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Introduction: We aimed to clarify the genetic background and molecular epidemiology of extended-spectrum beta-lactamase (ESBL)-producing Klebsiella pneumoniae (K. pneumoniae) at three geographically separated university hospitals in Japan. Methods: From January 2014 to December 2016, 118 ESBL-producing K. pneumoniae (EPKP) strains that were detected and stored at three university hospitals were collected. Molecular epidemiological analysis was performed using enterobacterial repetitive intergenic consensus (ERIC)-polymerase chain reaction (PCR) and multi-locus sequence typing (MLST). The ESBL type was determined using the PCR-sequence method. The presence of plasmid-mediated fluoroquinolone resistance (PMQR) genes was analyzed by PCR. We compared the relationships between PMQR gene possession/quinolone resistance-determining region (QRDR) mutation and levofloxacin (LVFX)/ciprofloxacin (CPFX) susceptibility. Results: The detection rate of EPKP was 4.8% (144/2987 patients). MLST analysis revealed 62 distinct sequence types (STs). The distribution of STs was diverse, and only some EPKP strains had the same STs. ERIC-PCR showed discriminatory power similar to that of MLST. The major ESBL genotypes were CTX-M-15-, CTX-M-14-, and SHV-types, which were detected in 47, 30, and 27 strains, respectively. Ninety-one out of 118 strains had PMQR genes and 14 out of 65 strains which were not susceptible to CPFX had QRDR mutations, and the accumulation of PMQR genes and QRDR mutations tended to lead to higher minimum inhibitory concentrations (MICs) of LVFX. Conclusions: At three geographically separated university hospitals in Japan, the epidemiology of EPKP was quite diverse, and no epidemic strains were found, whereas CTX-M-14 and CTX-M-15 were predominant.

Malassezia furfur is a lipophilic, yeast-like fungus that forms part of the normal human skin microflora and is associated with a wide range of infections, such as pityriasis versicolor, folliculitis, and systemic infections in immunocompromised patients. Although matrix-assisted laser desorption/ionization time-of-flight mass spectrometry has enabled rapid identification of Malassezia species, it is still a challenge to diagnose systemic infections because Malassezia fungemia can often be missed by automated blood culture systems. We report a case in which M. furfur in blood was detected by the presence of yeast-like fungi in blood smears. Yeast-like organisms were observed in the blood smears of a 3-year-old boy, taken over 2 weeks without any symptoms. He had undergone several courses of chemotherapy for neuroblastoma via an indwelling central venous catheter (CVC) that was placed in his right anterior chest for 11 months. Although the blood cultures obtained from an automated blood culture system were negative, M. furfur growth was detected in the subcultured blood taken from the CVC. The CVC was removed, and the scheduled chemotherapy was postponed. No systemic M. furfur bloodstream infection occurred; the infection resolved spontaneously without any specific treatment; only prophylactic fluconazole was administered. M. furfur fungemia may not be diagnosable by an automated blood culture system. Further, M. furfur may not cause infections in humans even when administered intravenously. This report may lead to the discovery of factors related to human infectivity of this disease in the future.

A 93-year-old woman was diagnosed with Lysinibacillus fusiformis bacteremia complicated with coma blisters. Initial gram staining for L. fusiformis indicated the presence of gram-negative rods; however, subsequent staining of colonies from Mueller-Hinton agar revealed the presence of gram-positive and gram-negative rods with spherical endospores, and Matrix-Assisted Laser Desorption/Ionization Time-of-Flight Mass Spectrometry (VITEK ® MS and microflex® LT/SH) definitively identified the organism as L. fusiformis. The two-week administration of piperacillin/tazobactam and ampicillin resulted in an improvement of the patient's general condition, and the skin lesions gradually improved.

Background In a previous retrospective observational study, a 3-day regimen of oseltamivir as post-exposure prophylaxis (PEP) for preventing transmission of influenza in wards was shown to be comparable to 7- to 10-day regimens provided index cases were immediately separated from close contacts. In order to confirm the efficacy of a 3-day regimen, we started to conduct a prospective, multi-center, single-arm trial. Methods This study is a prospective, multi-center, single-arm study designed by the Sectional Meeting of Clinical Study, Japan Infection Prevention and Control Conference for National and Public University Hospitals. Index patients with influenza are prescribed a neuraminidase inhibitor and are discharged immediately or transferred to isolation rooms. The close contacts are given oseltamivir as 75 mg capsules once daily for adults or 2 mg/kg (maximum of 75 mg) once daily for children for 3 days as PEP. All close contacts are monitored for development of influenza for 7 days after starting PEP. Discussion A 3-day regimen of oseltamivir as PEP has advantages over 7- to 10-day regimens in terms of costs, medication adherence and adverse effects. Trial registration The Institutional Review Board of Hokkaido University Hospital for Clinical Research, 015-0518, registered on November 11, 2016. UMIN Clinical Trials Registry, UMIN000024458, disclosed on October 31, 2016. https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000027881. Japan Registry of Clinical Trials, jRCTs011180015, disclosed on March 14, 2019. https://jrct.niph.go.jp/latest-detail/jRCTs011180015

Pseudomonas aeruginosa resistance is a major issue worldwide. Drug resistance is related to inappropriate antibiotic use. Because antipseudomonal agents have a wide spectrum, they must be used appropriately. The purpose of this study was to clarify the trends in antipseudomonal agent use in Japan based on sales data from 2006 to 2015. The total antipseudomonal agent use was increased significantly (r = 0.10, Pfor trend = 0.00040). The proportion of fluoroquinolones use was the highest throughout the year, accounting for 88.6-91.4%. The use of piperacillin/tazobactam significantly increased. The increased use of these drugs may be due to the launch of higher doses and additional indications. On the other hand, for antipseudomonal agents, parenteral carbapenems use was 2.7-3.7%, but it has remained unchanged over the years. In Japan, permit and notification systems have been introduced to prevent the inappropriate use of parenteral carbapenems in medical institutions. It was speculated that these efforts suppressed the inappropriate use of parenteral carbapenems. This study clarified the trend of antipseudomonal agent use in Japan from 2006 to 2015. It is important to continue monitoring antipseudomonal agents use to conduct appropriate antimicrobial resistance measures.

