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Aims Pyometra and cystitis caused by Escherichia coli are common diseases identified in canine or feline females. The origin of pyometra infection remains uncertain, and effective prevention strategies for this disease are still unknown. This study aimed to provide a phenotypic characterization, including antimicrobial resistance and virulence profiles, of endometrial pathogenic (EnPEC) and uropathogenic (UPEC) E. coli strains isolated simultaneously from the same animal. Methods and results Sixteen E. coli strains, from eight different animals, were analyzed in this study. The antimicrobial susceptibility profile of EnPEC and UPEC strains was determined using the disc diffusion method, which showed a similar susceptibility profile among strains (EnPEC and UPEC) from the same animal. The virulence profile of the strains was assessed through biofilm formation, as well as serum resistance abilities. EnPEC and UPEC strains from the same animal exhibited slight variations in their virulence and antimicrobial resistance capabilities. Overall, most of the strain pairs showed a high similarity in their ability to establish biofilms and survive in serum complement activity. Conclusions Overall, strains of E. coli isolated from both pyometra and cystitis in the same animal, despite presenting distinct clinical diseases, exhibit a wide phenotypic similarity, suggesting a common origin for the strains. [ABSTRACT FROM AUTHOR]

Antimicrobials are commonly prescribed and often misunderstood. With more than 50% of hospitalized patients receiving an antimicrobial agent at any point in time, judicious and optimal use of these drugs is paramount to advancing patient care. This narrative will focus on myths relevant to nuanced consultation from infectious diseases specialists, particularly surrounding specific considerations for a variety of antibiotics. [ABSTRACT FROM AUTHOR]

Background Fluoroquinolones (FQs) are associated with adverse effects and increasing resistance. However, uncomplicated cystitis remains a frequent reason for FQ use. Selective reporting involves withholding susceptibilities for select antimicrobial agents on microbiology reports, in hopes of dissuading use by providers. The purpose of this study was to investigate the impact of FQ susceptibility suppression on discharge prescribing for hospitalized patients with uncomplicated cystitis. Methods This retrospective quasi-experimental analysis was conducted among adult patients at a 350-bed academic medical center. Its aim was to compare the incidence of FQ prescribing for cystitis at hospital discharge, one year before and after implementation (1 March 2017–31 March 2019) of a policy to suppress FQ urinary susceptibility results for pansusceptible Klebsiella spp and Escherichia coli. FQ appropriateness and risk factors for FQ use were also examined. Results There was a relative risk reduction of 39% in discharge FQ prescribing when adjusted for discharge team (adjusted risk ratio, 0.61; 95% CI,.40–.93). Almost all FQ use was inappropriate, largely due to organisms' susceptibility to a guideline-preferred agent (n = 61). In multivariate analysis, odds ratios of discharge FQ prescribing were 0.22 (95% CI,.12–.39) for insured patients, 0.43 (95% CI,.21–.86) for patients with antibiotic allergy, and 57.8 (95% CI, 13.7–244) for those receiving inpatient FQ. Discharge from a medicine team was protective against discharge FQ prescribing. Conclusions With multidisciplinary inpatient medicine services and avoidance of inpatient FQ use, suppression of FQ susceptibilities on pansusceptible urine isolates for Klebsiella spp and E coli may represent an attractive strategy for antibiotic stewardship at hospital discharge. [ABSTRACT FROM AUTHOR]

Defining urinary tract infection (UTI) is complex, as numerous clinical and diagnostic parameters are involved. In this systematic review, we aimed to gain insight into how UTI is defined across current studies. We included 47 studies, published between January 2019 and May 2022, investigating therapeutic or prophylactic interventions in adult patients with UTI. Signs and symptoms, pyuria, and a positive urine culture were required in 85%, 28%, and 55% of study definitions, respectively. Five studies (11%) required all 3 categories for the diagnosis of UTI. Thresholds for significant bacteriuria varied from 103 to 105 colony-forming units/mL. None of the 12 studies including acute cystitis and 2 of 12 (17%) defining acute pyelonephritis used identical definitions. Complicated UTI was defined by both host factors and systemic involvement in 9 of 14 (64%) studies. In conclusion, UTI definitions are heterogeneous across recent studies, highlighting the need for a consensus-based, research reference standard for UTI. [ABSTRACT FROM AUTHOR]

Introduction In 2018, a unique maculopathy associated with chronic pentosan polysulfate sodium (PPS) use for the treatment of interstitial cystitis (IC) was described, where the authors detailed macular retinal pigment epithelial abnormalities in six patients. In this paper, a retrospective study of a larger patient pool at one large tertiary retina practice was undertaken to evaluate patients taking PPS and their macular findings. Materials and methods A retrospective chart review was performed on all patients presenting to a single large retina practice between 2011 and 2019. Patient's macular diagnosis, findings, optical coherence tomography scans, and macular auto-fluorescent scans were assessed. This project was Institutional Review Board (IRB) approved by the St Luke's Hospital IRB board (St Louis, MO, USA). Results Fifty-five patients were identified as taking PPS for IC. Fifty-three patients were found to have a diagnosis consistent with changes attributable to known macular diseases to include macular degeneration and pattern dystrophies. Two (4%) of fifty-five patients had macular findings suggestive of PPS toxicity. The first was a 58-year-old female with subtle retinal pigment epithelium (RPE) deposits on optical coherence tomography that exhibited hyper-autofluorescence. The second was a 72-year-old female with 14 years of PPS use who exhibited RPE excrescences and parafoveal areas of atrophy. Conclusions Pentosan polysulfate sodium may be the cause of macular findings in a small percentage of patients referred to a tertiary retina practice. Although causation of macular changes with PPS use has yet to be elucidated, clinicians should be aware of this possibility when assessing patients with atypical macular findings. Future longitudinal studies are necessary to evaluate a definitive relationship. This paper should remind all clinicians of the importance of a throughout review of the patient's medication list as novel toxicities may become apparent years after initial FDA trials. The strength of this study is the larger patient population compared to earlier studies, and the main weaknesses include the retrospective nature of the study, lack of family and genetic testing, and lack of multimodal imaging for all patients. [ABSTRACT FROM AUTHOR]

Gangrenous cystitis is a pathology that is rarely encountered in current urological practice. It is due to necrosis of the bladder wall, which may be superficial or involve the entire wall. Its exact pathogenesis is unknown, but several factors make its diagnosis based on cystoscopy or imaging. Its surgical treatment depends on the operative finding. In this report, the authors report a case of gangrenous cystitis in a 73-year-old patient with a history of prostatectomy and radiotherapy whose main manifestation was urinary retention. The diagnosis was made by computed tomography scan. Surgical exploration confirmed the diagnosis, thus imposing a partial cystectomy with an omentum base plasty. Despite a good postoperative clinical and biological evolution, the patient died in the intensive care unit following respiratory distress and ventricular tachycardia. This case reminds once again the high mortality associated with this pathology. [ABSTRACT FROM AUTHOR]

Recurrent urinary tract infections are a common health problem. The only comprehensive synthesis on antibiotic prophylaxis in the last 15 years has been a guideline-embedded meta-analysis. We conducted a systematic review and meta-analysis of randomized controlled trials published up to October 13, 2020, evaluating patients age ≥12 years with either ≥2 episodes of lower urinary tract infection (UTI) within 6 months or ≥3 in the past year. Placebo or antibiotics were allowed as comparators. Study quality was low. In the 11 placebo-controlled trials, the risk for developing UTI was 85% lower with prophylaxis in comparison with placebo (risk ratio [RR], 0.15; 95% CI, 0.08–0.29). In the 9 head-to-head trials, the efficacy of the antibiotic agents appeared similar: The pooled RR indicated no difference between nitrofurantoin and comparators (RR, 1.01; 95% CI, 0.74–1.37), nor trimethoprim (+/- sulfamethoxazole; RR, 1.34; 95% CI, 0.89–2.03) or norfloxacin and comparators (RR, 1.17; 95% CI, 0.43–1.70). Studies comparing intermittent (postcoital) with continuous strategies revealed intermittent application to be equally effective. [ABSTRACT FROM AUTHOR]

The article describes the case of a 43-year-old man with a four-month history of recurrent abdominal pain and one week of intermittent gross haematuria. Topics discussed include his medical history, findings on pathological examination, and initiation of a combined treatment of methyl-prednisolone and cyclophosphamide (CYC).

