Korean urobiome platform (KUROM) study for acute uncomplicated sporadic versus recurrent cystitis in women: Clinical significance.

PURPOSE: To investigate urine microbiome differences among healthy women, women with recurrent uncomplicated cystitis (rUC), and those with sporadic/single uncomplicated cystitis (sUC) to challenge traditional beliefs about origins of these infections. MATERIALS AND METHODS: Patients who underwent both conventional urine culture and next-generation sequencing (NGS) of urine were retrospectively reviewed. Symptom-free women with normal urinalysis results as a control group were also studied. Samples were collected via transurethral catheterization. RESULTS: In the control group, urine microbiome was detected on NGS in 83.3%, with Lactobacillus and Prevotella being the most abundant genera. The sensitivity of urine NGS was significantly higher than that of conventional urine culture in both the sUC group (91.2% vs. 32.4%) and the rUC group (82.4% vs. 16.4%). In urine NGS results, Enterobacterales, Prevotella, and Escherichia/Shigella were additionally found in the sUC group, while the recurrent urinary tract infection (rUTI)/rUC group exhibited the presence of Lactobacillus, Prevotella, Enterobacterales, Escherichia/Shigella, and Propionibacterium. Moreover, distinct patterns of urine NGS were observed based on menopausal status and ingestion of antibiotics or probiotics prior to NGS test sampling. CONCLUSIONS: Urine microbiomes in control, sUC, and rUTI/rUC groups exhibited distinct characteristics. Notably, sUC and rUC might represent entirely separate pathological processes, given their distinct urine microbiomes. Consequently, the use of urine NGS might be essential to enhancing sensitivity compared to conventional urine culture in both sUC and rUTI/rUC groups.

Homology of Escherichia coli isolated from urine and vagina and their antimicrobial susceptibility in postmenopausal women with recurrent cystitis.

Uropathogenic Escherichia coli (UPEC) is a typical cystitis-causing organism that can migrate from the vagina to the bladder and cause recurrent cystitis (RC). Few reports have compared the characteristics of urinary and vaginal UPEC in patients with RC. We carried out molecular biological analyses of Escherichia coli (E. coli) strains and their antimicrobial susceptibility to assess the association between urinary and vaginally UPEC. We included E. coli isolated from urinary and vaginal samples at the onset of cystitis in postmenopausal women with RC between 2014 and 2019 in our hospital. Pulsed-field gel electrophoresis (PFGE) was performed using a restriction enzyme (Xba I). These sequences were compared with 17 antimicrobial susceptibilities determined by a micro-liquid dilution method. Multilocus sequence typing (MLST) and classification of extended-spectrum ß-lactamase (ESBL) genotypes by multiplex polymerase chain reaction (PCR) were performed on ESBL-producing E. coli. We analyzed 14 specimens (each seven urine and vaginal) from seven patients in total. On PFGE, the similarity of urinary and vaginal E. coli per patient ranged from 89.5 to 100 %, including four patients with 100 % matches. MLST demonstrated that 29 % (4/14 specimens) were strain sequence type 131. Two specimens contained ESBL-producing strains and identified the CTX-M-27 genotype for each specimen. For each patient, antimicrobial susceptibilities between urinary and vaginal E. coli were mostly identical. Thus, urinary- and vaginally-derived E. coli were identical in postmenopausal women with RC. Management targeting both urinary and vaginal UPEC is essential for RC, indicating the importance of a vagina-targeted approach.

Blood plasma and urinary biomarkers of oxidative stress in cats with urethral obstruction.

