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Objectives: Linezolid is an antibiotic used to treat infectious diseases caused by vancomycin-resistant enterococci and methicillin-resistant Staphylococcus aureus. Recently, Enterococcus Spp.-carrying mobile linezolid resistance genes were reported. Herein, we report the complete genome sequence of Enterococcus raffinosus JARB-HU0741, which was isolated from a bile sample of a patient in Japan on May 5, 2021, and carries a linezolid resistance gene, cfr(B). Nevertheless, this isolate was susceptible to linezolid., Methods: Whole-genome sequencing was performed using HiSeq X FIVE (Illumina) and GridION (Oxford Nanopore Technologies). The sequence reads were assembled using Unicycler v0.4.8, and the complete genome was annotated using DFAST v1.2.18. Antimicrobial resistance genes were detected with Abricate v1.0.1, using the ResFinder database. The minimum inhibitory concentrations (MICs) were determined using broth microdilution and interpreted according to the guidelines of the Clinical and Laboratory Standards Institute., Results: E. raffinosus JARB-HU0741 contained a 3 248 808-bp chromosome and a 1 156 277-bp megaplasmid. cfr(B) was present in the Tn6218-like transposon, which was inserted into a gene encoding a PRD domain-containing protein present in the megaplasmid, but the isolate was susceptible to linezolid (MIC, 0.5 µg/mL). The Tn6218-like transposon was similar to the Tn6218 of Clostridioides difficile Ox3196 and the Tn6218-like transposon of Enterococcus faecium UW11733; however, three genes encoding a topoisomerase, an S-adenosylmethionine-dependent methyltransferase, and a TetR family transcriptional regulator were present in the previous Tn6218- or Tn6218-like transposon., Conclusion: This is the first report of the complete genome sequence of E. raffinosus carrying cfr(B). E. raffinosus carrying cfr(B) without linezolid resistance poses a threat, as it could serve as a reservoir for mobile linezolid resistance genes., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Objectives: The occurrence of linezolid resistance in enterococci has recently increased. Here, we report the genomic characterization of Enterococcus faecalis strain JARB-HU0796-isolated from the open pus of a patient in Hiroshima, Japan-which shows nonsusceptibility to linezolid (MIC of 4 µg/mL)., Methods: JARB-HU0796 whole-genome sequencing was performed using short-read sequencing with Illumina Hiseq X Five and long-read sequencing using GridION. These reads were collected using the assembly pipeline Unicycler and annotated with DFAST. Antimicrobial resistance genes were detected using the Abricate and ResFinder databases, and the sequence type identified using PubMLST. The antimicrobial susceptibility of JARB-HU0796 was determined with the Eiken dry-plate QH02 system., Results: The JARB-HU0796 complete genome contained a circular chromosome (2 722 585 bp) and two circular plasmids (85 996 bp and 58 872 bp). The chromosome harbours the optrA gene, which confers resistance to oxazolidinones and phenicols. JARB-HU0796 showed nonsusceptibility to linezolid and multidrug resistance to other antibiotics. MLST analysis identified JARB-HU0796 as ST476, similar to the optrA-positive E. faecalis ST476 isolates from swine (South Korea, 2020) and pet food (Switzerland, 2022). The optrA region of JARB-HU0796 is nearly identical to that of ST476 E. faecalis strain TZ2, isolated from humans (China, 2013)., Conclusions: To the best of our knowledge, this is the first report of the complete genome sequence of E. faecalis ST476 carrying optrA on a chromosome isolated from a patient in Japan. The strain may have originated in animals, suggesting that the organisms acquired resistance to linezolid because the optrA gene may be closely spread between animals and humans., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Mycoplasma hominis , Ureaplasma parvum , and Ureaplasma urealyticum are commensal bacteria that are associated with colonization and infection of the urogenital tract. However, colonization of the respiratory tract by these microorganisms in adults has not been fully investigated., Methods: Urine and respiratory tract samples (sputum, tracheal aspirates, and bronchoalveolar lavage) of patients aged 20-80 years were analyzed to detect the presence of M. hominis , U. parvum , and U. urealyticum using a conventional PCR method. The samples were submitted to the microbiological clinical laboratory of Hiroshima University Hospital from December 1, 2021 to May 31, 2022., Results: In total, 334 urine and 238 respiratory tract samples were analyzed. The overall detection rates of M. hominis , U. parvum , and U. urealyticum were 2.9%, 1.7%, and 2.3% in male urine; 7.0%, 13.8%, and 1.9% in female urine; 2.2%, 0%, and 2.2% in male respiratory tract; and 0%, 2.0%, and 0% in female respiratory tract, respectively. In urine samples, the detection rates of M. hominis , U. parvum , and U. urealyticum were significantly higher (p < 0.001) for women (29/159; 18.2%) than for men (10/175; 5.7%); however, in respiratory tract samples, the detection rates were not significantly different (p = 0.70) between women (2/101; 2.0%) and men (5/137; 3.7%). Further, both the urine and respiratory samples of 83 patients were analyzed. Three male samples were positive for M. hominis or U. urealyticum , and M. hominis and U. urealyticum were matched in both the urine and respiratory tract samples: M. hominis (n = 1), U. urealyticum (n = 1), M. hominis  +  U. urealyticum (n = 1)., Conclusion: M. hominis , U. parvum , and U. urealyticum were detected in the respiratory tract of not only the young patients, but also of patients aged 50-60 years. Further studies are required to understand the relationship of these microorganisms in urogenital and respiratory tract samples with extra-genital infections., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors.)