Background: Among the plethora of urogynecological conditions possibly affecting women, some of them, less explored, have significant impacts on sexological and psychological health, with a mutual influence. Aim: The aim of this study was to investigate the sexological and psychological correlates of four urogynecological pathologies in a sample of women of childbearing age: overactive pelvic floor, vulvodynia, postcoital cystitis, and interstitial cystitis. Women cured of these conditions were also included, to assess the same aspects after the remission of physical symptoms. Methods: We recruited 372 women with an average age of 33.5 years through an online platform shared by a popular forum for women with urogynecological pathologies between March and May 2021. The participants filled out a socio-anamnestic questionnaire and a set of psychometric tests. Outcomes: Participant data were collected by use of the Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, Toronto Alexithymia Scale-20, Female Sexual Function Index, and Orgasmometer-F, and the SPSS (Statistical Package for Social Sciences) v.26 was used for data analysis. Results: Overactive pelvic floor was reported by 66.4% of the women, vulvodynia by 55%, postcoital cystitis by 58.8%, and interstitial cystitis by 8.3%, and these conditions were often comorbid with each other, with 9.4% and 7% of women reporting having suffered psychological and sexual abuse, respectively. The presence of past abuse was correlated with overactive pelvic floor (P < .05), vulvodynia (P < .01), and major depression (P < .01). Significantly more depression occurred in women with vulvodynia than in the other subgroups (P < .05), except for women with only an overactive pelvic floor. There was no difference between the subgroups in the occurrence of alexithymia, sexual function, and orgasm (P < .05). Interestingly, the prevalence of sexual dysfunction increased in cured women. Clinical implications: The lack of significant differences, except for depression, between the pathological subgroups suggests a similar clinical and psychological relevance of the four pathologies studied. The persistence of sexual dysfunctions in cured women may be related to a residual dysfunctional relational modality with the partner. Strengths and Limitations: The evaluation of both psychological and sexological variables in a group of less-explored urogynecological conditions represents a strength of this study, while a lack of a face-to-face assessment could represent a limitation. Conclusion: The results of the present study should promote psychosexological interventions in women with these diseases, both during the pathological state and after remission. [ABSTRACT FROM AUTHOR]

Cancer development and progression is often associated with inflammation. Late diagnosis of inflammation that directly leads to the development of neoplasm—cancer is associated with a reduction in the chance of successful treatment or is associated with therapeutic difficulties. A panel of chromogenic substrates was used for the qualitative determination of the specific activity of enzymes in urine of patients with confirmed inflammatory reaction and/or epithelial neoplasms in particular tumours at various stages of development. Urine of people with excluded inflammation was used as a control group. Proteolytic activity was determined in urine samples collected from patients with epithelial neoplasms and/or inflammation. What is more, we determine human neutrophil elastase activity-related inflammation based on the examination of urine samples. We suspect that the proteolytical activity of urine samples is due to neutrophil response to inflammation, which is directly related to cancer. This is the first study to determine elastolytic activity in bladder cancer urine samples. It supports wider use of urine for inflammation screening. [ABSTRACT FROM AUTHOR]

Background The emergence of antimicrobial resistance in uropathogens has generated interest in the use of nitrofurantoin in controversial populations, such as in males and those with renal dysfunction. The purpose of this study was to compare the efficacy and safety of nitrofurantoin for the treatment of cystitis in males and females with variable degrees of renal dysfunction. Methods A retrospective chart review was conducted in adult patients who received nitrofurantoin for acute cystitis in the outpatient setting. The primary outcome was clinical cure compared between males and females and across various renal function groups (creatinine clearances [CrCl] >60 mL/min, 30–60 mL/min, and <30 mL/min) following nitrofurantoin treatment. The secondary outcome was adverse events. Results A total of 446 patients were included, with 278 females and 168 males. The overall clinical cure rate was 86.5% (95% CI, 83.0%–89.4%; n = 386). The clinical cure rate did not vary between genders (odds ratio [OR], 0.6; 95% CI 0.35–1.04; P  = .085) or between patients with a CrCl >60 mL/min compared with those with CrCl 30–60 mL/min (OR, 1.01; 95% CI, 0.40–2.44; P  = 1). The 1 patient with a CrCl <30 mL/min was not included in the analysis. A history of benign prostatic hyperplasia (OR, 0.5; 95% CI, 0.26–0.99; P  = .045) or cirrhosis (OR, 0.21; 95% CI, 0.06–0.82; P  = .025) was associated with decreased odds of clinical cure. Adverse events occurred in 2% (n = 9) of patients. Conclusions There was no statistically significant difference in clinical cure with nitrofurantoin between genders or various renal functions. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the impact of a urinary tract infection (UTI) pocket card on preferred antibiotic prescribing for patients discharged from the emergency department (ED) with a diagnosis of cystitis. Methods A multicenter, retrospective, pre-post study was conducted to compare outcomes following the introduction of a UTI pocket card. The primary outcome was prescribing rates for institutional first-line preferred antibiotics (cephalexin and nitrofurantoin) versus other antimicrobials for cystitis. Secondary outcomes included prescriber adherence to recommended therapy in regards to discharge dose, frequency, duration, and healthcare utilization rates. Results The study included 915 patients in total, 407 in the preintervention group and 508 in the postintervention group. The frequency of preferred antibiotic prescribing was significantly increased after the introduction of a UTI pocket card compared to prior to its introduction (81.7% vs 72.0%, P = 0.001). Significant increases in prescribing of an appropriate antibiotic dose (78.0% vs 66.8%, P < 0.0001) and frequency (64.2% vs 47.4%, P < 0.0001) were also found post intervention. No significant differences were seen between the pre- and postintervention groups with regards to healthcare utilization rates. Conclusion A UTI pocket card increased preferred antibiotic prescribing for cystitis in the ED. This study provides data on a successful antimicrobial stewardship intervention in the ED setting. [ABSTRACT FROM AUTHOR]

Background: Urinary tract infection (UTI) is one of the most prevalent medical conditions among women seeking primary care. About 20-40% of the women have a UTI recurrence during their lifetime.Objective: To provide insight in the patterns of recurring annual dispensing for antibiotics commonly used for UTI treatment in women, aged 18 years or older, during a 5-year follow-up period in the Netherlands.Methods: The Dutch Foundation of Pharmaceutical statistics collects dispensing data from more than 90% of all community pharmacies. Pharmacies with complete data between years 2011 and 2017 were included. Women of age 18 years or older with a first dispensing of nitrofurantoin, fosfomycin, or trimethoprim in 2012 and a dispensing of any medication in 2017 were selected. For each year between 2013 and 2017, the proportions of women with recurring dispensing of nitrofurantoin, fosfomycin or trimethoprim were calculated and stratified for age categories.Results: Within 1517 eligible community pharmacies, 463 821 women, aged 18 years or older, were dispensed one of the antibiotics in 2012, and 239 292 women still visited the same pharmacy in 2017. About 56% of them received at least one recurring dispensing during 5 years of follow-up. Each year, ~20% of the source population had at least one recurring dispensing. Approximately 2% of the source population had at least one recurring dispensing in each year of follow-up.Conclusions: Over the 5-year study period, more than 50% of the source population had at least one recurring dispensing for uncomplicated UTI, most of them with at least 1 year without UTI dispensing in between. [ABSTRACT FROM AUTHOR]

