Causative Uropathogens Research Articles

P-1574. Asymptomatic Bacteriuria Not a Predictor of Clinical Failure in Uncomplicated Urinary Tract Infections (uUTI): A Prospective Analysis of Women Treated for uUTI from the REASSURE Trial

Abstract Background Per FDA Guidance, the primary efficacy endpoint for trials evaluating antimicrobials for treatment of UTI is a combined clinical/microbiologic response. Overall success requires both resolution of UTI symptoms and demonstration that the causative uropathogen is reduced to < 103 CFU/mL at a fixed time point after randomization, regardless of whether the patient is asymptomatic. Previously, we retrospectively evaluated the impact of post treatment asymptomatic bacteriuria (ASB) for Phase 3 clinical trial patients with UTI and found that ASB was not a predictor of subsequent clinical failure. In this study, we prospectively assessed the impact of post treatment ASB on subsequent clinical response for adult women with uUTI. Methods Study IT001-310 was a Phase 3 randomized, double-blind, double-dummy, active controlled trial to evaluate the safety and efficacy of sulopenem/probenecid (SUL) versus amoxicillin/clavulanate (AMC) for the treatment of uncomplicated UTI (uUTI). Adult women were randomized to receive SUL or AMC, both bid for 5 days. The primary efficacy outcome was overall success (combined clinical/microbiologic success) at the Test of Cure (TOC) visit in the mMITT population. ASB at TOC was prespecified as an additional efficacy endpoint to be assessed, and the presence of ASB at the End of Treatment (EOT) and TOC visit was evaluated to see if it impacted clinical response at the following visit. Results 2,222 women were randomized; 990 (44.6%) were in the mMITT population. ASB was the reason for nonresponse in 74 (14.2%) and 93 (19.9%) patients treated with SUL and AMC, respectively. As shown in the table, for both treatment arms, the presence of ASB at the EOT and TOC visit did not lead to clinical failure at the following visit. Conclusion SUL and AMC, both β-lactams, appear to have similar effects on the frequency of post treatment ASB. For patients in both treatment arms, the presence of ASB a week after completing UTI therapy was not a marker of subsequent clinical failure. The inclusion of ASB as part of the primary endpoint for studies of UTI should be reconsidered. Inclusion of microbiologic results from asymptomatic patients after complete resolution of uUTI symptoms is a practice inconsistent with available treatment recommendations. Disclosures Steven I. Aronin, MD, Iterum Therapeutics: Employee|Iterum Therapeutics: Employee|Iterum Therapeutics: Stocks/Bonds (Public Company)|Iterum Therapeutics: Stocks/Bonds (Public Company) Michael Dunne, MD, Iterum Therapeutics: Advisor/Consultant|Iterum Therapeutics: Board Member|Iterum Therapeutics: Stocks/Bonds (Public Company) Sailaja Puttagunta, MD, Iterum Therapeutics: Employee|Iterum Therapeutics: Employee|Iterum Therapeutics: Stocks/Bonds (Public Company)|Iterum Therapeutics: Stocks/Bonds (Public Company)

Patterns of Antibiotic Resistance in Urinary Tract Infections: A Retrospective Observational Study.

Urinary tract infections (UTIs) are among the most common bacterial infections, and antibiotic resistance complicates empiric treatment. This study aimed to describe recent resistance patterns among uropathogens in a tertiary-care teaching hospital to optimize empiric UTI management. This retrospective observational study included 280 patients diagnosed with UTIs at the Dr. Patnam Mahender Reddy Institute of Medical Sciences, Hyderabad, over a six-month period from June 2023 to November 2023. Urine culture and antibiotic susceptibility data were collected from electronic medical records. Patient demographics, including age, sex, and comorbid diabetes, were recorded. Causative uropathogens and their resistance rates to commonly prescribed UTI antibiotics were analyzed. Empiric antibiotic treatment patterns and outcomes were talked about. These included clinical cure, recurrence, susceptibility match, and microbiologic eradication. The mean age of patients was 43.5 years, with 196 (70%) being female and 70 (25%) having diabetes. Escherichia coli caused 210 (75%) of UTIs, Klebsiella pneumoniae 42 (15%), Proteus mirabilis 14 (5%), Enterococcus faecalis 8 (3%), and Staphylococcus saprophyticus 6 (2%). E. coli resistance rates were 48% for ampicillin, 25% for ciprofloxacin, 18% for trimethoprim/sulfamethoxazole (TMP/SMX), and 5% for nitrofurantoin. K. pneumoniae resistance rates were 89% for ampicillin, 67% for ciprofloxacin, 44% for TMP/SMX, and 22% for nitrofurantoin. The most frequently prescribed antibiotic was nitrofurantoin (45%), then ciprofloxacin (35%). Clinical cure was achieved in 75% of cases. Recurrent UTIs within four weeks occurred in 25% of cases. Treatment matched urine culture susceptibility in 82% of patients. The rising fluoroquinolone resistance highlights the need for current local data to guide empiric UTI treatment. Nitrofurantoin had low resistance rates and was an effective first-line therapy. Ongoing monitoring of resistance patterns in UTIs is essential to optimize antibiotic selection.

