptom Score (ACSS), a suitable tool for diagnosis and patient-reported outcome in female patients with acute uncomplicated cystitis (UC). Methods After certified translation into American-English and cognitive assessment, the clinical validation of the ACSS was performed as an embedded study in a US phase II trial (ClinicalTrials.gov Identifier: NCT03129295). Results A total of 167 female patients with typical symptoms of UC were included in the study following 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 favoured 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. Conclusion 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.
with infection. A composite risk score was created using retained factors in stepwise multivariab... more with infection. A composite risk score was created using retained factors in stepwise multivariable logistic regression modeling. RESULTS: A cohort of 74 patients was identified with obstructive urolithiasis evaluated for decompression due to concern for UTI of whom only 37 (50%) had a true UTI. The standard model of serum WBC > 15 or temperature > 38 C had an AUC of only 0.68 to predict true UTI. Conversely, a data-derived 5-point risk score (1-point for each of the following: positive gram stain, >50 WBCs/hpf on urine microscopy, perinephric fat stranding on CT, serum C-reactive protein (CRP) > 21.95, and serum procalcitonin (PCT) > 0.36) had an AUC of 0.92 (Figure). The chances of a true UTI increased from 5% to 60% to 93% among patients with risk scores of 0-1, 2, and 3-5, respectively (p<0.001). CONCLUSIONS: Currently, only 50% of patients with a suspected UTI and an obstructing stone are ultimately found to have a true UTI. A risk score (consisting of gram stain, pyuria, perinephric fat stranding, CRP, and PCT) outperformed standard clinical variables in predicting a true UTI in patients with obstructing urolithiasis. We are currently validating this score to help elucidate which patients with obstruction and clinical suspicion for infection require decompression.
<strong><em>Objective:</em></strong> Development and validation of a simp... more <strong><em>Objective:</em></strong> Development and validation of a simple and standardized self-reporting questionnaire for acute uncomplicated cystitis (AUC) assessing typical and differential symptoms, quality of life and possible changes after therapy in female patients with AUC. <b><i>Materials and Methods:</i></b> Literature research, development and evaluation of the Acute Cystitis Symptom Score (ACSS), an 18-item self-reporting questionnaire including (a) six questions about 'typical' symptoms of AUC, (b) four questions regarding differential diagnoses, (c) three questions on quality of life and (d) five questions on additional conditions which may affect therapy. The ACSS was evaluated in 286 women (mean age 32.3 ± 12.3 years) in the Russian and Uzbek language. Measurements of reliability, validity, predictive ability and responsiveness were performed. <b><i>Results:</i></b> Cronbach's alpha for the ACSS was 0.89, split-half reliability was 0.92 and correlation between halves was 0.85. Mann-Whitney test revealed significant difference scores of the 'typical' domain between patients and controls (10.75 vs. 2.02, p &lt; 0.001). The optimal threshold score was 6 points, with a 94% sensitivity and 90% specificity to predict AUC. The symptom score decreased significantly when comparing before and after therapy (10.7 vs. 2.1, p &lt; 0.001). <b><i>Conclusion:</i></b> The new validated ACSS is accurate enough and can be recommended for clinical studies and practice for initial diagnosis and monitoring treatment of AUC. Evaluation in other languages is in progress.
Purpose: The Acute Cystitis Symptom Score (ACSS) was developed as a self-reporting questionnaire ... more 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.
The acute uncomplicated cystitis in women is one of the most frequently diagnosed bacterial infec... more The acute uncomplicated cystitis in women is one of the most frequently diagnosed bacterial infection. A clinically symptomatic urinary tract infection must be differentiated from the asymptomatic bacteriuria, which is not considered an infection but rather a colonization which should not be treated. For the antimicrobial therapy according to the European guidelines the old oral antibiotics (fosfomycin trometamol, nitrofurantoin, pivmecillinam) should be prescribed, against which E. coli is still susceptible in over 90%. With new therapeutic concepts not mainly the elimination of bacteria but rather the treatment of the inflammatory (over)reaction of the host is highlighted. To establish the significance of these therapeutic options as compared to the standard antibiotic therapy, the results of the ongoing and planned phase 3 studies need to be awaited. Thus reliable clinical measuring parameters for diagnostics and outcome are needed. The acute cystitis symptom score (ACSS) was developed and validated in Russian and Uzbec languages. Because of its high reliability, validity and predictive value it can be used not only in daily practice but also for clinical studies for the diagnosis of an acute uncomplicated cystitis in women.
