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OBJECTIVE: This multicenter study aimed to analyze the risk factors for fluoroquinolone (FQ) resistance and to clarify the clinical characteristics of acute bacterial prostatitis (ABP) in Japan. METHODS: A total of 124 patients clinically diagnosed with ABP at 13 medical institutions participating in the Japanese Research Group for Urinary Tract Infection between January and December 2017 were retrospectively reviewed. RESULTS: Of the 124 patients included in this study, 37 were outpatients, and 87 were inpatients. The main underlying medical conditions before the onset of ABP were severe dysuria, urinary retention, transurethral manipulation, indwelling urinary catheter, and transrectal prostate biopsy (TRBx). The main symptoms were fever (≥37.5 °C), prostate tenderness, dysuria, micturition pain, urinary retention, and macrohematuria. Bacteremia was observed in 14 patients. Prostatic abscess was observed in three patients. Escherichia coli was the predominant organism, accounting for 48 % (51/106). FQ-resistant E. coli was detected in 33 % (17/51), and extended-spectrum beta-lactamase-producing E. coli in 12 % (6/51). TRBx (odds ratio [OR] = 48.60, 95 % confidence interval [CI]: 5.49-430.00, p < 0.001) and inpatient status (OR = 29.00, 95 % CI: 1.95-430.00, p = 0.014) were risk factors for the detection of FQ-resistant bacteria. CONCLUSIONS: The detection rate of FQ-resistant bacteria was significantly higher with TRBx ABP and inpatient status. These findings have important implications for the management of ABP and antimicrobial treatment, especially for TRBx ABP, which should be considered a separate category.
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Neisseria gonorrhoeae is one of the important pathogens of sexually transmitted infections. N. gonorrhoeae is rapidly becoming antimicrobial resistant, and there are few drugs that are effective in the initial treatment of gonorrhea. To understand the trends of antimicrobial susceptibility of N. gonorrhoeae, the Surveillance Committee of the Japanese Society of Infectious Diseases, the Japanese Society for Chemotherapy, and the Japanese Society of Clinical Microbiology conducted the third nationwide antimicrobial susceptibility surveillance of N. gonorrhoeae isolated from male urethritis. The specimens were collected from male patients with urethritis at 30 facilities from May 2016 to July 2017. From the 159 specimens collected, 87 N. gonorrhoeae strains were isolated, and 85 were tested for susceptibility to 21 antimicrobial agents. All strains were non-susceptible to penicillin G. Seven strains (8.2%) were ß-lactamase-producing strains. The rates of susceptibility to cefixime and cefpodoxime were 96.5% and 52.9%, respectively. Three strains were non-susceptible with a minimum inhibitory concentration (MIC) of 0.5 mg/L for cefixime. None of the strains were resistant to ceftriaxone or spectinomycin. The susceptibility rate for ciprofloxacin was 23.5% (20 strains), and no strains showed intermediate susceptibility. The susceptibility rate against azithromycin was 81.2%, with one strain isolated with a MIC of 8 mg/L against azithromycin. The results of this surveillance indicate that ceftriaxone and spectinomycin, which are currently recommended for gonococcal infections in Japan, appear to be effective. It will be necessary to further expand the scale of the next surveillance to understand the current status of drug-resistant N. gonorrhoeae in Japan.