Our objective was to describe the duration of antibiotic therapy for the management of common outpatient conditions. The median duration of antibiotic courses for most common conditions, except for acute cystitis, was 10 days, in many cases exceeding guideline-recommended durations. [ABSTRACT FROM AUTHOR]

Non‐lactose‐fermenting Escherichia coli (NLFEC) has a few descriptive studies restricted to human infections. In the present study, isolates of NLFEC obtained from urine samples of dogs with hyperadrenocorticism were characterized regarding their virulence ability, biofilm formation capacity and antimicrobial susceptibility profile. Escherichia coli lactose‐fermenting strains from urinary infection in dogs with the same conditions were analysed to provide comparisons. The non‐lactose‐fermenting E. coli strains were classified as belonging to clade I E. coli, whereas the lactose‐fermenting strains were classified in phylogroup B2. All strains presented virulence markers to adhesion, iron acquisition, toxins, colicin and cytotoxin production, and biofilm regulation. Components of the extracellular matrix in addition to the in vitro biofilm formation ability were observed in the strains. Multidrug resistance (MDR) profiles were observed by in vitro susceptibility tests to all NLFEC strains. In summary, non‐lactose‐fermenting uropathogenic E. coli from dogs behaves similar to lactose‐fermenting E. coli, exhibiting MDR profile, and pathogenic potential of promote animal infections. [ABSTRACT FROM AUTHOR]

Background BK virus-associated hemorrhagic cystitis (BKV-HC) is a serious complication after hematopoietic stem cell transplantation (HSCT). Methods A retrospective review was performed to determine the frequency of BKV-HC and identify risk factors and renal morbidity associated with BKV-HC in pediatric HSCT recipients at our institution. Results A total of 314 pediatric recipients underwent allogeneic HSCT for either malignant (173, 55.1%) or nonmalignant disorders (141, 44.9%) from January 1, 2011, to December 31, 2015, with a minimum follow-up of 5 years post-HSCT. Severe BKV-HC (grades 3 and 4) was prevalent in 46 out of 67 (68.7%) recipients. Timing to presentation of severe BKV-HC (grades 3 and 4) occurred at a median of 37 days (26, 74; IQ1, IQ3) post-HSCT, with the duration of macroscopic hematuria lasting a median of 37.5 days (18, 71; IQ1, IQ3). In the first 60 days post-HSCT, peak acute kidney injury (AKI) stages 2 and 3 were seen more frequently in HSCT recipients who developed BKV-HC than those without (P =.004). Similarly, during post-HSCT days 61 to 100, peak AKI stage 3 was also more frequently seen in HSCT recipients who already developed BKV-HC prior to or during this time period than those without BKV-HC (P =.0002). Recipients who developed BKV-HC within 1 year of HSCT had more frequent mild to moderate chronic kidney disease (CKD stages 2-3) than those without BKV-HC (P =.002 and.007, respectively). On multivariate analysis, BKV-HC was associated with all-cause mortality (hazard ratio [HR]: 2.22; 95% confidence interval [CI]: 1.35-3.65). The following clinical variables were associated with time to development of HC on multivariate analysis: age (subdistribution HR [sHR] 1.11; 95% CI: 1.06-1.16) and myeloabalative conditioning regimen (sHR 4.2; 95% CI: 2.12-8.34). Conclusions Pediatric HSCT patients with BKV-HC experience significant morbidity and mortality. Renal morbidity, including AKI and CKD, is associated with BKV-HC. [ABSTRACT FROM AUTHOR]

Benign prostatic hyperplasia (BPH) is an age-related debilitating prostatic disease that is frequently associated with prostatic inflammation and bothersome lower urinary tract symptoms (LUTS). Animal models have shown that formalin- and bacterial-induced prostatic inflammation can induce bladder dysfunction; however, the underlying mechanisms contributing to prostatic inflammation in BPH and bladder dysfunction are not clear. We previously reported that E-cadherin expression in BPH is downregulated in hyperplastic nodules compared with expression in adjacent normal tissues. Here, we explored the potential consequences of prostatic E-cadherin downregulation on the prostate and bladder in vivo using an inducible murine model of prostate luminal epithelial-specific deletion of Cdh1. The prostate-specific antigen (PSA)-CreERT2 transgenic mouse strain expressing tamoxifen-inducible CreERT2 recombinase driven by a 6-kb human PSA promoter/enhancer was crossed with the B6.129- Cdh1 tm2Kem/J mouse to generate bigenic PSA-CreERT2/ Cdh1 -/- mice. Deletion of E-cadherin was induced by transient administration of tamoxifen when mice reached sexual maturity (7 weeks of age). At 21 to 23 weeks of age, the prostate, bladder, and prostatic urethra were examined histologically, and bladder function was assessed using void spot assays and cystometry. Mice with Cdh1 deletion had increased prostatic inflammation, prostatic epithelial hyperplasia, and stromal changes at 21 to 23 weeks of age, as well as changes in bladder voiding function compared with age-matched controls. Thus, loss of E-cadherin in the murine prostate could result in prostatic defects that are characteristic of BPH and LUTS, suggesting that E-cadherin downregulation could be a driving force in human BPH development and progression. [ABSTRACT FROM AUTHOR]

Purpose A protocol was started within a large health system to automatically test all confirmed extended-spectrum beta-lactamase (ESBL)–producing Escherichia coli urine isolates for susceptibility to fosfomycin, an antibiotic not routinely included in such testing in most institutions. This study assessed the effectiveness of the protocol at reducing carbapenem use for the definitive treatment of ESBL E. coli urinary tract infection (UTI) through several endpoints. Methods Eighty and 99 patients were compared pre- and postintervention, respectively. The primary outcome was the proportion of patients who received definitive carbapenem therapy. Key secondary outcomes included median total carbapenem days of therapy (DOT), discharge on intravenous UTI antibiotics, and median total antibiotic DOT. Results Preprotocol vs postprotocol definitive carbapenem use was seen in 59 of 80 patients (73.8%) and 71 of 99 patients (71.7%) (95% confidence interval [CI] for difference, -11.1% to 15.1%; P = 0.76). The rates of step-down to oral agents pre- and postintervention were 15 of 59 (25.4%) and 35 of 71 (49.3%) (P = 0.004). Median carbapenem DOT in those receiving carbapenems decreased from 8 to 4 days (95% CI, -5 to -1 days; P = 0.001). Median total DOT decreased from 10 to 8 days (95% CI, -3 to -1 days; P = 0.002). Conclusion Implementation of a laboratory policy to automatically test ESBL positive E. coli for fosfomycin susceptibility did not reduce the percentage of patients receiving at least 1 dose of carbapenem treatment. It did result in a larger percentage reduction in step-down use of intravenous antibiotics for UTI prior to discharge, reduction in carbapenem DOT, and reduction in total antibiotic DOT. [ABSTRACT FROM AUTHOR]

Objectives CYC remains an important treatment option for Behçet's syndrome (BS) patients with life-threatening manifestations. However, adverse events may occur with CYC and this has led to increased use of biologic agents in other vasculitides. We investigated short and long term adverse events associated with CYC use in BS patients. Methods We conducted a retrospective chart review of all BS patients treated with CYC between 1972 and 2006. Patients were called in and a standard form was used for collecting demographic characteristics, indication for CYC, its cumulative dose and short term adverse events, defined as those causing discontinuation of CYC, hospitalization and/or death, long term adverse events, including infertility and malignancy, and outcome. Results Of 5790 BS patients, 198 (3.4%) had used at least one dose of CYC. Main indications were vascular or neurological involvement. After a median follow-up of 17 years, 52 (26%) patients had died, 113 (57%) could be contacted, and 33 (17%) were lost to follow-up. Vascular involvement was the leading cause of death (n  = 27). Seventeen (9%) patients experienced short term adverse events with haemorrhagic cystitis being the most common. After a median follow-up of 25 years (interquartile range: 15–26 years), 17 malignancies occurred in 15 (8%) patients. Infertility was experienced by 26 (30%) patients. Conclusion Long term adverse events such as malignancy and infertility were major problems in our BS patients treated with CYC. These results underline the need for safer treatment modalities that are at least as effective as CYC. [ABSTRACT FROM AUTHOR]