Bacterial Uropathogens causing Urinary Tract Infection at Hetauda Hospital

Introduction: Urinary tract infection is the infection of the uroepithelium that mainly affects kidney, ureter, urinary bladder and urethra. The causative agents of urinary tract infections are bacteria and fungi. Among these, bacteria are the most causative uropathogens of urinary tract infections. Objectives: The objective of this study is to isolate, identify, characterized and perform antibiotic sensitivity test from the bacterial isolates. Methods: A descriptive cross-sectional study was conducted from March 2023 to May 2023. Ethical approval was obtained from Institutional Review Committee (IRC), Madan Bhandari Academy of Health Sciences, IRC-32-079. Total of 1120 urine samples were collected during this study. Convenient sampling technique was used for this study. Clean catch or mid-stream urine was collected in a sterile container. All urine samples were submitted to Department of Microbiology for culture. A set of biochemical tests were done for bacterial identification. Antibiotic sensitivity test was performed by Kirby-Bauer disk diffusion method. Results: Total of 1120 urine samples were collected from patients suspected to Urinary Tract Infections. Total urine culture positive was 340 (30.36%). Of these bacterial isolates, Escherichia coli (248, 73%) was the most common species, followed by Klebsiella species (26, 7.6%), Staphylococcus saprophyticus (23, 6.76%) and Enterococcus fecalis (18, 5.3%). Conclusion: As prevalence of bacteria causing urinary tract infections is increasing day by day; so its proper isolation, identification, characterization with their antibiotic profile is necessary as it forms the base line for the clinicians to choose appropriate antimicrobial agents for empirical as well as rational treatment for UTIs.

Microbial Etiology and Resistance Patterns of Urinary Tract Infection at a Tertiary Care Centre – A Hospital based Study

Urinary tract infections (UTIs) are among the most common infections diagnosed in clinical practice. Treatment is often initiated before microbiological confirmation and anti-microbial susceptibility testing. With the rapidly rising antibiotic resistance treatment failures are not uncommon. Beta-lactamase production by gram-negative bacteria causing UTI is the commonest mode of drug resistance. The aim of current study was to detect and determine the hospital based prevalence of UTI, causative uropathogens and their antimicrobial susceptibility patterns. A total of 9,518 clean catch, mid stream urine samples were processed over 2 years. Semi-quantitative urine cultures and AST were performed. Diverse underlying resistance mechanisms were determined by detecting ESBLs, Carbapenemases, AmpC β-Lactamases, and Metallo-β-Lactamases through various standardized phenotypic methods. Out of the 9,518 samples tested 1171 (12.3%) were culture positive. Majority (66.7%) were from female patients. Highest prevalence (60%) was seen in patients > 40 years of age. E. coli (48%) was the predominant causative organism, followed by Enterococcus spp. (23%). Among GNB high resistance rates were observed against Beta-lactams, Beta-lactam/β-lactamase inhibitor combinations, and fluoroquinolones. 34.5% of GNB were confirmed as ESBL, 40% as carbapenemase, 36.5% as AmpC β-Lactamase, and 41.5% as MBL producers. We found very high levels of resistance against a broad range of antibiotics including the most widely used β-lactam group. With the resistance slopes getting steeper and steeper empirical treatment of UTIs might be fraught with the danger of many failures. Culturing and performing AST for all patients with UTI might be a prudent step for their rationale treatment and a step forward in halting the emergence of further resistance.

227. Impact of Asymptomatic Bacteriuria on Primary Efficacy Analyses in the Evaluation of Novel Antimicrobials for the Treatment of Patients with Urinary Tract Infection

Abstract Background Per FDA Guidance, the primary efficacy endpoint for trials evaluating antimicrobials for treatment of uncomplicated urinary tract infection (uUTI) and complicated urinary tract infection (cUTI) is a combined clinical/microbiologic outcome response. Overall success requires both resolution of UTI symptoms and demonstration that the causative uropathogen is reduced to < 103 CFU/mL at a fixed time point after randomization, regardless of whether the patient is symptomatic. In clinical practice, it is not standard of care to routinely screen for or treat asymptomatic bacteriuria (ASB), nor to obtain ‘proof of cure’ cultures. In the clinical trial setting, the impact of post-treatment asymptomatic bladder recolonization on the rates of microbiologic response, re-infection, or emergence of resistance is unknown. Methods Study IT001-301 and -302 are double blind, double-dummy, Phase 3 randomized trials comparing sulopenem to comparator for patients with pyuria, bacteriuria, and clinical signs/symptoms of uUTI and cUTI, respectively. In Study 301, 1671 ambulatory female adults with uUTI were randomized to oral sulopenem bid x 5d or oral ciprofloxacin bid x 3d. In Study 302, 1395 hospitalized adults with cUTI were randomized to sulopenem IV once daily x 5d followed by oral sulopenem bid or ertapenem IV once daily x 5d followed by either oral ciprofloxacin or amoxicillin-clavulanate bid, depending on baseline uropathogen susceptibility. The primary endpoint was overall (clinical + microbiologic) response in micro-MITT population at TOC visit (D12 in uUTI study and D21 in cUTI study). Results Figure 1 Conclusion Different classes of antibiotics appear to have a differential effect on the frequency of post-treatment ASB with quinolones having a lower rate relative to beta-lactams. The presence of ASB a week or more after completing UTI therapy was not associated with a higher rate of clinical relapse for UTI patients; treatment with ciprofloxacin was associated with the selection of resistant pathogens in the post-treatment flora. Inclusion of ASB in the primary endpoint for studies of UTI should be reconsidered as it implies that a post-treatment culture should be obtained to document resolution of infection, a practice inconsistent with available treatment recommendations. Disclosures Steven I. Aronin, MD, Iterum Therapeutics: Stocks/Bonds Michael Dunne, MD, Iterum Therapeutics: Advisor/Consultant|Iterum Therapeutics: Board Member|Iterum Therapeutics: Stocks/Bonds Sailaja Puttagunta, MD, Iterum Therapeutics: Stocks/Bonds.