Background and Objectives: Acute uncomplicated cystitis (AC) is common among women. Acute onset o... more Background and Objectives: Acute uncomplicated cystitis (AC) is common among women. Acute onset of specific typical symptoms may serve as reliable criteria for developing a cost-effective strategy to make an accurate diagnosis of AC. We aimed to evaluate the diagnostic values of most common symptoms and signs of AC depending on their presence and severity. Methods: The current trial was designed as a case-control study. Data derived from the Acute Cystitis Symptom Score (ACSS) database were analyzed. Diagnostic values of the symptoms and their severity were assessed via the calculations of the sensitivity and specificity, odds ratio, positive and negative likelihood ratios. The strength of associations was estimated by the coefficient of correlation (Pearson’s R). Results: Data from 819 female subjects (423 Patients, 396 controls) with the mean age of 37.1 ± 15.3 were analyzed. Highest diagnostic values for AC in this study belonged to dysuria, urgency, and frequency. Interestingly, complaints of vaginal discharge was not found to decrease the odds for having AC in the study population. Conclusions: The severity of the symptom is even more essential than just its presence for an accurate diagnosis. The ACSS is an accurate tool and may be recommended for clinical practice and studies for diagnosis of AC in women. Further studies and unification of terms are need.
Real-world data were collected to examine antimicrobial resistance (AMR) prevalence, treatment pa... more Real-world data were collected to examine antimicrobial resistance (AMR) prevalence, treatment patterns, and clinical outcomes among female patients with uncomplicated urinary tract infection (uUTI) in Germany. Data were from a retrospective physician-based chart review completed by physicians treating patients with uUTI. Non-pregnant women aged ≥ 12 years, with a uUTI diagnosis, an E. coli-positive urine culture between January 2017–December 2019, and susceptibility test results for ≥ 4 drug classes were eligible. Patients were stratified into three cohorts by drug class susceptibility: susceptible to all (SUS), resistant to one or two drug classes (DR1/2), and resistant to ≥ 3 (MDR) drug classes tested. Among 386 eligible patients [SUS (67.1%); DR1/2 (29.0%); MDR (3.9%)], AMR prevalence was highest for FMIs (18.3%) and lowest for fluoroquinolones (5.2%). The most prescribed drugs were fosfomycin in SUS (44.0%), DR1/2 (41.4%), and fluoroquinolones in MDR (40.0%). Treatment for uUTI...
Background: the nature of alpha-D-mannose - natural aldohexose sugar, C-2 glucose epimer, whose i... more Background: the nature of alpha-D-mannose - natural aldohexose sugar, C-2 glucose epimer, whose intended use is for preventing urinary tract infections - in the interaction with E. coli is addressed in order to drive the issue of its regulatory classification as a medicinal product or medical device. Methods: PRISMA systematic review approach was applied; Delphi Panel method used to target consensus on statements retrieved from evidence. Results: Based of regulatory definitions and research evidences, the mechanism of D-mannose does not involve a metabolic or immunological action while there is an uncertainty regarding the pharmacological action. Specific interaction between the product and the bacteria within the body occurs, but its nature is inert: it does not induce a direct response activating or inhibiting body processes. Moreover, the action of D-mannose takes place, even if inside the bladder, outside the epithelium on bacteria that have not yet invaded the urothelial tissue...
Background: A catheter allowing a release of antibacterial substances such as antiseptics into th... more Background: A catheter allowing a release of antibacterial substances such as antiseptics into the bladder could be a new way of preventing biofilm formation and subsequent catheter-associated urinary tract infections. Methods: Minimal inhibitory and bactericidal concentration (MIC/MBC) determinations in cation-adjusted Mueller-Hinton broth and artificial urine were performed for 4 antiseptics against 3 uropathogenic biofilm producers, Escherichia coli, Pseudomonas aeruginosa, and Proteus mirabilis. Furthermore, effects of octenidine and polyhexanide against catheter biofilm formation were determined by quantification of biofilm-producing bacteria. Results: Sodium hypochlorite showed MIC/MBC values between 200 and 800 mg/L for all strains tested. Triclosan was efficient against E. coli and P. mirabilis (MIC ≤2.98 mg/L) but ineffective against P. aeruginosa. Octenidine and polyhexanide showed antibacterial activity against all 3 species tested (MIC 1.95–7.8 and 3.9–31.25 mg/L). Both ...