Although renal failure in burn patients results from some defined reasons, there are various causes which are still unclear. BK virus is a human polyomavirus, which, in case of reactivation, can cause late-onset renal dysfunction and cystitis among immunodeficient patients such as transplant, pregnant, diabetic, and HIV patients. Regarding the related challenges, Polyomavirus BK (BKV), as a ubiquitous virus, is considered as one of the potential threats in the occurrence of Polyomavirus-associated nephropathy (PAN). Hypovolemia, occurring due to the weakness of the immune system, may be regarded as the major reason for the possibility of PAN as a risk factor in burn patients. Accordingly, this study was designed to evaluate the reactivation of BKV as a probable risk factor for renal failure or a problem in the future life of burn patients. This case-control study was conducted from October 2014 to September 2016, during which 270 patients were admitted to the burn unit. The patients were divided into two groups of case and control according to the inclusion criteria, and 20 patients were assigned to each group. The serum samples were first assessed for BKV-IgG and then were quantified by specific quantitative real-time polymerase chain reaction for BKV load. Positive samples were assessed for changes in noncoding regulatory region (NCRR) compared to Archetype strain by PCR sequencing method. Amplified sequences were analyzed for NCRR arrangement while the reactivation was assessed through these changes in NCRR. In both groups, patients were seropositive for BKV-IgG. Eight patients (40%) in the case group and two patients (10%) in the control group were found to be positive for BKV DNA with a load of ≥1000 and ≥100 copies/ml, respectively. There was a significant association between BKV DNA and kidney injury in the case group. The NCRR of DNA-positive samples had a large rearrangement compared to standard strain, but they showed relatively high similarity. Compared with other patients, burn patients are among the most susceptible ones to PAN, which can be considered as a major risk factor in the treatment of burn patients and optimizing their therapy. [ABSTRACT FROM AUTHOR]

Background: Acute uncomplicated cystitis is one of the most common diagnoses for which antibiotic treatment is prescribed in the outpatient setting. Despite the availability of national guidelines, there remains a wide pattern in prescriber choices for therapy. Recent data portray a picture of consistently longer durations than recommended prescribed in outpatient settings.Objective: The objective was to evaluate the effect of a system-based intervention on adherence to guideline-recommended durations of therapy for uncomplicated cystitis in the outpatient setting.Methods: This quasi-experimental study included women aged 18-64 years who were seen at five family medicine clinics at an academic medical centre and were prescribed targeted antibiotics for uncomplicated cystitis (nitrofurantoin monohydrate/macrocrystals 100 mg, trimethoprim-sulfamethoxazole 160/800 mg or ciprofloxacin 250 mg). The intervention involved revising or adding pre-filled, but modifiable, default prescribing instructions in the electronic health record (EHR) for the targeted antibiotics. We evaluated adherence to guideline-recommended duration of therapy as well as days of therapy (DOT) before and after the intervention.Results: A total of 787 pre-intervention and 862 post-intervention cases were included. Adherence to recommended duration of therapy increased from 29.4% to 76.3% (P < 0.01). The average DOT decreased by 23% from 6.6 to 5.1 (P < 0.01).Conclusion: A stewardship intervention consisting of revising/adding default prescribing instructions to targeted antimicrobials in an EHR was associated with increased adherence to recommended durations of therapy for uncomplicated cystitis and reduction of unnecessary antibiotic exposure. More studies are needed to confirm effectiveness across multiple medical record platforms. [ABSTRACT FROM AUTHOR]

Background: It is unknown whether nitrofurantoin 50 mg normal-release every 6 h (NF50) and nitrofurantoin 100 mg extended-release every 12 h (NF100) are equally effective for treating cystitis in primary care. In the Netherlands, GP prescription of either option largely depends on pharmacy procurement, rather than on patient-related factors.Methods: GP data between January 2013 and July 2018 were retrospectively collected. Inclusion criteria were the use of nitrofurantoin for uncomplicated cystitis, complicated cystitis or cystitis in pregnancy. Criteria for early and late failure were a second antibiotic prescription for cystitis or pyelonephritis within 14 and 28 days post-prescription, respectively. Crude and confounder-adjusted (CA) risk differences (RDs) were estimated using linear regression. Instrumental variable analysis and CA instrumental variable analysis used GP practice proportion of NF50 versus NF100 use as the instrumental variable.Results: For uncomplicated cystitis (n=46855), treatment with NF50 and NF100 resulted in late failure in 9.7% and 9.6%, respectively. The CA RD, instrumental variable RD and CA instrumental variable RD were 0.2% (95% CI=-0.5 to 0.8), -0.7% (95% CI=-1.7 to 0.3) and 0.0% (95% CI=-0.9 to 1.0), respectively. In complicated cystitis (n=10767), late failure occurred in 10.9% and 11.1% after using NF50 and NF100, respectively [CA RD=0.5% (95% CI=-1.2 to 1.8), instrumental variable RD=-0.8% (95% CI=-3.4 to 1.8) and CA instrumental variable RD=-0.3% (95% CI=-3.0 to 2.4)]. For cystitis in pregnancy (n=1087), NF50 and NF100 resulted in late failure in 13.4% and 7.8%, respectively [CA RD=-5.4% (95% CI=-10.0 to -1.4), instrumental variable RD=-8.9% (95% CI=-16.0 to -1.8) and CA instrumental variable RD=-8.9% (95% CI=-16.0 to -1.7)]. No differences were observed in early failure.Conclusions: In patients with cystitis in pregnancy, NF100 was associated with a lower incidence of late clinical failure compared with NF50. We found no differences in clinical failure between NF50 and NF100 for uncomplicated and complicated cystitis. [ABSTRACT FROM AUTHOR]

Feline idiopathic cystitis (FIC) is a common urinary disorder in domestic cats. Clinical signs include straining or failing to urinate, frequent urination, and discolored urine. Inflammation is a key characteristic in the pathogenesis of cystitis. We assessed circulating inflammatory markers in a retrospective study in cats housed in the Hill's colony diagnosed with cystitis (n = 4; 15.2 to 18.6yr) and in control cats (n = 8; 5.9 to 16.5 yr). Blood samples were collected at end-of-life immediately before necropsy after they had lived their full lives. End-of-life pathology reports indicated inflammation and presence of inflammatory infiltrates in the bladder with some cats also showing renal inflammation. RNA was extracted from blood collected in PAXgene tubes, and gene expression investigated using NanoString nCounter platform. Analysis was performed using the nSolver software. There was a significant increase in IRAK4, a kinase that activates the NFκB proinflammatory signaling pathway, in FIC when compared with controls (1.56, P < 0.05). Small molecule inhibitors of IRAK4 are being developed as targets of inflammation. Signaling molecules in the NFκB pathway were also significantly increased including Rel A (p65 subunit; 1.3 fold), NFκB1 (p100 subunit; 1.3 fold), IKBKB (1.29 fold), and TANK (1.46 fold) in FIC cats (all P < 0.05). Another signaling pathway contributing to pro-inflammatory signaling is the JAK/STAT pathway. There was a significant increase in JAK2 (1.65) and STAT3 (1.48). Blockade of JAK2/STAT3 pathway can attenuate cytokine synthesis and reduce inflammation. STAT6 was also significantly increased in FIC cats (1.35). Activation of STAT6, by IL-4 and IL-13, can lead to systemic inflammation. Activation of the complement immune pathway was also seen in FIC. While the complement system is important for an innate immune response, its sustained activation leads to chronic pathological inflammation. There was a significant increase in complement C1s, an initiator of classical complement activation pathway, in FIC cats (1.43; P < 0.05). A late component, complement C7, was also upregulated in FIC (2.01 fold; P < 0.05). C7 binds to the C5b-6 complex which eventually becomes part of the terminal complement complex. Increased abundance of C7 and eventual terminal complement complex are associated with increased inflammation and may be important in the progression of FIC. There was also an increase in PECAM1 in FIC cats (1.87; P < 0.05). Signaling through PECAM1 leads to the activation of neutrophils and monocytes. DUSP1 was also elevated in FIC (2.24; P < 0.05). Increased abundance of DUSP1 is hypothesized to be a predictor of chronic subclinical inflammation in humans with cardiovascular disease. Our results identify activation of pro-inflammatory signaling pathways that may be potential targets for alleviating inflammation in cystitis. Pathogenesis of FIC is likely multi-factorial, and nutritional intervention to attenuate the activation of inflammatory pathways may be an important strategy in the management of cystitis. [ABSTRACT FROM AUTHOR]

