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.

The third nationwide surveillance of antimicrobial susceptibility against Neisseria gonorrhoeae from male urethritis in Japan, 2016-2017.

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.

Nationwide surveillance of the antimicrobial susceptibility of Chlamydia trachomatis from male urethritis in Japan: Comparison with the first surveillance report.

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.

Nationwide surveillance of the antimicrobial susceptibility of Chlamydia trachomatis from male urethritis in Japan.

Genital chlamydial infection is a principal sexually transmitted infection worldwide. Chlamydia trachomatis can cause male urethritis, acute epididymitis, cervicitis, and pelvic inflammatory disease as sexually transmitted infections. Fortunately, homotypic resistant C. trachomatis strains have not been isolated to date; however, several studies have reported the isolation of heterotypic resistant strains from patients. In this surveillance study, clinical urethral discharge specimens were collected from patients with urethritis in 51 hospitals and clinics in 2009 and 38 in 2012. Based on serial cultures, the minimum inhibitory concentration (MIC) could be determined for 19 isolates in 2009 and 39 in 2012. In 2009 and 2012, the MICs (MIC90) of ciprofloxacin, levofloxacin, tosufloxacin, sitafloxacin, doxycycline, minocycline, erythromycin, clarithromycin, and azithromycin were 2 µg/ml and 1 µg/ml, 0.5 µg/ml and 0.5 µg/ml, 0.125 µg/ml and 0.125 µg/ml, 0.063 µg/ml and 0.063 µg/ml, 0.125 µg/ml and 0.125 µg/ml, 0.125 µg/ml and 0.125 µg/ml, 0.016 µg/ml and 0.016 µg/ml, and 0.063 µg/ml and 0.063 µg/ml, respectively. In summary, this surveillance project did not identify any resistant strain against fluoroquinolone, tetracycline, or macrolide agents in Japan.

The second nationwide surveillance of the antimicrobial susceptibility of Neisseria gonorrhoeae from male urethritis in Japan, 2012-2013.

Worldwide, the most important concern in the treatment of sexually transmitted infections is the increase in antimicrobial resistant Neisseria gonorrhoeae strains including resistance to cephalosporins, penicillins, fluoroquinolones or macrolides. To investigate the trends of antimicrobial susceptibility among N. gonorrhoeae strains isolated from male patients with urethritis, a Japanese surveillance committee conducted the second nationwide surveillance study. Urethral discharge was collected from male patients with urethritis at 26 medical facilities from March 2012 to January 2013. Of the 151 specimens, 103 N. gonorrhoeae strains were tested for susceptibility to 20 antimicrobial agents. None of the strains was resistant to ceftriaxone, but the minimum inhibitory concentration (MIC) 90% of ceftriaxone increased to 0.125 µg/ml, and 11 (10.7%) strains were considered less susceptible with an MIC of 0.125 µg/ml. There were 11 strains resistant to cefixime, and the MICs of these strains were 0.5 µg/ml. The distributions of the MICs of fluoroquinolones, such as ciprofloxacin, levofloxacin and tosufloxacin, were bimodal. Sitafloxacin, a fluoroquinolone, showed strong activity against all strains, including strains resistant to other three fluoroquinolones, such as ciprofloxacin, levofloxacin and tosufloxacin. The azithromycin MICs in 2 strains were 1 µg/ml.

High dose rate 192Ir brachytherapy source model Monte Carlo dosimetry: mHDR-v2 and mHDR-v2r.

After 2010, the source model of the microSelectron HDR Afterloader System was slightly modified from the previous model. Granero et al. named the modified source model "mHDR-v2r (revised model mHDR-v2)" and the previous model "mHDR-v2". They concluded that the dosimetric differences arising from the dimensional changes between the mHDR-v2 and mHDR-v2r designs were negligible at almost all locations (within 0.5% for r ≥ 0.25 cm), the two-dimensional anisotropy function difference between the two sources is found 2.1% at r = 1.0 cm when compared with the results of the other experimental group. To confirm this difference, we performed a full Monte Carlo simulation without energy-fluence approximation. This is useful near the radiation source where charged-particle equilibrium does not hold. The two-dimensional anisotropy function of the TG-43U1 dataset showed a few percent difference between the mHDR-v2r and mHDR-v2 sources. There was no agreement in the immediate vicinity of the source (0.10 cm and 0.25 cm), when compared to Granero et al. in mHDR-v2r sources. The differences in these two-dimensional anisotropy functions were identified.

