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.

Surfactant Protein A Inhibits Growth and Adherence of Uropathogenic Escherichia coli To Protect the Bladder from Infection.

Surfactant protein A (SP-A) is a multifunctional host defense collectin that was first identified as a component of pulmonary surfactant. Although SP-A is also expressed in various tissues, including the urinary tract, its innate immune functions in nonpulmonary tissues are poorly understood. In this study, we demonstrated that adherence of uropathogenic Escherichia coli (UPEC) to the bladder was enhanced in SP-A-deficient mice, which suggests that SP-A plays an important role in innate immunity against UPEC. To understand the innate immune functions of SP-A in detail, we performed in vitro experiments. SP-A directly bound to UPEC in a Ca2+-dependent manner, but it did not agglutinate UPEC. Our results suggest that a bouquet-like arrangement seems unsuitable to agglutinate UPEC. Meanwhile, SP-A inhibited growth of UPEC in human urine. Furthermore, the binding of SP-A to UPEC decreased the adherence of bacteria to urothelial cells. These results indicate that direct action of SP-A on UPEC is important in host defense against UPEC. Additionally, adhesion of UPEC to urothelial cells was decreased when the cells were preincubated with SP-A. Adhesion of UPEC to urothelial cells is achieved via interaction between FimH, an adhesin located at bacterial pili, and uroplakin Ia, a glycoprotein expressed on the urothelium. SP-A directly bound to uroplakin Ia and competed with FimH for uroplakin Ia binding. These results lead us to conclude that SP-A plays important roles in host defense against UPEC.

Selective culture of Escherichia coli to prevent infective complications of transrectal ultrasound-guided prostate biopsy: Clinical efficacy and analysis of characteristics of quinolone-resistant Escherichia coli.

OBJECTIVES: To evaluate a regimen of targeted prophylaxis using rectal swab culture in patients undergoing transrectal ultrasound-guided prostate biopsy, and to investigate the characteristics of isolated fluoroquinolone-resistant Escherichia coli. METHODS: A prospective study was carried out from June 2013 through December 2014. Rectal swabs were cultured on agar plates containing either 2 µg/mL levofloxacin or 1 µg/mL sitafloxacin before transrectal ultrasound-guided prostate biopsy. Patients with susceptible organisms received levofloxacin or sitafloxacin, whereas those with resistant organisms received directed antimicrobial prophylaxis according to the results of the antimicrobial susceptibility test. Patients with infectious complications after prostate biopsy were identified, and characteristics of patients carrying fluoroquinolone-resistant Escherichia coli were analyzed. RESULTS: A total of 397 men underwent transrectal ultrasound-guided prostate biopsy. Of these patients, 74 (18.6%) had fluoroquinolone-resistant Escherichia coli. All fluoroquinolone-resistant Escherichia coli were susceptible to amikacin and meropenem. The risk factor for possible fluoroquinolone-resistant Escherichia coli was age of ≥73 years. Three (0.7%) patients who received appropriate antimicrobial prophylaxis had high-grade fever after the prostate biopsy. However, the pathogens were not fluoroquinolone-resistant Escherichia coli. CONCLUSIONS: Targeted antimicrobial prophylaxis in patients undergoing transrectal ultrasound-guided prostate biopsy can be associated with reducing severe infectious complications caused by fluoroquinolone-resistant Escherichia coli.

Surfactant protein A (SP-A) and SP-A-derived peptide attenuate chemotaxis of mast cells induced by human ß-defensin 3.

