Multidrug resistance among uropathogenic clonal group A E. Coli isolates from Pakistani women with uncomplicated urinary tract infections.

OBJECTIVE: Multi-drug resistance (MDR) has notably increased in community acquired uropathogens causing urinary tract infections (UTIs), predominantly Escherichia coli. Uropathogenic E. coli causes 80% of uncomplicated community acquired UTIs, particularly in pre-menopausal women. Considering this high prevalence and the potential to spread antimicrobial resistant genes, the current study was conducted to investigate the presence of clinically important strains of E. coli in Pakistani women having uncomplicated cystitis and pyelonephritis. Women belonging to low-income groups were exclusively included in the study. Seventy-four isolates from urine samples were processed, phylotyped, and screened for the presence of two Single Nucleotide Polymorphisms (SNPs) particularly associated with a clinically important clonal group A of E. coli (CgA) followed by antibiotic susceptibility testing and genome sequence analysis. RESULTS: Phylogroup B2 was most prevalent in patients and 44% of isolates were positive for the presence of CgA specific SNPs in Fumarate hydratase and DNA gyrase subunit B genes. Antibiotic susceptibility testing showed widespread resistance to trimethoprim-sulfamethoxazole and extended-spectrum beta-lactamase production. The infection analysis revealed the phylogroup B2 to be more pathogenic as compared to the other groups. The genome sequence of E. coli strain U17 revealed genes encoding virulence, multidrug resistance, and host colonization mechanisms. CONCLUSIONS: Our research findings not only validate the significant occurrence of multidrug-resistant clonal group A E. coli (CgA) in premenopausal Pakistani women suffering from cystitis and pyelonephritis but also reveal the presence of genes associated withvirulence, and drug efflux pumps. The detection of highly pathogenic, antimicrobial-resistant phylogroup B2 and CgA E. coli strains is likely to help in understanding the epidemiology of the pathogen and may ultimately help to reduce the impact of these strains on human health. Furthermore, the findings of this study will particularly help to reduce the prevalence of uncomplicated UTIs and the cost associated with their treatment in women belonging to low-income groups.

The effects of a galectin-3 inhibitor on bladder pain syndrome in mice with cyclophosphamide-induced cystitis.

AIMS: To explore the effect of blocking galectin-3 in the bladder pain syndrome associated with interstitial cystitis. METHODS: A galectin-3 inhibitor was used to treat mice with cyclophosphamide-induced cystitis. The expression of galectin-3 in bladder tissues and urine was examined by immunohistochemistry and enzyme-linked immunosorbent assay (ELISA), respectively. Suprapubic-pelvic pain, bladder voiding, bladder pain-like nociceptive behavior, and referred hyperalgesia were assessed. The weights of the bladders were also measured, and inflammatory cell infiltration and inflammatory cytokine levels were examined by histopathological evaluation. The inflammatory cytokines interleukin 1ß (IL-1ß), nerve growth factor (NGF), IL-6, and tumor necrosis factor α (TNF-α) were measured by ELISA. RESULTS: Increases in galectin-3 levels, inflammation, bladder weight, and bladder pain-related symptoms were observed in bladders with cyclophosphamide-induced cystitis. Administration of the galectin-3 inhibitor significantly mitigated bladder pain-related symptoms and inflammatory response. In response to the 500 µM dose of the galectin-3 inhibitor, nociceptive behaviors, nociceptive score, and bladder-to-body weight ratios were reduced by 65.1%, 65.3%, and 40.3%, respectively, while 500 µM Gal-3 inhibitor increased pelvic pain threshold by 86.7%. Moreover, galectin-3 inhibitor treatment inhibited the inflammation. Compared to untreated CYP-induced mice, there were significant changes in the levels of IL-1ß (41.72 ± 2.05 vs. 18.91 ± 2.26 pg/mg tissues), NGF (9.64 ± 0.38 vs. 1.88 ± 0.05 pg/mg tissues), IL-6 (42.67 + 1.51 vs. 21.26 + 2.78 pg/mg tissues, and TNF-α (22.02 ± 1.08 vs. 10.70 ± 0.80 pg/mg tissues) in response to the highest dose of the Gal-3 inhibitor subgroup (500 µM), and 500 µM Gal-3 inhibitor reduced mast cell infiltration ratios by 71.8%. CONCLUSIONS: The galectin-3 inhibitor relieved pelvic pain, urinary symptoms, and bladder inflammation in mice with cyclophosphamide-induced cystitis. Thus, galectin-3 inhibitors may be novel agents in interstitial cystitis treatment.