Omadacycline, an aminomethylcycline, is a novel member of the tetracycline class of antibiotics. It has received approval by the US Food and Drug Administration for the treatment of community-acquired bacterial pneumonia and acute bacterial skin and skin structure infections, and is available in both oral and intravenous formulations. It is also being evaluated in clinical trials for the treatment of cystitis and pyelonephritis. The omadacycline molecule was designed to overcome tetracycline resistance and has broad-spectrum activity that includes gram-positive bacteria, gram-negative bacteria, anaerobes, atypicals, and other drug-resistant strains, like methicillin-resistant Staphylococcus aureus , as well as Yersinia pestis and Bacillus anthracis , organisms of biodefense interest. Omadacycline has minimal drug-drug pharmacokinetic interactions and a favorable safety profile, with the most common adverse events being gastrointestinal symptoms. [ABSTRACT FROM AUTHOR]

Background: Use of nitrofurantoin has increased significantly since its recent repositioning as a first-line agent for uncomplicated cystitis by multiple guidelines. However, current dosing regimens were developed in an era before robust pharmacokinetic testing and may not be optimal. Furthermore, formulations have been modified over the years.Objectives: To reassess the plasma and urinary pharmacokinetic profile of macrocrystalline nitrofurantoin in two commonly used dosing regimens.Methods: In this open-label, randomized crossover pharmacokinetic trial, 12 healthy adult female volunteers were randomized to receive oral nitrofurantoin 100 mg q8h on days 1 and 2 and, after a washout period, 50 mg q6h on days 30 and 31, or the same dosing schemes in reversed order. Urine and blood were collected at steady state and analysed by UPLC. Pharmacokinetic analysis was performed by WinNonlin.Results: Plasma peak concentrations were low (mean 0.33 mg/L, SD 0.08, and 0.69 mg/L, SD 0.35, after 50 and 100 mg, respectively) and dose dependent. The AUC0-24 was higher (6.49 versus 4.43 mg·h/L, P = 0.021) for the 100 mg q8h dosing regimen, but the dose-normalized AUC was similar for the two regimens. In contrast, urinary concentrations were dose independent: increasing the nitrofurantoin dose delayed the time to peak urinary concentration, while steady-state AUC0-24 values remained unchanged (943.49 and 855.95 mg·h/L at 50 mg q6h and 100 mg q8h, respectively).Conclusions: Plasma concentrations were relatively low and dose dependent. The dose-independent urinary concentrations suggest that excretion of nitrofurantoin into the urine is saturable. Pharmacodynamic studies are urgently required to determine the impact of these findings. [ABSTRACT FROM AUTHOR]

Asymptomatic bacteriuria (ASB) is a common finding in many populations, including healthy women and persons with underlying urologic abnormalities. The 2005 guideline from the Infectious Diseases Society of America recommended that ASB should be screened for and treated only in pregnant women or in an individual prior to undergoing invasive urologic procedures. Treatment was not recommended for healthy women; older women or men; or persons with diabetes, indwelling catheters, or spinal cord injury. The guideline did not address children and some adult populations, including patients with neutropenia, solid organ transplants, and nonurologic surgery. In the years since the publication of the guideline, further information relevant to ASB has become available. In addition, antimicrobial treatment of ASB has been recognized as an important contributor to inappropriate antimicrobial use, which promotes emergence of antimicrobial resistance. The current guideline updates the recommendations of the 2005 guideline, includes new recommendations for populations not previously addressed, and, where relevant, addresses the interpretation of nonlocalizing clinical symptoms in populations with a high prevalence of ASB. [ABSTRACT FROM AUTHOR]

Background: The distinguishing characteristics of extraintestinal pathogenic Escherichia coli (ExPEC) strains are incompletely defined.Methods: We characterized 292 diverse-source human Escherichia coli isolates (116 from fecal specimens, 79 from urine specimens [of which 39 were from patients with cystitis and 40 were from patients with pyelonephritis], and 97 from blood specimens) for phylogenetic group, sequence type complex (STc), and 49 putative extraintestinal pathogenic E. coli (ExPEC)-associated virulence genes. We then assessed these traits and ecological source as predictors of illness severity in a murine sepsis model.Results: The study isolates exhibited a broad range of virulence in mice. Most of the studied bacterial characteristics corresponded significantly with experimental virulence, as did ecological source and established molecular definitions of ExPEC and uropathogenic E. coli (UPEC). Multivariable modeling identified the following bacterial traits as independent predictors of illness severity both overall and among the fecal and clinical (ie, urine and blood) isolates separately: fyuA (yersiniabactin receptor), kpsM K1 (K1 capsule), and kpsM II (group 2 capsules). Molecular UPEC status predicted virulence independently only among fecal isolates. Neither ecological source (ie, clinical vs fecal) nor molecular ExPEC status added predictive power to these traits, which accounted collectively for up to 49% of the observed variation in virulence.Conclusions: Among human-source E. coli isolates, specific accessory traits and phylogenetic/clonal backgrounds predict experimental virulence in a murine sepsis model better than does ecological source. [ABSTRACT FROM AUTHOR]

Background: Urinary tract infections (UTIs) are among the most common bacterial infections and a frequent indication for antibiotic use. Fosfomycin, an important oral antibiotic for outpatient UTIs, remains a viable option for MDR uropathogens. We aimed to perform pharmacodynamic profiling simulating urinary concentrations to assess the adequacy of the current dosing regimen.Methods: A dynamic in vitro bladder infection model was developed, replicating urinary fosfomycin concentrations after gastrointestinal absorption, systemic distribution and urinary elimination. Concentrations were measured by LC-MS/MS. Twenty-four Enterobacteriaceae strains (Escherichia coli, Klebsiella pneumoniae and Enterobacter cloacae; MIC range 0.25-64 mg/L) were examined. Pathogen kill and emergence of resistance was assessed over 72 h.Results: Observed in vitro fosfomycin concentrations accurately simulated urinary fosfomycin exposures (Tmax 3.8 ± 0.5 h; Cmax 2630.1 ± 245.7 mg/L; AUC0-24 33 932.5 ± 1964.2 mg·h/L). Fifteen of 24 isolates regrew, with significant rises in fosfomycin MIC (total population MIC50 4 to 64 mg/L, MIC90 64 to > 1024 mg/L, P = 0.0039; resistant subpopulation MIC50 128 to > 1024 mg/L, MIC90 >1024 mg/L, P = 0.0020). E. coli and E. cloacae isolates were killed with pharmacokinetic/pharmacodynamic EI50 of fAUC0-24/MIC = 1922, fCmax/MIC = 149 and fTime>4×MIC = 44 h. In contrast, K. pneumoniae isolates were not reliably killed.Conclusions: Using dynamic in vitro simulations of urinary fosfomycin exposures, E. coli and E. cloacae isolates with MIC >16 mg/L, and all K. pneumoniae isolates, were not reliably killed. Emergence of resistance was significant. This challenges fosfomycin dosing and clinical breakpoints, and questions the utility of fosfomycin against K. pneumoniae. Further work on in vitro dose optimization is required. [ABSTRACT FROM AUTHOR]