Human ß-defensin 3 (hBD3) is known to be involved in mast cell activation. However, molecular mechanisms underlying the regulation of hBD3-induced mast cell activation have been poorly understood. We previously reported that SP-A and SP-A-derived peptide 01 (SAP01) regulate the function of hBD3. In this study, we focused on the effects of SP-A and SAP01 on the activation of mast cells induced by hBD3. SAP01 directly bound to hBD3. Mast cell-mediated vascular permeability and edema in hBD3 administered rat ears were decreased when injected with SP-A or SAP01. Compatible with the results in rat ear model, both SP-A and SAP01 inhibited hBD3-induced chemotaxis of mast cells in vitro. Direct interaction between SP-A or SAP01 and hBD3 seemed to be responsible for the inhibitory effects on chemotaxis. Furthermore, SAP01 attenuated hBD3-induced accumulation of mast cells and eosinophils in tracheas of the OVA-sensitized inflammatory model. SP-A might contribute to the regulation of inflammatory responses mediated by mast cells during infection.

The efficacy of faropenem for patients with acute cystitis caused by extended spectrum ß-lactamase producing Escherichia coli.

The number of patients with acute cystitis caused by extended spectrum ß lactamase (ESBL)-producing Escherichia coli (E. coli) is increasing gradually. Although it is reported that ESBL-producing E. coli are sensitive to faropenem (FRPM), there are few clinical studies on the efficiency of FRPM against acute cystitis caused by the bacteria. Therefore, we retrospectively reviewed the medical charts of patients with acute cystitis caused by ESBL-producing E. coli who were treated with the oral antimicrobial agent faropenem (FRPM) in our institution from June 2011 to May 2015. Ten patients with acute cystitis caused by ESBL producing E. coli were treated with FRPM. Although clinical cure was achieved in 9 of them, it reoccurred in 3. This study revealed that the treatment regimen with FRPM for patients with acute cystitis caused by ESBL-producing E. coli is promising. However, a non-negligible number of recurrences were caused by ESBL-producing E. coli because of the nature of underlying diseases or pathologies in the urinary tract.

A case of infective endocarditis and pyogenic spondylitis after transrectal ultrasound guided prostate biopsy.

We report a patient with infective endocarditis and pyrogenic spondylitis occurring simultaneously. The patient was a 59-year-old man. He was suspected of having prostate cancer due to a high prostate-specific antigen concentration noted in a checkup. He then underwent a transrectal ultrasound guided prostate biopsy with cefotiam as antimicrobial prophylaxis. He had a fever higher than 38 °C and lumbar pain for a few days after the biopsy. Enterococcus faecalis was isolated from 2 sets of blood culture. Magnetic resonance imaging revealed an abnormal image at C7/Th1 with a signal decrease in T1-weighted sequences and signal increase in T2-weighted sequences that were suspected to be due to bone destruction. Therefore, he was diagnosed as having pyogenic spondylitis by an orthopedist. At the same time, he complained of palpitation and a heart murmur was detected. Then transesophageal echocardiography was performed by a cardiologist and it revealed vegetation in his left ventricle and aortic regurgitation, and finally acute cardiac insufficiency was determined. He was treated with tazobactam/piperacillin and aortic valve displacement surgery. Based on the results of the prostate biopsy and image inspection, he was diagnosed as having localized prostate cancer. He was treated by androgen deprivation therapy and external beam radiation therapy. We have to keep in mind that E. faecalis can be a potential pathogen for severe infectious complications after prostate biopsy, especially if a cephalosporin is selected for antimicrobial prophylaxis.

Do patients who complain of lower urinary tract symptoms frequently have clinically significant pyuria?

There is still controversy about whether post-void residual (PVR) urine volume affects the onset of urinary tract infection (UTI). In addition, although male patients with lower urinary tract symptoms (LUTS) might potentially have PVR, the association between LUTS and UTI or asymptomatic pyuria with or without bacteriuria remains unclear. We studied the frequency of asymptomatic pyuria, with and without bacteriuria, in patients with LUTS without a previous history of urinary tract manipulation at the first visit and their sequential courses. This retrospective study was done by reviewing medical charts. A total of 453 male patients who complained of LUTS and visited our outpatient clinic in 2008 were included in this study. The frequency of pyuria, with or without bacteriuria, in this study at the first visit was 4.9%. The median PVR volumes at the initial examination were 79 ml in the 22 patients with pyuria and 22 ml in the 431 patients without pyuria. The difference of the PVR volume between the patients with pyuria and those without pyuria was statistically significant (p = 0.0095). Twelve patients were treated with alpha-blockers without antimicrobial chemotherapy and pyuria disappeared in 5 (41.7%) of them. However, the decrease in the rate of PVR was not significantly different between the patients with persisting pyuria and those without pyuria. A not negligible number of patients with LUTS had pyuria at the first visit; however, there was no febrile UTI in their clinical course even if they received no urological manipulation.