The potential hazards of extended-spectrum antibiotic therapy for patients with community-acquired pneumonia (CAP) with low risk for drug-resistant pathogens (DRPs) remain unclear; however, risk assessment for DRPs is essential to determine the initial antibiotics to be administered. The study objective was to assess the effect of unnecessary extended-spectrum therapy on the mortality of such patients.A post hoc analysis was conducted after a prospective multicenter observational study for CAP. Multivariable logistic regression analysis was performed to assess the effect of extended-spectrum therapy on 30-day mortality. Three sensitivity analyses, including propensity score analysis to confirm the robustness of findings, were also performed.Among 750 patients with CAP, 416 with CAP with a low risk for DRPs were analyzed; of these, 257 underwent standard therapy and 159 underwent extended-spectrum therapy. The 30-day mortality was 3.9% and 13.8% in the standard and extended-spectrum therapy groups, respectively. Primary analysis revealed that extended-spectrum therapy was associated with increased 30-day mortality compared with standard therapy (adjusted odds ratio 2.82; 95% confidence interval 1.20-6.66). The results of the sensitivity analyses were consistent with those of the primary analysis.Physicians should assess the risk for DRPs when determining the empirical antibiotic therapy and should refrain from administering unnecessary extended-spectrum antibiotics for patients with CAP with a low risk for DRPs.

Aims Klebsiella pneumoniae is a major cause of healthcare-associated infections. In this study, we aimed to develop a rapid and simple genotyping method that can characterize strains causing nosocomial infections. Methods and results The PCR-based open reading frame (ORF) typing (POT) method consists of two multiplex PCR reactions that were designed to detect 25 ORFs specific to bacterial genetic lineages, species, antimicrobial-resistant genes (blaCTX-M group-1, blaCTX-M group-9, blaIMP and blaKPC), a capsular K1-specific gene and a virulence factor gene (rmpA/A2). The electrophoresis results are then digitized. A total of 192 strains (136 clinical and 8 reference strains of K. pneumoniae, 33 clinical and 1 reference strains of K. variicola and 14 clinical strains of K. quasipneumoniae) were classified into 95, 26 and 11 POT values, respectively. The distribution patterns of ORFs among K. pneumoniae correlated well with multilocus sequence typing (MLST). Furthermore, closely related species could be distinguished and key antimicrobial resistance and hypervirulence genes were identified as part of POT. Conclusions The POT method was developed and validated for K. pneumoniae. In comparison to MLST, the POT method is a rapid and easy genotyping method for monitoring transmission events by K. pneumoniae in clinical microbiology laboratories. Significance and Impact of the Study The POT method supplies clear and informative molecular typing results for K. pneumoniae. The method would facilitate molecular epidemiological analysis in infection control and hospital epidemiology investigations.

The prognostic significance of absolute lymphocyte count (ALC) and absolute neutrophil count (ANC) remains unclear in patients with postoperative pneumonia (POP). The study objectives were to investigate the prognostic effects of ALC and ANC in POP patients, and to evaluate the time courses of ALC and ANC during hospitalization. This post-hoc analysis of a single-center prospective observational study evaluated consecutive POP patients, and comparatively analyzed community-acquired pneumonia (CAP) patients to highlight features of POP. In total, 228 POP patients and 1027 CAP patients were assessed. Severe lymphopenia (ALC 7500 cells/μL) was associated with better survival, whereas CAP patients with neutrophilia tended to have a lower survival rate. Prolonged lymphopenia and delayed increase in neutrophils were characteristic time-course changes of non-survivors in POP. The time courses of ALC and ANC between survivors and non-survivors in POP trended differently from those in CAP. Our study showed that ALC and ANC at pneumonia diagnosis can serve as prognostic factors in POP patients. Differences in time-course changes of ALC and ANC between survivors and non-survivors may provide important information for future immunological research in pneumonia.

Background Novel coronavirus disease 2019 (COVID-19) refers to infection with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pathogen, and has spread to pandemic levels since its inception in December 2019. While several risk factors for severe presentation have been identified, the clinical course for end-stage renal disease (ESRD) patients on maintenance hemodialysis with COVID-19 has been unclear. Previous studies have revealed that some antiviral agents may be effective against COVID-19 in the general population, but the pharmacokinetics and pharmacodynamics of these agents in ESRD patients remain under investigation. Favipiravir, an antiviral agent developed for treatment of influenza, is one candidate treatment for COVID-19, but suitable dosages for patients with renal insufficiency are unknown. Here we provide a first report on the efficacy of favipiravir in a patient with ESRD undergoing hemodialysis. Case presentation The case involved a 52-year-old woman with COVID-19 who had been undergoing maintenance hemodialysis three times a week for 3 years due to diabetic nephropathy. She had initially been treated with lopinavir/ritonavir and ciclesonide for 5 days, but developed severe pneumonia requiring invasive positive-pressure ventilation. Those antiviral agents were subsequently switched to favipiravir. She recovered gradually, and after 2 weeks was extubated once the viral load of SARS-CoV-2 fell below the limit of detection. Although concentrations of several biliary enzymes were elevated, no major adverse events were observed. Conclusion Favipiravir may be an effective option for the treatment of COVID-19-infected patients with ESRD.

Background In 2018, the Japanese medical reimbursement system was revised to introduce a fee for the implementation of an antimicrobial stewardship (AS) fee for pediatric patients. The purpose of this study was to evaluate physicians’ prescription behavior following this revision. Methods We conducted a retrospective observational study from January 1, 2017 to September 30, 2018 of pediatric ( Results The frequency of antibiotic prescription decreased after AS fee implementation, regardless of whether the facility claimed the AS fee, but tended to be lower in facilities that claimed the fee. Additionally, the frequency of antibiotic prescription decreased in all age groups. Despite the reduced frequency of antibiotic prescription, consultation behavior did not change. Conclusions The AS fee system, which compensates physicians for limiting antibiotic prescriptions, helped to reduce unnecessary antibiotic prescription and is thus a potentially effective measure against antimicrobial resistance.