[Risk Factors of Late-Onset Hemorrhagic Cystitis after Allogeneic Hematopoietic Stem Cell Transplantation].

To analyze the risk factors for late-onset hemorrhagic cystitis (LOHC) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), the risk factors for the progression of LOHC to severe LOHC, and the effect of LOHC on survival. METHODS: The clinical data of 300 patients who underwent allo-HSCT at the First Affiliated Hospital of Chongqing Medical University from January 2015 to December 2021 were retrospectively analyzed. The relevant clinical parameters that may affect the occurance of LOHC after allo-HSCT were selected for univariate and multivariate analysis. Then, the differences in overall survival (OS) and progression-free survival (PFS) between different groups were analyzed. RESULTS: The results of multivariate analysis showed that the independent risk factors for LOHC after allo-HSCT were as follows: age≤45 years old (P =0.039), intensified conditioning regimen with fludarabine/cladribine and cytarabine (P =0.002), albumin≤30 g/L on d30 after transplantation (P =0.007), CMV-DNA positive (P =0.028), fungal infection before transplantation (P =0.026), and the occurrence of grade Ⅱ - Ⅳ aGVHD (P =0.006). In the transplant patients who have already developed LOHC, the occurance of LOHC within 32 days after transplantation (P =0.008) and albumin≤30 g/L on d30 after transplantation (P =0.032) were independent risk factors for the progression to severe LOHC. The OS rate of patients with severe LOHC was significantly lower than that of patients without LOHC (P =0.041). CONCLUSION: For the patients aged≤45 years old and with intensified conditioning regimen, it is necessary to be vigilant about the occurrence of LOHC; For the patients with earlier occurrence of LOHC, it is necessary to be vigilant that it develops into severe LOHC. Early prevention and treatment of LOHC are essential. Regular monitoring of CMV-DNA and albumin levels, highly effective antiviral and antifungal therapies, and prevention of aGVHD are effective measures to prevent the occurrence and development of LOHC.

Purine nucleoside phosphorylase inhibition is an effective approach for the treatment of chemical hemorrhagic cystitis.

Hemorrhagic cystitis may be induced by infection, radiation therapy, or medications or may be idiopathic. Along with hemorrhagic features, symptoms include urinary urgency and frequency, dysuria (painful urination), and visceral pain. Cystitis-induced visceral pain is one of the most challenging types of pain to treat, and an effective treatment would address a major unmet medical need. We assessed the efficacy of a purine nucleoside phosphorylase inhibitor, 8-aminoguanine (8-AG), for the treatment of hemorrhagic/ulcerative cystitis. Lower urinary tract (LUT) function and structure were assessed in adult Sprague-Dawley rats, treated chronically with cyclophosphamide (CYP; sacrificed day 8) and randomized to daily oral treatment with 8-AG (begun 14 days prior to CYP induction) or its vehicle. CYP-treated rats exhibited multiple abnormalities, including increased urinary frequency and neural mechanosensitivity, reduced bladder levels of inosine, urothelial inflammation/damage, and activation of spinal cord microglia, which is associated with pain hypersensitivity. 8-AG treatment of CYP-treated rats normalized all observed histological, structural, biochemical, and physiological abnormalities. In cystitis 8-AG improved function and reduced both pain and inflammation likely by increasing inosine, a tissue-protective purine metabolite. These findings demonstrate that 8-AG has translational potential for reducing pain and preventing bladder damage in cystitis-associated LUT dysfunctions.

Ketamine cystitis following ketamine therapy for treatment-resistant depression - case report.

BACKGROUND: Ketamine is a novel and exciting putative antidepressant medication for patients with treatment-resistant depression. A complication commonly seen in frequent and heavy recreational use of ketamine is ulcerative cystitis, which presents with lower urinary tract symptoms (LUTS) and upper renal tract damage and can be seen in over 25% of regular users. Although Ketamine-induced cystitis (KIC) is a recognised complication in recreational use of ketamine, its occurrence in therapeutic use of ketamine in depression has so far not been reported. The exact pathogenesis of KIC is currently unknown, making treatment and prevention advice much more difficult. Early diagnosis of KIC and immediate cessation of ketamine has been shown to improve adverse urinary tract symptoms and prevent further damage. CASE PRESENTATION: We present a case of a 28-year-old female who was started on ketamine treatment for depression, and who then developed symptoms of KIC, which was confirmed by urine microscopy, culture and analysis. CONCLUSIONS: To our knowledge, this is the first reported case of KIC in a patient receiving treatment-dose ketamine as part of their antidepressant therapy.