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Anti-Infecciosos , Gonorreia , Uretrite , Humanos , Masculino , Neisseria gonorrhoeae , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Cefixima/farmacologia , Cefixima/uso terapêutico , Ceftriaxona/uso terapêutico , Azitromicina/uso terapêutico , Espectinomicina/farmacologia , Espectinomicina/uso terapêutico , Uretrite/tratamento farmacológico , Uretrite/epidemiologia , Uretrite/microbiologia , Japão/epidemiologia , Gonorreia/tratamento farmacológico , Gonorreia/epidemiologia , Anti-Infecciosos/uso terapêutico , Testes de Sensibilidade MicrobianaRESUMO
Although testosterone replacement therapy (TRT) is the first-choice method used worldwide for late-onset hypogonadism (LOH), clinical benefits are not seen in all cases. This study was conducted to determine the predictors of TRT efficacy for LOH. Fifty-six patients who visited our Men's Health Clinic (Kawanishi City Medical Center, Kawanishi and Hyogo Medical University, Nishinomiya, Hyogo, Japan) between November 2003 and June 2021 with data available before and after TRT were enrolled. They were divided into responders (Group 1; n = 45, accounting for 80.4%) and nonresponders (Group 2; n = 11, accounting for 19.6%) based on the clinical response to TRT, including patient satisfaction. Factors noted before TRT included age, body mass index, aging males' symptoms score, sexual health inventory for men, luteinizing hormone, follicular-stimulating hormone, testosterone, free testosterone, prolactin (PRL), estradiol (E2), and testosterone/estradiol (T/E2) ratio in serum. For statistical analysis, a multivariable logistic regression model was used. Univariate analysis revealed PRL (odds ratio [OR]: 0.9624; 95% confidence interval [CI]: 0.9316-0.9943, P < 0.05), E2 (OR: 0.8692; 95% CI: 0.7745-0.9754, P < 0.05), and T/E2 ratio (OR: 1.1312; 95% CI: 1.0106-1.2661, P < 0.05) to be predictive factors. Multivariate analyses showed that T/E2 ratio was an independent predictive factor (OR: 1.1593; 95% CI: 1.0438-1.2875, P < 0.01). The present results suggest that a low value for T/E2 ratio may predict a reduced response to TRT. The T/E2 ratio threshold to predict nonresponders based on receiver-operating characteristics (ROC) curve analysis was shown to be 17.3. Although additional studies with larger number of patients are necessary, we propose the determination of serum E2 level and testosterone level prior to performing TRT.
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OBJECTIVE: To determine the UPOINT-positive domain numbers and evaluate the significance of the sexual dysfunction domain in patients with chronic prostatitis or chronic pelvic pain (CP/CPPS) in Japan. METHODS: A total of 58 patients with CP/CPPS with moderate or greater symptoms were included. Symptom severity was determined by > 14 on the chronic prostatitis symptom index (CPSI). The main outcome was to confirm the number and distribution of the positive UPOINT domains in this group. As secondary outcomes, the correlation between positive domain numbers and CPSI scores was evaluated. We also examined whether the sexual dysfunction subdomain, as determined by the five-item international index of erectile function, could improve the correlation with symptom severity. RESULTS: The mean age was 48.6 ± 15.4 years, CPSI score 24.3 ± 6.1, and positive UPOINT domain number 2.4 ± 0.9. The distribution of each positive domain was 67.2% for urinary, 15.5% for psychosocial, 75.8% for organ-specific, 3.4% for infection, 5.1% for neurological/systemic conditions, and 75.8% for tenderness. Although the mean CPSI total scores tended to increase with an increasing number of positive UPOINT domains, a significant correlation was not observed (r = 0.134, p = 0.312). The sexual dysfunction domain was positive in 62.0% of the cases, but the correlation could not be improved. CONCLUSIONS: Urinary, organ specific, and tenderness domains were mainly observed in patients with CP/CPPS. When patients with moderate or grater CPSI scores are clinically evaluated, clinicians should recognize that the UPOINT-positive domain and CPSI score are clinically and pathologically different concepts. (250 words).
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Dor Pélvica , Prostatite , Adulto , Doença Crônica , Humanos , Masculino , Pessoa de Meia-Idade , Dor Pélvica/diagnóstico , Dor Pélvica/patologia , Dor Pélvica/fisiopatologia , Fenótipo , Prostatite/diagnóstico , Prostatite/patologia , Prostatite/fisiopatologia , Índice de Gravidade de DoençaRESUMO
The Urogenital Sub-committee and the Surveillance Committee of the Japanese Society of Chemotherapy, The Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology conducted the second nationwide surveillance of the antimicrobial susceptibility of Chlamydia trachomatis. In this second surveillance study, clinical urethral discharge specimens were collected from patients with urethritis in 26 hospitals and clinics from May 2016 to July 2017. Based on serial cultures, the minimum inhibitory concentration (MIC) could be determined for 41 isolates; the MICs (MIC90) of ciprofloxacin, levofloxacin, tosufloxacin, sitafloxacin, doxycycline, minocycline, erythromycin, clarithromycin, azithromycin and solithromycin were 2 µg/ml (2 µg/ml), 1 µg/ml (0.5 µg/ml), 0.25 µg/ml (0.25 µg/ml), 0.125 µg/ml (0.063 µg/ml), 0.125 µg/ml (0.125 µg/ml), 0.25 µg/ml (0.25 µg/ml), 0.031 µg/ml (0.031 µg/ml), 0.25 µg/ml (0.125 µg/ml), and 0.016 µg/ml (0.008 µg/ml), respectively. In summary, this surveillance project did not identify any strains resistant to fluoroquinolone, tetracycline, or macrolide agents in Japan. In addition, the MIC of solithromycin was favorable and lower than that of other antimicrobial agents. However, the MIC of azithromycin had a slightly higher value than that reported in the first surveillance report, though this might be within the acceptable margin of error. Therefore, the susceptibility of azithromycin, especially, should be monitored henceforth.