The dissemination of difficult-to-treat carbapenem-resistant Enterobacterales (CRE) is of great concern. We clarified the risk factors underlying CRE infection mortality in Japan.We conducted a retrospective, multicentre, observational cohort study of patients with CRE infections at 28 university hospitals from September 2014 to December 2016, using the Japanese National Surveillance criteria. Clinical information, including patient background, type of infection, antibiotic treatment, and treatment outcome, was collected. The carbapenemase genotype was determined using PCR sequencing. Multivariate analysis was performed to identify the risk factors for 28-day mortality.Among the 179 patients enrolled, 65 patients (36.3%) had bloodstream infections, with 37 (20.7%) infections occurring due to carbapenemase-producing Enterobacterales (CPE); all carbapenemases were of IMP-type (IMP-1: 32, IMP-6: 5). Two-thirds of CPE were identified as Enterobacter cloacae complex. Combination therapy was administered only in 46 patients (25.7%), and the 28-day mortality rate was 14.3%. Univariate analysis showed that solid metastatic cancer, Charlson Comorbidity Index ≥3, bloodstream infection, pneumonia, or empyema, central venous catheters, mechanical ventilation, and prior use of quinolones were significant risk factors for mortality. Multivariate analysis revealed that mechanical ventilation (OR: 6.71 [1.42-31.6], P = 0.016), solid metastatic cancers (OR: 5.63 [1.38-23.0], P = 0.016), and bloodstream infections (OR: 3.49 [1.02-12.0], P = 0.046) were independent risk factors for 28-day mortality.The significant risk factors for 28-day mortality in patients with CRE infections in Japan are mechanical ventilation, solid metastatic cancers, and bloodstream infections.

Background Prediction of inpatients with community-acquired pneumonia (CAP) at high risk for severe adverse events (SAEs) requiring higher-intensity treatment is critical. However, evidence regarding prediction rules applicable to all patients with CAP including those with healthcare-associated pneumonia (HCAP) is limited. The objective of this study is to develop and validate a new prediction system for SAEs in inpatients with CAP. Methods Logistic regression analysis was performed in 1334 inpatients of a prospective multicenter study to develop a multivariate model predicting SAEs (death, requirement of mechanical ventilation, and vasopressor support within 30 days after diagnosis). The developed ALL-COP-SCORE rule based on the multivariate model was validated in 643 inpatients in another prospective multicenter study. Results The ALL-COP SCORE rule included albumin (2/FIO2 ratio (2 (> 45 mmHg, 2 points), HCO3− ( 2/3, 2 points; 1/2–2/3, 1 point). Patients with 4–5, 6–7, and ≥ 8 points had 17%, 35%, and 52% increase in the probability of SAEs, respectively, whereas the probability of SAEs was 3% in patients with ≤ 3 points. The ALL-COP SCORE rule exhibited a higher area under the receiver operating characteristic curve (0.85) compared with the other predictive models, and an ALL-COP SCORE threshold of ≥ 4 points exhibited 92% sensitivity and 60% specificity. Conclusions ALL-COP SCORE rule can be useful to predict SAEs and aid in decision-making on treatment intensity for all inpatients with CAP including those with HCAP. Higher-intensity treatment should be considered in patients with CAP and an ALL-COP SCORE threshold of ≥ 4 points. Trial registration This study was registered with the University Medical Information Network in Japan, registration numbers UMIN000003306 and UMIN000009837.

Understanding risk factors for antibiotic resistance (AR) in patients with hospital-acquired pneumonia (HAP) and ventilator-associated pneumonia (VAP) is important to select appropriate initial antibiotics and reduce broad-spectrum antibiotic overuse. However, available evidence is limited. We aimed to identify risk factors for AR in those patients.This prospective observational study was conducted at a tertiary-care hospital. Pathogens with AR were defined as those resistant to ampicillin-sulbactam or ceftriaxone. Risk factors for AR in patients with HAP and VAP were assessed using penalized logistic regression analysis.In total, 557 patients with HAP and VAP were enrolled. Pathogens were isolated from 315 patients, with AR identified in 68.3% (215/315). Among antibiotic-resistant pathogens (ARPs), Pseudomonas aeruginosa was isolated most frequently, followed by methicillin-resistant Staphylococcus aureus (MRSA). Significant risk factors for AR were chronic renal diseases (adjusted odds ratio: 2.82, 95% confidence interval: 1.79-7.83), history of ARP infection/colonization within the past 1 year (2.80, 1.90-7.02), bedridden state (1.84, 1.28-3.91), tube feeding (1.58, 1.09-2.98), and peripheral or central venous catheterization (1.57, 1.06-2.96). Additionally, a risk factor for ARPs that should be treated with anti-MRSA antibiotics was prior MRSA infection/colonization history. Those for ARPs requiring dual antipseudomonal antibiotics included prior non-MRSA ARP or MRSA infection/colonization history and bedridden state.The five factors we highlighted can be important criteria for identifying patients at risk of AR. Physicians should consider these potential risk factors when selecting antibiotics for initial empirical therapy in patients with HAP and VAP.

The spread of third-generation cephalosporin-resistant Gram-negative bacteria is a serious concern in acute and post-acute care settings. This study aimed to understand the epidemiology and molecular background of fecal colonization of resistant Enterobacterales in elderly people.In December 2015-December 2017, stool or rectal swab samples were collected from 101 elderly patients receiving home care, using long-term care facilities (LTCF), and living in nursing homes repeatedly at 3-9-month intervals. Patient clinical background data were collected from medical records. After phenotypic screening for extended-spectrum β-lactamase (ESBL), AmpC-type β-lactamase or carbapenemase production, drug resistance genes of isolates were analyzed using polymerase chain reaction (PCR). ESBL-producing Escherichia coli isolates obtained from the same patients in repetitive screenings were analyzed using PCR-based ORF typing. Risk factors for persistent carriage of resistant Enterobacterales were analyzed using multivariate analysis.Resistant Enterobacterales isolates were detected in 37 of 101 (36.6%) and 29 of 80 (36.3%) residents in first and second screenings, respectively. ESBL-producing E. coli accounted for 80% isolates, the most common being CTX-M-9-group β-lactamase producers. Molecular epidemiological analysis revealed probable transmissions of ESBL-producing E. coli; 58% of ESBL-producing E. coli colonizers were persistent colonizers at least after 3 -month intervals. Age87 years and LTCF residence were independent risk factors for persistent carriage of ESBL-producing E. coli.We showed, for the first time, high persistent colonization rate of ESBL-producing E. coli among elderly people in post-acute care settings with probable horizontal transmission. We also identified significant risk factors for persistent colonization.

