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To clarify the etiology, patients' characteristics and risk factors for community-onset AP (Acinetobacter species pneumonia), we conducted this case-control study. We reviewed all patients with community-onset AP at our institute from 2010 until 2018. We defined non-AP group as a control. The patients with non-Acinetobacter spp. pneumonia (non-AP) were randomly selected during the study period without clinical information based on medical records' list among patients with community-onset pneumonia. The age (±2 years) and sex were matched to the patients with community-onset AP, and the ratio was AP:non-AP group = 1:3. Patients' characteristics, clinical outcomes, pathogens isolated and drug susceptibility were evaluated by comparing AP and non-AP group. The mean age of community-onset AP group was 79 years. They were 8 males and 5 females. The 30-day and in-hospital mortality rates of community-onset AP were 23% (v.s. 3%, p = 0.049) and 31% (v.s. 5%, p = 0.029) respectively, which are higher than the control group. Heavy alcohol consumption (23% v.v. 0%, p = 0.023), higher Charlson Comorbidity index (3.2 v.s. 2.0, p = 0.046) and lobar pneumonia by chest radiology (50% v.s. 23%, p = 0.071) were seen more frequently in community-onset AP than in the control group. In conclusion, community-onset AP shows poor outcomes despite the appropriate antibiotic therapy. Heavy alcohol history might be a risk factor of AP. Patients with community-onset AP could have more comorbidity and poor general conditions than the control group., (Copyright © 2019. Published by Elsevier Ltd.)

Background: The Japanese Respiratory Society recently updated its prognostic guidelines for pneumonia, recommending that pneumonia severity be evaluated using the sequential organ failure assessment (SOFA) and quick SOFA (qSOFA) scoring systems in a therapeutic strategy flowchart. However, the efficacy and accuracy of these tools are still unknown., Methods: All patients with community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP) who were admitted to the study institution between 2014 and 2017 were enrolled in this study. Pneumonia severity on admission was evaluated by A-DROP, CURB-65, PSI, I-ROAD, qSOFA, and SOFA scoring systems. Prognostic factors for 30-day mortality were also analyzed., Results: This study included 406 patients, 257 male (63%) and 149 female (37%). The median age was 79 years (range 19-103 years). The 30-day and in-hospital mortality rates were both 5%. With respect to the diagnostic value of the predictive assessments for 30-day mortality, the area under the receiver operating characteristic curve (AUROC) value for the SOFA score was 0.769 for CAP patients and 0.774 for HCAP patients. Further, the AUROC values for the SOFA score in CAP and HCAP patients with a qSOFA score ≥2 were 0.829 and 0.784, respectively, for 30-day mortality., Conclusions: qSOFA and SOFA scores were able to correctly evaluate the severity of CAP and HCAP., (Copyright © 2019 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

A 76-year-old Japanese woman was admitted due to uncontrolled cellulitis of the right lower leg. She had deep vein thrombosis on the right limb. Moreover, she had a long history of rheumatoid arthritis treated with corticosteroids. Skin biopsy and lumbar puncture were performed to diagnose disseminated cryptococcosis. She was administered antifungal agents (liposomal amphotericin B and 5-fluorocytosine). On treatment day 14, debridement was performed, and cryptococcosis was controlled. However, she developed toxic megacolon due to Clostridioides difficile infection (CDI). On day 32, she was transferred to the intensive care unit due to severe acidosis and acute kidney injury secondary to CDI-related toxic megacolon. Vancomycin, metronidazole, and tigecycline were administered for treatment of CDI. After several weeks of intensive care, toxic megacolon was improved, but renal replacement therapy was discontinued according to the patient's will. On day 73, she died of renal failure. We experienced a complex of rare diseases, Cryptococcus neoformans cellulitis and Clostridioides difficile-related toxic megacolon. Both diseases were presumed to be the result of corticosteroid and methotrexate use. Hence, careful monitoring is required when treating immunocompromised hosts to reduce the risk of developing complications., (Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objective: Current phenotypic methods for extended-spectrum β-lactamase (ESBL), AmpC β-lactamase (AmpC), and carbapenemases fail to detect isolates that co-produce other classes of β-lactamases. In this study, we have developed a novel assay (Applied Multiplex Disk Method: AMU-DM) for the phenotypic detection and identification of β-lactamases produced by Enterobacteriaceae., Methods: We evaluated the performance of the method by comparison with PCR results for 78 Enterobacteriaceae clinical isolates that were positive by the ESBL screening test and negative by the ESBL confirmation test. Additionally, one NCTC strain and four ATCC strains were also included in the test population for the study as reference., Results: For 79/83 (95%) isolates tested, the AMU-DM results matched those obtained by PCR. The concordance rates were 31/31 (100%), 11/11 (100%), 3/3 (100%), 0/1 (0%), 15/15 (100%), 16/19 (84%), and 3/3 (100%) for AmpC, ESBL and AmpC co-production, Klebsiella pneumoniae carbapenemase (KPC), KPC and ESBL co-production, metallo β-lactamase (MBL), MBL and ESBL co-production, and MBL and AmpC co-production, respectively., Conclusion: The AMU-DM is convenient to perform, economical, and highly sensitive in identifying ESBLs, AmpCs, and carbapenemases. Our method may be useful in clinical settings for the implementation of relevant infection control measures and for surveillance purposes., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Brevibacteria are obligate aerobic gram-positive rods that are associated with milk products and are also found on human skin. Brevibacterium has been reported as a rare cause of catheter related blood steam infection mainly in immunocompromised hosts such as malignancies or AIDS patients., Case Presentation: A 94-year old woman, which had a past history of diabetes mellitus and chronic heart failure, presented with high fever associated with decreased oral intake and appetite loss and was admitted to our institute. A physical examination at the time of presentation was unremarkable. On day 2, both blood cultures collected on admission became positive with coryneform organism within 24 h without Staphylococci and Brevibacterium species were identified by Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Subsequently, genetic investigation by 16S ribosomal RNA analysis was performed in order to identify the organism. Finally, the result identified this pathogen as Brevibacterium paucivorans with 99.5% homology on the Ez taxon database. The patient was started empirically on meropenem and teicoplanin for broad-spectrum antibiotic coverage. The patient's fever finally abated and labs were also improved. On day 14, the antibiotic therapy was discontinued. The site of infections was unknown. We hereby report a case of Brevibacterium paicivorans bacteremia in an immunocompetent patient and review cases of Brevibacterium specises bacteremia previously reported. This is the first case of B. paucivorans bacteremia as far as we could search., Conclusion: Physicians and microbiologists should be aware that Brevibacteria are uncommon but important agents which could cause opportunistic infections in immunocompetent.