Objectives: To define guidelines for BK polyomavirus (BKPyV)-associated haemorrhagic cystitis (BKPyV-HC) after paediatric and adult HSCT.Methods: Review of English literature and evidence-based recommendations by expert consensus.Results: BKPyV-HC occurs in 8%-25% of paediatric and 7%-54% of adult recipients undergoing allogeneic HSCT. Diagnosis requires the triad of cystitis, macro-haematuria and high urine BKPyV loads >7 log10 copies/mL, and exclusion of other relevant aetiologies. BKPyV viraemia is frequent and may serve as a more specific semiquantitative follow-up marker. No randomized controlled trials are available to inform antiviral prophylaxis or treatment. However, hyper-hydration and/or bladder irrigation showed limited prophylactic value. Fluoroquinolones are not effective for prophylaxis or treatment, but rather increase antibiotic resistance. Hyperbaric oxygen or fibrin glue is marginally effective based on small case series from correspondingly equipped centres. Although cidofovir has been reported to improve and/or reduce BKPyV viraemia or viruria, the current data do not support its regular use.Conclusions: BKPyV-HC remains a disabling unmet clinical need in HSCT that requires novel approaches supported by proper clinical trials. [ABSTRACT FROM AUTHOR]

Yongdamsagan-tang (YDSGT) has been used clinically for the treatment of acute- and chronicurethritis, cystitis, orchitis and hypertension in Korea. In this study, a powerful method based on high-performance liquid chromatography (HPLC) with photodiode array (PDA) detection was established and validated for the quantitative analysis of eight components: chlorogenic acid, gentiopicroside, liquiritin apioside, liquiritin, nodakenin, baicalin, wogonoside and glycyrrhizin in YDSGT extract. The compounds were separated with a Gemini C18 analytical column (column temperature: 40°C; mobile phase: 0.1% (v/v) aqueous trifluoroacetic acid (A) and acetonitrile (B); flow rate: 1.0 mL/min; injection volume: 10 μL). The PDA detector scanned the range 190-800 nm and the marker compounds were monitored at 254, 275, 325 and 335 nm. The correlation coefficients of all compounds were 1.000 and the results showed excellent linearity. The lower limits of detection and quantification of the analytes were 0.01-0.09 μg/mL and 0.03-0.28 μg/mL, respectively. The extraction recoveries of the marker compounds were 98.13-103.86%, with relative standard deviation values not exceeding 2.10%. The precision of intra- and inter-day measurements were 0.09-1.78% and 0.12-2.09%, respectively. The content of the eight marker compounds in the freeze-dried YDSGT extract were 1.41-23.71 mg/g. [ABSTRACT FROM AUTHOR]

A prospective study conducted in a Thai general practice clinic demonstrated a high prevalence (91.3%) of inappropriate empirical antibiotic use in women with uncomplicated cystitis and 42.6% Escherichia coli fluoroquinolone resistance. An annual update of antimicrobial resistance surveillance data of uropathogens may permit targeted treatment of patients in hospital care. [ABSTRACT FROM AUTHOR]

Background: Fluoroquinolone-non-susceptible Escherichia coli isolated from patients with acute uncomplicated cystitis are a matter of increasing concern. Cefditoren pivoxil is an oral, β-lactamase-stable, extended-spectrum cephalosporin that is effective against fluoroquinolone-non-susceptible bacteria.Objectives: To evaluate the clinical and microbiological efficacies of cefditoren pivoxil against acute uncomplicated cystitis and to determine the optimal duration of cefditoren pivoxil treatment.Methods: We compared 3 and 7 day regimens of cefditoren pivoxil in a multicentre, randomized, open-label study.Results: A total of 104 female patients with acute uncomplicated cystitis were enrolled and randomized into 3 day (n = 51) or 7 day (n = 53) treatment groups. At first visit, 94 bacterial strains were isolated from the 104 participants of which 81.7% (85/104) were E. coli. Clinical and microbiological efficacies were evaluated 5-9 days following administration of the final dose of cefditoren pivoxil. The clinical efficacies of the 3 and 7 day groups were 90.9% (40/44) and 93.2% (41/44), respectively (P = 1.000). The microbiological efficacies of the 3 and 7 day groups were 82.5% (33/40) and 90.2% (37/41), respectively (P = 0.349). There were no adverse events due to cefditoren pivoxil treatment, with the exception of a mild allergic reaction in one patient, after which the cefditoren pivoxil was exchanged for another antimicrobial.Conclusions: Cefditoren pivoxil is safe and effective for uncomplicated cystitis, with no significant differences in clinical and microbiological efficacies between 3 and 7 day regimens. [ABSTRACT FROM AUTHOR]

Urinary tract infections (UTIs) are among the most commonly treated bacterial infections. Over the past decade, antimicrobial resistance has become an increasingly common factor in the management of outpatient UTIs. As treatment options for multidrugresistant (MDR) uropathogens are limited, clinicians need to be aware of specific clinical and epidemiological risk factors for these infections. Based on available literature, the activity of fosfomycin and nitrofurantoin remain high for most cases of MDR Escherichia coli UTIs. Trimethoprim-sulfamethoxazole retains clinical efficacy, but resistance rates are increasing internationally. Beta-lactam agents have the highest rates of resistance and lowest rates of clinical success. Fluoroquinolones have high resistance rates among MDR uropathogens and are being strongly discouraged as first-line agents for UTIs. In addition to accounting for local resistance rates, consideration of patient risk factors for resistance and pharmacological principles will help guide optimal empiric treatment of outpatient UTIs. [ABSTRACT FROM AUTHOR]

Urinary tract infections (UTIs) caused by uropathogenic Escherichia coli (UPEC) are common infections in humans. Despite the substantial healthcare cost represented by these infections, the human immune response associated with the infection immediately following the onset of symptoms in patients remains largely undefined. We performed a prospective study aimed at defining the milieu of urinary cytokines in adult inpatients in the 24–48 h period immediately following hospital admission for acute cystitis due to UPEC. Urine samples, analyzed using 27-target multiplex protein assays, were used to generate immune profiles for patients and compared to age- and gender-matched healthy controls. The levels of multiple pro-inflammatory cytokines were significantly elevated in urine as a result of infection, an observation consistent with prior findings in murine models and clinical literature. We also identified significant responses for several novel factors not previously associated with the human response to UTI, including Interleukin (IL)-4, IL-7, IL-9, IL-17A, eotaxin, Granulocyte-macrophage colony-stimulating factor (GM-CSF) and several growth factors. These data establish crucial parallels between the human immune response to UPEC and murine model UTI studies, and emphasize the complex but poorly defined nature of the human immune response to UPEC, particularly in the immediate period following the onset of symptoms for acute cystitis. [ABSTRACT FROM AUTHOR]