The Enterobacter cloacae complex (ECC) is one of the most common causes of bacteremia and leads to poor clinical outcomes. The aim of this study was to clarify the antimicrobial susceptibility profiles and genetic backgrounds of non-carbapenemase-producing reduced-carbapenem-susceptible (RCS) ECC blood isolates in Japan using agar dilution antimicrobial susceptibility testing, whole-genome sequencing, and quantitative polymerase chain reaction for ampC, ompC, and ompF transcripts. Forty-two ECC blood isolates were categorized into RCS and carbapenem-susceptible groups based on the minimum inhibitory concentration of imipenem. The RCS ECC blood isolates belonged to distinct species and sequence types and produced varying class C β-lactamases. The E. roggenkampii, E. asburiae, and E. bugandensis isolates belonged only to the RCS group. Some E. hormaechei ssp. steigerwaltii isolates from the RCS group exhibited AmpC overexpression caused by amino acid substitutions in AmpD and AmpR along with ompF downregulation. These findings suggest that non-carbapenemase-producing RCS ECC blood isolates are genetically diverse.

Bacterial translocation, in which intestinal bacteria pass through the intestinal wall, enter the blood circulation, and spread to other sites of the body, is thought to cause bacteremia and sometimes febrile neutropenia (FN) in patients who receive cancer chemotherapy. We collected blood samples from 39 patients with various cancers at baseline and after chemotherapy began (during chemotherapy) and explored how frequently bacteria could be detected in the blood using a highly-sensitive, bacterial rRNA-targeted reverse transcription quantitative polymerase chain reaction (PCR) assay. Bacterial traces, typically Escherichia coli and Enterobacter spp., were detected in 10 patients (25.6%) at baseline and 11 patients (28.2%) during chemotherapy. The bacterial traces were positive either at baseline or during chemotherapy in 3 (60%) of 5 patients who had FN, and 6 (46%) of 13 patients aged 65 years or older. These findings support the notion that bacterial translocation occurs in patients with cancer regardless of whether they receive chemotherapy and can lead to the development of FN and other treatment-related infections.

BACKGROUND: Hospital outbreaks of antimicrobial-resistant (AMR) bacteria should be detected and controlled as early as possible. AIM: To develop a framework for automatic detection of AMR outbreaks in hospitals. METHODS: Japan Nosocomial Infections Surveillance (JANIS) is one of the largest national AMR surveillance systems in the world. For this study, all bacterial data in the JANIS database were extracted between 2011 and 2016. WHONET, a free software for the management of microbiology data, and SaTScan, a free cluster detection tool embedded in WHONET, were used to analyse 2015–2016 data of eligible hospitals. Manual evaluation and validation of 10 representative hospitals around Japan were then performed using 2011–2016 data. FINDINGS: Data from 1,031 hospitals were studied; mid-sized (200–499 bed) hospitals accounted for 60%, followed by large (≥ 500 beds) hospitals (24%) and small (< 200 beds) hospitals (16%). Large hospitals resulted in more clusters detected. Most of the clusters included five or fewer patients. From the in-depth analysis of 10 hospitals, approximately 80% of the detected clusters were unrecognised by infection control staff because the bacterial species involved were not included in the priority pathogen list for routine surveillance. In particular, in two hospitals, clusters of more susceptible isolates were detected before outbreaks of more resistant pathogens. CONCLUSION: WHONET-SaTScan can automatically detect clusters of epidemiologically-related patients based on isolate resistance profiles beyond lists of high-priority AMR pathogens. If clusters of more susceptible isolates can be detected, it may allow early intervention in infection control practices before outbreaks of more resistant pathogens occur.

Campylobacter enteritis (En) is the most frequently diagnosed bacterial En worldwide, including in Japan. Campylobacter spp. can also cause bloodstream infection (BSI), reactive arthritis, and Guillain-Barré syndrome. The purpose of this study was to clarify the characteristics of Campylobacter jejuni strains that cause BSI in comparison with En-causing strains. BSI strains (n = 40) and En strains that caused food poisoning (n = 67) were collected in Japan. Our study revealed that ST-4526 was predominant in BSI strains, and the overall distribution of sequence types was similar in both BSI and En strains. Differences in CPS type distribution might be related to the pathogenesis of bacteremia. Quinolone resistance rates were higher than those reported in previous studies, and strains resistant to both quinolones and tetracyclines were more frequently observed in BSI strains. Finally, we report a case of mixed infection with different STs in BSI.

We herein report a 59-year-old woman with a 2-year history of chronic bursitis of the hand who took 50 mg/day prednisolone for several autoimmune diseases. Mycobacteroides abscessus subsp. massiliense was isolated from the abscess and blood culture. Combination therapy (imipenem/cilastatin, amikacin, and clarithromycin) was administered for a month. Two months later, M. massiliense was detected from a blood culture again, and disseminated lesions were found. Clarithromycin and sitafloxacin were administered following eight weeks of the same regimen. Six months after the diagnosis, M. massiliense was isolated from a blood culture, and she expired due to multiple organ failure.