Background: Pantoea is a Gram-negative, non-encapsulated, non-spore-forming, ubiquitous straight rod which can be isolated from geographical and ecological sources such as plant surfaces, buckwheat seeds, human feces, and the environment. The genus Pantoea is a rare pathogen in a clinical setting, and is divided into 20 different species such as Pantoea agglomerans, Pantoea ananatis, Pantoea deleyi, Pantoea dispersa, Pantoea septica, Pantoea stewartii or Pantoea rwandensis. Pantoea dispersa has been reported to cause other infections, including respiratory infections, neonatal sepsis, and bloodstream infections. We report a case of Pantoea dispersa bacteremia caused by acute cholangitis. This is the first case report of Pantoea dispersa bacteremia caused by acute cholangitis as far as we had searched., Case Presentation: A 38-year-old Japanese woman suffered from acute cholangitis; a blood culture showed that Gram-negative rod was positive. The treatment was successful with intravenously administered meropenem, and it was switched to orally administered levofloxacin according to microbiological susceptibility. The organism was identified as Pantoea dispersa by both genetic investigation by 16S ribosomal RNA and additional biochemical tests. To the best of our knowledge, this is the first case report of Pantoea dispersa bacteremia caused by acute cholangitis., Conclusion: The epidemiology and clinical features of Pantoea dispersa are still unknown. More cases of infections caused by Pantoea dispersa might be revealed with advancing technical methods, such as matrix-assisted laser desorption/ionization time-of-flight mass spectrometry or 16S ribosomal RNA analysis. Physicians must know that a variety of infections caused by Pantoea dispersa could occur in immunocompromised as well as immunocompetent patients.

Background: Any immunological mechanisms induced by influenza virus could cause severe secondary bacterial superinfection such as those by Streptococcus pyogenes [group A streptococcus (GAS)], Streptococcus pneumoniae or Staphylococcus aureus. Over recent years, the frequency of pleural empyema has increased in children with influenza infection. We present a severe case of acute empyema caused by S.pyogenes after influenza A infection., Case Presentation: A previously healthy 39-year old woman was diagnosed as influenza A and received oral Oseltamivir 75 mg twice daily for 5 days. She had no vaccination of influenza A. Although her influenza A infection improved, she complained of fever and cough to our institute. Chest radiography showed encapsulated pleural effusion of the left lung and pleural effusion which was consistent with acute empyema. Then, she was diagnosed as having acute empyema and was admitted to our institute. Streptococcus pyogenes was identified by pleural fluid culture on day 4. thus, MNZ was changed to clindamycin (CLDM) 600 mg three times a day. While thoracic drainage with intrapleural urokinase and combination antibiotic therapy of ceftriaxone and CLDM were performed, her general condition and chest radiographic findings were not improved. She received video-assisted thoracic debridement on day 10. After the operation, the antibiotic therapy was changed to ABPC 6 g daily iv. Due to good clinical course, the antibiotic therapy was switched to oral amoxicillin 500 mg three times daily on day 28. Then, she was discharged., Conclusion: Influenza A virus infection could lead to severe GAS infection, while the latter can occur in otherwise healthy individual as well. Physician must consider the possibility of severe GAS infection after influenza A infection.

Introduction: With an increase in the incidence of Staphylococcus aureus infections in the healthcare settings and in the community, trimethoprim/sulfamethoxazole (TMP/SMX) has been suggested as a convenient treatment option. However, the appropriate dosage regimen of TMP/SMX is unclear., Objective: This study aimed to examine the pharmacokinetics/pharmacodynamics (PK/PD) of TMP/SMX against S. aureus using a neutropenic murine thigh infection model., Methods: Five S. aureus isolates with TMP/SMX (1:5 fixed ratio) minimum inhibitory concentrations (MICs) of 0.032-64 μg/mL were tested. The antimicrobial efficacy of TMP/SMX (1-689 mg/kg/day: dose shown as SMX dosage) was calculated as the change in bacterial density after 24 h of treatment. The plasma concentrations of TMP/SMX were detected using high-performance liquid chromatography., Results: After TMP/SMX single dose (130 mg/kg), the half-life, area under the blood concentration curve (AUC0-∞), and the protein binding ratio of SMX were 1.5 h, 718.2 μg h/mL, and 73.0 ± 8.3%, respectively. The free AUC/MIC and free %time (%T) above the MIC of SMX were better correlated with the in vivo antimicrobial activity than Cmax/MIC (free AUC/MIC, R2 = 0.69; free %T > MIC, R2 = 0.71; free Cmax/MIC, R2 = 0.53). The distributed doses (2-3 times per day) of TMP/SMX (130, 260, and 390 mg/kg/day) showed higher antimicrobial activity than the single dosage. However, TMP/SMX did not show its antimicrobial activity at <100% free %T > MIC., Conclusions: The TMP/SMX treatment demonstrated that the free AUC/MIC of SMX was the better predictor of the PK/PD index of TMP/SMX., (© 2020 S. Karger AG, Basel.)

We determined the optimal antimicrobial in the sodium mercaptoacetic acid double disk synergy test (SMA-DDST) for the detection of IMP-1-producing Pseudomonas aeruginosa isolates in Japan and evaluated the performance of the test. Fifty-four P. aeruginosa clinical isolates were tested, including 39 IMP-1 producers and 15 non-metallo-β-lactamase (MBL)-producing carbapenem- and ceftazidime (CAZ)-resistant isolates. The SMA-DDST was performed with CAZ, cefepime (CFPM), imipenem (IPM), meropenem (MEPM), doripenem (DRPM), or biapenem (BIPM)-containing disks. The sensitivity of the SMA-DDST with CAZ, CFPM, IPM, MEPM, DRPM, and BIPM was 39/39 (100%), 36/39 (92%), 18/39 (46%), 8/39 (21%), 19/39 (49%), and 36/39 (92%), respectively. The specificity was 15/15 (100%) for all SMA-DDSTs. This suggests that the isolates may have a resistance mechanism other than MBL production for IPM, MEPM, or DRPM. Since the CAZ resistance mechanism in P. aeruginosa is the same as that of CFPM, but differs from that of carbapenems, we conclude that combining CAZ with BIPM SMA-DDSTs can prevent any failure in the detection of IMP-1-producing P. aeruginosa., (Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