Risk Factors Associated With Antimicrobial Resistance and Adverse Short-Term Health Outcomes Among Adult and Adolescent Female Outpatients With Uncomplicated Urinary Tract Infection.

Increasing antimicrobial resistance makes treating uncomplicated urinary tract infections (uUTIs) difficult. We compared whether adverse short-term outcomes among US female patients were more common when initial antimicrobial therapy did not cover the causative uropathogen. This retrospective cohort study used data from female outpatients aged ≥12 years, with a positive urine culture and dispensing of an oral antibiotic ±1 day from index culture. Isolate susceptibility to the antimicrobial initially dispensed, patient age, and history of antimicrobial exposure, resistance, and all-cause hospitalization within 12 months of index culture were evaluated for associations with adverse outcomes during 28-day follow up. Outcomes assessed were new antimicrobial dispensing, all-cause hospitalization, and all-cause outpatient emergency department/clinic visits. Of 2366 uUTIs, 1908 (80.6%) were caused by isolates susceptible and 458 (19.4%) by isolates not susceptible (intermediate/resistant) to initial antimicrobial treatment. Within 28 days, patients with episodes caused by not susceptible isolates were 60% more likely to receive a new antimicrobial versus episodes with susceptible isolates (29.0% vs 18.1%; 95% confidence interval, 1.3-2.1; P < .0001). Other variables associated with new antibiotic dispenses within 28 days were older age, prior antimicrobial exposure, or prior nitrofurantoin-not-susceptible uropathogens (P < .05). Older age, prior antimicrobial-resistant urine isolates, and prior hospitalization were associated with all-cause hospitalization (P < .05). Prior fluoroquinolone-not-susceptible isolates or oral antibiotic dispensing within 12 months of index culture were associated with subsequent all-cause outpatient visits (P < .05). New antimicrobial dispensing within the 28-day follow-up period was associated with uUTIs where the uropathogen was not susceptible to initial antimicrobial treatment. Older age and prior antimicrobial exposure, resistance, and hospitalization also identified patients at risk of adverse outcomes.

The microbial load and the severity of morphological changes in the prostate during infection with various titers of uropathogens: a comparison of data from an animal model study

Introduction. It has been established in an animal model that coagulase-negative staphylococci (Staphylococcus haemolyticus) and anaerobes (Peptococcus niger) cause the development of an acute inflammatory process in the prostate when inoculated with 103 CFU/ml. At the same time, data have been published indicating the pathogenic potential of these microorganisms on a titer of 102 CFU/ml. But it was confirmed for the model of acute obstructive pyelonephritis. In addition, the characteristics of the formation of the inflammatory response at different times were determined, which require detailed verification and comparative characteristics with those during infection with a causative uropathogen (Escherichia coli).Objective. Based on the results of the experiment, to carry out: 1) an evaluation of the relationship between the dynamics of microbial load and the degree of pathomorphological changes in prostate tissues during infection with various uropathogens in a titer of 103 CFU/ml; 2) an evaluation of the degree of microbial load and severity of histological changes in prostate tissues on follow-up day 7 with transurethral infection with various uropathogens in a subpathogenic titer of 102 CFU/ml; 3) a fundamental comparative analysis of the indicators of contamination and the severity of inflammatory changes on follow-up day 7 after the inoculation of various uropathogens in titers of 102 and 103 CFU/ml.Materials and methods. The animal model was performed using the FELASA and ARRIVE guidelines. Lab animals: 20 New Zealand rabbits. Uropathogens: E. coli, S. haemolyticus, and P. niger. Infectious titers: 102.3 cfu/ml. Uropathogen inoculation technique: topical transurethral. Randomization: all laboratory animals were divided into 4 groups depending on the uropathogen (3 experimental, 1 control). Follow-up periods: day 1, 3, 7 and 14 for a titer of 103 CFU/ml, and day 7 for a titer of 102 CFU/ml. At the end of the follow-up, euthanasia and autopsy were performed with the extraction of the urogenital organ complex. Hereafter, biopsies were taken from various parts of the prostate. Cultural and histological studies of prostate tissues were carried out using standard methods. The results were analyzed using Statistica 10.2 (StatSoft Inc., Tulsa, OK, USA) and GraphPad Prism 9 (GraphPad Software Inc., Graphpad Holdings LLC, San Diego, CA, USA) programs through descriptive and nonparametric statistics.Results. Bacterial contamination of prostate tissue was determined in all cases of infection with differences (p &lt; 0.05) in some indicators between the E. coli and P. niger groups at different observation periods, but only in the case of inoculation of the test titer of 103 CFU/ml. Histological evaluation of prostate tissues after inoculation with 103 CFU/ml verified the presence of acute destructive changes in the prostate from the follow-up day 1, which were more pronounced in the S. haemolyticus and E. coli groups. However, similar characteristics of the development of the inflammatory process in the form of hyper-eosinophilic infiltration in the early stages and pronounced congestion of the prostatic glands were identified in the S. haemolyticus and P. niger groups. Comparison of trends in dynamic changes of microbial load (rise / decline) and severity of pathological changes (increase / resolution) in prostate tissues in established follow-up periods showed the presence of relative synchronization of trends (from days 1 to 7) in the S. haemolyticus and P. niger groups, and complete synchronization in the E. coli group. When comparing the median microbial load of the prostate on the follow-up day 7, no intergroup (p &gt; 0.05) differences were found both in cases of infection with a titer of 103 CFU/ml, and when compared with the data on contamination for a test titer of 102 CFU/ml, at the same time observations. At once, when E. coli and S. haemolyticus were infected at a subpathogenic titer of 102 CFU/ml, inflammatory changes were recorded that had a mild diffuse character, in relation to those after inoculation of these pathogens in a titer of 103 CFU/ml. In turn, P. niger induced the development of low-intensity focal alteration in isolated areas of prostate tissues.Conclusions. Detailed analysis of culture and histological data showed that E. coli, S. haemolyticus and P. niger have significant pathogenic potential at titer of 103 CFU/ml. In turn, when the titer decreases to 102 CFU/ml, E. coli and S. haemolyticus retain their pathogenic potential, but the severity of the inflammatory reaction is significantly reduced. It was also found that a change in bacterial contamination affects the severity of the inflammatory process in all groups during seven follow-up days at a given test titer.