[Some problems for dosage form based on questionnaire surveying compliance in patients taking tamsulosin hydrochloride].

After the dosage form of tamsulosin hydrochloride was changed from a capsule to on orally disintegrating tablet (ODT, Harnal D), we often received patient complaints and noted an increase in noncompliance with medication regimens. The change in dosage form appeared to cause poor compliance by patients who had become accustomed to the light pink/white capsule over many years. Therefore, we carried out a questionnaire survey of patients taking the ODT form to determine the effects of changing the dosage form and the usefulness of the ODT. Most (92%) of respondents took the ODT with water. In addition, 16% missed taking the medicine after the change in dosage form. ODT is a dosage form that is easy to take for patient with dysphagia, or those on restricted water intake. However, it appears that elderly men and patients with visual disorders cannot distinguish the ODT from other medicines and this affects patient compliance. In conclusion, all pharmaceutical companies should consider the design of medications in terms of coloration, indications, or shape in anticipation of the aging society in future, so that patients can distinguish them. Furthermore, sufficient pharmaceutical care is needed to improve both compliance and safety management for the elderly.

A Monte Carlo investigation of the dose distribution for 60Co high dose rate brachytherapy source in water and in different media.

In this study, the dosimetric characterization for The BEBIG 60Co High Dose Rate (HDR) brachytherapy source model Co0.A86 was investigated and the validity of the EGS5 Monte Carlo code to reproduce the dosimetric parameters in water phantom was checked. In addition, the dose distribution for different tissue phantoms was calculated. The BEBIG 60Co HDR brachytherapy source was modeled using EGS5 Monte Carlo simulation code. A description of the source design, geometry and materials used in this work were provided. According to the update TG43-U1 formalism of AAPM, the air kerma strength, the dose rate constant, 2D rectangular dose distribution in water were calculated, moreover, the results of the radial dose function were obtained in water and different tissue phantoms; bone, lung, adipose tissue, breast and muscle. The obtained results were tabulated and presented in graphical formats for the comparison with available data. The calculated value of the air kerma strength of this study, 3.0419 U Bq-1, agree well with that of the other Monte Carlo calculation. The 2D look-up along-away rectangular dose were obtained in water, the results were similar to the published data for all distances larger than 1 cm, for the distances near to the source region on the transversal source axis small differences are apparent. The radial dose function were presented in graphical format for the comparison between the dose distribution in water and different tissue phantoms. The EGS5 results obtained in this study shows good consistency with the published data for the dosimetric parameters of the of the BEBIG 60Co HDR brachytherapy source. It seems that the radial dose function calculated in water differed in tissue phantoms due to the atomic composition and densities for media that are not taken account by the TG43-U1 formalism.

Measurement and analysis of induced activities in concrete irradiated using high-energy neutrons at KENS Neutron Spallation Source Facility.

Precise estimation of induced activities in concrete shields for high-energy accelerator facilities is one of the most important issues that need to be solved, not only for the reduction of exposure for workers, but also for the reduction of radioactive wastes. Irradiation experiments have been performed by using the 500 MeV Neutron Spallation Source Facility in KEK. The large concrete assembly was placed in the direction of 0 degrees to the beamline. Two kinds of samples were placed at several positions in the assembly. The irradiation period was about 1 week and induced activities in the samples were measured until approximately 1.5 y after irradiation. From the comparison between the experiment and the available Monte Carlo calculation code system, good agreement was obtained for 24Na, 47Sc, 47Ca and 54Mn within a factor 2; however, large discrepancies were observed for some other nuclides.

Methylenetetrahydrofolate reductase genotype, vitamin B12, and folate influence plasma homocysteine in hemodialysis patients.