As the reagent that can simultaneously detect bacterial nucleic acid/drug-resistant genes from the culture-positive liquid of blood cultures, Verigene ® system includes the Verigene ® Gram-Positive Blood Culture test (BC-GP) and the Verigene ® Gram Negative Blood Culture test (BC-GN). This study used BC-GN to identify the names of bacteria from stock strains, urine samples, and sputum specimens and detect drug-resistant genes. The stock strains included 28 clinical isolates, 9 urine samples in which the target bacterial strain grew to 106CFU/ml or more in culture, and 9 sputum specimens in which the target bacterial strain grew to 105CFU/ml or more in culture. The bacterial identification and detection of drug-resistant genes used quality Matrix Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry (MALDI-TOF MS) analysis and conventional PCR method, respectively, followed in comparison with the results of Verigene ® . As a result, the measurement results of Verigene ® for the stock strains and urine samples had a high concordance rate with MALDI-TOF MS analysis and PCR method. On the other hand, the concordance rate of the sputum specimens with the Verigene ® measurement results was only 40% (4 out of 10 specimens). These results suggest that BC‒GN can be an effective tool for AMR rapid diagnosis if the measurement target includes not only bacterial strains in the culture-positive liquid of blood cultures, but also other bacterial strains and urine.

Introduction: While the emergence and spread of carbapenem-resistant enterobacteriaceae (CRE) carriage and infections are serious threats to public health worldwide, its prevalence and epidemiology are still unknown., Methods and Patients: For the purpose of examining the prevalence, patients' background and risk factors for CRE carriage and infections, we conducted this case-control study. We retrospectively reviewed all patients isolating CRE at Aichi Medical University hospital from January 2010 until March 2017. The patients isolated with carbapenem-susceptible enterobacteriaceae (CSE) were randomly selected during the study period., Results: A total of 26 patients, isolating 28 CRE infections were enrolled in this study. The detection rate of CRE carriage and infection was 0.22% (28/12,600). Compared to the CSE group, the CRE group had poorer PS and higher CCI scores. The CRE group tended to stay longer in hospital (121 v.s. 63 days, p = 0.052) and admission fee was much more expensive than CSE group (220,710 v.s. 69,904 JPY, p < 0.001). PS 2-4 (ECOG) and CCI≧3 (p = 0.002), prior hospitalization within 90 days (p = 0.006) and prior antibiotics use within 90 days (p = 0.005) were risk factors for acquisition of CRE by univariate analysis. The combination of PS 2-4 and CCI≧3 was an independent risk factor for CRE carriage and infection by multivariate logistic regression analysis., Conclusion: The combination of PS 2-4 (ECOG) and CCI score≧3 was an independent risk factor of CRE carriage and infections. The CRE group tended to stay longer in hospital, and the medical expense was much more expensive than those in the CSE group., (Copyright © 2018 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Frequency of Treponema pallidum invasion into cerebrospinal fluid (CSF) has not been clear at this present. Since it is impossible to culture T. pallidum in vitro at this present, we need molecular based-approach to detect it in CSF. Additionally, neurosyphilis is usually a late sequela, however it might result in asymptomatic neurosyphilis even at primary or secondary syphilis. This study was to reveal the frequency of T. pallidum invasion into CSF especially at primary or secondary syphilis with polymerase chain reaction (PCR) test. All patients were visited the Aichi Medical University Hospital or Izumi ladies' clinic between 2016 and 2017. Clinical CSF samples were collected from patients with early and late stages of syphilis. The PCR was done using primers targeting the tpN47gene. CSF samples were collected from 9 patients (4 patients with primary syphilis, 3 with secondary syphilis, and 1 early latent syphilis and 1 with late latent syphilis). PCR showed positive reaction in 2 of 7 (28.6%) primary and secondary syphilis patients, in 1 of 1 (100%) early latent syphilis patients, and in 1 of 1 (100%) late latent syphilis patients. Despite its lack of sensitivity for use alone as a diagnostic test, this PCR test should be preferred for the diagnosis of neurosyphilis. Because, T. pallidum was detected in the 28.6% CSF of patients at primary and secondary syphilis, which indicated that they invade the central nervous system from the early stages of infection. However, studies in a larger population are required to confirm these preliminary results., (Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

The Japanese Respiratory Society newly updated the prognostic guidelines for pneumonia in 2017. Quick Sequential Organ Failure Assessment (qSOFA) and Sequential Organ Failure Assessment (SOFA) score are used to evaluate the severity of pneumonia and to select the therapy for pneumonia. This is a retrospective study at Aichi Medical University hospital from January to December of 2016 to investigate the accuracy and usefulness of qSOFA and SOFA score in evaluating the severity and prognosis of healthcare-associated pneumonia (HCAP). A total of 81 HCAP patients were enrolled in this study. Both the 30-day and in-hospital mortality were 7.5% (6/81). qSOFA≧2 was in 33/78 patients (42%) and <2 in 45/78 patients (58%), showing a 30-day mortality of 9.1% (3/33) and 6.7% (3/45) (p = 0.45), respectively. Comparing with qSOFA≧2 and < 2 group, HCAP patients with qSOFA≧2 had much higher A-DROP (31. v.s. 2.2, p < 0.001), CURB-65 (2.7 v.s. 1.9, p < 0.001), PSI (133 v.s. 114, p = 0.014), I-ROAD (2.7 v.s. 1.9, p < 0.001) and SOFA scores (3.8 v.s. 2.8, p < 0.001). With respect to the diagnostic value of predictive values for 30-day mortality among HCAP patients, the area under the receiver-operating characteristic curve for SOFA score was 0.930 with a statistical significance (p < 0.001). The SOFA score cutoff value was 4 and had a sensitivity of 20%, a specificity of 100%, a positive predictive value of 100%, and a negative predictive value of 68%. In conclusion, SOFA core could be one of the most useful tools in evaluating the severity of HCAP., (Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objective From November 24 to December 9, 2013, an outbreak of the influenza (flu) A (H3) virus occurred in a tertiary-care university hospital (1,014 beds). We herein report the prophylactic effect of anti-flu agents for controlling the flu outbreak. Methods We administered pre- or post-exposure prophylaxis with anti-flu agents in flu outbreak. To test the effectiveness of prophylaxis in a flu outbreak, we used the posterior mean of the reproductive value during the pre- and post-intervention period. We also simulated the probability distribution of new flu cases. We performed an analysis to quantify the strength of the intervention effect. Results A total of 97 people were diagnosed with flu before the intervention, and 7 were diagnosed after the intervention. A molecular analysis of the flu virus revealed that this outbreak was due to the flu A (H3) virus. A total of 3,702 people received prophylaxis. There was a significant reduction in the reproductive value from 1.89 [95% confidence interval (CI), 1.59 to 2.24] to 0.65 (95% CI, 0.02 to 1.00) after the intervention (p<0.001). Conclusion Prophylaxis with anti-flu agents, along with prompt identification and isolation of infected individuals, was effective in reducing the impact of a flu outbreak in a hospital.