Objectives: The objective of this study was to evaluate the pharmacokinetics and safety of cidofovir administered via the intravesicular route to patients with haemorrhagic cystitis following allogeneic HSCT (allo-HSCT).Methods: Patients with gross haematuria and confirmed BK or adenovirus viruria following allo-HSCT were prospectively enrolled in an open-label pharmacokinetic study (ClinicalTrials.gov registration: NCT01816646). Three hours after an oral probenecid dose (2 g), cidofovir (2.5-5 mg/kg in 50-100 mL of normal saline) was given via a transurethral catheter for up to 2 h of dwell time. Serial plasma samples were obtained over 24 h and assayed for cidofovir concentrations using LC-MS/MS. A custom pharmacokinetic model with a time-limited absorption compartment was fitted to the concentration-time profile of each patient. Systemic drug exposure was expressed as AUC0-24, by integrating the best-fit profile with respect to time.Results: Six subjects (mean ± SD age = 38 ± 21 years) with baseline serum creatinine <1.4 mg/dL were enrolled. Mean values for volume of distribution, clearance and elimination half-life were 19.5 L, 5.6 L/h and 2.8 h, respectively. Compared with the reported AUC0-24 for an equivalent intravenous dose, intravesicular instillation of cidofovir resulted in 1%-74% of the corresponding systemic exposure. Owing to primarily lower abdominal pain, only two patients were able to tolerate a 2 h dwell time. One patient developed a >50% increase in serum creatinine within 7 days of administration.Conclusions: Intravesicular administration of cidofovir resulted in highly variable systemic exposures. The safety and efficacy of intravesicular cidofovir should be further evaluated before routine use. [ABSTRACT FROM AUTHOR]

Background. The updated 2010 Infectious Diseases Society of America guidelines recommended 3 first-line therapies for uncomplicated cystitis: nitrofurantoin, trimethoprim-sulfamethoxazole (TMP-SMX), and fosfomycin, while fluoroquinolones (FQs) remained as second-line agents. We assessed guideline concordance for antibiotic choice and treatment duration after introduction of the updated guidelines and studied patient characteristics associated with prescribing of specific antibiotics and with treatment duration. Methods. We used the Epic Clarity database (electronic medical record system) to identify all female patients aged =18 years with uncomplicated cystitis in 2 private family medicine clinics in the period of 2011-2014. For each eligible visit, we extracted type of antibiotic prescribed, duration of treatment, and patient and visit characteristics. Results. We included 1546 visits. Fluoroquinolones were the most common antibiotic class prescribed (51.6%), followed by nitrofurantoin (33.5%), TMP-SMX (12.0%), and other antibiotics (3.2%). A significant trend occurred toward increasing TMP-SMX and toward decreasing nitrofurantoin use. The duration of most prescriptions for TMP-SMX, nitrofurantoin, and FQs was longer than guidelines recommendations (longer durations were prescribed for these agents in 82%, 73%, and 71% of the prescriptions, respectively). No patient or visit characteristic was associated with use of specific antibiotics. Older age and presence of diabetes were independently associated with longer treatment duration. Conclusions. We found low concordance with the updated guidelines for both the choice of drug and duration of therapy for uncomplicated cystitis in primary care. Identifying barriers to guideline adherence and designing interventions to decrease overuse of FQs may help preserve the antimicrobial efficacy of these important antimicrobials. [ABSTRACT FROM AUTHOR]

Background. In hematopoietic stem cell transplantation (HSCT), late hemorrhagic cystitis (HC) has been associated with BK virus (BKV) infection. We assessed the value of plasma BKV load in predicting HC. Methods. Plasma and urine BKV-DNA load were assessed prospectively in 107 pediatric patients. Results. Twenty patients developed grade II and III HC, with 100-day cumulative incidence of 18.8%. At diagnosis of HC, the median load of BKV DNA was 2.3 × 10³ copies/mL. A plasma BKV-DNA load of 10³ copies/mL had a sensitivity of 100% and a specificity of 86% with a negative predictive value (NPV) of 100% and a positive predictive value (PPV) of 39% for HC. A urine BKV-DNA load of >107 copies/mL had a sensitivity of 86% and a specificity of 60% with a NPV of 98% and a PPV of 14% for HC. A BKV load of 10³ copies/mL on plasma was significantly associated with HC in multivariate analysis (hazard ratio [HR], 6.1; P = .0006). Patients with HC had a significantly higher risk of mortality than patients who did not have HC (HR, 2.6; P = .018). Conclusions. The above values were used to monitor plasma BKV-DNA load, and they provided a better prediction of patients at risk of HC than urine BKV-DNA load. [ABSTRACT FROM AUTHOR]

Encrusted cystitis is a rare condition characterized by encrustation of the bladder mucosa with associated chronic inflammation induced by urea-splitting bacterial infection--most commonly, Corynebacterium urealyticum. Moreover, it usually occurs in immunocompromised patients, especially recipients of renal transplants or patients with a history of previous urological procedures. Due to the rarity of the entity and the slow growth of Corynebacterium species, appropriate treatment is often delayed due to difficulties in diagnosis and resistance to numerous antibiotics. We report a case of encrusted cystitis caused by Corynebacterium glucuronolyticum, another urea- splitting microbe, in a 57-year-old previously healthy Caucasian man with no known predisposing factors. The timely diagnosis and management in this otherwise healthy patient was facilitated by characteristic imaging, cystoscopy, and histologic findings confirmed by results of prolonged urine cultures and 16S ribosomal RNA (rRNA) gene sequencing of the microbe. [ABSTRACT FROM AUTHOR]

Background. Cathelicidin is a proposed defender against infection of the urinary tract via its antimicrobial properties, but its activity has not been delineated in a dedicated cystitis model. Methods. Female C57Bl/6 mice, wild type or deficient in cathelin-related antimicrobial peptide (CRAMP; an ortholog of the sole human cathelicidin, LL-37), were infected transurethrally with the cystitis-derived uropathogenic Escherichia coli (UPEC) strain UTI89. Infection course was evaluated by bladder titers, intracellular bacterial community quantification, and histological analysis. Immune responses and resolution were characterized through cytokine profiling, microscopy, and quantitation of epithelial recovery from exfoliation. Results. CRAMP-deficient mice exhibited significantly lower bladder bacterial loads and fewer intracellular bacterial communities during acute cystitis. Although differences in bacterial titers were evident as early as 1 hour after infection, CRAMP-deficient mice showed no baseline alterations in immune activation, uroepithelial structure, apical expression of uroplakins (which serve as bacterial receptors), or intracellular bacterial growth rate. CRAMP-deficient hosts demonstrated less intense cytokine responses, diminished neutrophil infiltration, and accelerated uroepithelial recovery. Conclusions. Mice lacking the antimicrobial peptide cathelicidin experienced less severe infection than wild-type mice in a well-established model of cystitis. Although CRAMP exhibits in vitro antibacterial activity against UPEC, it may enhance UPEC infection in the bladder by promoting epithelial receptivity and local inflammation. [ABSTRACT FROM AUTHOR]

Recent studies have resulted in major changes in the management of urinary tract infections (UTIs) in children. The present statement focuses on the diagnosis and management of infants and children >2 months of age with an acute UTI and no known underlying urinary tract pathology or risk factors for a neurogenic bladder. UTI should he ruled out in preverbal children with unexplained fever and in older children with symptoms suggestive of UTI (dysuria, urinary frequency, hematuria, abdominal pain, back pain or new daytime incontinence). A midstream urine sample should be collected for urinalysis and culture in toilet-trained children; others should have urine collected by catheter or by suprapubic aspirate. UTI is unlikely if the urinalysis is completely normal. A bagged urine sample may be used for urinalysis but should not be used for urine culture. Antibiotic treatment for seven to 10 days is recommended for febrile UTI. Oral antibiotics may be offered as initial treatment when the child is not seriously ill and is likely to receive and tolerate every dose. Children <2 years of age should be investigated after their first febrile UTI with a renal/bladder ultrasound to identify any significant renal abnormalities. A voiding cystourethrogram is not required for children with a first UTI unless the renal/bladder ultrasound reveals findings suggestive of vesicoureteral reflux, selected renal anomalies or obstructive uropathy. [ABSTRACT FROM AUTHOR]