Third nationwide surveillance of bacterial pathogens in patients with acute uncomplicated cystitis conducted by the Japanese surveillance committee during 2020 and 2021: Antimicrobial susceptibility of Escherichia coli, Klebsiella pneumoniae, and Staphylococcus saprophyticus.

The Japanese surveillance committee conducted a third nationwide surveillance of antimicrobial susceptibility of acute uncomplicated cystitis at 55 facilities throughout Japan between April 2020 and September 2021. In this surveillance, we investigated the susceptibility of Escherichia coli (E. coli), Klebsiella pneumoniae (K. pneumoniae), and Staphylococcus saprophyticus (S. saprophyticus) for various antimicrobial agents by isolating and culturing bacteria from urine samples. In total, 823 strains were isolated from 848 patients and 569 strains of target bacteria, including E. coli (n = 529, 92.9 %), K. pneumoniae (n = 28, 4.9 %), and S. saprophyticus (n = 12, 2.2 %) were isolated. The minimum inhibitory concentrations of 18 antibacterial agents were determined according to the Clinical and Laboratory Standards Institute manual. In premenopausal patients, there were 31 (10.5 %) and 20 (6.8 %) fluoroquinolone (FQ)-resistant E. coli and extended-spectrum ß-lactamase (ESBL)-producing E. coli, respectively. On the other hand, in postmenopausal patients, there were 75 (32.1 %) and 36 (15.4 %) FQ-resistant E. coli and ESBL-producing E. coli, respectively. The rate of FQ-resistant E. coli and ESBL-producing E. coli in post-menopausal women was higher than that for our previous nationwide surveillance (20.7 % and 32.1 %: p = 0.0004, 10.0 % and 15.4 %; p = 0.0259). For pre-menopausal women, there was no significant difference in the rate of FQ-resistant E. coli and ESBL-producing E. coli between this and previous reports, but the frequency of FQ-resistant E. coli and ESBL-producing E. coli exhibited a gradual increase. For appropriate antimicrobial agent selection and usage, it is essential for clinicians to be aware of the high rate of these antimicrobial-resistant bacteria in acute uncomplicated cystitis in Japan.

Intravesical liposomal tacrolimus for hemorrhagic cystitis: a phase 2a multicenter dose-escalation study.

BACKGROUND: Hemorrhagic cystitis (HC) is an inflammatory disease of the bladder with sustained hematuria for which there is currently no approved drug treatment. We evaluated a liposomal tacrolimus preparation (LP-10) in patients with refractory moderate to severe sterile HC. METHODS: This phase 2a dose-escalation study assessed the safety and efficacy of up to 2 intravesical instillations of LP-10 (2, 4, or 8 mg tacrolimus) in 13 patients with HC. Primary efficacy outcomes were changes from baseline in the number of bleeding sites on cystoscopy, microscopic urine analysis for red blood cells (RBCs), and hematuria on dipstick. Additional efficacy measures included urinary incontinence, frequency, and urgency on a 3-day diary and cystoscopy global response assessment (GRA). Blood samples for pharmacokinetic (PK) assessment were obtained in all patients. RESULTS: Intravesical LP-10 was well tolerated, with no treatment-related severe or serious adverse events (AEs) and only 3 drug-related AEs (artificial urinary sphincter malfunction, dysuria, and bladder spasms). LP-10 blood levels showed short durations of minimal systemic uptake. Treatment resulted in significant improvements in bleeding on cystoscopy, RBC counts in urine, hematuria on dipstick, and urinary incontinence. Bleeding on cystoscopy and urinary incontinence showed dose-dependent improvements that were more pronounced in the 4 mg and 8 mg dose groups. All dose groups showed a significant improvement in cystoscopy GRA. CONCLUSION: LP-10 was well tolerated, with clinically relevant efficacy seen in improvements in cystoscopic bleeding, hematuria, and urinary incontinence. The benefit-risk profile supports the further clinical development of LP-10 at a tacrolimus dose of 4 mg.