Community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA) is pathogenic to healthy individuals and a significant issue throughout the world. Panton-Valentine leukocidin gene (pvl)-positive sequence type (ST) 8-staphylococcal cassette chromosome (SCC) mec type IV (ST8-IV) as represented by the USA300 clone, is the most prevalent CA-MRSA in many countries. However, the prevalence of pvl-positive CA-MRSA was limited in Japan. Here, we report the incidence of pvl-positive community-onset MRSA (CO-MRSA) isolated from 10 patients seen between 2009 and 2014 at a Japanese university hospital. All patients were Japanese and eight cases involved severe skin infections. Antimicrobial susceptibility patterns of the pvl-positive isolates were consistent with those of a typical CA-MRSA clone. Detailed molecular epidemiological analyses showed that three isolates were ST8-IV USA300 clones, whereas the other seven were ST30-IV (three isolates), ST30-I (one isolate), ST59-V (two isolates), and ST1-V (one isolate) clones. No clear difference of infection severity was found between the patients associated with the USA300 clone and those with the other clones. Our findings show that, not only the USA300 clone, but also diverse pvl-positive CO-MRSA clones exist in the community and cause severe skin infections in Japan., (Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objects: Changes in patients' background and life environment could contribute to increase healthcare-associated (HCA) empyema. There are no guidelines and statements for HCA empyema., Methods: We retrospectively reviewed all patients with empyema who were admitted to the Aichi Medical University Hospital, Japan between 2008 and 2015. We evaluated patients' characteristics, microbial profiles, treatment and outcomes, and analyzed prognostic factors for 90-day mortality., Results: A total of 48 patients were enrolled in this study. They were categorized into community-acquired (CA) empyema (16 patients) and healthcare-associated (HCA) empyema (32 patients). HCA empyema patients had higher Charlson comorbidity index (CCI) scores, and poorer performance status (PS) than CA empyema patients. Potentially-drug resistant (PDR) pathogens were seen more frequently in HCA empyema than in CA empyema. Compared with survival and death groups, the death group showed higher CCI scores and poorer PSs than the survival group. The death group had more malignancy than the survival group. PDR pathogens were detected more frequently in the death group than in the survival group. Multivariate analysis showed that emergence of PDR pathogens and malignancies were independent poor prognostic factors for 90-days mortality among empyema., Conclusion: The etiology and bacteriology of HCA empyema are quite different from those of CA empyema. Especially, the mortality of HCA empyema was higher than the one of CA empyema. Emergence of PDR pathogens in the pleural fluid detected by culture, pulmonary disease and malignancies were independent poor prognostic factors among CA and HCA empyema by multivariate logistic regression analysis., (Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

A 67-year-old Japanese female with back pain and severe cachexia visited our hospital. The diagnosis was disseminated Mycobacterium avium complex infection (dMAC) with multiple bone involvement. Anti-mycobacterial chemotherapy was started, but fever persisted and dislocation of cervical vertebrae has made her bedridden. Because anti-interferon (IFN)-γ autoantibody was positive, four doses of rituximab 375 mg/m 2 , every 7 day, were administered. Soon after treatment, progression of osteolytic lesions and wasting has stopped. We proved that rituximab has recovered IFN-γ signaling as shown by IFN-γ-induced STAT1 phosphorylation. It can be a promising option for dMAC cases with anti-IFN-γ autoantibody.

Background: Some reported that organizing pneumonia (OP) may occur after influenza A infections including swine-origin influenza A (H1N1). However, OP associated with influenza B infection has never been reported. We report the first case of secondary OP associated with viral pneumonia caused by influenza B., Case Presentation: A 23-year old woman was diagnosed as viral pneumonia caused by type B influenza. Despite of antiviral therapy, abnormal chest shadows were not improved. Bronchoscopy and transbronchial lung biopsy showed organizing pneumonia due to viral pneumonia caused by influenza B. Corticosteroid therapy was started at 30 mg daily (0.5 mg/kg), and the dose was reduced to 25, 20, 15 or 10 mg per day every month with symptomatic and radiological resolution. Even after corticosteroid therapy was discontinued, we did not confirm disease recurrence., Conclusions: Physicians should be aware of the possibility for SOP and severe viral pneumonia even in case of type B as well as type A influenza infections.