BACKGROUND: This study aimed to investigate variations of the oxidative status in cats affected by urethral obstruction (UO) under Feline Idiopathic Cystitis (FIC) and Bacterial Cystitis (BC), in comparison with a group of healthy subjects. In both groups, the levels of several markers (either direct or indirect) indicative of the oxidative attack and of the antioxidant response were analyzed on plasma and urine samples. In particular, the plasma samples were evaluated for nitric oxide (NO), hydroperoxides derived by reactive oxygen activity (d-ROMs test), superoxide anion (O2-), glutathione peroxidase activity (GPx), superoxide dismutase activity (SOD), and ferric reducing antioxidant power (FRAP test); while on urine the levels of NO, d-ROMs, FRAP, SOD, malondialdehyde (MDA) and 8-hydroxydeoxyguanosine (8-OHdG) were measured. Urine of UO patients was also subjected to urine-culture test. RESULTS: The analytical data on plasma showed that UO, independently of the FIC or BC etiology, induced the insurgence of oxidative stress conditions at the systemic level. In the urine of the UO patients, except for SOD that increased, the markers of redox status were markedly decreased due probably their compromised filtration, thus suggesting involvement of renal function (assessed also by the high levels of plasma creatinine and proteinuria) with no oxidative damage of the lower urinary tract. Moreover, the adoption of a novel oxidative stress index' (OSI) allowed to establish, by means of a numerical value, the different degrees of oxidative stress conditions for single UO patients, both in terms of oxidative attack and antioxidant response. CONCLUSIONS: Feline urethral obstruction, induced by Idiopathic Cystitis and Bacterial Cystitis, causes oxidative stress conditions at the systemic level that do not interest the lower urinary tract. Despite to the high variability of the profiles of oxidative stress indexes both in healthy and UO patients, the determination of OSI made possible the evaluation of their single degrees of oxidative stress. Possibly the results of this investigation can be compared with those of correspondent pathologies both in humans and in other animal species.

[Immunological parameters of urine in differential diagnosis of chronic recurrent cystitis in women].

INTRODUCTION: Chronic recurrent cystitis (CRC) is a complex multifaceted problem of modern uroinfectology. OBJECTIVE: To study the immunological parameters of urine in patients with chronic recurrent cystitis depending on the etiological factor. MATERIALS AND METHODS: The prospective study included 71 patients aged 20-45 years who had previously been diagnosed with recurrent lower urinary tract infection: chronic recurrent cystitis (CRC) during an exacerbation period. Based on the results of bacteriological and PCR studies of urine, scraping of the urethra and vagina, depending on the dominant etiological factor, the patients were divided into three groups: group 1 (n=30) - with papillomavirus CRC (PVI-CRC), group 2 (n=30) - with bacterial CRC (B - CRC), group 3 (n=11) - with candida CRC (C - CRC). Analysis of the assessment of immunological parameters of urine was carried out using an enzyme-linked immunosorbent assay (ELISA-BEST). RESULTS: Based on the results of an immunological study of urine in the study groups, characteristic specific changes in the level of interleukins and interferons were identified, which made it possible to determine a protocol for the differential diagnosis of CRC. CONCLUSIONS: Our study shows the advisability of testing interleukins in urine (IL-1 beta, IL-6, IL-8); these indicators can serve as scoring criteria in the differential diagnosis of CRC of various origins. CONCLUSIONS: , it is reasonable to study the level of IFN-2b and IFN; when identifying the functional inferiority of the IFN system in women with CRC, correction of the IFN system is necessary.

No viable bacterial communities reside in the urinary bladder of cats with feline idiopathic cystitis.

Urinary microbial diversities have been reported in humans according to sex, age and clinical status, including painful bladder syndrome/interstitial cystitis (PBS/IC). To date, the role of the urinary microbiome in the pathogenesis of PBS/IC is debated. Feline idiopathic cystitis (FIC) is a chronic lower urinary tract disorder affecting cats with similarities to PBS/IC in women and represents an important problem in veterinary medicine as its aetiology is currently unknown. In this study, the presence of a bacterial community residing in the urinary bladder of cats with a diagnosis of FIC was investigated. Nineteen cats with clinical signs and history of FIC and without growing bacteria in standard urine culture were included and urine collected with ultrasound-guided cystocentesis. Bacterial community was investigated using a culture-dependent approach consisted of expanded quantitative urine culture techniques and a culture-independent approach consisted of 16S rRNA NGS. Several methodological practices were adopted to both avoid and detect any contamination or bias introduced by means of urine collection and processing which could be relevant due to the low microbial biomass environment of the bladder and urinary tract, including negative controls analysis. All the cats included showed no growing bacteria in the urine analysed. Although few reads were originated using 16S rRNA NGS, a comparable pattern was observed between urine samples and negative controls, and no taxa were confidently classified as non-contaminant. The results obtained suggest the absence of viable bacteria and of bacterial DNA of urinary origin in the urinary bladder of cats with FIC.