Clinical isolates of Clostridioides difficile sometimes exhibit multidrug resistance and cause diarrhea after antibiotic administration. Metronidazole and vancomycin are often used as therapeutic agents, but resistance to these antibiotics has been found clinically. Therefore, the development of alternative antimicrobial agents is needed. Nisin A, produced by Lactococcus lactis, has been demonstrated to be effective against C. difficile infection. In this study, we evaluated the susceptibility of 11 C. difficile clinical isolates to nisin A and found that they could be divided into 2 groups: high and low susceptibility. Since CprABC and DltDABC, which are responsible for nisin A efflux and cell surface charge, respectively, have been reported to be related to nisin A susceptibility, we investigated the expression of cprA and dltA among the 11 strains. cprA expression in all strains was induced by nisin A, but dltA expression was not. The expression levels of both genes did not correlate with nisin A susceptibility in these clinical isolates. To evaluate cell surface charge, we performed a cytochrome C binding assay and found no relationship between charge and nisin A susceptibility. Then, we determined the whole genome sequence of each clinical isolate and carried out phylogenetic analysis. The 11 isolates separated into two major clusters, which were consistent with the differences in nisin A susceptibility. Furthermore, we found common differences in several amino acids in the sequences of CprA, CprB, and CprC between the two clusters. Therefore, we speculated that the different amino acid sequences of CprABC might be related to nisin A susceptibility. In addition, C. difficile strains could be divided in the same two groups based on susceptibility to epidermin and mutacin III, which are structurally similar to nisin A. These results suggest that genotypic variations in C. difficile strains confer different susceptibilities to bacteriocins., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Ide et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Purpose: Tumor-infiltrating lymphocytes (TILs) are known to predict the therapeutic effect in breast cancer. Although a preoperative tissue biopsy can be used to evaluate TILs, TILs that are heterogeneously distributed might require examination of all preoperative tissue biopsy samples. We have recently reported that the TIL ultrasonography (US) score, as determined by characteristic US findings, provides excellent predictive performance for lymphocyte predominant breast cancer (LPBC). We herein aimed to determine whether the preoperative TIL-US score can more accurately predict LPBC than preoperative tissue biopsy., Methods: We assessed 161 patients with invasive breast cancer that were treated with curative surgery between January 2014 and December 2017. Stromal lymphocytes were examined on preoperative tissue biopsy tissues and surgical pathological specimens. Breast cancer samples with ≥ 50% stromal TILs were defined as pre-LPBC (preoperative tissue biopsy) and LPBC (surgical pathological specimens). Useful factors for predicting LPBC were searched among clinicopathological factors., Results: The TIL-US score cutoff value for predicting LPBC was 4 points based on the receiver operating characteristic curves (area under the curve: 0.88). Several significant predictors for LPBC were revealed by the undertaken multivariate logistic regression analysis (odds ratios: TIL-US score, 26.8; pre-LPBC, 18.6; HER2, 9.2; all, p < 0.05). The sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 0.74, 0.89, 0.85, 0.67, and 0.92 for the TIL-US score, respectively, and 0.51, 0.98, 0.87, 0.91, and 0.86 for the pre-LPBC, respectively., Conclusion: TIL-US scores can predict LPBC preoperatively and are characterized by a significantly high sensitivity and negative predictive value., (© 2022. The Author(s), under exclusive licence to The Japan Society of Ultrasonics in Medicine.)

We retrospectively analyzed seven patients with Actinotignum schaalii bacteremia in a tertiary hospital in Japan. Pyelonephritis was the most frequent source of bacteremia, followed by Fournier's gangrene and pyometra. All patients with pyelonephritis had underlying urological conditions, ureteral stents, nephrostomy, ureteral stones, or ureterocele., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Several factors related to anti-spike(S) IgG antibody titers after mRNA COVID-19 vaccination have been elucidated, but the magnitude of the effects of each factor has not been fully understood. This cross-sectional study assessed anti-S and anti-nucleocapsid (N) antibody titers on 3744 healthy volunteers (median age, 36 years; IQR, 24-49 years; females, 59.0%) who received two doses of mRNA-1273 or BNT162b2 vaccine and completed a survey questionnaire. Multiple regression was conducted to identify factors associated with antibody titers. All but one participant tested positive for anti-S antibodies (99.97%). The following factors were independently and significantly associated with high antibody titer: < 3 months from vaccination (ratio of means 4.41); mRNA-1273 vaccine (1.90, vs BNT162b2); anti-N antibody positivity (1.62); age (10's: 1.50, 20's: 1.37, 30's: 1.26, 40's: 1.16, 50's: 1.15, vs ≧60's); female (1.07); immunosuppressive therapy (0.54); current smoking (0.85); and current drinking (0.96). The largest impact on anti-S IgG antibody titers was found in elapsed time after vaccination, followed by vaccine brand, immunosuppressants, previous SARS-CoV-2 infection (anti-N antibody positive), and age. Although the influence of adverse reactions after the vaccine, gender, smoking, and drinking was relatively small, they were independently related factors., (© 2022. The Author(s).)