How do we understand the disagreement in the frequency of surgical site infection between the CDC and Clavien-Dindo classifications?

To clarify the discrepancy in the incidence and severity of surgical site infections (SSI) for radical cystectomy between reports based on the CDC guideline and those using the Clavien-Dindo classification we evaluated 449 consecutive patients who underwent radical cystectomy for bladder cancer between 1990 and 2012. Of the 115 (25.6%) patients with SSI defined by the CDC guideline, 89 could be analyzed. We compared the SSI rates and severity defined by the CDC guideline and Clavien-Dindo classifications. There were 58 patients with superficial SSI, 16 with deep SSI, and 15 with organ/space SSI according to the CDC guideline. All patients with organ/space SSI were judged as "not having SSI" by the Clavien-Dindo classification. They were classified as having "intestinal prolapse", "intestinal fistula", "abdominal abscess" and "pelvic abscess." There was a significant association between the treatment duration and depth of SSI based on the CDC guideline by Spearman's rank-correlation coefficient (p < 0.001, r = 0.614) and with the grade of complications (p < 0.001, r = 0.632) in the Clavien-Dindo classification. Multivariate analysis showed that patients with grade III SSI in the Clavien-Dindo classification needed a significantly longer treatment duration. It is necessary to be aware that a discrepancy can occur automatically due to the different natures of the definitions. Using the CDC guideline, we can effectively estimate the future treatment period when SSI occurs. With the Clavien-Dindo classification, grade III SSI requires a longer treatment duration.

Emergence of antimicrobial-resistant uropathogens isolated from pediatric patients with cystitis on daily clean intermittent catheterization.

One of the major complications of clean intermittent catheterization (CIC) is urinary tract infection (UTI). Recent reports showed that community-acquired UTIs caused by antimicrobial-resistant pathogens were gradually presenting in adults. However, there have been few reports about UTIs caused by antimicrobial-resistant bacteria in pediatric patients. Therefore, we retrospectively reviewed the medical charts of 45 children with CIC due to neurogenic bladder dysfunction from January 2010 to March 2013. Sixty-two episodes of cystitis occurred in 27 patients. Seventy bacterial strains were isolated from urine samples. The rate of Gram-negative bacteria was 84.3%. Six extended-spectrum ß-lactamase (ESBL)-producing Escherichia coli (E. coli) strains were isolated from 4 patients. An ESBL-producing Proteus mirabilis strain and a methicillin-resistant Staphylococcus aureus strain were isolated from one patient each. Most of the pathogens of cystitis in the pediatric patients with CIC were Gram-negative bacilli, especially E. coli. We should be aware that ESBL producing E. coli as potential pathogens cause cystitis and regularly survey antimicrobial susceptibility to understand the resistant strains that develop.

Serum antimicrobial concentrations for surgical antimicrobial prophylaxis in radical nephrectomy and radical prostatectomy.