Hyperhomocysteinemia, a well-recognized cardiovascular risk factor, is frequent in hemodialysis (HD) patients. A common polymorphism in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene, C-->T substitution at nucleotide 677, is associated with homocysteine (Hcy) level elevation. We examined whether three factors involved in the methionine cycle could influence plasma Hcy concentrations in HD patients: MTHFR polymorphism; vitamin B12, an essential cofactor; and folate, the substrate. In a cross-sectional study, serum vitamin B12, folate, and plasma Hcy were measured and MTHFR genotyping was performed in 534 HD patients. Effects of MTHFR genotypes, vitamin B12, and folate on plasma Hcy levels were examined in 450 HD patients not administered vitamin B12 or folate. To examine the effect of vitamin B12 on plasma Hcy concentrations, we compared plasma Hcy concentrations in HD patients with and without vitamin B12 supplementation. To examine whether functional vitamin B12 deficiency exists even in HD patients with normal vitamin B12 concentrations, 15 HD patients (serum vitamin B12 concentrations, 250 to 2,100 pg/mL) were treated with vitamin B12 (mecobalamin, 1.5 mg/d) for 8 weeks. Serum concentrations of methylmalonic acid (MMA) and vitamin B12 were measured. Hcy levels were higher and folate levels were lower in patients with the TT and CT genotypes compared with patients with the CC genotype. Analysis of covariance to determine independent predictors of high Hcy levels identified low serum vitamin B12 and folate levels and high albumin (Alb) levels in CC-genotype patients, low folate levels and high Alb levels in CT-genotype patients, and low folate levels in TT-genotype patients. Plasma Hcy levels were lower in CC- and CT-genotype patients with vitamin B12 supplementation than in those without supplementation. Vitamin B12 supplementation for 8 weeks significantly reduced MMA concentrations in HD patients with normal serum vitamin B12 concentrations. These results indicate that MTHFR genotype influences the correlation of Hcy level with vitamin B12 and folate levels in HD patients. Functional vitamin B12 deficiency may exist, even in HD patients with normal vitamin B12 concentrations. The efficacy of vitamin B12 and folate supplementation on plasma Hcy levels may depend on MTHFR genotype.

Myocardial blood flow parameters derived from contrast replenishment using harmonic power Doppler imaging are underestimated by ultrasound signal attenuation.

The effect of ultrasound signal attenuation on myocardial blood flow parameters derived from contrast replenishment was evaluated using harmonic gray-scale (HGS) and harmonic power Doppler (HPD) imaging. In vitro experiments were performed in a flow model, whereas in vivo experiments were performed in 5 open-chest dogs. In each study, intermittent HGS and HPD images were acquired at various pulsing intervals during contrast infusion. A silicone pad was interposed between the transducer and target region to simulate attenuation conditions. Baseline-subtracted HGS and HPD signal intensities were measured with and without silicone pad, and myocardial blood flow parameters A and beta were calculated using contrast replenishment. Attenuation with HGS images could be offset by baseline subtraction, as baseline images provided the reference for attenuation. However, attenuation with HPD images could not be compensated for, as baseline signal intensity was theoretically 0. In HGS mode, silicone attenuation produced no significant decreases in A and beta. In HPD mode, however, A and beta were significantly decreased by silicone attenuation (A, P <.001; beta, P <.05). Compared with nonattenuated regions, myocardial blood flow parameters in attenuated regions are underestimated when HPD imaging is used. Baseline-subtracted HGS imaging may be useful to compensate for thoracic wall attenuation.

Monte Carlo calculation of depth doses for small field of CyberKnife.

PURPOSE: A Monte Carlo (MC) model of CyberKnife was developed as a quality assurance tool. The percentage depth dose (%dd) was verified by using this model. MATERIALS AND METHODS: An MC model was developed with Electron Gamma Shower version 4 (EGS4) in two steps: (1) a model of the CyberKnife treatment head and (2) a model of the collimator and phantom. The bremsstrahlung spectrum was calculated using the first model, and this spectrum was then used to calculate %dds with the second model. The calculated %dds for a large field (60 mm diameter) and three small fields (30, 15, and 5 mm diameter) were compared with those measured with a diamond detector. RESULTS AND DISCUSSION: The MC-calculated and measured %dd-curves for the 60 mm diameter field were in excellent agreement (<1.85%), thus confirming the validity of the model. Discrepancies between the calculated and measured %dd-curves increased with decreasing field size, with considerable discrepancy (11.62%) for the 5 mm diameter field due to lateral electron disequilibrium. Accurate dose can be determined with MC even in small fields. CONCLUSION: The MC technique can provide reliable standard data for accurate dose delivery with high-technology radiotherapies using small beams.

[A case of secondary hyperparathyroidism with an ectopic intrathyroid gland successfully diagnosed and controlled by percutaneous ethanol injection therapy (PEIT)].