Descriptive management of suspected acute cystitis in adult patients by French general practitioners during remote consultation.

OBJECTIVES: The main objective of this study was to analyze French general practitioners' (GP) online prescriptions for suspected acute cystitis using a single nationwide teleconsultation platform. PATIENTS AND METHODS: First, a descriptive study of management for suspected cystitis was conducted from the 1st of January to the 31st of December 2020. After which, following pedagogical intervention, a pre/post descriptive analysis of the antibiotics prescribed was carried out. RESULTS: Some 496,041 teleconsultations (TCs) were carried out in 2020 on the Qare platform. Among them, 15,089 TCs for cystitis with ICD-10 encoding (N30) were analyzed. Fosfomycin trometamol was the most prescribed antibiotic (n = 10297, 69%), while fluoroquinolones (n = 1568, 10.6%) were the second. Urine test strip was prescribed in 3157 (20%) and urine culture in 7033 (47%) of the TCs. July-August 2020 and July-August 2021 were compared and while a significant drop in fluoroquinolone prescriptions and a major increase in Fosfomycin trometamol were observed, there was no change in the prescriptions of urine culture. An average antibiotic conformity rate of 61.5% was observed before the intervention, and 68.8% afterwards. CONCLUSIONS: Cystitis is a recurrent reason for remote consultation. The study demonstrated sizable over-prescription of urine culture, ultrasound, and fluoroquinolones. Intervention should be improved and strengthened to guarantee continuous training and awareness of GP's on appropriate cystitis prescriptions in telemedicine.

Personalized Metabolic Profile by Synergic Use of NMR and HRMS.

A new strategy that takes advantage of the synergism between NMR and UHPLC-HRMS yields accurate concentrations of a high number of compounds in biofluids to delineate a personalized metabolic profile (SYNHMET). Metabolite identification and quantification by this method result in a higher accuracy compared to the use of the two techniques separately, even in urine, one of the most challenging biofluids to characterize due to its complexity and variability. We quantified a total of 165 metabolites in the urine of healthy subjects, patients with chronic cystitis, and patients with bladder cancer, with a minimum number of missing values. This result was achieved without the use of analytical standards and calibration curves. A patient's personalized profile can be mapped out from the final dataset's concentrations by comparing them with known normal ranges. This detailed picture has potential applications in clinical practice to monitor a patient's health status and disease progression.

The clinical research of 5 steps sequential method for whole treatment of hemorrhagic radiation cystitis in china.

Background: Curing hemorrhagic cystitis remains a challenge. We explore a continuous and effective treatment for hemorrhagic radiation cystitis. Methods: The data of patients in 6 provincial cancer hospital urology departments between April 2015 and December 2019 was reviewed retrospectively. Patients were classified as moderate and severe groups. The 5-steps sequential method was adopted. Two groups were initiated with step 1 and step 3 respectively. Step 1 was symptomatic treatment. Thrombin solution or sodium hyaluronate was administrated for bladder irrigation in step 2. Step 3 was transurethral electrocoagulation. Step 4 was interventional embolization. Step 5 was HBO therapy. OABSS was used to assess the improvement of patients' symptoms. The outcome was evaluated after at least 6 months of follow-up. Results: A total of 650 patients (56 men and 594 women), mean age 71.2 years, were enrolled in the 5 steps sequential method. 582 patients were classified as moderate and 68 severe group. In moderate group, the cure rate of step 1 was 61.2% (356/582), 80.4% (468/582) after step 2, 93.1% (542/582) after step 3, 96.2% (560/582) after step 4, and 99.8% (581/582) after step 5. In severe group, the cure rate was 54.4% (37/68) after step 3, 76.5% (52/68) after step 4, and 94.1% (64/68) after the step 5 respectively. The mean OABSS scores of both groups significantly decreased after 5 steps sequential method treatment (P<0.01). Conclusions: Our results show hemorrhagic radiation cystitis can be cured in 5 steps, and the 5 steps sequential method is welcomed and effective. Therapy efficacy depends on the number of steps adopted and the severity of hematuria.

Prostate cancer survivors with symptoms of radiation cystitis have elevated fibrotic and vascular proteins in urine.

