Acute adverse events of ultra-hypofractionated whole-breast irradiation after breast-conserving surgery for early breast cancer in Japan: an interim analysis of the multi-institutional phase II UPBEAT study.

BACKGROUND: The applicability of ultra-hypofractionated (ultra-HF) whole-breast irradiation (WBI) remains unknown in Japanese women. This study aimed to evaluate the safety and efficacy of this approach among Japanese women and report the results of an interim analysis performed to assess acute adverse events (AEs) and determine whether it was safe to continue this study. METHODS: We enrolled Japanese women with invasive breast cancer or ductal carcinoma in situ who had undergone breast-conserving surgery, were aged ≥ 40 years, had pathological stages of Tis-T3 N0-N1, and had negative surgical margins. Ultra-HF-WBI was delivered at 26 Gy in five fractions over one week. When the number of enrolled patients reached 28, patient registration was paused for three months. The endpoint of the interim analysis was the proportion of acute AEs of grade ≥ 2 (Common Terminology Criteria for Adverse Events v5.0) within three months. RESULTS: Of the 28 patients enrolled from seven institutes, 26 received ultra-HF-WBI, and 2 were excluded due to postoperative infections. No AEs of grade ≥ 3 occurred. One patient (4%) experienced grade 2 radiation dermatitis, and 18 (69%) had grade 1 radiation dermatitis. The other acute grade 1 AEs experienced were skin hyperpigmentation (n = 10, 38%); breast pain (n = 4, 15%); superficial soft tissue fibrosis (n = 3, 12%); and fatigue (n = 1, 4%). No other acute AEs of grade ≥ 2 were detected. CONCLUSIONS: Acute AEs following ultra-HF-WBI were within acceptable limits among Japanese women, indicating that the continuation of the study was appropriate.

New patient setup procedure using surface-guided imaging to reduce body touch and skin marks in whole-breast irradiation during the COVID-19 pandemic.

This study aimed to assess the effectiveness of a new patient-setup procedure using surface-guided imaging during the coronavirus disease 2019 (COVID-19) pandemic for left-sided whole-breast irradiation with deep inspiration breath-hold. Two setup procedures were compared regarding patient positioning accuracy for the first 22 patients. The first was a traditional setup (T-setup) procedure that used a surface-guided system after patient setup with traditional skin marks and lasers. The second procedure involved a new setup (N-setup) that used only a surface-guided system. The positioning accuracy of the remaining 23 patients was assessed using a setup that combined marker reduction and the N-setup procedure. No significant difference was observed in positioning accuracy between the two setups. The positioning accuracy of the marker-reduction setup was within 3 mm in all directions. The N-setup procedure may be a useful strategy for preventing infection during or after the COVID-19 pandemic.

Multi-institutional phase II study of ultra-hypofractionated whole-breast irradiation after breast-conserving surgery for breast cancer in Japan: Kyoto Radiation Oncology Study Group (UPBEAT study).

PURPOSE: The UK-FAST-Forward study showed that ultra-hypofractionated whole-breast irradiation (ultra-HF-WBI) involving five fractions of 26 Gy radiation over 1 week was not inferior to HF-WBI. However, it is not used in Japan due to safety concerns. In April 2022, we commenced a multi-institutional, single-arm, phase II trial. Our aim is to confirm the safety of ultra-HF-WBI after breast-conserving surgery (BCS) for breast cancer in Japanese women. METHOD: We plan to enroll 98 patients from 13 institutions. The primary endpoint is the proportion of late adverse events of grades ≥2 within 3 years. DISCUSSION: We believe that this highly promising clinical study can positively impact the Japanese guidelines for breast cancer treatment. The results will help us decide whether or not ultra-HF-WBI can be used as a more convenient alternative to WBI. REGISTRATION NUMBER AND DATE: This trial was registered in the UMIN Clinical Trials Registry (UMIN000047080) on March 4, 2022.

Emotional Experiences of Skin Markings Among Patients Undergoing Radiotherapy and Related Factors: A Questionnaire-Based Cross-Sectional Study.