Antimicrobial resistance in urinary pathogens and culture-independent detection of trimethoprim resistance in urine from patients with urinary tract infection

BackgroundAlthough urinary tract infections (UTIs) are extremely common, isolation of causative uropathogens is not always routinely performed, with antibiotics frequently prescribed empirically. This study determined the susceptibility of urinary isolates from two Health and Social Care Trusts (HSCTs) in Northern Ireland to a range of antibiotics commonly used in the treatment of UTIs. Furthermore, we determined if detection of trimethoprim resistance genes (dfrA) could be used as a potential biomarker for rapid detection of phenotypic trimethoprim resistance in urinary pathogens and from urine without culture.MethodsSusceptibility of E. coli and Klebsiella spp. isolates (n = 124) to trimethoprim, amoxicillin, ceftazidime, ciprofloxacin, co-amoxiclav and nitrofurantoin in addition to susceptibility of Proteus mirabilis (n = 61) and Staphylococcus saprophyticus (n = 17) to trimethoprim was determined by ETEST® and interpreted according to EUCAST breakpoints. PCR was used to detect dfrA genes in bacterial isolates (n = 202) and urine samples(n = 94).ResultsResistance to trimethoprim was observed in 37/124 (29.8%) E. coli and Klebsiella spp. isolates with an MIC90 > 32 mg/L. DfrA genes were detected in 29/37 (78.4%) trimethoprim-resistant isolates. Detection of dfrA was highly sensitive (93.6%) and specific (91.4%) in predicting phenotypic trimethoprim resistance among E. coli and Klebsiella spp. isolates. The dfrA genes analysed were detected using a culture-independent PCR method in 16/94 (17%) urine samples. Phenotypic trimethoprim resistance was apparent in isolates cultured from 15/16 (94%) dfrA-positive urine samples. There was a significant association (P < 0.0001) between the presence of dfrA and trimethoprim resistance in urine samples containing Gram-negative bacteria (Sensitivity = 75%; Specificity = 96.9%; PPV = 93.8%; NPV = 86.1%).ConclusionsThis study demonstrates that molecular detection of dfrA genes is a good indicator of trimethoprim resistance without the need for culture and susceptibility testing.

CATHETER ASSOCIATED URINARY TRACT INFECTION DUE TO PROLONGED CATHETERIZATION AND ITS CAUSATIVE UROPATHOGENS

Background: The presence of a urinary catheter is the most important risk factor for bacteriuria and Catheter-associated urinary tract infection (CA-UTI). The objective of this study was to determine the frequency of catheter associated urinary tract infections and most common causative uropathogens due to prolonged catheterization. Methods: This descriptive, cross-sectional study was carried out in the Department of Microbiology, Abbas Institute of Medical Sciences, Muzaffarabad from January to December 2019. Total 270 patients of critical patient care areas and wards with age range 18–70 years were selected. Patients suffering from UTI prior to catheterization, suffering from complicated UTI, and already catheterized at the time of admission were excluded. Urine samples were collected from the distal end of urinary catheters under strict aseptic techniques. Samples were cultured and growing microbes identified on the basis of gram stain, colony morphology, and biochemical reactions. Results: Catheter associated urinary tract infections due to prolonged catheterization of patients for more than 48 hours were found in 143 (52.96%) patients. The frequency of common causative uropathogens was: E. coli in 67 (47.18%), Kleibsella spp in 15 (10.56%), Proteus spp in 10 (7.04%), Pseudomonas spp in 8 (5.63%), Staphylococci in 14 (9.86%), Enterococci in 13 (9.15%) and other organisms in 15 (10.56%) patients. Conclusion: The frequency of catheter associated urinary tract infections with E. coli as the bacterial pathogen causing UTI due to prolonged catheterization is quite high. Pak J Physiol 2021;17(4):19?22

Predictive Value of Urinalysis and Recent Antibiotic Exposure to Distinguish Between Bacteriuria, Candiduria, and No-Growth Urine.