To evaluate the current methods of surgical antimicrobial prophylaxis from the viewpoint of pharmacokinetics for patients undergo urologic surgery, this study was designed to measure the serum concentrations of two different prophylactic antimicrobial agents in different types of urologic surgery. This prospective study included 39 patients with prostate cancer, renal pelvic cancer, ureteral cancer or renal cancer treated by radical surgery from August 2005 to March 2006. Blood samples were taken intraoperatively at 30 min and 180 min after the beginning of the first administration. The half-life of the beta phase of cefazolin is 2.46 h and that of piperacillin is 0.7 h according to their manufacturers. The average serum concentration of cefazolin at 30 min was 144 µg/mL in the prostatectomy group and 175 µg/mL in the nephrectomy group. At 180 min, the average concentration of cefazolin was 37 µg/mL in prostatectomy group and 59 µg/mL in the nephrectomy group. The average concentration of piperacillin at 30 min was 134 µg/mL in the prostatectomy group and 137 µg/mL in the nephrectomy group. At 180 min, the average concentration of piperacillin was 10 µg/mL in the prostatectomy group and 22 µg/mL in the nephrectomy group. Thus, the concentration at 180 min after the beginning of infusion was different according to the half-life of each antimicrobial agent. Therefore, up-to-date guidelines for surgical antimicrobial prophylaxis that deal with additional types of intraoperative prophylaxis should be consulted if the operation exceeds two half-lives of the prophylactic antimicrobial agents used in real-life clinical practice.

Clinical analysis of febrile neutropenia in urological anticancer chemotherapy: retrospective single center study.

OBJECTIVES: The aims of this study were to clarify the frequency and prognosis of febrile neutropenia (FN) in patients who received urological anticancer chemotherapy. METHODS: Between May 2005 and January 2010, 141 patients underwent urological anticancer chemotherapy at the Sapporo Medical University Hospital, Sapporo, Japan. They consisted of 124 men and 17 women aged 62 (range 16-80) years. The patients underwent a total of 626 treatment courses of urological anticancer chemotherapy. RESULTS: Of the 626 urological anticancer chemotherapy courses, grades 3 and 4 neutropenia occurred in 451 (72.0 %) courses. FN developed in 57 (9.1 %) courses in which 7 (12.3 %) and 50 (87.7 %) patients were classified as high risk and low risk, respectively, according to the Multinational Association for Supportive Care in Cancer (MASCC) risk index scoring system. There was no anticancer chemotherapy-related death in either the high- or low-risk group. The frequencies of bacteria isolated from courses with FN were 0 and 10.0 % for the high- and low-risk groups, respectively. CONCLUSIONS: According to the MASCC scoring system, there were fewer patients in the high-risk group than in the low-risk group in this study. There were no cases of anticancer chemotherapy-related death in either group. Therefore, urological anticancer chemotherapy can be conducted safely with the proper management of neutropenia and FN.

[Significance of Procalcitonin Measurement in Cases with Febrile Condition during Chemotherapy for Urological Cancer].

We examined the usefulness of measurement of procalcitonin (PCT) for patients, who developed febrile neutropenia during cancer chemotherapy for urological cancer. Of the Patients who underwent cancer chemotherapy for bladder, renal pelvic or ureteral, and testicular cancer in our department from 2010 to 2013, 51 had febrile events. Their clinical courses and PCT values were retrospectively reviewed and analyzed. PCT was positive in 12 patients and negative in 39. The duration with febrile status was significantly longer in the PCT-positive group than in the PCT-negative group. There was no significant difference between the blood count values in each group, but C-reactive protein (CRP) was significantly higher in the PCT-positive group than in the PCT-negative group. There were no significant differences between the 2 groups in other tests with blood. There were 12 patients with febrile neutropenia (FN) but all were classified into low-risk by the MASCC scoring system. Four of these 12 patients were positive for PCT. Our results suggested that, in patients with a fever of 37.5°C or more during the course of cancer chemotherapy for urologic cancer, bacteremia possibly existed if the patient was positive for PCT. In addition, the duration of fever tended to be longer and the condition was more severe. When the patients with urological cancer undergo cancer chemotherapy manifest high-grade fever, PCT is promising and valuable as an indicator of the severity of infection.

The single N-glycan deletion mutant of soluble ErbB3 protein attenuates heregulin ß1-induced tumor progression by blocking of the HIF-1 and Nrf2 pathway.