Purpose: Patients undergoing radiotherapy often have their skin marked. Previous studies on skin markings examined the durability and physical effects of the markings, but no study has focused on patients' emotional experiences toward the markings. This study aimed to clarify how patients undergoing radiotherapy feel about skin markings, as well as factors that affect patients' emotional experiences. Patients and Methods: We conducted a cross-sectional study using a self-administered questionnaire and medical records. Participants were patients aged ≥20 years undergoing cancer radiotherapy at a designated cancer care hospital. The primary outcome was the level of uncomfortable emotions toward skin markings, and the secondary outcome was the level of favorable ratings on skin markings. To examine factors related to uncomfortable emotions, ordinal logistic regression analysis was performed. Results: Questionnaire forms were distributed to 153 patients, and responses were collected from 132 (86%). Among 108 patients included in the analysis, 56% (59/105, excluding 3 who did not answer this question) responded that they were uncomfortable with skin markings. The proportion of patients who favorably rated skin markings was 63% (59/93, excluding 15 who did not answer this question). No factors were significantly associated with the primary outcome. Conclusion: Many patients accepted skin markings with resignation, as they understood the necessity of the markings in their treatment. Medical staff should understand the emotional experiences of patients toward skin markings and take sufficient care to ensure that they are provided with explanations, including the impact of skin markings on their daily lives, as well as a sense of security that treatment is being performed in a precise manner.

[2.2]- and [3.3]Paracyclophane as Bridging Units in Organic Dyads for Visible-Light-Driven Dye-Sensitized Hydrogen Production.

Novel donor-acceptor dyads containing [2.2]- and [3.3]paracyclophane (PCP) as the bridging moiety were synthesized and used to effectively fabricate dye-sensitized hydrogen production systems. All the prepared compounds had a phenothiazine and a cyanoacrylic acid/pyridinyl acrylonitrile moiety acting as an electron donor and acceptor, respectively. Although cyclic voltammetry measurements showed similar electron-donating properties among all the synthesized dyads, the lowest absorption energy of the [2.2]PCP moiety was lower than that of the [3.3]PCP one; this was due to its shorter distance between benzene rings, which could effectively drive the charge transfer between the donor and acceptor chromophores. Under visible light (>395 nm), a dyad-loaded photocatalyst in a 0.5 M aqueous glycerol solution generated detectable hydrogen gases. The optimal turnover number and photocurrent order exhibited the same trend as the hydrogen production rate since the suggested number of excited photons played a critical role in hydrogen production.

Development of a plan complexity mitigation algorithm based on gamma passing rate predictions for volumetric-modulated arc therapy.

BACKGROUND AND PURPOSE: Volumetric-modulated arc therapy (VMAT) is a complex rotational therapy technique in which highly conformal dose distribution can be realized by varying the speed of gantry rotation, multileaf collimator (MLC) shape, and dose rate. However, the complexity of the technique creates a discrepancy between the calculated and measured doses. Thus, to mitigate the plan complexity in VMAT, this study aimed to develop an algorithm and evaluate its usefulness by conducting a feasibility study. MATERIALS AND METHODS: A total of 50 patients who underwent VMAT between September 2015 and December 2020 were arbitrarily selected for this study. Specifically, patients with less than 85% gamma passing rate (GPR) at 5%/1 mm or 3%/2 mm criterion were selected randomly. Using the GPR prediction model, problematic MLC positions that contribute to a decrease in GPR were identified. Those problematic MLC positions were optimized using a limited nonlinear algorithm under mechanical limitations. Additionally, the dose prescription for the target was re-normalized. The VMAT modulated complexity score (MCSv ), averaged aperture area (AA), and monitor unit per gray (MU/Gy) were evaluated as plan complexity parameters. Calculated doses in patient geometry were evaluated for the target and its surrounding region. In addition, an ArcCHECK cylindrical diode array was used to measure the dose, and GPRs at 5%/1 mm and 3%/2 mm criteria were evaluated to analyze the difference between the mitigated and original plans. The difference was calculated using the mean ± standard deviation. RESULTS: The differences between the MCSv , AA, and MU/cGy values for the mitigated and original plans were 0.8 ± 1.7 (×10-2 ), 42.7 ± 57.9, and -5.6 ± 8.5, respectively. Regarding the calculated dose, the dose volume parameters were consistent within 1% for the target and the surrounding region. The differences between the mitigated and original plans were 1.8 ± 2.9% and 1.3 ± 1.8% for GPRs at 5%/1 mm and 3%/2 mm, respectively. CONCLUSIONS: This feasibility study resulted in the development of an algorithm with the potential to mitigate plan complexity and improve the GPR for VMAT under minor leaf position modifications.