Radiation for pelvic cancers can result in severe bladder damage and radiation cystitis (RC), which is characterized by chronic inflammation, fibrosis, and vascular damage. RC development is poorly understood because bladder biopsies are difficult to obtain. The goal of this study is to gain understanding of molecular changes that drive radiation-induced cystitis in cancer survivors using urine samples from prostate cancer survivors with history of radiation therapy. 94 urine samples were collected from prostate cancer survivors with (n = 85) and without (n = 9) history of radiation therapy. 15 patients with radiation history were officially diagnosed with radiation cystitis. Levels of 47 different proteins were measured using Multiplex Luminex. Comparisons were made between non-irradiated and irradiated samples, and within irradiated samples based on radiation cystitis diagnosis, symptom scores or hematuria. Statistical analysis was performed using Welch's t-test. In prostate cancer survivors with history of radiation therapy, elevated levels of PAI 1, TIMP1, TIMP2, HGF and VEGF-A were detected in patients that received a radiation cystitis diagnosis. These proteins were also increased in patients suffering from hematuria or high symptom scores. No inflammatory proteins were detected in the urine, except in patients with gross hematuria and end stage radiation cystitis. Active fibrosis and vascular distress is detectable in the urine through elevated levels of associated proteins. Inflammation is only detected in urine of patients with end-stage radiation cystitis disease. These results suggest that fibrosis and vascular damage drive the development of radiation cystitis and could lead to the development of more targeted treatments.

Favorable Outcomes of Repeat Electrofulguration Procedures in Women With Antibiotic-refractory Recurrent Urinary Tract Infections.

OBJECTIVE: To evaluate the efficacy of repeat endoscopic electrofulguration in women with antibiotic-refractory, recurrent urinary tract infections (RUTIs) with persistent symptoms after 1 electrofulguration. METHODS: An institutional review board-approved, prospectively maintained database of non-neurogenic women with RUTIs, persistent symptoms and endoscopic findings of bladder wall inflammation after 1 electrofulguration, and minimum 6 months follow-up was reviewed. Endoscopic success was defined as complete resolution of previous lesions without new lesions seen during office cystoscopy 6 months after second electrofulguration. Clinical success was defined as no urinary tract infections at last follow-up; improvement as 1-2 treated infections/year; and failure as ≥3 treated infections/year, daily antibiotic suppression, or another electrofulguration (third or fourth). RESULTS: From 2006 to 2018, 58/70 (83%) women with median age 70 years and median follow-up 26 months were included, and 53/58 had endoscopic data 6 months postsecond electrofulguration. Endoscopic success was noted in 26 (49%), and 21/26 had <3 UTIs within the last year of follow-up, vs 2/27 (7%) with endoscopic failure (P = .001). Among those with clinical failure, 6/30 (20%) remained on suppressive antibiotics, 9/30 (30%) required intravenous antibiotic courses, and 2 proceeded to cystectomy. Of 24 women who underwent a third electrofulguration, 11/24 (46%) were clinically successful or improved at median 22 months follow-up. Urine cultures from the year of last follow-up revealed extended-spectrum beta lactamase producing strains (50%) and strains resistant to >3 antibiotics (43%). CONCLUSION: Women with persistent RUTIs following 1 electrofulguration may benefit from a second or even third procedure.

Impact of extended infusional mesna prophylaxis on the incidence of BK viruria and hemorrhagic cystitis following post-transplantation cyclophosphamide and CTLA4Ig-based haploidentical transplantation.