Background. Despite stable overall antibiotic use between 2007 and 2011 in The Netherlands, use of nitrofurantoin and trimethoprim increased by 32%. The background of this increased antibiotic use against uropathogens is unknown. Objectives. To determine whether increased use of urinary tract infection antibiotics is caused by changes in patients’ consultation or physicians’ prescribing behaviour and to investigate attitudes and opinions of women with respect to cystitis management and antibiotics. Methods. Consultation and prescribing for International Classification of Primary Care (ICPC) codes U01 (dysuria), U02 (frequency), U05 (other urination problems), U70 (pyelonephritis) and U71 (cystitis) were determined from 2007 to 2010, using routinely collected primary health care data. Separately, behaviour of women with respect to managing cystitis, consultation and opinions towards (delayed) antibiotic treatment were studied using questionnaires in 2012. Results. Consultation for U02 and U71 significantly increased from 93 to 114/1000 patient-years from 2007 to 2010; proportion of episodes in which an antibiotic was prescribed remained constant. Questionnaires revealed that urination problems and pain were dominant complaints of cystitis; pain medication, however, was not adequately used. One-third of women directly consult upon first symptoms, whereas the majority awaits an average of 4 days. Sixty-six per cent of women report to be willing to postpone antibiotic use. Conclusion. Increased use of urinary tract infection antibiotics may be caused by increased consultation for cystitis in primary care. Future research should focus on the outcomes of adequate pain medication, enhanced diagnostic procedures and of delaying antibiotic use in cystitis management. [ABSTRACT FROM PUBLISHER]

This study reports the release of draft genome sequences of five isolates of uropathogenic Escherichia coli ( UPEC), isolated from patients suffering from uncomplicated cystitis in 2012 in Ann Arbor, Michigan. Phylogenetic analyses revealed that these strains belonged to E. coli phylogroups B2 and D and are closely related to known UPEC strains. Comparative genomic analysis revealed that more conserved proteins were shared between these recent isolates and UPEC strains causing cystitis than those causing pyelonephritis. Additional genomic comparisons identified that three isolates encode a type III secretion system ( T3 SS) and a putative T3 SS effector gene cluster along with an invasin-like outer membrane protein. The presence of T3 SS genes is a rare occurrence among UPEC strains. These genomes further substantiate the heterogeneity of the gene pool of UPEC and provide a foundation for comparative genomic studies using recent clinical isolates. [ABSTRACT FROM AUTHOR]

Background. Escherichia coli O25b:H4-ST131 represents a predominant clone of multidrug-resistant uropathogens currently circulating worldwide in hospitals and the community. Urinary tract infections (UTIs) caused by E. coli ST131 are typically associated with limited treatment options and are often recurrent.Methods. Using established mouse models of acute and chronic UTI, we mapped the pathogenic trajectory of the reference E. coli ST131 UTI isolate, strain EC958.Results. We demonstrated that E. coli EC958 can invade bladder epithelial cells and form intracellular bacterial communities early during acute UTI. Moreover, E. coli EC958 persisted in the bladder and established chronic UTI. Prophylactic antibiotic administration failed to prevent E. coli EC958–mediated UTI. However, 1 oral dose of a small-molecular-weight compound that inhibits FimH, the type 1 fimbriae adhesin, significantly reduced bacterial colonization of the bladder and prevented acute UTI. Treatment of chronically infected mice with the same FimH inhibitor lowered their bladder bacterial burden by >1000-fold.Conclusions. In this study, we provide novel insight into the pathogenic mechanisms used by the globally disseminated E. coli ST131 clone during acute and chronic UTI and establish the potential of FimH inhibitors as an alternative treatment against multidrug-resistant E. coli. [ABSTRACT FROM PUBLISHER]

Urinary tract infections are often caused by strains of uropathogenic Escherichia coli (UPEC), which are becoming increasingly resistant to antibiotics. This review considers UPEC pathogenic mechanisms along with current management strategies and emerging therapies.Acute cystitis is one of the most commonly encountered bacterial infections and is responsible for substantial morbidity and high medical costs in the United States and across the globe. Though generally considered to be self-limiting and easily treated with antibiotics, urinary tract infections (UTIs) are often incompletely resolved by antibiotic therapy and frequently recur. This is in part due to the ability of uropathogenic bacteria to invade, replicate, and persist within host epithelial cells. The biological complexity of these infections combined with a dramatic rise in antibiotic-resistant pathogens highlight the need for alternative therapies. In this review we examine current management strategies for UTIs, as well as emerging treatments, including novel compounds that block bacterial interactions with the urothelium and vaccines focused on preventing both acute and recurrent infections. [ABSTRACT FROM AUTHOR]

Objectives Recurrent urinary tract infections (UTIs) are a problem affecting both women and men. Animal experiments and in vitro studies indicate that statins might prevent recurrent UTIs. We assessed the effects of pravastatin on UTI antibiotic prescribing among adults. Methods A post hoc analysis was conducted with data from PREVEND IT, a trial among participants randomized to receive pravastatin, fosinopril or placebo in a 2 × 2 factorial design over 4 years. Trial data were linked to the pharmacy prescription database IADB.nl. The primary outcome was the number of prescriptions with a nitrofuran derivate, a sulphonamide or trimethoprim as a proxy for UTI antibiotic prescribing. Generalized estimating equations were used to estimate the effect on the number of UTI antibiotic prescriptions. Cox regression was used to determine the effect on first and second (recurrent) UTI antibiotic prescriptions. Results Of the 864 trial participants, 655 were eligible for analysis. During an average follow-up of 3.8 years, 112 (17%) participants received at least one UTI antibiotic prescription. Intention-to-treat analyses showed that pravastatin was associated with a reduced total number of UTI antibiotic prescriptions (relative risk, 0.43; 95% CI, 0.21–0.88) and occurrence of second UTI antibiotic prescriptions [hazard ratio (HR), 0.25; 95% CI, 0.08–0.77]. No significant effect on occurrence of first UTI antibiotic prescriptions was found (HR, 0.83; 95% CI, 0.57–1.20). Fosinopril was associated with an increased occurrence of first UTI antibiotic prescriptions (HR, 1.82; 95% CI, 1.16–2.88). Combination therapy with fosinopril and pravastatin did not significantly influence the number of UTI antibiotic prescriptions. Conclusions This study suggests that pravastatin can reduce the occurrence of recurrent UTIs. Larger studies among patients with recurrent UTIs are warranted. [ABSTRACT FROM PUBLISHER]

Background The purpose of present study was to characterize uropathogenic Escherichia coli (UPEC) associated with acute cystitis in Indian women. Methods In this prospective descriptive study we investigated phylogenetic background and virulence genotypes for 15 genes by multiplex PCR and in vitro biofilm formation ability of 172 E. coli strains and explored possible association amongst them. Results Most isolates (81, 47.1%) belonged to group B2 and A (50, 29.1%); few were from groups B1 (22, 12.7%) and D (19, 11.1%). The mean virulence scores of phylogroups A, B1, B2 and D were 3.3, 4.0, 4.6 and 4.9, respectively. We found higher prevalence of fimH, traT iutA, kpsMII, papG allele II and fyuA genes indicating putative role of adhesins, iron acquisition systems and protectins in causing bladder infection. Total 145 (84.3%) isolates produced biofilm; majority were weak biofilm producers and there was no significant difference in intensity and biofilm formation ability amongst various phylogroups or virulence scores. The phylogenetic distribution was different from western studies, including a lower prevalence of group B2 (dominant but not a majority), followed by group A, and some traditionally group B2-associated virulence genes were more prevalent in phylogroup A isolates. Conclusions Distribution of virulence genotypes and phylotypes can vary with geographical location and the isolates from western countries cannot be treated as prototypes for Asian cystitis isolates. [ABSTRACT FROM PUBLISHER]