Objectives: This study was designed to evaluate the sodium mercaptoacetic acid double disk synergy test (SMA-DDST), the Etest metallo-β-lactamase (MBL) MP/MPI (Etest MP/MPI), and the Mastdiscs ID Carbapenemase Detection Disc Set (MAST-CDS) for the detection of MBL-producing Enterobacteriaceae isolates in Japan., Methods: Fifty-one clinical isolates and four reference strains were tested. These isolates included 40, 4, and 11 IMP-, New Delhi MBL (NDM)-, and non-MBL-producers, respectively. SMA-DDST was performed with meropenem (MEPM)-containing disks., Results: Sensitivities were 38/44 (86%), 40/44 (91%), and 15/44 (34%), and the cost ratio was 1:9.4:3.8 for MEPM-SMA-DDST:Etest MP/MPI:MAST-CDS, respectively. The specificity was 11/11 (100%) for all assays. MEPM-SMA-DDST detected IMP-producing isolates with high sensitivity (38/40; 95%), but the assay was inadequate for NDM-producing isolates (0/4; 0%). The Etest MP/MPI detected both IMP- (36/40; 90%) and NDM-producing isolates (4/4; 100%), but was the most expensive. MAST-CDS detected IMP-producing isolates with low sensitivity (11/40; 28%), but the assay worked well for NDM-producing isolates (4/4; 100%)., Conclusions: Our results indicated that MEPM-SMA-DDST was the most cost-effective assay for the detection of IMP-producing isolates. Therefore, we conclude that MEPM-SMA-DDST is the optimal available assay for clinical first-line screening in IMP-endemic areas such as Japan. However, this assay could not detect NDM-producing isolates, whereas the Etest MP/MPI and MAST-CDS could. When MEPM-SMA-DDST is negative, the Etest MP/MPI and MAST-CDS could be used to obtain supportive data and prevent detection failure for NDM-producing isolates., (Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objective: The purpose of this study is to compare the antimicrobial activity of human simulated exposures of tedizolid 200 mg daily, and linezolid 600 mg every 12 h for the treatment of complicated skin and skin structure infection (cSSSI) caused by MRSA and Peptostreptococcus anaerobius in both the neutropenic mice thigh mixed-infection models., Material and Method: Tedizolid phosphate and linezolid were used for all in vivo testing. A total of one MRSA and two P. anaerobius isolates were utilized. Antimicrobial efficacy was calculated for each isolate as the change in bacterial numbers (Δlog 10 CFU/ml) obtained in the treated mice after 24 h compared with the numbers in the starting control animals (0 h)., Results: The tedizolid and linezolid MICs for MRSA was 0.25 and 2 μg/ml. Tedizolid MIC for P. anaerobius was 0.12 μg/ml, and linezolid MICs for two P. anaerobius isolates were 0.5 and 1 μg/ml. In mixed infection model, tedizolid therapy showed similar antimicrobial activities for one MRSA and two P. anaerobius isolates evaluated, compared with linezolid therapy. Additionally, when comparing the activity of tedizolid and linezolid monotherapy between single infection and mixed infection model, antimicrobial activities of both antimicrobials were attenuated when mixed infection model was used., Conclusion: In the neutropenic murine thigh infection model, human simulated exposures of tedizolid and linezolid resulted in similar efficacies against MRSA, even though single and mixed infection models were used. These data support the clinical utility of tedizolid for use against MRSA and P. anaerobius in the treatment of cSSSI., (Copyright © 2017 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

We present the first case report of osteomyelitis due to Clostridium hydrogeniformans in a previously healthy 18-year-old male. He was admitted to our hospital because of an open contaminated fracture of the right arm after being blown into a drain in a motorbike accident. He underwent surgical debridement and treatment course of cefazolin. Although he responded well to these initial treatments, subcutaneous abscess and ulnar osteomyelitis developed 1 month after discharge. Second debridement was performed and specimens were collected from both the abscess and bone tissues. Only anaerobic culture showed a gas-producing Gam-positive rod. Conventional methods and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry could not accurately identify this organism. However, 16S rRNA gene sequence analysis determined the isolate as C. hydrogeniformans with 99.79% homology. The patient recovered after 90 days of antibiotic treatment, and had no evidence of recurrence. Anaerobic bacteria are more common as causative pathogens in osteomyelitis related to traumatic wounds and Clostridium spp. are particularly associated with open fractures, which is consistent with our case. Although the epidemiology and clinical characteristics of C. hydrogeniformans infection is poorly understood because of the limitations of currently available conventional methods of identification, clinicians need to consider this organism as a causative pathogen in a patient with osteomyelitis in traumatic wounds, especially contaminated by sewer water., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Here we report six cases of daptomycin (DAP)-induced eosinophilic pneumonia (DIEP) encountered at two medical centers and present a review of 43 DIEP patients from 26 studies to compare the clinical characteristics and radiographic findings of acute and chronic eosinophilic pneumonia (AEP; CEP). Four of the six patients did not exhibit respiratory symptoms, and one patient with only fever was misdiagnosed with DAP-induced fever. According to our literature review and the present findings, male sex and old age were dominant risk factors for DIEP. Fever and fine crackles were the most common clinical manifestations. The DAP dose and duration of administration were not significant risk factors for DIEP, and we also could not find any association between allergic predisposition and DIEP. Among the reviewed patients, 51.8% did not show more than 25% eosinophils in bronchoalveolar lavage, which is a criterion for the diagnosis of drug-induced eosinophilic pneumonia. Chest images of all patients showed CEP patterns such as multiple reticulonodular infiltrates in the subpleural region and diffuse bilateral pulmonary infiltrates with ground-glass opacities. However, 66.7% of patients also exhibited pleural effusion, a feature specific to AEP. All patients showed prompt recovery after DAP withdrawal. Our results suggest that clinicians should consider DIEP as a differential diagnosis when patients receiving DAP therapy, particularly men and elderly patients, present with fever, even in the absence of respiratory symptoms. Furthermore, they should be aware that the occurrence of DIEP is independent of the DAP dose and administration duration, and allergic reaction., (Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

This is the first report to test the loading dosage of colistin against Pseudomonas aeruginosa, including MDRP. Using in vivo murine thigh infection model, in the loading dosage regimen (Day 1:50 mg/kg q12 h, Day 2-3: 25 mg/kg q12 h) group, 5 to 6 log10 CFU/ml reduction compared with control were observed for both strains of P. aeruginosa with colistin MIC 0.5 and 1 μg/mL at 72 h. But, similar reduction was observed for the strains with colistin MIC 0.5 μg/mL only in normal dosage regimen (Day 1-3: 25 mg/kg q12 h) group. For P. aeruginosa with colistin MIC 1 μg/mL, colistin loading dosage regimens showed greater antimicrobial activity than that of without loading dosage group (p < 0.05). These data suggest that the colistin loading regimen would be one of the useful options for P. aeruginosa with antimicrobial resistance infection treatment., (Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Amikacin has been one of the important antimicrobial agents against Gram-negative pathogens. However, there is discrepancy regarding the amikacin initial dosage, with some reports recently recommending ≥25 mg/kg and others the conventional dosage (15-20 mg/kg). Hence, we evaluated the optimal initial dosing regimen of amikacin. Pharmacokinetic (PK) parameters were estimated using a population PK analysis. The pharmacodynamic (PD) target was a ratio of ≥8 between the concentration achieved 1 h after beginning the infusion (C peak ) and the minimal inhibitory concentration (MIC) of the liable bacteria. Based on the population PK parameters, we simulated individual C peak for several dosing regimens by Monte Carlo method and analyzed the C peak /MIC ratio for MICs from 0.5 to 32 μg/mL. This study included 35 infected patients (25 males), with a median (range) age and body weight of 70 (15-95) years and 49.5 (32.5-78) kg, respectively. A two-compartment model was used, and total body clearance (CL) significantly correlated with creatinine clearance, and volume of distribution (V d ) with body weight. Regarding the probability to achieve a C peak /MIC of ≥8, the 15 mg/kg regimen was sufficient to achieve the PK/PD target in ≥90% of patients for a MIC of 4 μg/mL or less. The cumulative fraction of response in Pseudomonas aeruginosa was that 76% of patients achieved a C peak /MIC of 8 with the amikacin dosage of 15 mg/kg/day. We suggest that the 15-mg/kg once-daily dosage of amikacin be recommended as the initial dosage. As its maintenance dosage, the 15 mg/kg/day amikacin dosage is needed for a MIC of ≤4 μg/mL, and amikacin monotherapy for a MIC of ≥8 μg/mL should be avoided.