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Chlamydia trachomatis , Uretrite , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Azitromicina/farmacologia , Farmacorresistência Bacteriana , Humanos , Japão/epidemiologia , Masculino , Testes de Sensibilidade Microbiana , Uretrite/tratamento farmacológico , Uretrite/epidemiologiaRESUMO
The Committee for the Development of Guidelines for Infection Control in the Urological Field, including Urinary Tract Management of the Japanese Urological Association, together with its systematic review team and external reviewers, have prepared a set of practice guidelines, an abridged version of which is published herein. These guidelines cover the following topics: (i) foundations of infection control, standard precautions, route-specific precautions, and occupational infection control (including vaccines); (ii) the relationship between urologists and infection control; (iii) infection control in urological wards and outpatient clinics; (iv) response to hepatitis B virus reactivation; (v) infection control in urological procedures and examinations; (vi) prevention of infections occurring in conjunction with medical procedures and examinations; (vii) responses to urinary tract tuberculosis and bacillus Calmette-Guérin; (viii) aseptic handling, cleaning, disinfection, and sterilization of urinary tract endoscopes (principles of endoscope manipulation, endoscope lumen cleaning, and disinfection); (ix) infection control in the operating room (principles of hand washing, preoperative rubbing methods, etc.); (x) prevention of needlestick and blood/bodily fluid exposure and response to accidental exposure; (xi) urinary catheter-associated urinary tract infection and purple urinary bag syndrome; and (xii) urinary catheter-associated urinary tract infections in conjunction with home care. In addressing these topics, the relevant medical literature was searched to the extent possible, and content was prepared for the purpose of providing useful information for clinical practice.
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Infecções Urinárias , Sistema Urinário , Endoscópios , Humanos , Controle de Infecções , Guias de Prática Clínica como Assunto , Infecções Urinárias/etiologia , Infecções Urinárias/prevenção & controle , UrologistasAssuntos
Carbono , Cateteres Urinários , Biofilmes , Escherichia coli , Humanos , Tecnologia , Cateteres Urinários/efeitos adversosRESUMO
A 51-year-old male was hospitalized at another hospital for aspiration pneumonia during gastrostomy management due to sequelae related to a cerebral hemorrhage. The patient was referred to our hospital because of gross hematuria and renal dysfunction following fasting and antibiotic administration. Serum creatinine was 10.54 mg/dl. Prothrombin time (PT) and PT-international standard ratio (PT-INR) were beyond the measurement range, while activated partial thromboplastin time (APTT) was 125 seconds, and protein induced by vitamin K absence or antagonist-II (PIVKA-II) was 117,591 mAU/ml. Computed tomography (CT) imaging showed blood clots in both upper urinary tracts and urinary tract obstruction was considered to be the cause of renal dysfunction. Based on the findings following fasting and long-term administration of antibiotics, including the N-methyl tetrazole thiol (NMTT) group, we considered that the cause was vitamin K deficiency. The patient was immediately treated with menatetrenone (20 mg). Four days after beginning administration, PT, PT-INR, and APTT were improved, and gross hematuria had disappeared. Thereafter, urine volume was increased and renal function became normalized, while PIVKA-II was decreased to the normal range. When a fasting patient has a bleeding tendency during antibacterial administration, it is necessary to consider treatment with vitamin K deficiency.