Background Health care associated urinary tract infections (HAUTI) is a common complicating facto... more Background Health care associated urinary tract infections (HAUTI) is a common complicating factor of urological practice. It is unclear what the appropriate empirical antibiotic choices are and how infection control policies (ICP) influence this. The aim of this study is to use probabilistic approaches towards the problem. That is to determine the chances of coverage of empirical antibiotic choices in HAUTIs and their annual trends in Europe. In addition, the impact of departmental self-reported compliance with catheter management and regulated usage of prophylactic antibiotics policies was tested. The estimated chances of coverage of antibiotics and further probabilistic calculations are carried out using the Global Prevalence of Infections in Urology (GPIU) annual surveillance study European data.
Background Health care-associated urinary tract infection (HAUTI) consists of unique conditions (... more Background Health care-associated urinary tract infection (HAUTI) consists of unique conditions (cystitis, pyelonephritis and urosepsis). These conditions could have different pathogen diversity and antibiotic resistance impacting on the empirical antibiotic choices. The aim of this study is to compare the estimated chances of coverage of empirical antibiotics between conditions (cystitis, pyelonephritis and urosepsis) in urology departments from Europe. Methods A mathematical modelling based on antibiotic susceptibility data from a point prevalence study was carried. Data were obtained for HAUTI patients from multiple urology departments in Europe from 2006 to 2017. The primary outcome of the study is the Bayesian weighted incidence syndromic antibiogram (WISCA) and Bayesian factor. Bayesian WISCA is the estimated chance of an antibiotic to cover the causative pathogens when used for first-line empirical treatment. Bayesian factor is used to compare if HAUTI conditions did or did n...
The broad-spectrum C-8-cyano-fluoroquinolone finafloxacin displays enhanced activity under acidic... more The broad-spectrum C-8-cyano-fluoroquinolone finafloxacin displays enhanced activity under acidic conditions. This phase II clinical study compared the efficacies and safeties of finafloxacin and ciprofloxacin in patients with complicated urinary tract infection and/or pyelonephritis. A 5-day regimen with 800 mg finafloxacin once a day (q.d.) (FINA05) had results similar to those of a 10-day regimen with 800 mg finafloxacin q.d. (FINA10). Combined microbiological and clinical responses at the test-of-cure (TOC) visit were 70% for FINA05, 68% for FINA10, and 57% for a 10-day ciprofloxacin regimen (CIPRO10) in 193 patients (64 for FINA05, 68 for FINA10, and 61 for CIPRO10) of the microbiological intent-to-treat (mITT) population. Additionally, the clinical effects of ciprofloxacin on patients with an acidic urine pH (80% of patients) were reduced, whereas the effects of finafloxacin were unchanged. Finafloxacin was safe and well tolerated. Overall, 43.4% of the patients in the FINA05 ...
Urinary tract infections are the most common bacterial infections encountered in ambulatory and l... more Urinary tract infections are the most common bacterial infections encountered in ambulatory and long-term care settings in the United States. Urine samples are the largest single category of specimens received by most microbiology laboratories and many such cultures are collected from patients who have no or questionable urinary symptoms. Unfortunately, antimicrobials are often prescribed inappropriately in such patients. Antimicrobial use, whether appropriate or inappropriate, is associated with the selection for antimicrobial-resistant organisms colonizing or infecting the urinary tract. Infections caused by antimicrobial-resistant organisms are associated with higher rates of treatment failures, prolonged hospitalizations, increased costs and mortality. Antimicrobial stewardship consists of avoidance of antimicrobials when appropriate and, when antimicrobials are indicated, use of strategies to optimize the selection, dosing, route of administration, duration and timing of antimicrobial therapy to maximize clinical cure while limiting the unintended consequences of antimicrobial use, including toxicity and selection of resistant microorganisms. This article reviews successful antimicrobial stewardship strategies in the diagnosis and treatment of urinary tract infections.
International Journal of Antimicrobial Agents, 2018
To examine the serum bactericidal activity of colistin-sulphate (CS) and azidothymidine (AZT) com... more To examine the serum bactericidal activity of colistin-sulphate (CS) and azidothymidine (AZT) combinations, time-kill curves were performed in native and heat-inactivated human serum with five colistin-resistant and four colistin-susceptible Gram-negative strains. The serum samples were spiked according to the median and minimum plasma peak concentrations measured in a phase 1 clinical study, in which seven healthy subjects received 3-times (q12) 1h-IV-infusions of 4, 2 and 2 million international units (MIU) colistin-methanesulfonate (CMS) co-administered with 200, 100 and 100 mg AZT, respectively. This trial was performed to assess the pharmacokinetics and safety of CMS/AZT-combination therapy. Minimal bactericidal concentrations of CS in native, but not heat-inactivated serum, were strongly reduced compared to Mueller-Hinton-Broth for all tested Enterobacteriaceae, except one colistin-resistant (serum-resistant) strain. For colistin-susceptible strains, the minimum CS concentration after 2 MIU CMS dosage was already bactericidal in native and heat-inactivated serum. Median, but not minimum, CS concentrations after 2 MIU CMS dosage were sufficient to kill the serum-resistant, colistin-resistant E.coli strain in native serum. In heat-inactivated serum, even the median CS concentration after 2 MIU CMS dosage was not bactericidal for all colistin-resistant strains. In general, combinations with AZT accelerated killing of colistin-resistant E.coli or showed bactericidal activity even if the substances alone were not bactericidal. Thus, the combination with AZT potentiates the bactericidal effect of colistin against colistin-resistant E.coli strains. Although the dosage of 2 MIU CMS plus AZT may be sufficient to treat infections with colistin-susceptible strains, for infections caused by colistin-resistant E.coli the dosing should be further optimized.