MafA, NeuroD1, and HNF1ß synergistically activate the Slc2a2 (Glut2) gene in ß-cells.

Glucose transporter type 2 (GLUT2), encoded by the SLC2A2 gene, is an essential component of glucose-stimulated insulin secretion in pancreatic islet ß-cells. Like that of the gene encoding insulin, expression of the SLC2A2 gene expression is closely linked to ß-cell functionality in rodents, but the mechanism by which ß-cell-specific expression of SLC2A2 is controlled remains unclear. In this report, to identify putative enhancer elements of the mouse Slc2a2 gene, we examined evolutional conservation of the nucleotide sequence of its genomic locus, together with ChIP-seq data of histone modifications and various transcription factors published in previous studies. Using luciferase reporter assays, we found that an evolutionarily conserved region (ECR) located approximately 40 kbp downstream of the transcription start site of Slc2a2 functions as an active enhancer in the MIN6 ß-cell line. We also found that three ß-cell-enriched transcription factors, MafA, NeuroD1, and HNF1ß, synergistically activate transcription through this 3' downstream distal enhancer (ECR3') and the proximal promoter region of the gene. Our data also indicate that the simultaneous binding of HNF1ß to its target sites within the promoter and ECR3' of Slc2a2 is indispensable for transcriptional activation, and that binding of MafA and NeuroD1 to their respective target sites within the ECR3' enhances transcription. Co-immunoprecipitation experiments suggested that MafA, NeuroD1, and HNF1ß interact with each other. Overall, these results suggest that promoter-enhancer communication through MafA, NeuroD1, and HNF1ß is critical for Slc2a2 gene expression. These findings provide clues to help elucidate the mechanism of regulation of Slc2a2 gene expression in ß-cells.

Appropriate margin for planning target volume for breast radiotherapy during deep inspiration breath-hold by variance component analysis.

BACKGROUND: This study aimed to quantify errors by using a cine electronic portal imaging device (cine EPID) during deep inspiration breath-hold (DIBH) for left-sided breast cancer and to estimate the planning target volume (PTV) by variance component analysis. METHODS: This study included 25 consecutive left-sided breast cancer patients treated with whole-breast irradiation (WBI) using DIBH. Breath-holding was performed while monitoring abdominal anterior-posterior (AP) motion using the Real-time Position Management (RPM) system. Cine EPID was used to evaluate the chest wall displacements in patients. Cine EPID images of the patients (309,609 frames) were analyzed to detect the edges of the chest wall using a Canny filter. The errors that occurred during DIBH included differences between the chest wall position detected by digitally reconstructed radiographs and that of all cine EPID images. The inter-patient, inter-fraction, and intra-fractional standard deviations (SDs) in the DIBH were calculated, and the PTV margin was estimated by variance component analysis. RESULTS: The median patient age was 55 (35-79) years, and the mean irradiation time was 20.4 ± 1.7 s. The abdominal AP motion was 1.36 ± 0.94 (0.14-5.28) mm. The overall mean of the errors was 0.30 mm (95% confidence interval: - 0.05-0.65). The inter-patient, inter-fraction, and intra-fractional SDs in the DIBH were 0.82 mm, 1.19 mm, and 1.63 mm, respectively, and the PTV margin was calculated as 3.59 mm. CONCLUSIONS: Errors during DIBH for breast radiotherapy were monitored using EPID images and appropriate PTV margins were estimated by variance component analysis.