Background: This longitudinal study aimed to determine chronological changes in the seroprevalence of prior SARS-CoV-2 infection, including asymptomatic infections in Hiroshima Prefecture, Japan., Methods: A stratified random sample of 7,500 residents from five cities of Hiroshima Prefecture was selected to participate in a three-round survey from late 2020 to early 2021, before the introduction of the COVID-19 vaccine. The seroprevalence of anti-SARS-CoV-2 antibodies was calculated if at least two of four commercially available immunoassays were positive. Then, the ratio between seroprevalence and the prevalence of confirmed COVID-19 cases in Hiroshima was calculated and compared to the results from other prefectures where the Ministry of Health, Labour and Welfare conducted a survey by using the same reagents at almost the same period., Results: The numbers of participants in the first, second, and third rounds of the survey were 3025, 2396, and 2351, respectively and their anti-SARS-CoV-2 antibodies seroprevalences were 0.03% (95% confidence interval: 0.00-0.10%), 0.08% (0.00-0.20%), and 0.30% (0.08-0.52%), respectively. The ratio between the seroprevalence and the prevalence of confirmed COVID-19 cases in Hiroshima was 1.2, which was smaller than that in similar studies in other prefectures., Conclusions: The seroprevalence of anti-SARS-CoV-2 antibodies in Hiroshima increased tenfold in a half year. The difference between seroprevalence and the prevalence of confirmed COVID-19 cases in Hiroshima was smaller than that in other prefectures, suggesting that asymptomatic patients were more actively detected in Hiroshima.

Eggerthella lenta is an important cause of anaerobic bloodstream infections and is associated with high mortality. However, there are few reports of E. lenta infection in Japan. This study aimed to evaluate the clinical and microbiological characteristics of bacteremia caused by E. lenta in Hiroshima, Japan. We retrospectively analyzed E. lenta bacteremia patients at the Hiroshima University Hospital between January 2012 and December 2020. During the study period, 14 patients with E. lenta bacteremia were identified. All E. lenta isolates were cultured in anaerobic bottles, and the median time to blood culture positivity was 52.9 h. In most cases (85.6%), the source of E. lenta bacteremia was associated with intra-abdominal infections, and colon perforation was the most frequent source of E. lenta bacteremia (42.9%, n = 6). Antimicrobial susceptibility testing showed high minimal inhibitory concentrations (MIC) of piperacillin-tazobactam (TZP) and 100% susceptibility to ampicillin-sulbactam, carbapenems, and metronidazole. This study demonstrates that E. lenta bacteremia is associated with intra-abdominal infections, particularly colon perforation, and a high MIC of TZP. When gram-positive anaerobes are detected in the blood cultures of patients with severe intra-abdominal infections, clinicians should suspect E. lenta, and it may be better to change antimicrobial agents from TZP., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: We investigated whether contrast-enhanced ultrasonography (CEUS) scores can predict lymphocyte-predominant breast cancer (LPBC)., Patients and Methods: We evaluated 75 patients who underwent US and CEUS. LPBC was defined as tissues with ≥50% stromal tumour-infiltrating lymphocytes (TILs) preoperatively. Characteristic US images predicting LPBC were evaluated using TIL-US scores via three ultrasonic tissue characteristics: Shape, internal echo level, and posterior echoes. TIL-CEUS was evaluated based on TIL-US plus CEUS., Results: TIL-US and TIL-CEUS cut-offs for predicting LPBC were 4 and 6 (area under the curve=0.93 and 0.96, respectively) points based on receiver operating characteristics curves. Sensitivity, specificity, and accuracy values (95% confidence intervaI) were 0.94 (0.77-0.99), 0.75 (0.70-0.77), and 0.80 (0.72-0.82); and 0.94 (0.78-0.99), 0.86 (0.81-0.87), and 0.88 (0.80-0.90) for TIL-US and TIL-CEUS, respectively. TIL-CEUS score was a significant single predictor for LPBC in multivariate logistic regression (p=0.001)., Conclusion: TIL-CEUS can be used for preoperative LPBC prediction and detection., Competing Interests: The Authors declare that they have no conflicts of interest., (Copyright 2021, International Institute of Anticancer Research.)

The urinary antigen test (UAT) is a rapid diagnostic method for pneumococcal pneumonia, but the high false-negative rate of 30% may affect its reliability. To maximize the utility of UAT, it is necessary to investigate the patient factors affecting UAT results. However, there is no report elucidating the association between its utility and pre-existing lung abnormalities. We retrospectively reviewed 388 patients with pneumococcal pneumonia confirmed by blood and/or sputum culture tests. Finally, 94 of 388 patients who had the results of UAT and computed tomography scans were enrolled to evaluate the association between the utility of UAT and patient factors including pulmonary emphysema and fibrosis. The overall positive rate of UAT was 69.1%. The positive rates of UAT in the patients with emphysema were significantly lower than those in individuals without emphysema (33.3% and 77.6%, p < 0.001). Univariate logistic regression analysis showed that the presence of emphysema was associated with a low positive rate (odds ratio 6.944, 95% confidence interval 2.268-21.231). Multivariate logistic analysis showed that the presence of emphysema and lower levels of serum blood urea nitrogen (BUN) were significantly and independently associated with a low positive rate. The combination of emphysema and BUN can potentially stratify the positive rate of UAT in patients with pneumococcal pneumonia. Patients with pneumococcal pneumonia and emphysema have a lower positive rate of UAT. Additionally, the combination of emphysema and serum BUN value may be useful to evaluate the reliability of the negative results of pneumococcal UAT.