Patterns of the use of anti-methicillin-resistant Staphylococcus aureus (MRSA) agents in Japan might be influenced by the launch of new anti-MRSA agents, the publication of relevant guidelines, and the increase in the number of generic medicines. However, as anti-MRSA agents are included in multiple anatomical therapeutic chemical classifications, such as glycopeptides and aminoglycosides, the trends of the use of individual anti-MRSA agents remain unclear. Here, we aimed to clarify the trends of anti-MRSA agent use in Japan from 2006 to 2015 based on sales data. Total anti-MRSA agent use was found to have significantly increased from 2006 to 2015 (P

In Japan, there is no national surveillance study of Clostridioides (Clostridium) difficile infection (CDI), and details about the epidemiology and treatment status of CDI are unknown. Additionally, clinical practice guidelines (CPGs) for CDI are published by four different institutions. All CPGs recommend that the antimicrobials, vancomycin (VCM) and metronidazole (MNZ), should be selected according to disease severity. However, the trends for VCM and MNZ use in Japan remain unclear. Therefore, this study was aimed at clarifying the secular trends for VCM and MNZ use based on sales data from 2006 to 2015 and discussing its impact on CDI status and drug costs. This is the first study to clarify the antibiotic use trends for CDI treatment. We found that the total use increased over time (r = 0.0013, P

A 47-year-old man with acute myeloid leukemia and myelodysplastic-related changes relapsed after an allogenic bone marrow transplant and received a cord blood transplant as salvage therapy. The patient developed febrile neutropenia that was resistant to broad-spectrum antibiotics and multiple, painful, nodular skin lesions on his trunk and extremities before engraftment. A skin biopsy and blood culture found mold, and the subsequent microscopic examination, mass spectrometry, and DNA sequencing of the fungal colonies identified Fusarium solani. The patient's fever and skin lesions began to improve with the administration of liposomal amphotericin B at 5 mg/kg/day. Neutrophilic engraftment occurred on day 19. Stage 3 acute skin graft-versus-host disease was cured by the application of topical steroid. Unexpectedly, a change from liposomal amphotericin B to voriconazole on day 38 exacerbated the Fusarium infection. The Fusarium infection was finally cured by the administration of liposomal amphotericin B for a total of 19 weeks. Neutrophilic engraftment, an immediate definitive diagnosis, the sufficient and long-term administration of appropriate antifungal medication, and avoidance of the systemic administration of steroids might have contributed to the successful outcome of this patient.

Background The aim of this study was to review the surgical outcomes of patients who underwent major hepatectomy with extrahepatic bile duct resection after preoperative biliary drainage with a particular focus on the impact of preoperative biliary colonization/infection caused by multidrug-resistant pathogens. Methods Medical records of patients who underwent hepatobiliary resection after preoperative external biliary drainage between 2001 and 2015 were reviewed retrospectively. Prophylactic antibiotics were selected according to the results of drug susceptibility tests of surveillance bile cultures. Results In total, 565 patients underwent surgical resection. Based on the results of bile cultures, the patients were classified into three groups: group A, patients with negative bile cultures (n = 113); group B, patients with positive bile cultures without multidrug-resistant pathogen growth (n = 416); and group C, patients with multidrug-resistant pathogen–positive bile culture (n = 36). The incidence of organ/space surgical site infection, bacteremia, median duration of postoperative hospital stay, and the mortality rate did not differ among the three groups. The incidence of incisional surgical site infection and infectious complications caused by multidrug-resistant pathogens was significantly higher in group C than in groups A and B. Fifty-two patients had postoperative infectious complications caused by multidrug-resistant pathogens. Multivariate analysis identified preoperative multidrug-resistant pathogen–positive bile culture as a significant independent risk factor for postoperative infectious complications caused by multidrug-resistant pathogens (P Conclusion Major hepatectomy with extrahepatic bile duct resection after biliary drainage can be performed with acceptable rates of morbidity and mortality using appropriate antibiotic prophylaxis, even in patients with biliary colonization/infection caused by multidrug-resistant pathogens.

To evaluate the optimal duration of antimicrobial prophylaxis in patients undergoing "complicated"' major hepatectomy with extrahepatic bile duct resection.To date, 4 randomized controlled trials (RCTs) have assessed the duration of antimicrobial prophylaxis after hepatectomy. However, all of these previous studies involved only "simple" hepatectomy without extrahepatic bile duct resection.Patients with suspected hilar obstruction scheduled to undergo complicated hepatectomy after biliary drainage were randomized to 2-day (antibiotic treatment on days 1 and 2) or 4-day (on days 1 to 4) groups. Antibiotics were selected based on preoperative bile culture. The primary endpoint was the incidence of postoperative infectious complications.In total, 86 patients were included (43 patients in each arm) without between-group differences in baseline characteristics. Bile culture positivity was similar between the 2 groups. No significant between-group differences were observed in surgical variables. The incidence of any infectious complications was similar between the 2 groups (30.2% in the 2-day group and 32.6% in the 4-day group). The positive rate of systemic inflammatory response syndrome and the incidence of additional antibiotic use were almost identical between the 2 groups. According to Clavien-Dindo classification, grade 3a or higher complications occurred in 23 patients (53.5%) in the 2-day group and 29 patients (67.4%) in the 4-day group (P = 0.186). Postoperative hospital stay was not different between the 2 groups.Two-day administration of antimicrobial prophylaxis is sufficient for patients undergoing hepatectomy with extrahepatic bile duct resection [Registration number: ID 000009800 (University Hospital Medical Information Network, http://www.umin.ac.jp)].

Purpose Our objective was to evaluate the utility of the national database (NDB) based on health insurance claims data for antimicrobial use (AMU) surveillance in medical institutions in Japan. Methods The population-weighted total AMU expressed as defined daily doses (DDDs) per 1000 inhabitants per day (DID) was measured by the NDB. The data were compared with our previous study measured by the sales data. Trend analysis of DID from 2011 to 2013 and subgroup analysis stratified by antimicrobial category and age group were performed. Results There was a significant linear correlation between the AMUs measured by the sales data and the NDB. Total oral and parenteral AMUs (expressed in DID) were 1.04-fold from 12.654 in 2011 to 13.202 in 2013 and 1.13-fold from 0.734 to 0.829, respectively. Percentage of oral form among total AMU was high with more than 94% during the study period. AMU in the children group (0–14 years) decreased from 2011 to 2013 regardless of dosage form, although the working age group (15–64 years) and elderly group (65 and above years) increased. Oral AMU in the working age group was approximately two-thirds of those in the other age groups. In contrast, parenteral AMU in the elderly group was extremely high compared to the other age groups. Conclusions The trend of AMU stratified by antimicrobial category and age group were successfully measured using the NDB, which can be a tool to monitor outcome indices for the national action plan on antimicrobial resistance.