The impact of age on the risk of ipsilateral breast tumor recurrence after breast-conserving therapy in breast cancer patients with a > 5 mm margin treated without boost irradiation.

BACKGROUND: The boost irradiation to the tumor bed following whole-breast irradiation (WBI) reduced the risk of ipsilateral breast tumor recurrence (IBTR). However, in Japan, almost all patients with a margin ≤5 mm receive boost irradiation to the tumor bed, but the decision to perform boost irradiation for those with a margin > 5 mm is dependent on the institution. Thus, institutional guidelines on utilizing boost irradiation for patients aged ≤40 or ≤ 50 years vary. We investigated the IBTR rate to assess the appropriate age for boost irradiation to the tumor bed with a margin > 5 mm. METHODS: From January 1993 to December 2010, 419 patients with early-stage breast cancer and negative margins (> 5 mm) after breast-conserving surgery received WBI without boost irradiation. The Gray test was used to compare the cumulative incidence of IBTR among patients aged ≤40, 41-50, and ≥ 51 years. Hazard ratios were estimated using the Fine and Gray models. Furthermore, as a subgroup analysis, we investigated whether IBTR depended on the use of systemic therapy, such as anthracycline or taxane regimens. RESULTS: The median follow-up time was 9.3 years. In multivariate analysis, only age predicted IBTR (p = 0.047). The 10-year IBTR rate was 15.7% in patients aged ≤40, 3.8% in those aged 41-50, and 2.0% in patients aged ≥51 years. The difference between patients aged ≤40 and 41-50 years was statistically significant (p = 0.045), whereas the difference between patients aged 41-50 and ≥ 51 years was not significant (p = 0.21). CONCLUSIONS: In our institutional surgical setting, when boost irradiation is performed only for patients with a margin ≤5 mm, the IBTR rate after WBI without boost irradiation was significantly higher in patients aged ≤40 years, suggesting that boost irradiation should be used for patients in this age group.

Limited expression of functional cytochrome p450 2c subtypes in the liver and small intestine of domestic cats.

1. Compared to information for herbivores and omnivores, knowledge on xenobiotic metabolism in carnivores is limited. The cytochrome P450 2C (CYP2C) subfamily is recognized as one of the most important CYP groups in human and dog. We identified and characterized CYP2C isoforms and variants in cat, which is an obligate carnivore. 2. Quantitative RT-PCR and immunoblot analyses were carried out to evaluate the expression of CYP2C in the liver and small intestine. A functional CYP2C isoform was heterologously expressed in yeast microsomes to determine the enzymatic activity. 3. Cat had two CYP2C genes, 21 and 41, in the genome; however, CYP2C21P was a pseudogene that had many stop codons. Three splicing variants of CYP2C41 were identified (v1-v3), but only one of them (v1) showed a complete deduced amino acid sequence as CYP2C protein. Transcripts of feline CYP2C41v1 were detected but the amounts were negligible or very small in the liver and small intestine. Immunoreactivity to an antihuman CYP2C antibody was confirmed in the recombinant feline CYP2C41v1 but not in the feline liver. 4. Recombinant feline CYP2C41v1 metabolized several substrates, including dibenzylfluorescein that is specific to human CYP2C. 5. The results suggest a limited role of functional CYP2C isoforms in xenobiotic metabolism in cat.

Dosimetric advantages afforded by a new irradiation technique, Dynamic WaveArc, used for accelerated partial breast irradiation.