It has been well documented that activation of the ErbB3-PI3K-Akt pathway is implicated in tumor survival and progression. We previously demonstrated that the single N-glycan deletion mutant of soluble ErbB3 protein (sErbB3 N418Q) attenuates heregulin ß1-induced ErbB3 signaling. The active PI3K-Akt pathway augments the nuclear accumulation of hypoxia inducible factor (HIF)-1α, which activates the transcription of many target genes and drives cancer progression. In this study, we focused on the effects of sErbB3 N418Q mutant on nuclear accumulation of HIF-1α. Pretreatment with the sErbB3 N418Q mutant suppressed heregulin ß1-induced HIF-1α activation in MCF7 cells. Similar results were also obtained in other breast cancer cell lines, T47D and BT474. Interestingly, these suppressive effects were not observed with the sErbB3 wild type. In addition, pretreatment with the sErbB3 N418Q mutant suppressed the cell migration of MCF7 cells induced by heregulin ß1. Furthermore, incubation with heregulin ß1 also induced the nuclear accumulation of Nrf2, and this effect was also reduced by the sErbB3 N418Q mutant, but not the sErbB3 wild type. These findings indicated that the sErbB3 N418Q mutant suppressed malignant formation of cancer cells by blocking of the HIF-1α and Nrf2 pathways.

Surgical site infection of scrotal and inguinal lesions after urologic surgery.

To clarify the incidence of surgical site infection (SSI) after urological scrotal and inguinal surgical procedures and the preventive effect of antimicrobial prophylaxis for SSI, retrospective analysis was performed. The patients who underwent scrotal and inguinal operations from 2001 to 2010 were included in this analysis. A first or second generation cephalosporin was administered as antimicrobial prophylaxis just before the start of surgery and no additional prophylaxis was conducted. The surgery was classified into 76 (38%) cases with testicular sperm extraction (TESE), 72 (36%) with radical orchiectomy, 29 (14.5%) with bilateral orchiectomy (surgical castration) and 23 (11.5%) with other scrotal and inguinal operations. The median age and age range were 36 years and 18-81 years, respectively. SSI occurred in 7 (3.5%) cases. The frequencies of SSI were 6.5% in the patients with urological inguinal surgery and 1.6% in those with scrotal surgery. The frequency of SSI in the patients with urological inguinal surgery was not negligible even though it is considered a clean operation, and further analysis is warranted to prevent SSI.

Surfactant protein D inhibits adherence of uropathogenic Escherichia coli to the bladder epithelial cells and the bacterium-induced cytotoxicity: a possible function in urinary tract.

The adherence of uropathogenic Escherichia coli (UPEC) to the host urothelial surface is the first step for establishing UPEC infection. Uroplakin Ia (UPIa), a glycoprotein expressed on bladder urothelium, serves as a receptor for FimH, a lectin located at bacterial pili, and their interaction initiates UPEC infection. Surfactant protein D (SP-D) is known to be expressed on mucosal surfaces in various tissues besides the lung. However, the functions of SP-D in the non-pulmonary tissues are poorly understood. The purposes of this study were to investigate the possible function of SP-D expressed in the bladder urothelium and the mechanisms by which SP-D functions. SP-D was expressed in human bladder mucosa, and its mRNA was increased in the bladder of the UPEC infection model in mice. SP-D directly bound to UPEC and strongly agglutinated them in a Ca(2+)-dependent manner. Co-incubation of SP-D with UPEC decreased the bacterial adherence to 5637 cells, the human bladder cell line, and the UPEC-induced cytotoxicity. In addition, preincubation of SP-D with 5637 cells resulted in the decreased adherence of UPEC to the cells and in a reduced number of cells injured by UPEC. SP-D directly bound to UPIa and competed with FimH for UPIa binding. Consistent with the in vitro data, the exogenous administration of SP-D inhibited UPEC adherence to the bladder and dampened UPEC-induced inflammation in mice. These results support the conclusion that SP-D can protect the bladder urothelium against UPEC infection and suggest a possible function of SP-D in urinary tract.