PurposeUrinary tract infections are diagnosed by clinical symptoms and detection of causative uropathogen. Antibiotics are usually not indicated in candiduria and no-growth urine. We aimed to develop a predictive score to distinguish bacteriuria, candiduria, and no-growth urine, and to describe the distribution of microorganisms in urine.Patients and MethodsA single-center, retrospective cohort study was conducted between January 2017 and November 2017. Patients with concomitant urinalysis and urine culture were randomly sorted for a clinical prediction model. Multivariable regression analysis was performed to determine factors associated with bacteriuria, candiduria, and no-growth urine. A scoring system was constructed by rounding the regression coefficient for each predictor to integers. Accuracy of the score was measured by the concordance index (c-index).ResultsThere were 8091 positive urine cultures: bacteria 85.6%, Candida 13.7%. Randomly selected cases were sorted into derivation and validation cohorts (448 cases and 272 cases, respectively). Numerous yeast on urinalysis predicted candiduria with complete accuracy; therefore, it was excluded from a score construction. We developed a NABY score based on: positive nitrite, 1 point; Antibiotic exposure within 30 days, –2 points; numerous Bacteria in urine, 2 points; few Yeast in urine, –2 points; moderate Yeast in urine, –5 points. The c-index was 0.85 (derivation) and 0.82 (validation). A score ≥0 predicted 76% and 54% of bacteriuria in the derivation and validation cohorts, respectively. A score ≤−3 predicted 96% of candiduria in both cohorts.ConclusionNumerous yeast on urinalysis and the NABY score may help identify patients with a low risk of bacteriuria in whom empiric antibiotics for UTIs can be avoided.

Antimicrobial Resistance Patterns and ESBL of Uropathogens Isolated from Adult Females in Najran Region of Saudi Arabia.

Background: To explore the prevalence of urinary tract infections (UTIs) among female patients in the Najran region of Saudi Arabia and determine their antimicrobial resistance pattern. Methods: This study was conducted on 136 urine samples collected from outpatient departments (OPDs) of the different government hospitals in the Najran region of Saudi Arabia. Over one year, the results of susceptibility testing reports of outpatient midstream urine samples from three government hospitals were prospectively evaluated. Results: Of 136 urine samples, only 123 (90.45%) were found to show significant growth for UTIs, from which 23 different uropathogens were identified. Escherichia coli (58.5%) was the most commonly isolated organism, followed by Klebsiella pneumoniae (8.1%). The isolated microorganism showed increased resistance patterns from 3.3% to 62.6%, with an overall resistance of 27.19%. Meropenem was the most effective antimicrobial, followed by amikacin and ertapenem (0.47%, 0.91%, and 1.5% resistance, respectively). At the same time, ampicillin and cephazolin were the least (62.6% and 59.5% resistance, respectively) effective. Overall, eleven (8.94%) uropathogens isolates were ESBLs, among which there were eight (6.5%) Escherichia coli, one (0.81%) Klebsiella pneumoniae, one (0.81%) Klebsiella oxytoca, and one (0.81%) Citrobacter amalonaticus. Conclusions: E. coli remains the most commonly isolated causative uropathogens, followed by Klebsiella species. The prevalence of pathogenic E. coli and Klebsiella species underscores the importance of developing cost-effective, precise, and rapid identification systems to minimize public exposure to uropathogens. Antibiotic susceptibility data revealed that most of the isolates were resistant to the majority of the antibiotics. The patients with UTIs in the Najran region of Saudi Arabia are at a high risk of antibiotic resistance, leading to significant problems in outpatient department (OPD) treatment outcomes and raising the alarm for the physician to change their empiric treatment.

Does the current resistance situation allow the empirical use of Bactrim® in patients with urinary tract infections?

Urinary tract infections (UTIs) are frequent reasons for consultation in primary care and the choice of empirical antibiotic therapy is determined by the local resistance patterns of the causative uropathogens.

Urinary Microbiome Characteristics in Female Patients with Acute Uncomplicated Cystitis and Recurrent Cystitis.