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Insuficiência Renal , Deficiência de Vitamina K , Antibacterianos , Hematúria/etiologia , Humanos , Masculino , Pessoa de Meia-Idade , Deficiência de Vitamina K/complicaçõesRESUMO
INTRODUCTION: The aim of this study was to monitor the development of drug-resistant bacteria isolated from acute uncomplicated cystitis (AUC) and to evaluate methodology of the survey conducted by collecting only clinical data. METHODS: We enrolled female patients at least 16 years of age diagnosed with AUC in 2018. Patient information including age, menopausal status, and results of bacteriological examination were collected and analyzed regardless of bacterial identification, antimicrobial susceptibility testing or extended-spectrum ß-lactamase (ESBL) detection method. RESULTS: A total of 847 eligible cases were collected. Escherichia coli (E. coli) was the most frequently isolated bacterial species at about 70%, with proportions of fluoroquinolone-resistant E. coli (QREC) and ESBL-producing E. coli isolates at 15.6% and 9.5% of all E. coli isolates, respectively. The proportion of Staphylococcus saprophyticus (S. saprophyticus) was significantly higher in premenopausal women. Regarding the drug susceptibility of E. coli, isolates from Eastern Japan had significantly higher susceptibility to cefazolin, cefotiam and cefpodoxime and lower susceptibility to levofloxacin in postmenopausal women. ESBL-producing E. coli isolates had a high susceptibility to tazobactam-piperacillin, cefmetazole, carbapenems, aminoglycosides, and fosfomycin. In S. saprophyticus, the susceptibility to ß-lactams including carbapenems was 40-60%. CONCLUSIONS: The proportions of QREC and ESBL-producing E. coli were increasing trends and lower susceptibility to LVFX in postmenopausal women was observed. Such surveillance, consisting of the collecting only clinical data, could be conducted easily and inexpensively. It is expected to be continuously performed as an alternative survey to conventional one collecting bacterial strains.
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Cistite , Infecções por Escherichia coli , Infecções Urinárias , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bactérias , Cistite/tratamento farmacológico , Cistite/epidemiologia , Escherichia coli , Infecções por Escherichia coli/tratamento farmacológico , Infecções por Escherichia coli/epidemiologia , Feminino , Humanos , Japão/epidemiologia , Testes de Sensibilidade Microbiana , Infecções Urinárias/tratamento farmacológico , beta-LactamasesRESUMO
The antimicrobial susceptibility patterns of bacterial pathogens isolated from patients with complicated urinary tract infections were analyzed using national surveillance data. The data consisted of 881 bacterial strains from eight clinically relevant species. The data were collected for the third national surveillance project from January 2015 to March 2016 by the Japanese Society of Chemotherapy, the Japanese Association for Infectious Disease, and the Japanese Society of Clinical Microbiology. Surveillance was undertaken with the cooperation of 41 medical institutions throughout Japan. Fluoroquinolone required a MIC90 of 2-64 mg/L to inhibit the 325 Escherichia coli strains tested and the proportion of levofloxacin resistant E. coli strains increased to 38.5% from 29.6% in 2011 and 28.6% in 2008. The proportion of levofloxacin resistant strains of Pseudomonas aeruginosa and Enterococcus faecalis decreased from previous reports and the proportion of multidrug-resistant P. aeruginosa and carbapenem-resistant Enterobacteriaceae remained low. Among methicillin-resistant Staphylococcus aureus (MRSA) strains, strains with reduced susceptibility to vancomycin (minimum inhibitory concentration, 2 µg/mL) increased to 14.7% from 5.5%. Bacterial strains that produced extended-spectrum ß-lactamase included E. coli (79 of 325 strains, 24.3%), Klebsiella pneumoniae (9 of 177 strains, 7.7%), and Proteus mirabilis (6 of 55 strains, 10.9%). The proportion of extended-spectrum ß-lactamase producing E. coli and K. pneumoniae strains increased from previous surveillance reports.