Significance of anaerobic bacteria in postoperative infection after radical cystectomy and urinary diversion or reconstruction.

Radical cystectomy followed by urinary diversion or reconstruction (RC) is a standard treatment for patients with muscle-invasive bladder cancer. In these operations, a high frequency of complications, especially postoperative infection, has been reported. However, there have only been a few studies about postoperative anaerobic bacterial infection. To clarify the significance and role of anaerobic bacteria in postoperative infection, we retrospectively analyzed cases in which postoperative infection by these organisms developed. A total of 126 patients who underwent RC from 2006 to 2010 were included in this study. Various types of postoperative infection occurred in 66 patients. Anaerobic bacterial infections were detected with cultures for urine and blood in one case, for blood in two cases, and for surgical wound pus in four. The frequency of postoperative anaerobic bacterial infection in RC was less than that of colon surgery. However, this study revealed the possible development of a nonnegligible number of postoperative anaerobic bacterial infections. Therefore, we should consider anaerobic bacteria as possible pathogens in postoperative infection after RC.

Antimicrobial susceptibility and penicillin-binding protein 1 and 2 mutations in Neisseria gonorrhoeae isolated from male urethritis in Sapporo, Japan.

The spread of antimicrobial-resistant Neisseria gonorrhoeae worldwide is a critical issue in the control of sexually transmitted infections. The purpose of this study was to clarify recent trends in the susceptibility of N. gonorrhoeae to various antimicrobial agents and to compare these data with our previous data. Minimum inhibitory concentrations (MICs) of various antimicrobial agents were determined in N. gonorrhoeae strains clinically isolated from male gonococcal urethritis. In addition, amino acid sequencing of penicillin-binding protein (PBP) 2, encoded by the penA gene, was analyzed so that genetic analysis of mosaic PBP 2 could clarify the susceptibility of the strains to cefixime and other cephalosporins. The susceptibility rate for ceftriaxone, cefodizime, and spectinomycin, agents whose use is recommended by the guideline of the Japanese Society of Sexually Transmitted Infections (JSSTI), was 100 %. The susceptibility rates of the strains to penicillin G and ciprofloxacin were lower than those in previous reports. Mosaic PBP 2 structures were detected in 51.9 % of the strains and the MICs of the strains with the mosaic PBP 2 to cefixime were much higher than those of the strains without the mosaic PBP 2. In the clinical situation, the treatment regimen recommended by the JSSTI remains appropriate; however, the susceptibility to cephalosporins should be intensively surveyed because strains with mosaic PBP 2 were commonly detected.

[Prospective multi-institutional analysis according to the "Japanese guidelines for prevention of perioperative infections in urological field"].

OBJECTIVE: The "Japanese guidelines for prevention of perioperative infections in urological field" was edited by the Japanese Urological Association in 2007. They are the first Japanese guidelines for antimicrobial prophylaxis specifically to prevent perioperative infections in the urological field. We report here the results of a multicenter prospective study conducted to examine the validity and usefulness of these guidelines. PATIENTS AND METHODS: The subjects were 513 patients who had undergone urological surgeries between July and September 2008 at 10 nationwide university institutions in the Japanese Society of UTI Cooperative Study Group. These surgeries were transurethral resection of bladder (TURBT), transurethral resection of prostate (TURP), adrenalectomy, nephrectomy, nephroureterectomy, radical prostatectomy and total cystectomy. Analysis was performed on patient information, surgical procedures, types and durations of administration of prophylactic antibiotic agents, and the presence of surgical site infections (SSI) and remote infections (RI). RESULTS: Of 513 patients, 387 (75.4%) were administered prophylactic antibiotic agents according to the guidelines. In these patients, the incidences of SSI and RI were 5.9% and 4.1%, respectively. Multivariate analysis showed that significant factors for SSI were the surgical risk (according to the ASA physical status classification system), diabetes, and operation time, and that the only significant factor for RI was the operation time. CONCLUSIONS: More large-scale study and evidences are necessary in order to demonstrate the validity and usefulness of these guidelines.