Hemorrhagic cystitis (HC) has been reported with increased frequency following post-transplantation cyclophosphamide (PTCy)-based haploidentical hematopoietic cell transplantation (HCT) along with a strong association with BK viruria. We prospectively evaluated the incidence of BK viruria and HC in 115 patients (median age 20 years, 2-65) undergoing PTCy-based haploidentical HCT with (n = 71) or without (n = 44) CTLA4Ig. HC prophylaxis consisted of a continuous infusion of mesna 30 min prior and 48 h post-PTCy. The overall incidence of BK viruria was 65.7%. None with BK viruria < 104 copies/ml developed clinical symptoms (n = 65). The incidence of BK viruria ≥ 104 copies/ml was 7.1% (n = 8) and 75% developed HC. The incidence of HC was 5.4% at a median of 30 days. Both BK viruria ≥ 104 copies/ml and HC were strongly associated with acute GVHD (p < 0.001). A higher NRM was observed in those with BK viruria ≥ 104 copies/ml, related to GVHD and its complications (41.7% vs 12.6%, p = 0.04). The incidences of acute GVHD, vis-à-vis, overall BK viruria, BK viruria ≥ 104 copies/ml, and HC, tended to be lower in patients receiving CTLA4Ig. Thus, extended infusional mesna, coupled with significant reduction in alloreactivity along with possible preservation of antiviral immunity associated with the use of CTLA4Ig, was probably responsible for a much lower incidence of BK viruria and resultant HC than reported previously following PTCy-based haploidentical HCT.

Symptom- and urinalysis-based approach to diagnosing urinary tract infections in children with neuropathic bladders.

BACKGROUND: Accurately diagnosing urinary tract infections (UTI) in children with neuropathic bladders can be difficult given the lack of specificity of both clinical symptoms and routine screening tests. We aimed to identify a priori unknown classes/groups of children with neuropathic bladder with respect to symptoms and UA results and examine their relationships with odds of UTI. METHODS: We used latent class analysis (LCA) to identify unobserved classes/groups of children with neuropathic bladder based on symptoms and urinalysis (UA) results, respectively. Demographic and clinical data were gathered by retrospective chart review of a cohort with neuropathic bladder. Symptoms and UA results were obtained by chart review of visits where urine culture was ordered. RESULTS: Around 193 patients were included in UA results analysis and 179 in symptom-based analysis. Two latent classes of patients were identified with respect to symptoms, labeled "pyelonephritis class" and "cystitis class," and two, with respect to UA results, were labeled "positive UA class" and "negative UA class." The pyelonephritis class had significantly higher odds of UTI compared to the asymptomatic class. While odds of UTI in cystitis class were higher than the asymptomatic class, this difference was not statistically significant. Positive UA class had significantly higher odds of UTI compared to negative UA class. CONCLUSION: Two unobserved classes/groups exist in children with neuropathic bladder with respect to symptoms, corresponding to cystitis and pyelonephritis, and two classes of UA results that correspond with either a positive or negative UA. Our results suggest a differential approach to treatments may be considered.

Evaluation of the trends and appropriateness of fluoroquinolone use in the outpatient treatment of acute uncomplicated cystitis at five family practice clinics.

WHAT IS KNOWN AND OBJECTIVE: Despite recommendations to avoid fluoroquinolones (FQs) as a first-line treatment for uncomplicated cystitis, recent data suggest that FQs remain widely prescribed. Therefore, the objectives of this study were to evaluate the appropriateness of empiric FQ use compared to nitrofurantoin for uncomplicated cystitis and to determine whether there are any trends or predictors of empiric FQ versus nitrofurantoin use for uncomplicated cystitis. METHODS: This retrospective study included women ages 19-64 years who were seen at five family medicine clinics and were prescribed targeted antibiotics (nitrofurantoin, ciprofloxacin or levofloxacin) for uncomplicated cystitis. Charts were reviewed to collect data, including symptoms, comorbidities, allergies, creatinine clearance, recent antibiotic use and urine culture data. Appropriateness of empiric selection was determined based on national guidelines and local susceptibility data. RESULTS AND DISCUSSION: A total of 677 patient encounters were screened for inclusion. Of those, 567 met the inclusion criteria: 395 nitrofurantoin and 172 FQs. Treatment was considered appropriate in 86.8% and 10.5% of cases that were prescribed nitrofurantoin and FQs, respectively (P < .01). There were four independent predictors of FQ use identified by multivariate logistical regression: clinic at which the patient was treated, age, nitrofurantoin use within 90 days prior to encounter and previous urine culture within one year with an organism non-susceptible to nitrofurantoin. WHAT IS NEW AND CONCLUSION: Despite recommendations against FQs for uncomplicated cystitis, they continue to be widely prescribed, and their use for this indication is often inappropriate. This highlights the need for additional interventions and education to improve use and preserve the utility of FQs.

Follicular cystitis in urine cytology: A clinical and cytopathologic study.