Background: Evaluation of fibrosis stage is important to monitor progression of liver disease and risk of hepatocellular carcinoma (HCC). While liver biopsy is the gold standard, the method is invasive and faces several limitations. The aim of this study was to determine correlations among METAVIR scores and FibroScan, Virtual-Touch tissue quantification (VTQ), fibrosis index based on four factors (FIB-4 index), and Mac-2 binding protein glycosylation isomer (M2BPGi) level, and for examine differences in the reliability of non-invasive methods to evaluate fibrosis., Methods: We used liver resection specimens from patients with hepatitis C virus (HCV), correlations were assessed between METAVIR scores and non-invasive method. Receiver operating characteristic (ROC) curves were generated to determine the sensitivity, specificity, and cut off values of the methods., Results: All Patients group: In F0-2 vs F3-4, the areas under the ROC curve (AUC) (0.85) of FibroScan was significantly higher than that (0.67) of FIB-4 index (p = 0.002) and that (0.67) of M2BPGi (p = 0.001). The AUC (0.83) of VTQ was significantly higher than that (0.67) of FIB-4 index (p = 0.01) and that (0.67) of M2BPGi (p = 0.002). In F0-3 vs F4, the AUC (0.86) of VTQ was significantly higher than that (0.65) of FIB-4 index (p = 0.04). The AUC (0.89) of FibroScan was significantly higher than that (0.65) of FIB-4 index (p = 0.002) and that (0.76) of M2BPGi (p = 0.02). Non-SVR group: In F0-2 vs F3-4, the AUC (0.85) of FibroScan was significantly higher than that (0.84) of FIB-4 index (p = 0.02) and that (0.73) of M2BPGi (p = 0.003). The AUC (0.84) of VTQ was significantly higher than that (0.74) of FIB-4 index (p = 0.04). In F0-3 vs F4, the AUC (0.91) of FibroScan was significantly higher than that (0.67) of FIB-4 index (p = 0.003) and that (0.78) of M2BPGi (p = 0.02). The AUC (0.88) of VTQ was significantly higher than that of FIB-4 index (0.67) and that of M2BPGi (0.78) (p = 0.04)., Conclusions: FibroScan and VTQ best reflected the results of hepatic fibrosis diagnosis using liver resection specimens among the four examination methods evaluated.

Background: The presence of tumor-infiltrating lymphocytes (TILs) is a prognostic factor for breast cancer. However, because of tumor tissue heterogeneity, an accurate and simple evaluation method is needed. We determined if preoperative characteristic ultrasonography (US) image findings are predictive of lymphocyte-predominant breast cancer (LPBC)., Methods: We evaluated 191 patients with invasive breast cancer treated by curative surgery between January 2014 and December 2017. Stromal lymphocytes in surgical pathological specimens were evaluated. Fifty-two patients with ≥ 50% stromal TILs were defined as having LPBC. Preoperative US images were examined for indicators of TILs. The US images with characteristic TILs were scored for prediction of LPBC., Results: Shape (more lobulated), internal echo level (weaker), and posterior echoes (stronger) were predictors of LPBC and used to assign the TILs-US scores (0-7 points); the score cutoff for predicting LPBC was 4 points (sensitivity, 0.73; specificity, 0.87; accuracy, 0.83) based on the receiver operating characteristics (ROC) curves (AUC 0.88). Multivariate logistic regression analysis identified nuclear grade (NG), OR 3.4; estrogen receptor (ER), OR 5.7; human epidermal growth factor receptor type-2 (HER2), OR 4.1; and TILs-US score, OR 14.9 as LPBC predictors (all, p < 0.05). The sensitivity, specificity, and accuracy for predicting LPBC were 0.75, 0.69, and 0.71 for NG and 0.33, 0.96, and 0.79 for ER and HER2, respectively. ROC analysis showed that the diagnostic abilities of NG, ER, and HER2 were lower than that of the TILs-US score., Conclusions: LPBC showed characteristic US imaging findings. The TILs-US score was an accurate preoperative predictor of LPBC.