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Bactérias/isolamento & purificação , Infecções Bacterianas/microbiologia , Testes de Sensibilidade Microbiana/métodos , Infecções Urinárias/epidemiologia , Infecções Urinárias/microbiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Bactérias/efeitos dos fármacos , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/epidemiologia , Farmacorresistência Bacteriana/efeitos dos fármacos , Enterococcus faecalis/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Feminino , Fluoroquinolonas/uso terapêutico , Humanos , Japão/epidemiologia , Klebsiella pneumoniae/efeitos dos fármacos , Levofloxacino/farmacologia , Masculino , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Pessoa de Meia-Idade , Proteus mirabilis/efeitos dos fármacos , Pseudomonas aeruginosa/efeitos dos fármacos , Infecções Urinárias/tratamento farmacológico , Vancomicina/uso terapêutico , Adulto JovemRESUMO
OBJECTIVES: To compare the optimal administration period of antimicrobial prophylaxis in patients undergoing transurethral enucleation of the prostate for benign prostatic hyperplasia. METHODS: We carried out a randomized controlled trial to compare the differences in incidence of perioperative genitourinary tract infection between single and multiple (3 days) administrations of cefazolin for transurethral enucleation of the prostate in benign prostatic hyperplasia patients without pyuria or bacteriuria between January 2015 and December 2018. RESULTS: This multicenter randomized controlled trial included 203 patients who underwent a transurethral enucleation of the prostate procedure. All received antimicrobial prophylaxis, and were randomized into those who received single-dose (n = 101) or multiple-dose (n = 102) therapy. The rate of genitourinary tract infection after transurethral enucleation of the prostate for all patients was 1.5%, whereas that in the single-dose group was 1.0% and in the multiple-dose group was 2.0%, which were not significantly different (P = 1.00). CONCLUSIONS: A single dose of antimicrobial prophylaxis as a prophylactic antibacterial drug is sufficient for patients undergoing transurethral enucleation of the prostate who do not have presurgical pyuria or bacteriuria.
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Terapia a Laser , Hiperplasia Prostática , Ressecção Transuretral da Próstata , Infecções Urinárias , Cefazolina/uso terapêutico , Humanos , Japão/epidemiologia , Masculino , Estudos Prospectivos , Próstata/cirurgia , Hiperplasia Prostática/cirurgia , Ressecção Transuretral da Próstata/efeitos adversos , Resultado do Tratamento , Infecções Urinárias/epidemiologia , Infecções Urinárias/etiologia , Infecções Urinárias/prevenção & controleAssuntos
Fosfomicina , Antibacterianos , Antibioticoprofilaxia , Biópsia , Masculino , Estudos Prospectivos , PróstataRESUMO
OBJECTIVES: To assess the effect of cernitin pollen extract on serum prostate-specific antigen level prostate biopsy candidates, and to develop an ideal protocol to avoid an unnecessary biopsy procedure. METHODS: A total of 61 patients were administrated cernitin pollen extract tablets (two tablets t.i.d.) for 30 days, and then underwent a prostate biopsy with ≥12 systematic and targeted biopsy cores obtained. Serum prostate-specific antigen levels were examined before and after administration of the pollen extract, and the change in serum prostate-specific antigen and the rate of change were analyzed in relation to negative and positive biopsy results for cancer. RESULTS: The mean change in serum prostate-specific antigen and rate of change after administration of cernitin pollen extract in all patients were -0.6 ± 1.4 ng/mL and -7.6 ± 16.1%, respectively, which were significantly different from the baseline values (P = 0.0003 and P = 0.0005, respectively). When prostate-specific antigen change values and rates were compared between patients negative and positive for cancer, a significant difference between those groups was observed (P = 0.04 and P = 0.03, respectively). CONCLUSIONS: The present study is the first to show that an ideal protocol using cernitin pollen extract has the potential to avoid an unnecessary prostate biopsy procedure in patients with elevated prostate-specific antigen, possibly caused by inflammation. Additional studies with greater numbers of participants are required to confirm our findings and develop an ideal protocol.