Despite being an important differential diagnosis of bladder tumor on cystoscopy, follicular cystitis (FC) is rarely diagnosed on cytologic material. We performed a retrospective study on cases of FC diagnosed on bladder biopsy and/or urine cytology in our institution. A total of 35 cases of FC were identified with a female predominance (F:M = 2:1). Hematuria was the most common clinical presentation. Cystoscopic findings included mass lesions, yellow plaques, and surface erythema. History of urinary tract infection was reported in 48% of the patients, and majority of those patients had positive concurrent urine culture, most commonly with beta-hemolytic streptococcus, Group B. A total of 17 out of 35 patients had urine cytology specimens. When the presence of follicular dendritic cells in clusters of variously sized lymphocytes is used as the cytological diagnostic criterion, 6 out of 17 cases were diagnosed as FC and 5 out of 6 were confirmed by concurrent biopsy. This retrospective study not only analyzed the clinical characteristics of FC but also elucidated the cytological diagnostic criteria of FC and confirmed its specificity.

Neutropenia and renal dysfunction due to intravesical cidofovir for virus-associated hemorrhagic cystitis after kidney and allogenic hematopoietic stem cell transplantations.

We present a patient with virus-associated hemorrhagic cystitis who underwent kidney and allogenic hematopoietic stem cell transplantations (allo-HSCT). Six months post-allo-HSCT, adenovirus hemorrhagic cystitis occurred, which has been in remission after a single dose of intravesical cidofovir. This might cause prolonged neutropenia and nephrotoxicity, suggesting cidofovir absorption in the blood.

[A new terminology for urinary cytopathology: The Paris System for Reporting Urinary Cytology (2015)]. / Une nouvelle terminologie pour la cytopathologie urinaire : le Système de Paris (2015).

As for the Bethesda system for cervical and thyroid cytopathology, a terminology for reporting urinary cytology has been published in 2015. The new "Paris System" provides a consensus terminology for urinary cytology which underlines the criteria for the recognition of high-grade urothelial carcinoma (HGUC) and of those excluding HGUC, or suspicious for HGUC. It also focuses on new rules to recognize and report the subgroup of "atypical urothelial cells". Here we describe and illustrate the various categories as in the reference book. We analyse the main diagnostic criteria, including microscopic features as well as the risk of malignancy associated to every diagnostic category.

Urinary K+ promotes irritative voiding symptoms and pain in the face of urothelial barrier dysfunction.

The internal surface of the bladder is lined by the urothelium, a stratified epithelium that forms an impermeable barrier to water and urine constituents. Abnormalities in the urothelial barrier have been described in certain forms of cystitis and were hypothesized to contribute to irritative voiding symptoms and pain by allowing the permeation of urinary K+ into suburothelial tissues, which then alters afferent signaling and smooth muscle function. Here, we examined the mechanisms underlying organ hyperactivity and pain in a model of cystitis caused by adenoviral-mediated expression of claudin-2 (Cldn2), a tight junction protein that forms paracellular pores and increases urothelial permeability. We found that in the presence of a leaky urothelium, intravesical K+ sensitizes bladder afferents and enhances their response to distension. Notably, dietary K+ restriction, a maneuver that reduces urinary K+, prevented the development of pelvic allodynia and inflammation seen in rats expressing Cldn2. Most importantly, intravesical K+ causes and is required to maintain bladder hyperactivity in rats with increased urothelial permeability. Our study demonstrates that in the face of a leaky urothelium, urinary K+ is the main determinant of afferent hyperexcitability, organ hyperactivity and pain. These findings support the notion that voiding symptoms and pain seen in forms of cystitis that coexist with urothelial barrier dysfunction could be alleviated by cutting urinary K+ levels.

Pharmacokinetics, Safety, and Clinical Outcomes of Omadacycline in Women with Cystitis: Results from a Phase 1b Study.