Background: Wisteria floribunda agglutinin positive human Mac-2-binding protein glycosylation isomer (M2BPGi) is a novel serum glycomarker for liver fibrosis. However, it is not known whether or not M2BPGi reflects only liver fibrosis. We measured serum M2BPGi levels in patients with acute liver injury., Methods: Fifty-one patients with acute liver injury were enrolled. M2BPGi levels were measured at the initial visit and at achievement of recovery. The relationship between M2BPGi values at the initial visit and clinical outcomes was analyzed., Results: Serum M2BPGi levels at the initial visit were elevated in 47 of 51 acute liver injury patients (8.33 ± 7.56 cutoff index). M2BPGi values were associated with prothrombin activity (r = -0.600, P = 0.001), total bilirubin level (r = 0.588, P = 0.001), and Model for End-Stage Liver Disease score (r = 0.490, P = 0.001) but not with aspartate aminotransferase (r = -0.070) and alanine aminotransferase (r = -0.073) levels. M2BPGi values at the initial visit were significantly higher in patients with acute liver failure (diagnosed by prothrombin activity of 40% or less; P < 0.001), subsequent development of hepatic coma (P = 0.036), and subsequent requirement of liver transplant (P = 0.014), and in a patient who died (P = 0.045). M2BPGi values decreased after aminotransferase level normalization in patients who recovered from acute liver injury; however, M2BPGi level was not a predictive factor for recovery with medical therapy., Conclusions: Serum M2BPGi values increased in patients with acute liver injury and decreased following recovery. The marker seems to reflect not only liver fibrosis but also other factors, such as liver inflammation, liver damage, and hepatocyte regeneration.

Vascular and/or perivascular involvements of sclerotic inflammation (perivasculitis) are a complication of immunoglobulin G4-related disease (IgG4-RD). We sought to examine clinical manifestations of perivasculitis by computed tomography (CT) in patients with elevated serum IgG4 levels, and then to evaluate some potential predictors of perivasculitis in definite IgG4-RD patients. From a database of patients with serum IgG4 measurements, we selected 81 patients with elevated serum IgG4 levels (≥135 mg/dl). Perivasculitis was defined radiologically as thickened contrast-enhanced rind surrounding the aorta and its major artery on CT imaging. We found 15 patients with perivasculitis; 10 patients in the definite (n = 37), four in the possible (n = 18), and one in the excluded (n = 26) IgG4-RD groups. Clinical predictors of perivasculitis were investigated in 34 untreated patients with definite IgG4-RD. Patients with perivasculitis (n = 10) had significantly higher age at diagnosis (74.2 ± 8.8 vs 63.5 ± 9.9 years, P = 0.006), higher levels of serum IgG4 (754 vs 292 mg/dl, P = 0.007) and C-reactive protein (CRP, 0.52 mg/dl vs 0.10 mg/dl, P = 0.001) than patients without perivasculitis (n = 24). The sensitivity and specificity of serum CRP ≥0.25 mg/dl for identifying perivasculitis in the definite IgG4-RD group were 100 and 71%, respectively (area under the receiver operating characteristic curve 0.863). Our results indicate that IgG4-related perivasculitis was associated with elevated levels of serum CRP and older age, and that CRP may be a useful marker for detecting perivascular involvement in IgG4-RD.

We have determined the DNA sequence of Klebsiella pneumoniae multidrug resistance plasmid pKPI-6, which is a self-transmissible IncN-type plasmid. pKPI-6 harboring blaIMP-6 and blaCTX-M-2 confers a stealth-type carbapenem resistance phenotype on members of the family Enterobacteriaceae that is not detectable with imipenem. pKPI-6 is already epidemic in Japan, favoring the dissemination of IMP-6 and CTX-M-2 in members of the family Enterobacteriaceae., (Copyright © 2015, American Society for Microbiology. All Rights Reserved.)

This in vitro study examined the combined effects of double antibacterial drugs against multidrug-resistant Pseudomonas aeruginosa (MDRP). The tested clinical isolates from Hiroshima University Hospital were 40 strains which met the criteria for MDRP, that is, the minimum inhibitory concentration (MIC) was > or = 16 microg/mL of meropenem, > or = 4 microg/mL of ciprofloxacin and > or = 32 microg/mL of amikacin. Using the original checkerboard plates for colistin (CL), arbekacin (ABK), aztreonam (AZT), rifampicin (RFP) and piperacillin (PIPC), MIC values were determined for single and double combinations. Based on the MIC values, fractional inhibitory concentration index values were calculated and the combined effects (synergy action or additive action) were evaluated. The three strongest drugs among the tested combinations were i) CL + RFP (synergy, 80.0%; additive, 17.5%), ii) RFP + ABK (synergy, 7.5%; additive, 70.0%) and iii) RFP + AZT (synergy, 5.0%; additive, 77.5%). In these cases, the arithmetic mean MIC value of each drug significantly decreased as follows: i) 1.38 microg/mL (alone) and 0.26 microg/mL (with RFP) for CL, 19.85 microg/mL (alone) and 1.85 microg/mL (with CL) for RFP; ii) 19.85 microg/mL (alone) and 7.53 microg/mL (with ABK) for RFP, 8.87 microg/mL (alone) and 2.79 microg/mL (with RFP) for ABK; iii) 19.85 microg/mL (alone) and 10.15 microg/mL (with AZT) for RFP, 28.3 microg/ mL (alone) and 6.65 microg/mL (with RFP) for AZT. Of 40 strains, metallo-beta-lactamase and aminoglycoside 6'-N-acetyltransferase were found in 20 and 37 strains, respectively; however, no significant influence of these factors was observed on the combined effects of i), ii) and iii). The results of this study provide an in vitro rationale for RFP plus CL, ABK or AZT as an effective combination therapy for MDRP infections, although the results should be verified and compared with other antibacterial drugs in further studies.