Traditionally, the diagnostic mainstay of recurrent urinary tract infection has been urinary culture. However, the causative uropathogen of recurrent cystitis has not been well established. Urine DNA next-generation sequencing (NGS) can provide additional information on these infections. Herein, we compared urine NGS results and urine cultures in patients with acute uncomplicated cystitis (AUC) and recurrent cystitis (RC), and evaluated the difference in microbiome patterns in the NGS results. Patients who underwent urine culture and NGS due to AUC or RC were retrospectively reviewed. All urine samples were collected via a transurethral catheter and studied utilizing a type of NGS called 16S ribosomal RNA gene amplification and sequencing. The sensitivity of urine NGS was significantly higher than that of conventional urine culture (69.0% vs. 16.7%, p < 0.05). The detection rate of urine NGS was slightly lower in the RC group than in the AUC group (67.7% vs. 72.7%). Microbiome diversity was significantly higher in the RC group compared to the AUC group (p = 0.007), and the microbiome composition was significantly different between the AUC and RC groups. In the urine NGS results, Pseudomonas, Acinetobacter, and Enterobacteriaceae were found in the AUC group, and Sphingomonas, Staphylococcus, Streptococcus, and Rothia spp. were detected in the RC group. Urine NGS can significantly increase the diagnostic sensitivity compared to traditional urine culture methods, especially in RC patients. AUC and RC patients had significant differences in bacterial diversity and patterns. Therefore, recurrent cystitis might be approached from a different perspective.

Monitoring of urinary microbiota and uropathogens' antibiotic resistance in one urological hospital

Introduction. There is no consensus on the management of patients with recurrent uncomplicated lower urinary tract infection (uLUTI), which makes it difficult to carry out effective therapy. Purpose of the study . To study the microbial patterns of urine and uropathogens' antibiotic resistance in a urological hospital from 2010 to 2017. Materials and methods . The results of bacteriological studies and the data of individual antibiotic susceptibility testing of patients with recurrent uLUTI (n = 502) were retrospectively analyzed. Inclusion criteria of the study: consent of patients to participate in the study, the presence of clinical manifestations of recurrent uLUTI in anamnesis, two episodes within six months or three during the year, leukocyturia in the urinalysis, the absence of sexually transmitted diseases at the time of the study and in anamnesis and also vaginal discharge. Bacteriological studies of the midstream morning urine sample before the prescription of antibiotic therapy were carried out with the determination of antibiotic sensitivity/resistance and production of extended-spectrum p-lactamases. In addition to the standard set of culture media, chromogenic media, aerobic and anaerobic culturing conditions were used. Statistical analysis was performed in the statistical processing and data visualization environment «R ver 3.2» («R Foundation for Statistical Computing», Vienna, Austria). Results. During the 8-year monitoring of the microbiota, the urine of patients with recurrent uLUTI was characterized by a microbial pattern certain constancy, but with the predominance (94.1% - 99.1%) of anaerobic-aerobic associations. The antibiotic resistance of most causative and debatable uropathogens increased, and the detection frequency of enterobacteria producing extended-spectrum p-lactamases also increased. Significant differences in the average levels of bacteriuria in the study period for most taxa of microorganisms were not detected. Conclusion. The detection frequencies of E. coli vary around 50.0%, for other causative pathogens a lower detection rate is noted, while non-clostridial anaerobic bacteria are excreted in 96.6% of cases in patients with recurrent uLUTI. The antibiotic resistance of causative and debatable pathogens and the detection frequencies of enterobacteria producing extended-spectrum p-lactamases are increasing, which necessitates a revision of the etiological structure and approaches to empirical therapy of recurrent uLUTI.

Current Antibiotic Resistance Trends of Uropathogens in Central Europe: Survey from a Tertiary Hospital Urology Department 2011-2019.

Monitoring of pathogen resistance profiles is necessary to guide empirical antibiotic therapy before culture and sensitivity results become available. The aim of this study was to describe current antibiotic resistance patterns of five most frequent causative uropathogens in a Department of Urology of a tertiary referral centre in Central Europe over a period of nine years. The Hospital Department of Clinical Microbiology database was used to extract data on all positive urine samples from inpatients in the Department of Urology between 2011 and 2019. Numbers of susceptible and resistant isolates per year were calculated for five most frequent uropathogens: Escherichia coli, Enterococcus spp., Klebsiella spp., Pseudomonas aeruginosa, and Proteus spp. Antimicrobial agents selected for the survey included: ampicillin, amoxicillin/clavulanic acid, piperacillin/tazobactam; cefuroxime, cefotaxime, ceftazidime and cefepime; ciprofloxacin and ofloxacin; gentamicin and amikacin; ertapenem, meropenem and imipenem; trimethoprim-sulfamethoxazole (co-trimoxazole), nitrofurantoin, colistin, and vancomycin. High resistance rates of Gram-negative uropathogens were demonstrated to most common antimicrobials, with statistically significant increasing or decreasing trends in some cases. No carbapenem-resistant Enterobacteriaceae were isolated. Vancomycin-resistant Enterococcus spp. strains were rare in our population.

Sporadic compared to recurrent urinary tract infections: Considerations for urogynecologic patients.