Aim. The aim of this observational study was to evaluate the effectiveness of a phytotherapic dru... more Aim. The aim of this observational study was to evaluate the effectiveness of a phytotherapic drug (Canephron N) in preventing urinary tract infection (UTI) in high-risk women undergoing urodynamic studies (UDS). Methods. The study protocol was approved by the local institutional ethical committee. Adult women with at least one risk factor for acquiring UTI (defined as: age over 70, elevated postvoid residual urine>100 ml, recurrent UTI, pelvic organ prolapse (POP) ≥II in POP-Q scale, and neurogenic bladder) had received after UDS either a single oral dose of fosfomycin trometamol (FT) (3 grams) or a phytodrug containing centaury herb, lovage root, and rosemary leaves (5 ml taken orally three times daily for one week). All patients included in the study had no pyuria according to urine dipstick (nitrite and/or blood and/or leukocyte esterase) and negative urine culture (CFU < 103/ml) before UDS. Urine samples were also tested 7 days after UDS. Results. Seventy-two high-risk pa...
The first note on urogenital TB was made by Porter in 1894 [2]. In 1937, Wildbolz [3] suggested t... more The first note on urogenital TB was made by Porter in 1894 [2]. In 1937, Wildbolz [3] suggested the term genitourinary TB. However, the term urogenital TB is more correct because kidney TB, which is usually primary, is diagnosed more often than genital TB.
The current European Association of Urology and European Section of Infection in Urology classifi... more The current European Association of Urology and European Section of Infection in Urology classification of urinary tract infections (UTIs) is a working instrument useful for daily patient assessment and clinical research. This new classification of UTI is based on clinical presentation, risk factors, and severity scale. Symptomatic UTIs are classified as cystitis, pyelonephritis, and urosepsis, considering that the urosepsis syndrome is the most severe form and that pyelonephritis is more severe than cystitis. The risk factors are phenotyped according to the ORENUC system: O indicates no known risk factors; R, risk of recurrent UTIs but without risk of a more severe outcome; E, extraurogenital risk factors; N, relevant nephropathic diseases; U, urologic resolvable (transient) risk factors; C, permanent external urinary catheter and unresolved urologic risk factors. Although clinical findings, culture tests, and microscopy remain the standard methods for diagnosing UTIs, improved detection of bacteria by novel diagnostic technologies, such as metagenomic sequencing (MGS), might change this paradigm in the future. Applying a culture-independent MGS technology allows detection of rich bacterial communities in urologic patients with ''sterile'' urine. However, the clinical relevance of detecting difficult-to-culture bacteria needs to be established by well-designed clinical studies. Patient summary: The current European Association of Urology Section of Infection in Urology classification of urinary tract infections (UTIs) is useful for patient assessment. Symptomatology and urine culture remain the standards for diagnosing UTIs. Novel technologies will further explore the interactions between the host and microorganisms in the urogenital tract.
What pathogens cause chronic prostatitis? There is an ongoing debate on which bacteria can be tak... more What pathogens cause chronic prostatitis? There is an ongoing debate on which bacteria can be taken as pathogens. In the most conservative approach
Background To develop and validate the American-English version of the self-reporting Acute Cysti... more Background To develop and validate the American-English version of the self-reporting Acute Cystitis Symptom Score (ACSS), a suitable tool for diagnosis and patient-reported outcome in female patients with acute uncomplicated cystitis (UC). Methods After certified translation into American-English and cognitive assessment, the clinical validation of the ACSS was performed as an embedded study in a US phase II trial (ClinicalTrials.gov Identifier: NCT03129295). Results A total of 167 female patients with typical symptoms of UC were included in the study following 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 favoured 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. Conclusion 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.
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Papers by Kurt Naber