Background: Among the different serotypes of Streptococcus pneumoniae, serotype 3 has received global attention. We report the fatal case of a 76-year-old Japanese man who had an invasive pneumococcal disease associated with pneumonia caused by serotype 3 S. pneumoniae., Case Presentation: The patient had a history of hypertension, laryngeal cancer, chronic obstructive pulmonary disease, and type 2 diabetes mellitus. Following a cerebral arteriovenous malformation hemorrhage, he underwent surgery to remove the hematoma and began rehabilitation. On day 66 of hospitalization, he suddenly developed a fever, and coarse crackles and wheezes were heard in his right lung. A diagnosis of hospital-acquired aspiration pneumonia was made, and initial treatment with piperacillin/tazobactam was started. Teicoplanin was added after S. pneumoniae was isolated from the blood culture, however, the patient died 5 days later. The S. pneumoniae detected in the sputum smear was serotype 3, showed mucoid colonies and susceptibility to penicillins, cephalosporins, carbapenems, and levofloxacin, but resistance to erythromycin., Conclusion: We experienced a fatal case of pneumonia caused by mucoid serotype 3 S. pneumoniae with a thick capsule. Serotype 3-associated pneumonia may develop a wider pulmonary infiltrative shadow, a prolonged therapeutic or hospitalization course, and a poor outcome. Careful observation and intervention are required, and the use of additional antibiotics or intravenous immunoglobulins should be considered in such cases. Pneumococcal immunization is also an important public health measure to minimize the development of severe infections caused by serotype 3 strains.

Background: Reports of Pseudomonas aeruginosa with high antimicrobial resistance have steadily emerged, threatening the utility of a mainstay in antipseudomonal therapy. This study evaluated the antimicrobial activities of various combination therapies against P. aeruginosa with high antimicrobial resistance, including multidrug-resistant P. aeruginosa (MDRP) using an in vitro and in vivo study., Methods: We evaluated 24 combination therapies, including colistin, aztreonam, meropenem, ceftazidime, ciprofloxacin, amikacin, rifampicin, arbekacin and piperacillin against 15 MDRP isolates detected at Aichi Medical University Hospital with the break-point checkerboard method. Based on the results of the in vitro study, we evaluated antimicrobial activity against highly antimicrobial-resistant P. aeruginosa with an in vivo murine thigh infection model., Results: The combination regimens including colistin and aztreonam showed higher antimicrobial activity against the 15 MDRP isolates. In the in vivo study, the high-dose colistin monotherapy (16 mg/kg every 12 h) achieved greater log10 CFU changes than the normal-dose colistin regimen (8 mg/kg every 12 h) against 5 P. aeruginosa isolates, including 2 MDRP isolates (p < 0.05). Aztreonam monotherapy (400 mg every 8 h) yielded bacterial densities similar to untreated control mice for the MDRP isolate evaluated. The combination therapy with a higher dose of colistin had superior antimicrobial activity against 5 P. aeruginosa with colistin (MIC 0.5 μg/ml) and aztreonam (MIC ≥128 μg/ml) than colistin monotherapy., Conclusion: The data suggest that the combination treatment of colistin and aztreonam could be the most useful for treating highly resistant P. aeruginosa with a higher susceptibility to colistin, including MDRP infections., (© 2016 S. Karger AG, Basel.)