Propolis as an adjunctive therapy for treatment of uncomplicated cystitis in women: A randomized double-blind placebo-controlled trial.

The current research is designed to investigate the effect of propolis supplementation on the clinical manifestations in women suffering from uncomplicated cystitis. In this randomized double-blind, placebo-controlled trial, 120 women with uncomplicated cystitis were selected and randomly assigned into two groups to receive two 500 mg capsules of propolis or placebo daily for 7 days along with ciprofloxacin (250 mg). Clinical symptoms including hematuria, urinary frequency, dysuria, suprapubic pain, and urgency, as well as bacteriuria, were assessed before and after the intervention. After supplementation, participants in the intervention group had significantly fewer days of urinary frequency (p < 0.001), dysuria (p = 0.005), and urgency (p = 0.03). However, there was no significant difference between the two groups regarding hematuria and suprapubic pain (p > 0.05). Furthermore, the severity of bacteriuria decreased significantly in both groups. In conclusion, it seems that propolis supplementation in women with uncomplicated cystitis could improve urinary frequency, dysuria, and urgency. However, further clinical trials should be conducted to fully understand the effects of propolis in women suffering from uncomplicated cystitis.

Predicting Antibiotic Susceptibility Among Patients With Recurrent Urinary Tract Infection Using a Prior Culture.

PURPOSE: Recurrent cystitis guidelines recommend relying on a local antibiogram or prior urine culture to guide empirical prescribing, yet little data exist to quantify the predictive value of a prior culture. We constructed a urinary antibiogram and evaluated test metrics (sensitivity, specificity, and Bayes' positive and negative predictive values) of a prior gram-negative organism on predicting subsequent resistance or susceptibility among patients with uncomplicated, recurrent cystitis. MATERIALS AND METHODS: We performed a retrospective database study of adults with recurrent, uncomplicated cystitis (cystitis occurring 2 times in 6 months or 3 times in 12 months) from urology or primary care clinics between November 1, 2016, and December 31, 2018. We excluded pregnant females, patients with complicated cystitis, or pyelonephritis. Test metrics were calculated between sequential, paired cultures using standard formulas. RESULTS: We included 597 visits from 232 unique patients wherein 310 (51.2%) visits had a urine culture and 165 had gram-negative uropathogens isolated. Patients with gram-negative uropathogens were mostly females (97%), with a median age of 58.5 years. Our antibiogram found 38.0%, 27.9%, and 5.5% of Escherichia coli isolates had resistance to trimethoprim-sulfamethoxazole, ciprofloxacin, and nitrofurantoin, respectively. Prior cultures (within 2 years) had good predictive value for detecting future susceptibility to first-line agents nitrofurantoin (0.85) and trimethoprim-sulfamethoxazole (0.78) and excellent predictive values (≥0.90) for cefepime, ceftriaxone, cefuroxime, ciprofloxacin, levofloxacin, gentamicin, tobramycin, piperacillin-tazobactam, and imipenem. CONCLUSIONS: Considerable antibiotic resistance was detected among E coli isolates in patients with recurrent, uncomplicated cystitis. Using a prior culture as a guide can enhance the probability of selecting an effective empirical agent.

Prospective Phycocompounds for Developing Therapeutics for Urinary Tract Infection.

Antibiotic resistance of bacteria is causing clinical and public health concerns that are challenging to treat. Infections are becoming more common in the present era, and patients admitted to hospitals often have drug-resistant bacteria that can spread nosocomial infections. Urinary tract infections (UTIs) are among the most common infectious diseases affecting all age groups. There has been an increase in the proportion of bacteria that are resistant to multiple drugs. Herein is a comprehensive update on UTI-associated diseases: cystitis, urethritis, acute urethral syndrome, pyelonephritis, and recurrent UTIs. Further emphasis on the global statistical incidence and recent advancement of the role of natural products in treating notorious infections are described. This updated compendium will inspire the development of novel phycocompounds as the prospective antibacterial candidate.

Emodin inhibits bladder inflammation and fibrosis in mice with interstitial cystitis by regulating JMJD3.