PURPOSE: To identify dosimetric advantages of the novel Dynamic WaveArc (DWA) technique for accelerated partial breast irradiation (APBI), compared with non-coplanar three-dimensional conformal radiotherapy (nc3D-CRT) and coplanar tangential volumetric modulated arc therapy (tVMAT) with dual arcs of 45-65°. METHODS: Vero4DRT enables DWA by continuous gantry rotation and O-ring skewing with movement of the multi-leaf collimator. We compared the dose distributions of DWA, nc3D-CRT and tVMAT in 24 consecutive left-sided breast cancer patients treated with APBI (38.5 Gy in 10 fractions). The average doses and volumes to the planning target volume (PTV) and organs at risk, especially heart and left anterior descending artery (LAD) were compared among DWA, nc3D-CRT and tVMAT. RESULTS: The doses and volumes to the PTVs did not differ significantly among the three plans. For the DWA plans, the mean dose to the heart was 0.2 ±â€¯0.1 Gy, less than those of the nc3D-CRT and tVMAT plans. The D2% values of the planning organ at risk volume of the LAD were 9.3 ±â€¯10.9%, 28.2 ±â€¯31.9% and 20.3 ±â€¯25.7% for DWA, nc3D-CRT and tVMAT, respectively. The V20Gy and V10Gy of the ipsilateral lung for the DWA plans were also significantly lower. CONCLUSIONS: DWA allowed to find a better compromise for OAR which overlapped with the PTV. Use of the DWA for APBI improved the dose distributions compared with those of nc3D-CRT and tVMAT.

Estimation of lung tumor position from multiple anatomical features on 4D-CT using multiple regression analysis.

To estimate the lung tumor position from multiple anatomical features on four-dimensional computed tomography (4D-CT) data sets using single regression analysis (SRA) and multiple regression analysis (MRA) approach and evaluate an impact of the approach on internal target volume (ITV) for stereotactic body radiotherapy (SBRT) of the lung. Eleven consecutive lung cancer patients (12 cases) underwent 4D-CT scanning. The three-dimensional (3D) lung tumor motion exceeded 5 mm. The 3D tumor position and anatomical features, including lung volume, diaphragm, abdominal wall, and chest wall positions, were measured on 4D-CT images. The tumor position was estimated by SRA using each anatomical feature and MRA using all anatomical features. The difference between the actual and estimated tumor positions was defined as the root-mean-square error (RMSE). A standard partial regression coefficient for the MRA was evaluated. The 3D lung tumor position showed a high correlation with the lung volume (R = 0.92 ± 0.10). Additionally, ITVs derived from SRA and MRA approaches were compared with ITV derived from contouring gross tumor volumes on all 10 phases of the 4D-CT (conventional ITV). The RMSE of the SRA was within 3.7 mm in all directions. Also, the RMSE of the MRA was within 1.6 mm in all directions. The standard partial regression coefficient for the lung volume was the largest and had the most influence on the estimated tumor position. Compared with conventional ITV, average percentage decrease of ITV were 31.9% and 38.3% using SRA and MRA approaches, respectively. The estimation accuracy of lung tumor position was improved by the MRA approach, which provided smaller ITV than conventional ITV.

Characterization of feline cytochrome P450 2B6.

1. Little is known about drug metabolism in carnivores. Although the domestic cat (Felis catus) is an obligate carnivore and is the most common companion animal, usage and dosage of many drugs are determined according to information obtained from humans and dogs. We determined the complete cDNA sequence of CYP2B6 from the feline lung. 2. Feline CYP2B6 consists of 494 deduced amino acids, showing highest identity with the dog CYP2B ortholog, followed by those of horse, pig, primate and human. 3. Feline CYP2B6 transcripts were expressed predominantly in the lung and slightly in the small intestine but not in the liver without significant sex-dependent differences. Western blot analysis with an anti-human CYP2B6 antibody confirmed the presence of CYP2B protein in the lung but not in the liver. 4. Feline CYP2B6 proteins heterologously expressed in Escherichia coli metabolized several substrates specific to human CYP2B6, including 7-ethoxy-4-(trifluoromethyl) coumarin (EFC). The metabolic activity was strongly inhibited by medetomidine and atipamezole, potent inhibitors of canine CYP2B11 (now officially CYP2B6) as well as by ticlopidine and sertraline, inhibitors selective to human CYP2B6. 5. The results suggest that feline CYP2B6 is a functional CYP2B ortholog that plays a role in the local defense mechanism in the cat respiratory system and intestine.