Pneumococcal biliary tract infections (PBTIs) were reported as rare due to the bacterium's bile solubility. The purpose of this study was to determine the occurrence and clinical characteristics of PBTIs. A retrospective case series review was conducted from January 2006 to August 2014 at a tertiary referral university hospital in Japan. Patients with a blood or bile culture positive for Streptococcus pneumoniae diagnosed with definite cholangitis or cholecystitis according to Tokyo Guideline 2013 were enrolled in this study. Data on clinical information, treatments, and outcomes were collected. During 104 months, 48 cases of positive blood cultures and 13 cases of positive bile cultures were recorded, and after excluding 43 and 5 of these, respectively, a total of 10 patients were diagnosed with PBTI. Most patients (9/10) had biliary tract problems and biliary devices in place. PBTIs were not rare; conversely, they were a relatively common cause of pneumococcal bacteremia in this center treating a high volume of biliary tract illnesses.

To gain insights on how visual information of the real world is filtered, compressed, and encoded by the vertebrate retinas, emulating in silico the spatiotemporal patterns of the graded and action potentials of neuronal responses to natural visual scenes on biological time scale is a feasible approach. As a basic platform for such an emulation, we here developed a compact hardware system comprising an analog silicon retina and a field-programmable gate array module. With utilizing the Izhikevich formalism, a retinal circuit model that emulates spiking of ganglion cells was implemented in this system. The emulated spike timing had the resolution of about 2 ms relative to the stimulus onset and was little affected by timings of the synchronous frame sampling in the silicon retina. Thus, the emulator can mimic the event-driven spike outputs of biological retinas. The system was useful for simultaneously visualizing neural images of both the graded potentials and the spikes in response to real live visual scenes. Since our emulator system is reconfigurable, it provides a flexible platform for investigating visual functions of retinal circuits under natural visual environment.

Background To clarify the molecular epidemiology of carbapenem-resistant Enterobacter cloacae complex (CREC) and the risk factors for acquisition of carbapenemase-producing E. cloacae complex (CPEC). Methods Using clinical CREC isolates detected in a Japanese university hospital over 4 years, carbapenemase production was screened with phenotypic methods. Carbapenemase genes were analysed by PCR and sequencing. Molecular epidemiological analyses were conducted with repetitive extragenic palindromic (REP)-PCR and multilocus sequence typing (MLST). CRECs were identified to the subspecies level by hsp60 sequencing. Whole-genome sequencing of plasmids was conducted. A case-control study was performed to identify risk factors for acquisition of CPEC among patients with CREC. Results Thirty-nine CRECs including 20 CPECs carrying blaIMP-1 were identified. Patients with CPEC had longer hospital stay before detection (26.5 days vs. 12 days, p = 0.008), a urinary catheter (odds ratio [OR], 5.36; 95% confidence interval [CI], 1.14–30.9; p = 0.023), or intubation (OR, 7.53; 95% CI, 1.47–53.8; p = 0.008) compared to patients without CPEC. Four genetically closely related CPEC clusters were observed, which showed that three of four CPEC clusters corresponded to E. asburiae (ST 53), E. hormaechei subsp. steigerwaltii (ST 113 and ST 1047) and E. cloacae subsp. cloacae (ST 513) by MLST and hsp60 sequencing. Seven representative plasmids shared structures with class I integron containing blaIMP-1 and IncHI2A replicon type. Conclusions A longer hospital stay, presence of a urinary catheter, and intubation are risk factors for CPEC acquisition. In addition to horizontal transmission of genetically indistinguishable CPECs, IncHI2A plasmid carrying blaIMP-1 appeared to be transferred among genetically different ECs.

Mycobacterium avium subsp. hominissuis (MAH) causes disease in both humans and swine; however, the genetic variations in MAH isolates are unclear. The aim of this study was to elucidate the genetic variations in MAH isolates from humans and swine in Japan. We analysed the 16S-23S rDNA internal transcribed spacer (ITS) sequence and variable number of tandem repeats (VNTRs) using the Mycobacterium avium tandem repeat loci, prevalence of ISMav6 and clarithromycin resistance for MAH isolates from patients with pulmonary MAC (pMAC) disease (n=69), and HIV-seropositive and blood culture-positive (HIV-MAC) patients (n=28) and swine (n=23). In the minimum spanning tree based on VNTR analysis, swine MAC isolates belonged to a cluster distinguishable from that of human pMAC isolates. Isolates from HIV-MAC were scattered throughout both clusters. The three major distinct sequevars, Mav-A, Mav-B and Mav-F, were determined according to 16S-23S rDNA ITS sequence analysis in addition to three new sequevars, Mav-Q, Mav-R and Mav-S. Mav-A and Mav-F comprised the majority of human pMAC strains; in contrast, Mav-B predominated in swine isolates. Distribution of ITS sequevars in the minimum spanning tree based on VNTR analysis showed similar clusters of isolates from different origins, i.e. human pMAC, HIV-MAC and swine. These results, together with ISMav6 possession and clarithromycin resistance, revealed the genetic diversity of MAH strains recovered from humans and swine. Molecular epidemiology and genetic characterization in the present study showed the distinctive genetic evolutionary lineage of MAH strains isolated from human pMAC diseases and swine.

We developed a vision sensor system that performs a scale-invariant feature transform (SIFT) in real time. To apply the SIFT algorithm efficiently, we focus on a two-fold process performed by the visual system: whole-image parallel filtering and frequency-band parallel processing. The vision sensor system comprises an active pixel sensor, a metal-oxide semiconductor (MOS)-based resistive network, a field-programmable gate array (FPGA), and a digital computer. We employed the MOS-based resistive network for instantaneous spatial filtering and a configurable filter size. The FPGA is used to pipeline process the frequency-band signals. The proposed system was evaluated by tracking the feature points detected on an object in a video. We developed a real-time vision system with analog/digital mixed architecture.The system consists of an analog MOS transistor resistive network (RN) and an FPGA.The RN conducts multi-scale filtering in real time with a low power consumption.The FPGA finds scale-invariant key points by frequency-band parallel processing.The system was combined with a PC to track a moving target of a varying scale.

The reported number of transcatheter aortic valve replacement-associated infective endocarditis (TAVR-IE) cases has been increasing worldwide, but information about the incidence and clinical features of fungal TAVR-IE is quite limited. We present a patient who acquired TAVR-IE caused by Candida parapsilosis four month after TAVR, who was successfully treated redo-aortic valve replacement and prolonged antifungal therapy.