PURPOSE: Interstitial cystitis/bladder pain syndrome (IC/BPS) is a devastating urological chronic pelvic pain condition. In search of a potential treatment, we investigated the effect of emodin on IC/BPS inflammation and fibrosis, and explore the potential mechanism. METHODS: An experimental model of interstitial cystitis was induced by cyclophosphamide, and human bladder smooth muscle cells were treated with lipopolysaccharide to establish the cell model in vitro. In both models, inflammation- and fibrosis-related indexes were measured after emodin administration. Furthermore, the specific antagonists were used to dig for the mechanisms underlying the response to emodin treatment. RESULTS: Emodin significantly ameliorated management of cystitis, reduced the amount of inflammatory cytokines (tumor necrosis factor-α, monocyte chemoattractant protein-1, interleukin-1ß, interleukin-8, and interleukin-6) in models, as well as reducing the synthesis of fibrosis marker including collagen1, collagen3, vimentin, fibronectin and α-smooth muscle actin. Further mechanism studies demonstrated that emodin inhibited inflammatory reaction and fibrosis through blocking lysine-specific demethylase 6B (JMJD3) expression via JAK/STAT, NF-κB and TGF-ß/SMAD pathways. CONCLUSIONS: Our study reveals the critical role of emodin-JMJD3 signaling in interstitial cystitis by regulating inflammation, fibrosis, and extracellular matrix deposition in cells and tissues, and these findings provide an avenue for effective treatment of patients with cystitis.

[The effect of a medicinal plant preparation on the frequency of episodes of exacerbation of recurrent cystitis and metabolic parameters in patients with type 2 diabetes mellitus taking glyphlosins].

BACKGROUND: The problem of recurrent urinary tract infections (UTI) in patients with type 2 diabetes mellitus (DM 2) is relevant, especially when there is a combination of predisposing factors, such as female gender, history of UTI episodes, and therapy with sodium glucose cotransporter type 2 (SGLT-2) inhibitors, and the choice of effective and safe means could cause some difficulties, including ina terms of the burden of antibiotic resistance. AIM: To evaluate the effectiveness and safety of the phytoproduct Canephron® N for the prevention of exacerbations of recurrent cystitis and the effect on metabolic parameters in patients with type 2 diabetes taking SGLT-2 inhibitors. MATERIALS AND METHODS: Prospective, randomized, open, parallel group study in 60 women. The main group took the drug Canephron® N for 3 months. The main parameters for evaluating were the frequency of recurrence of cystitis, level of albuminuria and LDL-cholesterol peroxidation product - malondialdehyde. RESULTS: Within 3 months of taking Canephron® N, exacerbations of chronic cystitis were diagnosed 2 times less often, a decrease in albuminuria was found in the form of an increase in the proportion of patients with an optimal level of albuminuria by 20%, a 50% reduction in the frequency of the initial increase in albuminuria, and the absence of moderate albuminuria in all patients at the end of course of therapy. A decrease in the level of MDA by 1.4 times was noted (p=0.019). CONCLUSION: Thus, the herbal drug Canephron® N can be used for accompanying therapy and prophylactic treatment in patients with recurrent cystitis on the background of DM 2, taking SGLT-2 inhibitors. The course of therapy should last at least 3 months.

[Onto-phylogenetic prerequisites for development of chronic cystitis in women].

INTRODUCTION: Urinary tract infections (UTIs) are among the most common bacterial infections. At the request "cystitis", there are 12,067 publications in the RSCI system (e.library) as of 10/08/2023 and 16,332 articles were screened in the Pubmed. This is evidence that the problem of cystitis is far from being resolved. MATERIAL AND METHODS: A total of 425 patients with bacterial vaginosis and 77 women with chronic recurrent cystitis were included in the study. In all patients, the vaginal biocenosis was assessed through molecular genetic testing. The examination included filling out the Russian version of the Acute Cystitis Symptom Score (ACSS), urinalysis, and urine culture. In addition, local microcirculation was measured using laser Doppler flowmetry (LDF). After examination, patients were prescribed basic therapy and randomly assigned to one of three groups. In a control group (n=17), only basic therapy, consisting of fosfomycin 3.0 once at night + furagin 100 mg after meals 3 times a day for 5 days was prescribed. In the main group 1, 29 women received basic therapy plus Superlymph suppositories 10 units 2 times a day vaginally for 10 days. In the main group 2, 31 patients received basic therapy plus suppositories Superlymph 10 units (rectally in the morning) and Acylact Duo (vaginally in the evening) for 10 days. RESULTS: Among 425 patients with bacterial vaginosis, 78 (18.3%) complained of various urinary disorders, but only 21 women (4.9% of those with vaginal dysbiosis and 26.9% with dysuria) had a diagnosis of cystitis. In all cases, it was an exacerbation of a chronic disease. Among 77 patients with chronic cystitis, normal vaginal flora was initially present in 32 patients (41.6%), and bacterial vaginosis was found in 45 (58.4%) cases. After therapy, positive results were noted in patients of all groups. Complete eradication of the pathogen occurred in 15 women (88.2%) who received only basic therapy; in the main groups 1 and 2, uropathogens were not detected in 27 (93.1%) and 28 (90.3%) cases, respectively. In the control group, the proportion of patients with normal vaginal flora remained virtually unchanged (41.2% [n=7] vs. 47.1% [n=8]). In the main group 1, the proportion of patients with normal vaginal flora almost doubled: from 41.4% (n=12) to 79.3% (n=23). In main group 2, restoration of vaginal flora was noted in 87.1% of cases. CONCLUSION: According to our data, only 4.9% of patients with bacterial vaginosis were diagnosed with chronic cystitis, however, 58.4% of patients with chronic cystitis had vaginal dysbiosis. The use of a complex of antimicrobial peptides and cytokines has significantly increased the bidirectional effect of therapy. Suppositories Superlymph in a combination with vaginal use of Acylact Duo allow to obtain the best results.