Efficacy and safety of desmopressin orally disintegrating tablets 25 and 50 µg in male patients with nocturia: A Japanese real-world multicenter clinical study.

OBJECTIVES: To clarify Japanese real-world clinical data on the use of desmopressin 25 and 50 µg orally disintegrating tablets (ODT) for male patients with nocturia and evaluate the predictive factors to improve nighttime frequency. METHODS: We retrospectively accumulated real-world clinical data from 27 institutions in Japan. Male patients with two or more episodes of nocturia who received desmopressin ODT for nocturnal polyuria (NP) from 2019 through 2021 were included. The primary endpoint was the change of nighttime frequency until 3 months after desmopressin administration. The secondary endpoints were to clarify the persistence rate, adverse events, and predictive factors of decreasing nighttime frequency. RESULTS: A total of 118 patients were eligible to participate in this study. The persistence rate of desmopressin on the Kaplan-Meier curve at week 12 was 51.3. The reason for discontinuation was mainly the occurrence of adverse events in 67 patients (56.8%), particularly hyponatremia in 7 patients (5.9%). Nighttime frequencies at baseline, - 1 month and 1 - 3 months after desmopressin administration were 4.1 ± 1.3, 2.9 ± 1.4 (P < .01), and 2.6 ± 1.3 (P < .01), respectively. The mean nighttime urine volume voided at baseline was significantly larger in patients whose nighttime frequency decreased by two or more times than in those with a decrease of less than two times. CONCLUSIONS: Desmopressin 25 and 50 µg ODT treatments are feasible for male patients with NP in Japanese real-world clinical practice. Patients with higher voided volumes, particularly in the nighttime, may have great benefit from desmopressin.

Serum testosterone level to predict the efficacy of sequential use of antiandrogens as second-line treatment following androgen deprivation monotherapy in patients with castration-resistant prostate cancer.

OBJECTIVE: We investigated whether serum testosterone after the failure of androgen deprivation monotherapy predicted the efficacy of antiandrogens added to androgen deprivation monotherapy as second-line treatments for patients with castration-resistant prostate cancer. METHODS: We reviewed 30 patients with castration-resistant prostate cancer who received maximal androgen blockade with addition of an antiandrogen (delayed maximal androgen blockade) (bicalutamide 80 mg daily for 21 patients and flutamide 375 mg daily for 9 patients) as the second-line treatment. The patients were divided into two groups by serum testosterone before delayed maximal androgen blockade: 22 in the testosterone ≥ 5 ng/dl group and 8 in the testosterone <5 ng/dl group. A prostate-specific antigen response was defined as a prostate-specific antigen decline of ≥ 50% from the pre-treatment level. RESULTS: The response rate was significantly higher in the testosterone ≥ 5 ng/dl group than in the testosterone <5 ng/dl group (77.3 vs. 37.5%, P =0.04). During the median follow-up period of 52.5 months, 24 patients (80.0%) developed prostate-specific antigen progression. A serum testosterone level of <5 ng/dl was an independent factor to predict prostate-specific antigen progression in a reduced and full model setting on multivariate analysis (hazard ratio 6.03, P =0.003 and 5.99, P =0.003, respectively). The 1-year prostate-specific antigen progression-free survival rate was significantly higher in the testosterone ≥ 5 ng/dl group than in the testosterone <5 ng/dl group (52.9 vs. 0%, P =0.002), as was cause-specific survival (5 years: 66.0 vs. 33.3%, P =0.007). CONCLUSIONS: Serum testosterone could play an important role when delayed maximal androgen blockade is indicated as the second-line treatment in patients with castration-resistant prostate cancer. Delayed maximal androgen blockade might be more beneficial in patients with a serum testosterone level of ≥ 5ng/dl.