This report described the experience of active surveillance culture implemented in response to the identification of a single carbapenemase-producing Escherichia coli in a Japanese university hospital. It revealed a horizontal transmission event and an additional asymptomatic carrier of carbapenemase-producing Escherichia coli with unique drug susceptibility and resistance gene profiles. Early implementation of active surveillance culture as a part of multifaceted infection control measures appeared to be useful to control further transmission of carbapenemase-producing Escherichia coli even in the low endemic facility. Further investigations on the timing and usefulness of active surveillance culture in the control of carbapenemase-producing Enterobacteriaceae would be warranted.

Background Bloodstream infection (BSI) is a severe complication in immunocompromised patients. Prompt identification of causative microorganisms would improve the outcome of BSI due to optimization of antimicrobial treatment. Next-generation sequencing (NGS) allows us to analyze comprehensively and quantitatively all microorganisms present in a clinical sample in comparison with blood culture. However, there are currently no established methods to identify causative pathogens by NGS. Methods BSI was defined by the following criteria: (i) pathogen isolated from blood culture and (ii) fever ≥38.0°C or C-reactive protein >1.0mg/dl. Thirty-five pediatric patients (12 with BSI and 23 with suspected BSI/negative blood culture) were enrolled. Plasma/serum samples were used for sequencing and the results were compared with those from blood culture. The bacterial reads per million reads of the sequence depth (BR) and relative importance values of the dominant bacteria (P1) were applied to identify causative pathogens. Results Sequencing reads of bacteria isolated in blood culture were identified by NGS in all plasma/serum samples at the onset of BSI. Additionally, bacteria isolated in blood culture were identical to the dominant bacteria by NGS in 8 of 12 patients with BSI. Causative microorganisms were detected when the NGS results fulfilled the criteria of BR >200 and P1 >0.5. In two patients with catheter-related BSI, causative bacteria were detected in the plasma/serum at 7 days before disease onset. Causative pathogens (Tatlockia micdadei, Escherichia coli, and human adenovirus 2) were identified in three of 23 patients in the suspected BSI group. A total of 62 resistance genes were detected in nine patients with sequences covering 5–100% of references. Conclusion An NGS-based approach has great potential for analysis of causative microorganisms in BSI and may help to diagnose a disease before disease onset. Antimicrobial resistance genes can also be found through sequence data processing. Disclosures All authors: No reported disclosures.

Summary Background Appropriate initial antibiotics are essential for the treatment of infectious diseases. However, some patients with pneumonia might develop adverse outcomes, despite receiving appropriate initial antibiotics. We aimed to clarify the risk factors for 30-day mortality in patients who received appropriate initial antibiotics and to identify potential candidates who would benefit from adjunctive therapy. Methods From March 15, to Dec 22, 2010, we did a prospective, observational study at ten medical institutions in hospitalised patients (aged ≥20 years) with pneumonia. We did a multivariable logistic regression analysis to calculate odds ratios (ORs) and 95% CI to assess the risk factors for 30-day mortality. This study was registered with the University Medical Information Network in Japan, number UMIN000003306. Findings The 30-day mortality was 11% (61 of 579 patients) in the appropriate initial antibiotic treatment group and 17% (29 of 168) in the inappropriate initial antibiotic treatment group. Albumin concentration of less than 30 mg/L (adjusted OR 3·39, 95% CI 1·83–6·28), non-ambulatory status (3·34, 1·84–6·05), pH of less than 7·35 (3·13, 1·52–6·42), respiration rate of at least 30 breaths per min (2·33, 1·28–4·24), and blood urea nitrogen of at least 7·14 mmol/L (2·20, 1·13–4·30) were independent risk factors in patients given appropriate initial antibiotic treatment. The 30-day mortality was 1% (one of 126 patients), 1% (two of 168), 17% (23 of 137), 22% (20 of 89), and 44% (14 of 32) for patients with no, one, two, three, and four or five risk factors, respectively. Interpretation Patients with two or more risk factors were at a higher risk of death during the 30 days assessed than were individuals with no or one risk factor, despite appropriate initial antibiotic treatment. Therefore, adjunctive therapy might be important for improving outcomes in patients with two or more risk factors. Funding Central Japan Lung Study Group.

Mycobacterium avium complex (MAC) infections are increasing annually in many countries. MAC strains are the most common nontuberculous mycobacterial pathogens isolated from respiratory samples and predominantly consist of two species, Mycobacterium avium and Mycobacterium intracellulare. The aim of this study was to analyze the molecular epidemiology and genetic backgrounds of clinical MAC isolates collected from The Netherlands, Germany, United States, Korea and Japan. Variable numbers of tandem repeats (VNTR) analysis was used to examine the genetic relatedness of clinical isolates of M. avium subsp. hominissuis (n=261) and M. intracellulare (n=116). Minimum spanning tree and unweighted pair group method using arithmetic averages analyses based on the VNTR data indicated that M. avium subsp. hominissuis isolates from Japan shared a high degree of genetic relatedness with Korean isolates, but not with isolates from Europe or the United States, whereas M. intracellulare isolates did not show any specific clustering by geographic origin. The findings from the present study indicate that strains of M. avium subsp. hominissuis, but not M. intracellulare, exhibit geographical differences in genetic diversity and imply that MAC strains may have different sources, routes of transmission and perhaps clinical manifestations.

Purpose. This study examined the risk factors for, and molecular mechanisms underlying, the increase in carbapenem minimum inhibitory concentrations (MICs) in clinical isolates of Pseudomonas aeruginosa. Methodology. Consecutive clinical isolates of P. aeruginosa were collected. The MicroScan WalkAway system detected more than fourfold increases in the MICs of carbapenems in P. aeruginosa isolates serially recovered from some patients during their clinical course. The clinical risk factors associated with this increase were examined by multiple logistic regression analysis. Western blot analysis and nucleotide sequencing of the oprD gene of 19 clonally related and paired P. aeruginosa isolates from the same patients were undertaken to examine the mechanisms underlying the increase in MICs. Results. The results showed that prior use of carbapenems (OR, 2.799; 95 % CI, 1.088–7.200; P=0.033) and the use of ventilators or tracheostomies (OR, 2.648; 95 % CI, 1.051–6.671; P=0.039) were risk factors for increased carbapenem MICs. Analysis of the underlying mechanisms revealed that loss of functional OprD protein due to mutation of the oprD gene tended to occur in P. aeruginosa isolates with imipenem MICs of more than 8 µg ml−1; a reduction in OprD expression was observed in P. aeruginosa isolates with imipenem MICs of 4 or 8 µg ml−1. This difference in the resistance mechanism was not correlated with the MICs of meropenem. Conclusion. This difference in the resistance mechanism of P. aeruginosa indicates a critical breakpoint at an imipenem MIC of 8 µg ml−1, in accordance with EUCAST criteria. Reducing carbapenem use will prevent P. aeruginosa clinical isolates from developing resistance to carbapenems.