[The efficiency of complex phytotherapy for the treatment of lower urinary tract infection in women].

Lower urinary tract infections (LUTI) are one of the most common urological diseases. Prevention of recurrences and development of chronic cystitis are among the key tasks in the treatment of women with LUTI. It consists of choosing adequate antibacterial therapy and preventive measures. Phytotherapy using various herbal preparations is considered to be one of the most common and effective preventive measure. Three clinical cases of effective treatment of patients with recurrent LUTI with Phytolysin paste and Phytolysin capsules as part of complex therapy are presented in the article, demonstrating the high efficiency of long-term courses of phytotherapy.

Uroprotective Potential of Campesterol in Cyclophosphamide Induced Interstitial Cystitis; Molecular Docking Studies.

Cyclophosphamide (CYP) is commonly used to treat cancer of the ovaries, breast, lymph, and blood system and produces interstitial cystitis (IC) via its urotoxic metabolite: i. e., acrolein. The present study was aimed to investigate the uroprotective effect of campesterol (a steroidal phytochemical) in cyclophosphamide induced IC. IC was induced by CYP (150 mg/kg, i. p.) in rats. The Enzyme linked immunosorbent assays for oxidative stress markers and Polymerase Chain Reaction (PCR) for inflammatory cytokines were carried out. The Tissue Organ Bath Technique was used for the evaluation of the spasmolytic effect of campesterol. Different pharmacological antagonists have been used to explore the mechanism of action of campesterol. Treatment with campesterol (70 mg/kg) reduced nociception (55 %), edema (67 %), hemorrhage (67 %), and protein leakage significantly (94 %). The antioxidant activity of campesterol was exhibited by a fall in MDA, NO, and an elevation in SOD, CAT, and GPX levels. Campesterol presented anti-inflammatory potential by decreasing IL-1, TNF-α, and TGF-ß expression levels. Histologically, it preserved urothelium from the deleterious effect of CYP. Campesterol showed a spasmolytic effect by reducing bladder overactivity that was dependent on muscarinic receptors, voltage-gated calcium and KATP channels, and cyclo-oxygenase pathways. In silico studies confirmed the biochemical findings. The findings suggest that campesterol could be valorized as a possible therapeutic agent against cyclophosphamide-induced interstitial cystitis.

Immune-related adverse events with severe pain and ureteral expansion as the main manifestations: a case report of tislelizumab-induced ureteritis/cystitis and review of the literature.

Immune checkpoint inhibitor (ICI) is an up-to-date therapy for cancer with a promising efficacy, but it may cause unique immune-related adverse events (irAEs). Although irAEs could affect any organ, irAEs-induced whole urinary tract expansion was rarely reported. Herein, we reported a 27-year-old male patient with thymic carcinoma who received the treatment of tislelizumab, paclitaxel albumin and carboplatin. He was hospitalized for severe bellyache and lumbago after 6 courses of treatment. Antibiotic and antispasmodic treatment did not relieve his symptoms. The imaging examinations reported whole urinary tract expansion and cystitis. Therefore, we proposed that the patient's pain was caused by tislelizumab-induced ureteritis/cystitis. After the discontinuation of tislelizumab and the administration of methylprednisolone, his symptoms were markedly alleviated. Herein, we reported a rare case of ICI-induced ureteritis/cystitis in the treatment of thymic cancer and reviewed other cases of immunotherapy-related cystitis and tislelizumab-related adverse events, which will provide a reference for the diagnosis and treatment of ICI-related irAEs.