Successful treatment of three cases of generalized pustular psoriasis with granulocyte and monocyte adsorption apheresis.

Generalized pustular psoriasis (GPP) is a rare form of psoriasis characterized by the presence of variable numbers of sterile pustules appearing in erythematous and scaly lesions, which are associated with moderate to severe constitutional symptoms. It can be life-threatening especially in the elderly; therefore, medical care must be performed in rapid succession of treatment especially in refractory cases. We have performed granulocyte and monocyte adsorption apheresis (GCAP) on three GPP cases associated with several systemic and laboratory findings. As a result, the edema, erythema and numbers of sterile pustules on the skin lesions were reduced dramatically in all three patients after the first sessions of GCAP therapy. The sizes of the psoriatic lesions were reduced in all three patients following a weekly GCAP treatment for 5 consecutive weeks. Psoriasis area and severity index on discharge had improved in all three patients. No serious adverse effects were observed for up to at least 8 months after treatment. We therefore considered GCAP as one effective alternative to currently existing therapies, especially for recalcitrant cases of GPP.

[Antimicrobial susceptibilityof clinical isolates of aerobic gram-negative bacteria in 2008].

We determined MICs of antibacterial agents against 1145 clinical strains of aerobic Gram-negative bacteria (22 species) isolated at 16 Japanese facilities in 2008. MICs were determined using mostly broth microdilution method and antibacterial activity was assessed. Strains producing extended-spectrum beta-lactamases (ESBL) accounted for 3.8% of Escherichia coli, 2.6% of Klebsiella pneumoniae, 6.8% of Klebsiella oxytoca, 5.5% of Proteus mirabilis and 1.8% of Proteus vulgaris. ESBL produced strains were 6.8% at K. oxytoca that increased compared with 3.2% and 5.5% at P. mirabilis that decreased compared with 18.8% in 2006. Among Haemophilus influenzae, 61.7% that decreased compared with 67.7% in 2006, equaled 58.7% in 2004, were strains when classified by penicillin-binding protein 3 mutation. Against Pseudomonas aeruginosa, the activity of most antibacterial agents was similar to that in 2006. Although two antibacterial agents that tobramycin showed an MIC90 of 1 microg/mL and doripenem showed an MIC90 of 4 microg/mL against P. aeruginosa have potent activity. Of all P. aeruginosa strains, 4.3% were resistant to six agents of nine antipseudomonal agents, that decreased compared to 12.2% in 2004 and 5.7% in 2006. Against other glucose-non-fermentative Gram-negative rods, the activity of most antibacterial agents was similar to that in 2006.

[Antimicrobial susceptibility of clinical isolates of aerobic gram-positive cocci and anaerobic bacteria in 2008].

The activity of antibacterial agents against aerobic Gram-positive cocci (25 genus or species, 1029 strains) and anaerobic bacteria (21 genus or species, 187 strains) isolated from clinical specimens in 2008 at 16 clinical facilities in Japan were studied using either broth microdilution or agar dilution method. The ratio of methicillin-resistant strains among Staphylococcus aureus and Staphylococcus epidermidis was 59.6% and 81.2%, suggesting that resistant strains were isolated at high frequency. Vancomycin (VCM), linezolid (LZD) and quinupristin/dalfopristin (QPR/DPR) had good antibacterial activity against methicillin-resistant S. aureus and methicillin-resistant S. epidermidis, with MIC90s of < or = 2 microg/mL. The ratio of penicillin (PC) intermediate and resistant strains classified by mutations of PC-binding proteins among Streptococcus pneumoniae was 92.0% that was highest among our previous reports. Cefpirome, carbapenems, VCM, teicoplanin (TEIC), LZD and QPR/DPR had MIC90s of < or = 1 microg/mL against PC-intermediate and resistant S. pneumoniae strains. Against all strains of Enterococcus faecalis and Enterococcus faecium, the MICs of VCM and TEIC were under 2 microg/mL, and no resistant strain was detected, suggesting that these agents had excellent activities against these species. 15.9% of E. faecalis strains and 1.2% of E. faecium strains showed intermediate to LZD. 17.1% of E. faecium strains showed intermediate or resistant to QPR/DPR. Against all strains of Clostridium difficile, the MIC of VCM was under 1 microg/mL, suggesting that VCM had excellent activity. Carbapenems showed good activity against Clostridiales, Bacteroides spp., and Prevotella spp., but one strain of Bacteroides fragilis showed resistant to carbapenems. And so, the susceptibility of this species should be well-focused in the future at detecting continuously.