The nationwide surveillance of antibacterial susceptibility to meropenem (MEPM) and other parenteral antibiotics against clinical isolates during 2012 in Japan was conducted. A total of 2985 strains including 955 strains of Gram-positive bacteria, 1782 strains of Gram-negative bacteria, and 248 strains of anaerobic bacteria obtained from 31 medical institutions were examined. The results were as follows; 1. MEPM was more active than the other carbapenem antibiotics tested against Gram-negative bacteria, especially against enterobacteriaceae and Haemophilus influenzae. MEPM was also active against most of the species tested in Gram-positive and anaerobic bacteria, except for multi-drug resistant strains including methicillin-resistant Staphylococcus aureus (MRSA). 2. Of all species tested, there were no species, which MIC90 of MEPM was more than 4-fold higher than those in our previous studies in 2009 or 2006. Therefore, the tendency to increase in antimicrobial resistance rates was not observed. 3. MEPM resistance against Pseudomonas aeruginosa was 17.8% (56/315 strains). Compared to our previous results, it was the lowest than that in 2006 and 2009. 4. Carbapenem-resistant Klebsiella pneumoniae, and multi-drug-resistant Acinetobacter species, which emerged in worldwide, were not observed. 5. The proportion of extended-spectrum beta-lactamase (ESBL) strains was 6.2% (59/951 strains) in enterobacteriaceae, which increased compared with that of our previous studies in 2009 or before. Whereas, the proportion of metallo-beta-lactamase strains was 1.6% (5/315 strains) in P. aeruginosa, which was stable. In conclusion, the results from this surveillance suggest that MEPM retains its potent and broad antibacterial activity and therefore is a clinically useful carbapenem for serious infections treatment at present, 17 years passed after available for commercial use in Japan.

Filamentous fungi were detected in the blood culture of a one-year-old boy after autologous peripheral blood stem cell transplantation. The patient was suspected to have aspergillosis and received micafungin. Fungi were isolated on potato dextrose agar medium and incubated at 37℃ for 2-5 days. Grayish, cottony colonies formed. A slide culture showed a spherical sporangium at the tips of the sporangiophores. The fungus could have been a zygomycete. The zygomycete was isolated from three blood cultures. The antifungal drug was changed from micafungin to liposomal amphotericin B, which resulted in an improvement in the patient's symptoms. Growth was observed at 37℃, but not 42℃ in a growth temperature test. Gene sequence analysis identified the fungus as Mucor velutinosus. To the best of our knowledge, this is the first time M. velutinosus has been detected in Japan, and this case is very rare. Zygomycetes are known to be pathogens that cause fungal infections in immunodeficient patients such as those with leukemia. They are difficult to identify by culture and are identified at autopsy in many cases. Therefore, culture examinations should be performed for immunodeficient patients with the consideration of zygomycetes.

Klebsiella pneumoniae resistant to almost all ß-lactams except imipenem designated as ISMRK (imipenem-susceptible meropenem-resistant Klebsiella) is emerging in Japan. All ISMRK carries bla(IMP-6) which differs from bla(IMP-1) by only a single nucleotide at position 640. We devised a rapid detection system of bla(IMP-6) by using ARMS PCR., (Copyright © 2011 Elsevier B.V. All rights reserved.)

We identified 5 Klebsiella pneumoniae isolates showing high resistance to β-lactams except imipenem and designated them ISMRK (imipenem-susceptible but meropenem-resistant Klebsiella). They carried the bla(IMP-6) and bla(CTX-M-2) on a self-transmissible plasmid. ISMRK may be falsely categorized as susceptible to carbapenems if imipenem is used to screen carbapenem resistance., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The antibacterial activity of meropenem (MEPM) and other parenteral antibiotics against clinical isolates of 2655 strains including 810 strains of Gram-positive bacteria, 1635 strains of Gram-negative bacteria, and 210 strains of anaerobic bacteria obtained from 30 medical institutions during 2009 was examined. The results were as follows; (1) MEPM was more active than the other carbapenem antibiotics tested against Gram-negative bacteria, especially against enterobacteriaceae and Haemophilus influenzae. MEPM was also active against most of the species tested in Gram-positive and anaerobic bacteria, except for multidrug resistant strains including methicillin-resistant Staphylococcus aureus (MRSA). (2) MEPM maintained potent and stable antibacterial activity against Pseudomonas aeruginosa. The proportion of MEPM-resistant strains to ciprofloxacin-resistant strains or imipenem-resistant strains were 53.1% and 58.0% respectively. (3) The proportion of extended-spectrum beta-lactamase (ESBL) strains was 3.1% (26 strains) in enterobacteriaceae. And the proportion of metallo-beta-lactamase strains was 2.0% (6 strains) in P. aeruginosa. (4) Of all species tested, there were no species except for Bacteroides fragilis group, which MIC90 of MEPM was more than 4-fold higher than those in our previous study. Therefore, there is almost no significant decrease in susceptibility of clinical isolates to meropenem. In conclusion, the results from this surveillance study suggest that MEPM retains its potent and broad antibacterial activity and therefore is a clinically useful carbapenem for serious infections treatment at present, 14 years passed after available for commercial use in Japan.