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Extratos Vegetais/administração & dosagem , Antígeno Prostático Específico/sangue , Neoplasias da Próstata/diagnóstico , Prostatite/tratamento farmacológico , Administração Oral , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia/efeitos adversos , Humanos , Japão , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Próstata/patologia , Neoplasias da Próstata/patologia , Curva ROC , Secale , Procedimentos DesnecessáriosRESUMO
Between November 2011 and November 2014, we performed a tunica albuginea incision with tunica vaginalis flap coverage (TAIï¼TVFC) on 5 out of 15 patients who underwent surgery for testicular torsion. Of those 15 patients, 7 underwent orchidopexy alone (Group A), 5 underwent TAIï¼TVFC (Group B), and 3 underwent an orchidectomy procedure (Group C). All were followed for 1 year and preservation of testicular volume ï¼50% on the contralateral side in ultrasound measurements was considered as salvaged. During the follow-up examinations, no testicular atrophy was noted in Group A. In Group B, tension and testis color were immediately improved in all 5 patients after TAIï¼TVFC, while blood perfusion was also improved after the operation. Also 3 patients in Group B were considered to be salvaged, while testicular atrophy occurred in 2 after 8 or more hours from onset until surgery. Our results indicated that TAIï¼ TVFC is useful for restoring blood flow after surgery for testicular torsion, although the so-called'Golden time'for torsion surgery has a significant impact in such cases.
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Fasciotomia , Torção do Cordão Espermático/cirurgia , Adolescente , Criança , Humanos , Masculino , Orquidopexia , Adulto JovemRESUMO
Although febrile complications are rarely encountered after a prostate biopsy procedure, in recent years the number of cases of fatal infection after that have increased along with increases in resistant bacteria. The available biopsy approaches are transrectal and transperineal, with the transrectal approach primarily used. As the invasion path of the puncture needle differs between these approaches, pretreatment and the method of administration of preventive antimicrobial drugs should be separately considered for infection prevention. Recently, the Japanese guidelines for perioperative infection prevention in the field of urology were revised after receiving approval from the Japanese Urological Association. With use of the transrectal approach, attempts have been made to selectively administer prophylactic antibiotics by confirming the presence or absence of resistant bacteria in rectal swab culture results before carrying out a prostate biopsy procedure because of potential problems associated with resistant bacteria in rectal flora. For preventive antibiotics, a single dose of oral quinolone is recommended for patients with low risk, whereas daily administrations of piperacillin/tazobactam are recommended for those considered to be high risk. In contrast, for the transperineal procedure, a single dose of oral quinolone is recommended as a preventive antibiotic. With both approaches, it is important to empirically administer broad-spectrum antimicrobials when occurrence of a febrile infection after a prostate biopsy procedure is confirmed.
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Antibacterianos/uso terapêutico , Antibioticoprofilaxia/normas , Infecções Bacterianas/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Guias de Prática Clínica como Assunto , Neoplasias da Próstata/diagnóstico , Administração Oral , Antibacterianos/farmacologia , Antibioticoprofilaxia/métodos , Bactérias/efeitos dos fármacos , Infecções Bacterianas/microbiologia , Biópsia/efeitos adversos , Biópsia/métodos , Farmacorresistência Bacteriana , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Masculino , Complicações Pós-Operatórias/microbiologia , Próstata/patologia , Neoplasias da Próstata/patologia , Quinolonas/farmacologia , Quinolonas/uso terapêutico , Reto/microbiologiaRESUMO
Renal cell carcinoma (RCC) is one of the most drug-resistant malignancies, and an effective therapy is lacking for metastatic RCC. Anisomycin is known to inhibit protein synthesis and induce ribotoxic stress. The aim of this study was to explore whether anisomycin enhances the cytotoxic effects of mapatumumab, a human agonistic monoclonal antibody specific for death receptor 4 (DR4), in human RCC cells. We examined the cytotoxicity of anisomycin alone and in combination with mapatumumab in human RCC cell lines and primary RCC cell cultures. RCC cells treated with anisomycin showed cytotoxicity in a dose-dependent manner. Anisomyin in combination with mapatumumab showed a synergistic effect not only in two human RCC cell lines but also in five primary RCC cell cultures. The synergy between anisomycin and mapatumumab for cytotoxicity was also observed for apoptosis. Interestingly, anisomycin significantly increased DR4 expression at both the mRNA and the protein level. Furthermore, the combination-induced cytotoxicity was significantly suppressed by a human recombinant DR4:Fc chimeric protein. The combination of anisomycin and mapatumumab also enhanced the activity of caspases 8 and 3, the downstream molecules of death receptors. These findings indicate that anisomycin sensitizes RCC cells to DR4-mediated apoptosis through the induction of DR4, suggesting that combinational treatment with anisomycin and mapatumumab might represent a novel therapeutic strategy for the treatment of RCC.