Secondary hyperparathyroidism (II HPT) is a major complication in chronic dialysis patients, and percutaneous ethanol injection therapy (PEIT) has become a useful alternative treatment for II HPT. However, the existence of ectopic parathyroid glands is a major problem when conducting PEIT. Ectopic parathyroid gland accepts 10-35% of II HPT, and the missing glands cannot be detected consistently by any imaging techniques, including scintigraphy. Intrathyroid parathyroid gland is as rare as about 1% and recurrence of missing glands after parathyroidectomy (PTx) has been reported in some cases. We report here a 52-year-old female in whom an ectopic parathyroid gland was defected successfully and intact-PTH controlled by tentative PEIT. At the first examination, a left parathyroid adenoma and a right thyroid goiter were pointed out by ultrasonography, CT and scintigraphy. PEIT was applied twice to the left parathyroid adenoma, but intact-PTH was not decreased. Ultrasonography, CT, 201Tl-99mTc subtraction scintigraphy and fine needle aspiration biopsy (FNAB) were performed again to search for the existence of ectopic glands. The results suggested that the right intrathyroid tumor was an ectopic parathyroid gland. Consequently, tentative PEIT was applied to the right intrathyroid tumor, and successful control of intact-PTH and serum Ca was eventually achieved. To our knowledge, this is the first reported case of secondary hyperparathyroidism with an ectopic intrathyroid gland that was successfully controlled by PEIT. In this case, it was suggested that tentative PEIT of intrathyroid tumor was a useful method for detecting an ectopic parathyroid gland.

[EGS5 code, outline and how to start using the code].

The outline of EGS5 code is described. History, scope (energy range and particle) of the simulation, major application of the code is mentioned. Physical processes in EGS5 code are described. Procedure to set up of input file and user code for new calculation is explained.

Three-dimensional reconstruction of coronary arteriole plexus image by contrast echocardiography using a high-frequency transducer.

OBJECTIVE: This study was established to examine the efficacy of a high-frequency liner probe for visualizing fine anatomy of coronary microcirculation. METHODS: The vessel size and its velocity-time integral at the anterior wall in dogs by real-time contrast echocardiography with high-frequency liner probe and pulse Doppler methods, and the coronary flow volume, were measured before and after adenosine triphosphate injection. A 3-dimensional (3D) image was reconstructed by the built-in 3D system using intermittent flash echocardiographic images. RESULTS: The increments of flow volume calculated from vessel sizes and velocity-time integral were well correlated with those of coronary flow volume. Using intermittent flash echocardiographic images, fine dots and lines of contrast echocardiographic-expected arterioles were evident, and easily and quickly reconstructed as coronary plexus by 3D system. CONCLUSION: A high-frequency liner probe provides the fine-vessel images to evaluate those morphologic changes; a 3D reconstruction image could provide new information about coronary arterioles.

Brief communications: visualization of coronary arteries in rats by 3-dimensional real-time contrast echocardiography.

Angiogenesis is under intense investigation to advance the treatment of various ischemic diseases. Small animals, such as mice and rats, are often used for this purpose. However, evaluating the structure of coronary arteries in small animals in situ is not easy. We succeeded in visualizing the coronary artery in rats on 3-dimensional real-time contrast echocardiography using a high-frequency transducer. These methods will be applied for more convenient assessment in a new study, examining issues such as angiogenesis using rats in situ.

[Efficacy of intravenous myocardial contrast echocardiography for assessment of perfusion area of the heart in mice].

BACKGROUND AND OBJECTIVES: Intravenous myocardial contrast echocardiography is used clinically, but use in small animals has not been evaluated. The conditions for myocardial opacification and the feasibility of myocardial contrast echocardiography were examined in mice. METHODS: Closed chest mice were examined. The left ventricular short-axis view at the mid papillary muscle level was recorded before and after NC100100 injection using a SONOS 5500 (PHILIPS). Real time and intermittent triggering (every 5 beats) myocardial contrast echocardiography was performed with a mechanical index of low (0.3), middle (0.7), and high (1.5). Open chest mice were examined after left anterior descending coronary artery ligation. Myocardial contrast echocardiography was performed using intermittent triggering imaging (every 5 beats) with high mechanical index (1.5). The ratio of the non-perfused area to the whole left ventricular wall area was compared with that of the non-stained area by Evans Blue. RESULTS: The left ventricular myocardium was opacified in any setting. Good opacification was acquired at middle mechanical index (0.7) in real time myocardial contrast echocardiography and at high mechanical index (1.5) in intermittent myocardial contrast echocardiography. The opacified and non-opacified myocardium were clearly identified in all mice with coronary ligation. The non-opacified area ratio showed a good correlation with the non-stained area ratio (y = 0.93x + 0.51, r = 0.94, p < 0.05). CONCLUSIONS: Myocardial contrast echocardiography can be used to assess myocardial perfusion and determine the ischemic area accurately in situ in the mouse.