Cuminum cyminum Ameliorates Urotoxic Effects of Cyclophosphamide by Modulating Antioxidant, Inflammatory Cytokines, and Urinary Bladder Overactivity: In vivo and in Silico Investigations.

Interstitial Cystitis (IC) is a chronic inflammatory disease that lacks effective treatment. The present study aimed to investigate the potential of aqueous ethanol extract of Cuminum cyminum (AEECC) on oxidative stress, inflammation and overactivity of urinary bladder induced by cyclophosphamide (CYP). Female Sprague-Dawley rats received intraperitoneal administration of cyclophosphamide (150 mg/kg, i. p. 1st , 4th , and 7th days). To investigate the urothelial damage, the bladder weight, nociception behavior, and Evans blue dye extravasation method was used. The antioxidants CAT, GPX and NO were measured. ELISA determined the IL-6 and TNF-α levels. The spasmolytic effect of AEECC was investigated on isolated bladder strips and its mechanisms were determined. The enhanced nociception behavior, bladder weight, vascular permeability, edema, hemorrhage, nitric oxide, IL-6 and TNF-α levels by CYP administration were significantly reduced by AEECC (250 and 500 mg/kg). A significant increase in serum antioxidant system such as CAT and GPx was also observed in AEECC-treated rats. The AEECC (3 mg/ml) significantly reduced urinary bladder tone in the strips pre-contracted with carbachol in both control and CYP-treated rats. This relaxation was demolished by atropine, nifedipine, glibenclamide, and indomethacin but not with propranolol. The plant extract showed the presence of antioxidant and anti-inflammatory phytochemicals. These results suggest that Cuminum cyminum offers uroprotective activity and can ameliorate CYP-induced bladder toxicity by modulating antioxidant parameters, pro-inflammatory cytokine levels and bladder smooth muscle overactivity. The in silico binding interactions of antioxidant 2I3Y and anti-inflammatory protein 1TNF with various ligands from Cuminum cyminum seeds revealed potential bioactive compounds with promising antioxidant and anti-inflammatory properties, providing valuable insights for drug development and nutraceutical research.

Antibiotic Resistance Patterns Among Uropathogens in Female Outpatients Affected by Uncomplicated Cystitis: Focus on Fosfomycin Trometamol.

OBJECTIVES: To report the resistance rate against fosfomycin trometamol among outpatient women with symptoms related to urinary tract infections over a 6-year period in a multicentre, cross-sectional study. METHODS: Urinary samples were collected from three high-volume laboratories from January 2015 to December 2020. The pattern of resistance to fosfomycin was analysed by using the Vitek II automated system. RESULTS: A total of 7289 urinary samples were collected and 8321 strains were analysed during the study period. The most commonly isolated uropathogen was Escherichia coli (n = 6583, 79.1%). The mean resistance rate against fosfomycin was 9.7% (range 7.1-11.3). No statistically significant difference was found between the three laboratories (P = 0.53). There was no significant increase in resistance rate during the study period. The mean resistance rate against fosfomycin was higher among extended-spectrum ß-lactamase (ESBL)-producing bacteria when compared with non-ESBL-producing strains (10.8% vs. 7.9%; P < 0.001). CONCLUSION: Uropathogens isolated from women affected by cystitis remained highly susceptible to fosfomycin. These findings confirm recommendations in international guidelines that advocate fosfomycin trometamol for empirical treatment of uncomplicated cystitis in women.

Daily fosfomycin versus levofloxacin for complicated urinary tract infections.

IMPORTANCE: Concerns over resistance and safety have been identified in the current treatment regimen for complicated urinary tract infections. Fosfomycin is a drug that is routinely used for the treatment of uncomplicated cystitis. This study shows that fosfomycin could be an oral alternative as step-down therapy for the treatment of complicated urinary tract infections, with a clinical cure rate comparable to levofloxacin but a lower microbiological success rate 3 weeks from start of antibiotics.