Background: With the prevalence of Helicobacter pylori (H. pylori) infection rapidly decreasing in Japan, endoscopic findings and dyspeptic symptoms need to be re-evaluated., Methods: In a health check-up program, endoscopy was performed on 530 young Japanese subjects (371 men and 159 women) born in the 1970s. Helicobacter pylori infection was evaluated using serology and a rapid urease test. Endoscopic gastritis was classified according to the Sydney classification system, in addition to nodular gastritis. Dyspeptic symptoms were also recorded before endoscopy., Results: Of the 530 subjects, 87 (16.4%) were H. pylori positive. Of the 443 H. pylori-negative subjects, 349 (78.8%) were considered to have endoscopically normal gastric mucosa. However, of the 87 H. pylori-positive subjects, only 19 (21.8%) tested normal (P < 0.001). The prevalence of several types of gastritis was significantly higher in H. pylori-positive subjects compared with H. pylori-negative subjects: atrophic gastritis (37.9% vs 1.1%, P < 0.001), flat erosive gastritis (29.9% vs 7.2%, P < 0.001), rugal hyperplastic gastritis (12.6% vs 0.0%, P < 0.001), and nodular gastritis (13.8% vs 0.0%, P < 0.001). Other types of gastritis were not related to H. pylori status. The prevalence of subjects with dyspeptic symptoms was significantly higher in H. pylori-positive subjects compared with H. pylori-negative ones (28.7% vs 6.5%, P < 0.001)., Conclusion: It is suggested that in consideration of its recent low prevalence and the slow increase in its infection, the prevalence of H. pylori-related gastritis will gradually decrease in Japan. Further studies will be required to ascertain if there is a need for H. pylori eradication in this young population., (Copyright 2005 Blackwell Publishing Asia Pty Ltd.)

Background: Follicular gastritis is thought to be caused by Helicobacter pylori infection. However, the pathophysiology of it remains unclear., Materials and Methods: We assessed gastric acidity in 15 patients with follicular gastritis, aged 20-37 years, using a 24-hour intragastric pH-metry, as well as by histologic and serologic evaluations; and compared it with that in other age-matched groups: 18 cases of H. pylori-positive antrum-predominant gastritis, 12 of pangastritis, and 24 H. pylori-negative normals. In eight cases with follicular gastritis, it was re-assessed 6 months after the eradication therapy for H. pylori., Results: During nighttime, the percentage of time with intragastric pH above 3.0 in follicular gastritis was significantly higher than that in normals (p<.0001), and in antrum-predominant gastritis (p<.001), but was comparable with that in pangastritis. In the daytime period, this parameter in follicular gastritis was significantly higher than that in normal (p<.001), in antrum-predominant gastritis (p<.001), and in pangastritis (p<.05). Marked mononuclear cell and neutrophil infiltration but no apparent glandular atrophy were observed in both the antrum and corpus. Serum pepsinogen I/II ratio was significantly lower in follicular gastritis than that in normals (p<.0001) and in antrum-predominant gastritis (p<.001), whereas serum gastrin was significantly higher than that in normals (p<.0001), in antrum-predominant gastritis (p<.01) and in pangastritis (p<.05). After eradication for H. pylori, all of the parameters in follicular gastritis were altered to the same ranges as those in normals., Conclusions: In follicular gastritis, gastric acidity is significantly reduced, but can be normalized by eradication of H. pylori. It can thus be speculated that inflammatory cytokines or H. pylori-infection-induced prostaglandins might strongly inhibit gastric acid secretion in follicular gastritis.

It was reported from a previous randomized trial (NEJM 329: 1848, 1993) that a moderate increase in the initial dose of cyclophosphamide and cisplatin improves the survival of patients with LDSCLC. Rapid administration of several active agents over a short treatment period, such as the CODE regimen, is a potentially usefully strategy for increasing the initial dose intensity. Based on these findings, we conducted a pilot study of CODE (C: 25 mg/m2, day 1, weeks 1-4, O: 1 mg/m2, day 1, weeks 2, 4, D: 40 mg/m2, day 1, weeks 1, 3, E: 80 mg/m2, days 1-3, weeks 1, 3) chemotherapy for the first 4 weeks followed by PE therapy (P: 80 mg/m2, day 1, E: 100 mg/m2, days 1-3, for 3 cycles) with concurrent TRT (1.5 Gy bid x 30 fr., total 45 Gy) to treat LDSCLC. From June 1996 through September 1996, 23 patients (pts) were enrolled, among whom 22 were eligible. The patients' characteristics were as follows: median age 65; M/F, 15/7; PS, 0/1/2,9/9/4; Stage II/IIIA/IIIB, 3/8/11. The relative dose intensities in the CODE phase for patients who received this treatment were 107% for P and 156% for E, compared with standard PE therapy. No treatment related death occurred in this series. Myelosuppression was the most frequent toxicity in both treatments. Grade 3 and 4 leukopenia and neutropenia occurred in 73% and 86% of patients in the CODE phase, and in 83% and 91% in the PE phase, respectively. Thrombocytopenia occurred in 14% of the patients in the CODE phase and in 37% in the cisplatin-etoposide phase. Other non-hematological toxicities were mild. There was no severe esophagitis or pneumonitis following radiation therapy. CR was observed in 13 (59%) of the 22 patients, and 9 (41%) patients showed PR, giving an overall response rate of 100%. A median survival time has not yet been ascertained. Our preliminary results indicate that CODE therapy followed by PE therapy with concurrent TRT has very high activity with acceptable toxicities. This treatment regimen should be compared with PE therapy and concurrent TRT in a randomized trial.