To describe the uropathogens and antimicrobial resistance patterns in women with singular, sporadic urinary tract infection (UTI) vs those with recurrent UTI (rUTI) in a urogynecologic population. This was a cross-sectional analysis of women treated for a UTI by a urogynecologic provider in a 1-year timeframe. Subjects were divided into two groups: (a) sporadic UTI-no history of rUTI and a single infection in the study timeframe and (b) rUTI-history of rUTI and ≥2 UTIs in the study timeframe. Our primary outcome was the difference in uropathogens between groups. Secondary aims were to investigate host characteristics associated with recurrent Escherichia coli infections and resistant uropathogens in the rUTI cohort. We had 265 women with 163 (61.5%) in the sporadic UTI group and 102 (38.5%) in the rUTI group. The most common uropathogens were E. coli (57.3%) and Klebsiella (11.7%). In the rUTI group, only 27 of 102 (26.5%) had all E. coli infections. There were differences between groups regarding age (P = .03) and proportion of neurogenic bladder (P = .01), intermittent self-catheterization (P < .01), antibiotic suppression (P < .01), and vaginal estrogen therapy (P < .01). In the rUTI cohort, there were no risk factors that were significantly associated with recurrent E.coli UTIs and vaginal estrogen therapy was associated with a higher odds of sensitive uropathogens (adjusted odds ratio, 3.12; confidence interval, 1.28-7.56). In those with rUTI, it was uncommon to have recurring E. coli UTIs and consistently sensitive uropathogens. Pretreatment urine cultures are important to verify causative uropathogens in this population.

Микробиота секрета простаты: сравнительный анализ хронического простатита категорий II и IIIA

Chronic bacterial prostatitis (CBP) and chronic prostatitis/chronic pelvic pain syndrome IIIa (CP/CPPS IIIa) are separate nosologies defined diagnostic verification criteria according to the NIH-NIDDK classification (1995). The identification of enterobacteria in the prostatic secretion (PS) has long been a criterion for the diagnosis of CBP, while PS in patients suffering CP/CPPS IIIa was considered as "sterile". However, the introduction of various methods of PS`s in-depth analysis and UPOINTS classification (2010) development with the allocation of site I (infection) allows us to consider the infectious factor as an etiological predictor of the initiation of inflammation in the prostate with CP/CPPS IIIa. Thus, the determination of the features of the taxonomic composition of microbiota in BP and CP/CPPS IIIa can act as a differentiating factor of these conditions. /Objective: performing a comparative analysis of the PS microbiota in patients suffering from CBP and CP/CPPS IIIa. Feature: full-scale, prospective, comparative, uncontrolled study. During the study, a staged PS`s bacteriological study was performed in 101 patients (aged 20-60 years) with prostatitis-like symptoms lasting more than 3 months and identified leukocytosis in PS (> 10x`). Stage I of the PS`s study: a standard nutrient medium and culturing conditions were used. Two comparison groups were formed according to the results of the initial bacteriological study: 49 patients were included in group 1 (CBP), in which E. coli, Klebsiella spp., Proteus spp. were identified in PS (causative uropathogens in CBP), in group 2 (CP/CPPS IIIa) included 52 patients, with no growth of the above microorganisms` taxa in the biomaterial and/or primary negative results of the study. Stage II of the PS`s study: an extended set of selective media and special cultivation conditions were used for accessory verification of bacteria in biomaterial. Biochemical identification of bacteria was carried out using test systems. Statistical processing of seeding rates was carried out using Statistica 10.2 package (StatSoft Inc., USA). In both groups, we used descriptive statistics methods and the Mann-Whitney U test to process the results of bacteriological studies. The significance of differences between the studied parameters was considered at the level of p<0.05 and p<0.01. Usage of an expanded set of selective media and special cultivation conditions (as compared with the results of the primary bacteriological culture of the exprimate) made it possible to collectively verify in PS to 28 species / genera of microorganisms in both groups (25 in group 1 and 24 in group 2). The taxonomic composition of the PS`s microbiota was almost identical in both groups and presented mainly in the form of multicomponent microbial associations. According to the results of analysis of the bacteria`s identification frequency in PS, it was found that in group 2 (CP/CPPS IIIa) significantly more often than in group 1 (CBP) discovered some representatives of the non-clostridial anaerobic flora (NAB: Peptococcus sp., Propionibacterium spp. and others), coagulase-negative staphylococci (CNS: S.haemolyticus, S.warneri) and certain taxa of gram-positive microorganisms (Corynebacterium spp. and Str. agalacticae). In turn, when analyzing the PS contamination, it was found that integrally in group 1 (CBP) in the samples of the biomaterial a higher titer of microorganisms was determined with a wide range of quantitative values, in relation to group 2 (CP/CPPS IIIa), where the titer indices were somewhat lower and had a smaller variation relative to the average. Identification in patients of both groups in PS of different mixed microbial associations, similar in the taxonomic spectral composition of microbiota, suggests that CP/CPPS IIIa in some cases is unverified CBP, which in turn necessitates a review of diagnostic and therapeutic strategies to achieve positive clinical result.