Background and Objective: In recent years, Streptococcus anginosus group (SAG) bacteria are becoming increasingly recognized as important pneumonia-causing pathogens. Although several small studies have been reported, the features of SAG pneumonia remain unclear, because the identification of SAG from sputum cultures is not routinely performed in most microbiology laboratories. The aim of this study was to elucidate the clinical characteristics of SAG pneumonia., Patient and Methods: This was a retrospective case-control study utilizing data obtained in our hospital between September 2009 and June 2016. We investigated 31 patients with SAG pneumonia (PWP), and also assessed the difference between the 31 PWP and 37 patients without pneumonia (PWOP) in whose sputum SAG was detected., Results: Seventy-one percent of the patients were men and the median age was 78 years in the PWP. Univariate analysis indicated that the PWP were significantly more often a bed-ridden (p < 0.01) with comorbid aspiration than were the PWOP (p < 0.05). Among the PWP, nursing and healthcare-associated pneumonia (NHCAP) was the more common type of pneumonia (54.8%). S. anginosus was detected significantly more frequently in sputum cultures of PWP than PWOP (p < 0.01), and multiple pathogens were detected more frequently in PWP (p < 0.01). Streptococcus constellatus was the most frequently detected pathogen in patients with a single bacterial infection. Empyema was observed only in patients with multiple bacteria., Conclusions: SAG should be recognized as important causative pathogens of pneumonia, particularly among elderly patients with underlying disease associated with aspiration. NHCAP was the more common type of SAG pneumonia in this study., (Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Neisseria meningitidis often causes meningitis and meningococcemia; however, meningococcal pneumonia is quite rare. Herein, we report a case of non-invasive meningococcal pneumonia initially misdiagnosed as pneumonia due to Moraxella catarrhalis on the basis of a Gram stain in a 43-year-old woman with asthma, type 2 diabetes mellitus, and schizophrenia. She visited our hospital following a 3-day history of fever, productive cough, and shortness of breath. Since her sputum smear revealed Gram-negative diplococcus and the chest radiograph showed infiltration in the lower right lung field, her initial diagnosis was pneumonia caused by M. catarrhalis. However, the next day, the sputum culture colonies were unlike those of M. catarrhalis, and matrix-assisted laser desorption/ionization time of flight mass spectrometry analysis revealed the pathogen to be N. meningitidis. As a result, we administered the appropriate treatment and ensured adequate infection prevention and control measures including, droplet precautions and prophylaxis provided to close contacts. Secondary infection did not occur. Although meningococcal pneumonia is not common, physicians should consider N. meningitidis when Gram-negative diplococci are observed in respiratory specimens, as N. meningitidis cannot be distinguished from M. catarrhalis with Gram staining alone. Moreover, it is also important to monitor the appearance of the pathogenic colonies and to closely coordinate with laboratory technicians to determine appropriate treatments. In this article, we review the previous case reports of meningococcal pneumonia reported in 1984-2015 in Japan, summarizing the clinical characteristics and comparing previous reviews of the literature., (Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Among the Citrobacter genus, the most commonly isolated bacteria from human specimens are Citrobacter freundii and Citrobacter koseri, and previous cases of infection due to Citrobacter braakii have been rarely reported. We present a case of bacteremia due to C. braakii in a 38-year-old woman with cervical cancer. She was admitted to our hospital with complaints of a fever, chills, and nausea. Blood culture results showed gram-negative bacilli identified as C. braakii via matrix-assisted laser desorption/ionization time-of-flight mass spectrometry analysis, although biochemical testing findings were suggestive of C. freundii. Since a rare pathogen was detected in the present case and the results of additional biochemical studies were suggestive of both C. braakii and Citrobacter farmeri, genetic analysis was conducted. Finally, the gram-negative bacilli were confirmed as C. braakii, a member of the C. freundii complex since 1993, by 16S ribosomal RNA gene sequencing analysis. The gastrointestinal tract was considered the portal of entry, because the patient had a rectal fistula and other cultures such as urine and vaginal discharge incubated species other than C. braakii. The patient recovered after receiving treatment with ciprofloxacin for 14 days. The epidemiology and clinical characteristics of C. braakii infection are still unknown because of the limitations in accurate identification by using currently available commercial biochemical testing and previously, only 6 cases of C. braakii infection have been reported. Physicians should focus on this species, because it causes community-acquired infections, although further studies are needed to clarify the clinical characteristics of C. braakii infections., (Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Gene sequence analysis methods, including 16S rRNA identification, allows accurate identification of Streptococcus species, which include phenotypically closely related species that are difficult to differentiate using conventional chemical methods. We report a case of bacteremia due to Streptococcus tigurinus, identified by 16S rRNA, in a 72-year-old woman with gastrointestinal cancer and ascites. She was hospitalized to undergo elective tumor-related surgery. Five days prior to undergoing surgery, she developed a fever with no obvious source of infection. Blood cultures identified gram-positive cocci. The patient's bacteremia was initially thought to be caused by an Enterococcus species, given her underlying gastrointestinal disease. However, alpha-hemolytic, mucoid, circular colonies were observed on sheep blood agar the following day. Although matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and biochemical testing suggested Streptococcus pneumoniae, we conducted further investigation to identify the bacterium, as the patient had no symptoms of infections usually related with S. pneumoniae such as pneumonia, meningitis, or sinusitis, and the bacteremia occurred 30 days after hospitalization. Finally, the gram-positive cocci were identified as S. tigurinus, assigned to the Streptococcus mitis group in 2012. Although the origin of infection was unclear, it was suspected that peritonitis or bacterial translocation from the gastrointestinal tract caused the bacteremia. This novel species was recently reported as being extremely pathogenic and different from other Streptococcus species. It has been reported to occur in cases of infectious endocarditis and bacteremia. In this article, we reviewed previous reports of S. tigurinus infection and summarized the clinical and pathogenetic features., (Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

The efficacy of arbekacin in patients with MRSA infections is influenced by the peak concentration (Cpeak)/MIC ratio (≧8). A daily arbekacin dose of 4-6 mg/kg is primarily used for the treatment of MRSA infection. However, clinical pharmacokinetic studies of arbekacin that evaluate changes in patients with different infectious diseases have been limited. This study was to evaluate the pharmacokinetics of arbekacin in different infectious diseases and to evaluate its dosing regimens. This work describes a single-centre, retrospective study. The pharmacokinetic parameters of arbekacin were calculated from individual serum-concentration data using WinNonlin ver. 6.3. A total of 331 serum samples were obtained from 170 patients. Our drug concentration-time data were well described by a two-compartment open model. The final model showed that drug clearance was related to creatinine clearance and that the total distribution volume (Vd) was related to actual body weight and the presence of bacteremia. The individual Vd in bacteremia patients was significantly higher than those of other patients (bacteremia: 29.7 ± 0.5 L, pneumonia: 20.8 ± 0.4 L, other infections: 21.4 ± 0.4 L; p < 0.05). Additionally, Monte Carlo simulation showed that target (Cpeak/MIC ≧ 8) attainment was only 10.1%, even at a dose of 6 mg/kg, especially for MRSA bacteremia patients with an arbekacin MIC = 2 μg/mL. In conclusion, our study revealed that the Vd may be higher in bacteremia patients than in patients with other infectious diseases. Therefore, an increase in the daily dose of arbekacin should be considered for bacteremia patients., (Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Previously, Veillonella species had been considered as nonpathogenic and rarely caused serious infections. We report a case of 25-year-old man with osteomyelitis caused by Veillonella species. He was admitted to the hospital due to an open fracture to the left radial bone caused by industrial washing machine accident, and emergency surgery was performed. However, wound infections occurred one week after the operation. Although Acinetobacter baumannii and Serratia marcescens were cultured from the pus, obligate anaerobic bacteria were not detected at that point. Debridement was repeated and antibiotics were changed according to the result of bacterial culture and drug sensitivity. Despite this, the infection was poorly controlled. On the 5th debridement, granulomatous bone tissues on pseudarthrosis were found for the first time at the infection site. Although no bacteria was detected with aerobic culture, anaerobic incubation revealed Gram-negative cocci which was later identified as Veillonella species by 16S rRNA gene sequence analysis. His condition improved without any additional debridement after adding effective antibiotics against Veillonella species. It is well known that prolonged infection with aerobes consumes oxygen in the infection site and leads the environment to more favorable conditions for anaerobic bacteria, thus we speculated that prolonged infection with bacteria such as S. marcescens induced the favorable environment for Veillonella species. Physicians should realize the importance of anaerobic culture method in routine practice, especially in complicated cases such as the present case. In this article, we reviewed case reports of Veillonella infection and summarized the clinical features of this organism., (Copyright © 2016. Published by Elsevier Ltd.)