Omadacycline, an aminomethylcycline antibiotic, is approved as once-daily intravenous (i.v.) and oral (p.o.) monotherapy for acute bacterial skin and skin structure infections and for community-acquired bacterial pneumonia, and it is under development for treatment of urinary tract infection (UTI). This is a phase 1b, randomized, open-label study of omadacycline in women with cystitis (defined as UTI symptoms and a positive urine leukocyte esterase test). Patients received omadacycline for 5 days (group 1: 200 mg intravenously on day 1, then 300 mg orally every 24 h [q24h]; group 2: 300 mg orally every 12 h [q12h] on day 1, then 300 mg orally q24h; group 3: 450 mg orally q12h on day 1, then 450 mg orally q24h). Blood and urine samples were collected over 5 days. Investigator-assessed clinical response was determined at end of treatment (EOT; day 6) and posttreatment evaluation (PTE; 5 to 9 days after last dosing). A total of 31 women were treated. At steady state (day 5), the range of mean omadacycline urine concentrations over 24 h across the groups was 17.94 to 48.12 µg/ml. The most common treatment-emergent adverse events were gastrointestinal (including nausea [60% to 73%] and vomiting [20% to 40%]) and were generally mild and transient. Investigator-determined clinical success was observed in 94% and 84% of patients at EOT and PTE, respectively, with similar results across groups. A favorable microbiological response at PTE was observed in 78% of patients who had a baseline pathogen. Omadacycline is partially excreted in urine and appears to be safe and well tolerated. These preliminary results indicate that omadacycline warrants further evaluation in larger controlled UTI studies.

What can we learn by examining variations in the use of urine culture in the management of acute cystitis? A retrospective cohort study with linked administrative data in British Columbia, Canada, 2005-2011.

INTRODUCTION: Urinary tract infections (UTI) are common community-based bacterial infections. Empiric antibiotic recommendations are guided by local resistance rates. Previous research suggests that cultures are overused for uncomplicated cystitis, but practice patterns have not been described in detail. Variations in culturing have implications for the interpretation of antibiotic resistance rates. METHODS: We used a retrospective cohort study to analyze variations in urine culturing among physicians, controlling for patient and physician characteristics. We identified all outpatient physician visits among adults and children for cystitis in British Columbia between 2005 and 2011 using administrative data and linked these to laboratory data on urine cultures. Using hierarchical generalized linear mixed models we explored variations in urine culture submissions for cystitis (ICD code 595) and the associations with patient and physician characteristics, stratified by patient sex. RESULTS: Urine cultures were associated with 16% of visits for cystitis among females and 9% among males, and 59% of visits overall were associated with antibiotic treatment. Older patients, patients with a recent antibiotic prescription, and long term care residents were significantly less likely to have a culture associated with a cystitis visit, whether male or female. Female physicians and physicians with 16-35 years' experience were more likely to culture, while international medical graduates were less likely-particularly for female visits. Notably, there was substantial unexplained variation among physicians after controlling for physician characteristics: we found a 24-fold variation in the odds of culturing a female UTI between physicians who were otherwise similar. CONCLUSION: Individual physicians show substantial variation in their propensity to submit cultures for cystitis visits. Reducing such variation and encouraging appropriate levels of culturing would support effective antibiotic use.

Host and Bacterial Markers that Differ in Children with Cystitis and Pyelonephritis.

OBJECTIVE: To determine whether treatment for urinary tract infections in children could be individualized using biomarkers for acute pyelonephritis. STUDY DESIGN: We enrolled 61 children with febrile urinary tract infections, collected blood and urine samples, and performed a renal scan within 2 weeks of diagnosis to identify those with pyelonephritis. Renal scans were interpreted centrally by 2 experts. We measured inflammatory proteins in blood and urine using LUMINEX or an enzyme-linked immunosorbent assay. We evaluated serum RNA expression using RNA sequencing in a subset of children. Finally, for children with Escherichia coli isolated from urine cultures, we performed a polymerase chain reaction for 4 previously identified virulence genes. RESULTS: Urinary markers that best differentiated pyelonephritis from cystitis included chemokine (C-X-C motif) ligand (CXCL)1, CXCL9, CXCL12, C-C motif chemokine ligand 2, INF γ, and IL-15. Serum procalcitonin was the best serum marker for pyelonephritis. Genes in the interferon-γ pathway were upregulated in serum of children with pyelonephritis. The presence of E coli virulence genes did not correlate with pyelonephritis. CONCLUSIONS: Immune response to pyelonephritis and cystitis differs quantitatively and qualitatively; this may be useful in differentiating these 2 conditions.