What is the Infectious Risk of Prostate Biopsy: The Global Prevalence of Infections in Urology (GPIU) Study

Background: Reports suggest an increase of life-threatening infectious complications following prostate biopsies (P-Bx). Methods: Risk factors and time trends in rates of infectious complications were evaluated in the multicentre, worldwide, prospective Global Prevalence of Infections in Urology (GPIU) study 2010-2018. The primary outcome was infectious complications after P-Bx. Uni- and multivariate statistical analysis, two-sample t and chi-square tests were used. Findings: Outcome data were available for 1556 men. Rates of symptomatic complications increased from 6.1% in 2010 to 10.2% in 2018. Prevalence of symptoms of urinary tract infections (UTI) justifying antibiotic treatment was 6.5%. Fluoroquinolone-based prophylaxis was administered in 79.7%. Transperineal P-Bx, repeated P-Bx, aminoglycosides as prophylaxis and histopathologic signs of inflammation in the prostate were risk factors to develop symptoms of UTI. Inflammation of the prostatic tissue was associated with a higher number of post-P-Bx symptoms. Of 88 urine cultures post-P-Bx, 33 were positive (37.5%). Escherichia coli was the most common causative uropathogen (75.8%). Resistance rate to fluoroquinolones was 60.0%. Following transrectal P-Bx, 3.9% of patients required hospitalization and 2.7% developed febrile infections. Two men (0.13%) died after transrectal P-Bx due to sepsis. Interpretation: Symptoms of UTI after P-Bx increased during study period. Inflammation of the prostatic tissue is associated with a higher number of post-P-Bx symptoms. Transrectal P-Bx was a risk factor for severe complications, such as febrile UTIs and mortality. Funding: European Section of Infections in Urology (ESIU), European Association of Urology (EAU), EAU Research Foundation (EAU RF), Technische Hochschule Mittelhessen (THM), Germany, Merian Iselin Foundation, Switzerland. Declaration of Interests: Authors have no potential conflict of personal interest to disclose that could give the appearance of potentially influencing the submitted work. Ethics Approval Statement: The GPIU study was approved by the Ethical Committee of the Justus Liebig University, Giessen, Germany (ethical vote: AZ:116/07). Due to the multicentric and multinational nature, obtaining regulatory approval was the responsibility of each study centre.

Diabetes mellitus and urinary tract infection: Causative uropathogens, their antibiotic susceptibility pattern and the effects of glycemic status.

Objective:To determine causative uropathogens and their antibiotic susceptibility pattern among Type-2 diabetics (T2D) with good and suboptimal glycemic control.Methods:A hospital based cross-sectional study was carried out in Peshawar from April–October, 2019. Four hundred consecutive T2D patients with symptomatic UTI or showing numerous pus cells on routine urinary examination attending outpatient clinic were included. As per the guidelines of the Clinical and Laboratory Standards Institute (CLSI), the urine samples collected were checked for identification of uropathogen by culture. Disc diffusion method was used to determined antimicrobial susceptibility.Results:Of the total (n=400) T2D patients, 205 (51.25%) showed microbial growth. Mean age of patients with UTI was 63.26 ±12.30 years. About two-third (63.9%) of the patients were females. Mean HbA1c was 8.80±2.20%. The frequency of patients with UTI was noticeably greater in the suboptimal glycemic control group 178(86.3%) compared to good control glycemic patients 27(13.7%). Significant mean difference in glycemic levels were observed (HbA1c = 5.86±0.48 and HbA1c = 9.25±2.02, respectively, P < 0.001). E. coli was the predominant pathogen isolated 120(71%), followed by Klebsiella pneumonia Spp (K. pn) 35(17.1%), Pseudomonas auregonosa (P. aeruginosa) 14(6.83%), Enterococcus 12 (5.85%) and Candida Spp were 2(0.98%). Both gram positive and negative-bacteria were highly susceptible to imipenem, meropenem, fosfomycin and nitrofurantoin.Conclusion:The frequency of UTI in diabetics was higher in female in comparison to male, and was significantly greater in the suboptimal glycemic control group. E. coli was the most typical isolate followed by K. pn. Imipenem, meropenem, fosfomycin and nitrofurantoin had high susceptibility profile against the isolated pathogens.

Association between urine pH and common uropathogens in children with urinary tract infections.

Urinary tract infections (UTIs) are one of the most common pediatric infections. Our objective in this study is to investigate the association between urine pH and uropathogens in pediatric patients. The source population comprised 26 066 paired urinalysis (UA) and urine culture (UC) samples obtained from pediatric patients. We classified the paired UA-UC samples into UTI positive (N=6348) and UTI negative (N=19 718) according to the colony forming units corresponding to the sampling source. We included UTI positive patients with infection caused by a single species of pathogen (N=5201) and frequency matched them with UTI negative patients (N=4729) by age, sex, sampling source, and visit type. This study included 5201 pediatric patients with UTIs and found that urine with Proteus mirabilis or Pseudomonas aeruginosa demonstrated the least acidic pH (mean pH=6.72 and 6.62, respectively), whereas urine with Escherichia coli or Klebsiella pneumoniae exhibited the most acidic pH (pH=6.21 and 6.18). After stratifying the UTI samples by their pH range (<6, 6-6.9, 7-7.9, and ≥8). The prevalence of P. mirabilis increased significantly across increasing pH categories. This research is the first epidemiological study that linked urine pH to specific uropathogens in a pediatric population. Both urine pH and age are associated with certain causative uropathogens. Urine that grew P. mirabilis or P. aeruginosa had the least acidic pH. Additional studies should validate the role of urine pH in predicting uropathogens and UTI.