[Antimicrobial susceptibility of clinical isolates of aerobic Gram-positive cocci and anaerobic bacteria in 2006].

The activity of antibacterial agents against aerobic Gram-positive cocci (26 species, 1022 strains) and anaerobic bacteria (23 species, 184 strains) isolated from clinical specimens in 2006 at 16 clinical facilities in Japan were studied using either broth microdilution or agar dilution method. The ratio of methicillin-resistant strains among Staphylococcus aureus and Staphylococcus epidermidis was 53.0% and 65.8%, suggesting that resistant strains were isolated at high frequency. Vancomycin (VCM) and quinupristin/dalfopristin (QPR/DPR) had good antibacterial activity against methicillin-resistant S. aureus and methicillin-resistant S. epidermidis, with MIC90s of < or = 2 micrcog/mL. The ratio of penicillin (PC) intermediate and resistant strains classified by mutations of PC-binding proteins among Streptococcus pneumoniae was 87.6%. Ceftriaxone, cefpirome, cefepime, carbapenem antibiotics, VCM, teicoplanin, linezolid(LZD) and QPR/DPR had MIC90s of < or = 1 microg/mL against PC-intermediate and resistant S. pneumoniae strains. Against all strains of Enterococcus faecalis and Enterococcus faecium, the MICs of VCM and TEIC were under 2 microg/mL, and no resistant strain was detected, suggesting that these agents had excellent activities against these species. 10.9% of E. faecalis strains or 3.5% of E. faecium strains showed intermediate or resistant to LZD. 24.4% of E. faecium strains showed intermediate or resistant to QPR/DPR. Against all strains of Clostridium difficile, the MIC of VCM were under 1 microg/mL, suggesting that VCM had excellent activity against C. difficile. Carbapenems showed good activity against Peptococcaceae, Bacteroides spp., and Prevotella spp. However since several strains of Bacteroides fragilis showed resistant to carbapenems and the susceptibility of this species should be well-focused in the future.

[Antimicrobial susceptibility of clinical isolates of aerobic Gram-negative bacteria in 2006].

We determined MICs of antibacterial agents against 1280 clinical strains of aerobic Gram-negative bacteria (19 genus or species) isolated at 16 Japanese facilities in 2006. MICs were determined using mostly broth microdilution method and antibacterial activity was assessed. Strains producing extended-spectrum beta-lactamases (ESBL) accounted for 3.7% of Escherichia coli, 2.7% of Klebsiella spp., and 11.4% of Proteus spp. Notably, 18.8% of Proteus mirabilis was found to produce ESBL higher than 16.7% in 2004. This result was higher extremely than other species. Among Haemophilus influenzae, only 1.2% produced beta-lactamase and 62.8% that increased compared with 57.7% in 2004, were beta-lactamase-negative ampicillin-resistant strains when classified by penicillin-binding protein 3 mutation. Although few antibacterial agents against Pseudomonas aeruginosa have potent activity, only three agents--doripenem, ciprofloxacin, and tobramycin-showed an MIC90 of 4 microg/mL. Of all P aeruginosa strains, 5.7% were resistant to six or more agents of nine antipseudomonal agents, a decrease compared to 8.7% in 2004. Against other glucose-non-fermentative Gram-negative bacteria, the activity of most antibacterial agents was similar to that in 2004.