Background: The purpose of this study was to examine the pharmacokinetics/pharmacodynamics of rifampicin against methicillin-susceptible Staphylococcus aureus (MSSA), methicillin-resistant S. aureus (MRSA), and vancomycin-intermediate S. aureus (VISA) in a neutropenic murine thigh infection model., Methods: Three S. aureus isolates (MSSA [ATCC 25923], MRSA and VISA [Mu50]) with rifampicin MIC 0.06 to >256 μg/mL were tested. The efficacy was calculated as the change in bacterial density. A maximum effect model was used to determine the PK/PD index that best described the dose-response data., Results: The area under the curve (AUC)/MIC and maximum concentration of drug in serum (Cmax/MIC) were the best correlated with in vivo efficacy (AUC/MIC, R(2) = 0.96; Cmax/MIC, R(2) = 0.97) for S. aureus ATCC 25923 strain, and the dose fractionation-response study did not show significantly different antimicrobial activity (p = 0.10). The AUC/MIC values associated with stasis and 1-log kill for the S. aureus ATCC 25923 strain were 386 and 952, respectively. On the other hand, no antimicrobial efficacy was observed against two strains (MRSA and VISA) with MIC of 128 μg/mL or more., Conclusion: Rifampicin demonstrated concentration-dependent killing. The AUC/MIC was a predictive PK/PD index., (Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Objective: To study the clinical characteristics and associated risk factors of infections caused by extended-spectrum β-lactamase (ESBL)-producing Enterobacteriaceae., Methods: A case-control study at a large university hospital in Japan, comparing patients who were infected or colonized with ESBL-producing Enterobacteriaceae (n = 212) and non-ESBL-producing Enterobacteriaceae (n = 2089) in 2010-2013. Data were collected from medical charts, retrospectively. Multivariate logistic regression analysis was used to explore risk factors of ESBL-producing Enterobacteriaceae (Escherichia coli, Klebsiella pneumoniae, Klebsiella oxytoca, Proteus mirabilis) infection or colonization for each pathogen, respectively., Results: ESBL-producing Enterobacteriaceae [E. coli (n = 113), K. oxytoca (n = 46), K. pneumoniae (n = 41), P. mirabilis (n = 12)] were taken from patients were identified in 1409 outpatient and 892 inpatients. Infection or colonization caused by ESBL-producing Enterobacteriaceae was considered to be hospital-acquired, healthcare-associated and community-acquired in 60.4%, 17.9% and 21.7% patients, respectively. Independent risk factors for ESBL-producing Enterobacteriaceae infection or colonization were male sex, cerebrovascular disease, intubation/tracheostomy, major surgery within 60 days (p < 0.001). Moreover, antimicrobial usage (more than 4 days) during preceding 60 days, especially aminoglycoside, oxazolidinone, tetracycline, fluoroquinolone, trimethoprim/sulfamethoxazole, and second- and fourth-generation cephalosporin were risk factors (p < 0.001). However, acquisition location of infection (hospital-acquired and community-onset) was not a risk factor (p > 0.05)., Conclusion: The problem of ESBL production is no longer limited to hospital-acquired infections. The presence of chronic illness, such as cerebrovascular disease, and recent antimicrobial use were independent risk factors for ESBL-producing Enterobacteriaceae infection or colonization., (Copyright © 2016 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

We report herein on a case of bacteremia caused by Ochrobactrum intermedium (O. intermedium) identified with biotyper matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). An 86-year-old man was admitted to our hospital with paralysis of the right side of the body and dysphagia. He was diagnosed as having a pontine infarction based on the brain MRI findings and was admitted to hospital to have anti-platelet therapy. Three days after admission, he had a fever. Although he had redness and swelling at the peripheral venous catheter insertion site, he was diagnosed as having aspiration pneumonia, since he had fine crackles on auscultation. Soon after taking two sets of blood cultures and removal of the peripheral venous catheter, sulbactam/ampicillin (SBT/ABPC) was administrated. Fifty three hours after incubation, gram-negative bacilli was detected from an aerobic bottle and identified as O. intermedium with MALDI-TOF MS (Bruker MS). Antimicrobial chemotherapy was changed to meropenem (MEPM). He was treated for a total of seven days, and recovered without relapse. Infection caused by O. intermedium has been very uncommon, however, O. intermedium has been recognized as an emerging pathogen in immunodeficient and immunocompetent patients. Since identification of Ochrobactrum species by biochemical methods could be difficult, MALDI-TOF MS might be helpful to clarify Ochrobactrum species just as in the present case.

We developed and evaluated of multiplex real-time PCR assay for detection of vancomycin-resistant genes (vanA, vanB, vanC1 and vanC2/C3) using the new, fully automated BD MAX platform. Ct value analyses of real-time PCR simultaneous repeatability test have showed the usefulness; coefficient of variation: CV (%) were determined 2.09%, 1.72%, 1.41% and 1.52% with vanA, vanB, vanC1 and vanC2/C3, respectively. We also evaluated with 43 strains of enterococci were characterized by conventional PCR method; 4/4 for vanA-positive, 14/14 for vanB-positive, 1/1 for vanB plus vanC1-positive, 6/6 for vanC1-positive, 4/4 for vanC2/C3- positive and 14/14 for all-van gene-negative strains were identified correctly. This assay was automatically performing before and after PCR operations previously done manually by operator, such as DNA extraction, sample dispensing and gel electrophoresis or the ethidium bromide dyeing. As a result, work burden and the risk of the contamination were largely reduced and were shortened to about half for measurement time. We conclude that this assay could greatly contribute to efficient and rapid detection of vancomycin-resistant genes.

We investigated vancomycin-resistant genes for clinical isolates of 353 vancomycin-resistant enterococci in the Aichi Medical University hospital and 120 vancomycin-resistant enterococci from the 8 facilities in Aichi prefecture between April 2008 and January 2013. We detected 8, 105, 21 and 4 strains of enterococci with vanA, vanB, vanC1 and vanC2/C3, respectively. Among enterococci with vancomycin-resistant genes, we detected 4, 3 and 2 enterococci of vancomycin MIC level 4 microg/mL with vanB, vanC1 and vanC2/C3, respectively. According to molecular analysis using repetitive-sequence-based PCR (rep-PCR) for enterococci with vanA or vanB genes, although there have been no similarity for Enterococcus faecium with vanA and Enterococcus faecalis with vanB, high similarity was shown among E. faecium with vanB, which might be nosocomial spread in each hospital. These results showed that molecular analysis for vancomycin-resistant genes would be useful for the management of healthcare-associated infections.