The prognosis of diffuse panbronchiolitis (DPB) has been remarkably improved after the development of low-dose erythromycin therapy, possibly due to anti-inflammatory rather than anti-infective mechanisms. Interestingly, DPB associated with lung cancer is quite rare. Here, we report an autopsy case of DPB who developed lung cancer after a long successful therapy with low-dose erythromycin.

A 64-year-old man underwent a medical checkup in May 1996 and was evaluated as class V using sputum cytology. Chest X-ray examination, bronchoscopy and chest computed tomography (CT) demonstrated no abnormalities. Thereafter, the patient was followed up with chest X-ray, bronchoscopy and chest CT at 3-month intervals. In December 1996, chest CT showed an increased density at the mediastinal side of the left upper bronchus, B1+2. There were no findings on bronchoscopy, but subsequent exfoliative cytology demonstrated keratinized malignant cells in samples obtained from left upper bronchus, B1+2. Although, it was difficult to identify localization of the tumor, left upper lobectomy was performed and the diagnosis of squamous cell carcinoma in situ was finally made. Here, we report on the course of this patient and discuss the diagnostic usefulness of sputum cytology as well as the pathogenesis of lung squamous cell carcinoma.

Background: Platinum drug resistance is an important problem in lung cancer chemotherapy. In this study, we examined lung-resistance protein (LRP) gene expression in vivo and in vitro in relation to platinum drug exposure., Materials and Methods: The expression levels of the LRP gene were assessed by the reverse transcription polymerase chain reaction, in 80 autopsy samples (40 lung tumors and 40 corresponding normal lung tissues), two lung cancer cell lines and in peripheral mononuclear cells collected from 8 lung cancer patients before and after platinum drug administration., Results: The LRP gene expression levels of autopsy specimens exposed antemortem to platinum drugs were not significantly different to those of specimens without platinum drug exposure, for both lung tumors and normal lung tissues. Our results also demonstrate that LRP gene expression was not induced by platinum drugs either in vitro or in vivo., Conclusions: The present results indicate that LRP gene expression is not associated with platinum drug exposure in lung cancer.

Purpose: To assess the usefulness of cine-magnetic resonance imaging (cine-MRI)in the evaluation of chest wall invasion, we compared the results of cine-MRI with those of computed tomography (CT) and ultrasonography (US)., Materials and Methods: Eleven patients were examined who had no pain and who were difficult to diagnose by routine examinations. MRI was performed with a Magnetom SP/4000, 1.5T unit (Siemens, Germany). For cine imaging, continuous turbo-FLUSH (ultra fast low angle shot) images were obtained at an orthogonal section to the chest wall during slow deep breathing. A CT scan was performed using a TCT 900S or Super Helix (Toshiba, Japan) at 1 cm intervals, with section thicknesses of 1 cm throughout the entire chest. US was performed with a model SSA-270A (Toshiba, Japan) with 7.5-MHz linear array scanners (PLF-705S; Toshiba, Japan)., Results: Sensitivity, specificity and accuracy were 67%, 75% and 73% for cine MRI, 67%, 63% and 64% for CT, 33%, 75% and 64% for US, respectively., Conclusions: These results indicate that cine MRI is potentially useful for the diagnosis of chest wall invasion of lung cancer.

Atypical adenomatous hyperplasia (AAH) of the lung has been regarded as a precancerous lesion of lung adenocarcinoma, but the biologic significance of this lesion is still not well understood. In this study, DNA histogram patterns and nuclear size were examined, using an image cytometer. We studied 14 cases of Type II pneumocyte hyperplasia (HP), 7 cases of adenomatous hyperplasia with slight or no nuclear atypia (AH), 21 cases of AAH, and 26 cases of adenocarcinoma. The difference in mean nuclear sizes between the HP (32.08 microns2) and the AH (32.86 microns2) was not significant but between the AH, the AAH (38.52 microns2), and the well-differentiated adenocarcinomas with mild nuclear atypia (51.12 microns2), statistically significant differences were observed (P < 0.05). Seven (33%) of the 21 cases of AAH and 22 (85%) of the 26 cases of adenocarcinoma showed aneuploid histogram patterns. The difference in the incidence of aneuploid pattern between AAH and adenocarcinomas was statistically significant (P < 0.01). All of the cases of HP and AH were diploid. Two of the seven aneuploid cases of AAH showed hyperdiploid DNA histogram patterns, and the remaining five showed polyploid histogram patterns with diploid and hyperdiploid stemlines. In these five cases, the small-sized nuclei showed a diploid stemline and the large-sized nuclei showed a hyperdiploid stemline. Our data indicated that AAH can be distinguished from HP, AH, or adenocarcinoma by morphometric analysis and that some cases of AAH that display aneuploid histogram patterns are precancerous lesions that may lead to adenocarcinoma.