SummaryBackground Methicillin-resistant Staphylococcus aureus bacteremia (MRSA-B) is associated with high mortality and implementing an appropriate antimicrobial stewardship (AS) program with treatment intervention is essential. The aim of this study was to evaluate the impact of AS with pharmacist intervention on patients with MRSA-B. Methods Patients who were diagnosed with MRSA-B between January 2012 and April 2013 were defined as the pre-intervention group, while those diagnosed between May 2013 and December 2015 were defined as the intervention group (ie, AS with pharmacist intervention). The factors affecting bundle compliance rates and mortality were analysed. Result The pre-intervention group comprised 43 patients and the intervention group comprised 51 patients. Bundle compliance rates were estimated as follows in the intervention group: an increase was observed in the appropriate duration of therapy (from 44.8% to 72.1%, P = .027), incidences of the early use of anti-MRSA drugs (from 62.3% to 82.4%, P = .038), and the number of negative follow-up blood cultures (from 40.0% to 80.0%, P

Drug-resistant pathogen (DRP) risk stratification is important for choosing a treatment strategy for community-onset pneumonia. Evidence for benefits of non-antipseudomonal β-lactam plus macrolide combination therapy (BLM) on mortality is limited in patients at low DRP risk. Risk factors for mortality remain to be clarified.Post hoc analysis using a prospective multicentre study cohort of community-onset pneumonia was performed to assess 30-day differences in mortality between non-antipseudomonal β-lactam monotherapy (BL) and BLM groups. Logistic regression analysis was performed to assess the therapeutic effect and risk factors for mortality in patients at low DRP risk.In total, 594 patients with community-onset pneumonia at low DRP risk (369 BL and 225 BLM) were analysed. The 30-day mortality in BL and BLM was 13.8% and 1.8%, respectively (P 0.001). Multivariate analysis showed that BLM reduced the 30-day mortality (adjusted odds ratio: 0.28, 95% CI: 0.09-0.87) compared with BL. Independent prognostic factors for 30-day mortality included arterial partial pressure of carbon dioxide (PaCOIn patients with community-onset pneumonia at low DRP risk, BLM treatment reduced 30-day mortality compared with BL. Independent risk factors for mortality are potential confounding factors when assessing antibiotic effects in randomized clinical trials.

G-protein-coupled receptors (GPCRs) form the largest family of transmembrane receptors, and their oligomerization has been suggested to be related to their functions. Despite extensive studies, their oligomeric states are highly controversial. One of the reasons is the overestimation of oligomerization by conventional methods. We recently established a stoichiometric analysis method for precisely determining the oligomeric state of membrane proteins on living cells with the combined use of the coiled-coil labeling method and a spectral imaging technique and showed that the prototypical class-A GPCR β

Objectives: The Mycoses Forum in Japan has developed management bundles for candidaemia to incorporate into bedside practice. The aim of this study was to investigate nationwide compliance with the bundles and their impact on clinical outcomes. Methods: Non-neutropenic patients treated with antifungals for candidaemia were surveyed. Bundles consist of nine items to complete. Data were sent to the central office between July 2011 and April 2012. Results: Six hundred and eight patients were analysed. The compliance rate for achieving all elements was 6.9%, and it increased to 21.4% when compliance was analysed by the bundle except for oral switch. There was a significant difference in clinical success between patients with and without compliance [92.9% versus 75.8% (P ¼0.011)]. Compliance with the bundles, however, failed to be an independent factor associated with favourable outcomes. When step-down oral therapy was excluded from the elements of compliance, compliance with the bundles was revealed to be an independent predictor of clinical success (OR 4.42, 95% CI 2.05 –9.52) and mortality (OR 0.27, 95% CI 0.13 – 0.57). Independent individual elements contributing to clinical success were removal of central venous catheters within 24 h, assessment of clinical efficacy on the third to the fifth day and at least 2 weeks of therapy after clearance of candidaemia. Conclusions: Compliance with the bundles for candidaemia had a beneficial effect on clinical outcomes. Promotion of the bundles approach may have the potential to narrow the gap between clinical evidence and bedside practice.

Identification of patients with drug-resistant pathogens at initial diagnosis is essential for treatment of pneumonia.To elucidate clinical features of community-acquired pneumonia (CAP) and healthcare-associated pneumonia (HCAP), and to clarify risk factors for drug-resistant pathogens in patients with CAP and HCAP.A prospective observational study was conducted in hospitalized patients with pneumonia at 10 institutions in Japan. Pathogens identified as not susceptible to ceftriaxone, ampicillin-sulbactam, macrolides, and respiratory fluoroquinolones were defined as CAP drug-resistant pathogens (CAP-DRPs).In total, 1,413 patients (887 CAP and 526 HCAP) were analyzed. CAP-DRPs were more frequently found in patients with HCAP (26.6%) than in patients with CAP (8.6%). Independent risk factors for CAP-DRPs were almost identical in patients with CAP and HCAP. These included prior hospitalization (adjusted odds ratio [AOR], 2.06; 95% confidence interval [CI], 1.23-3.43), immunosuppression (AOR, 2.31; 95% CI, 1.05-5.11), previous antibiotic use (AOR, 2.45; 95% CI, 1.51-3.98), use of gastric acid-suppressive agents (AOR, 2.22; 95% CI, 1.39-3.57), tube feeding (AOR, 2.43; 95% CI, 1.18-5.00), and nonambulatory status (AOR, 2.45; 95% CI, 1.40-4.30) in the combined patients with CAP and HCAP. The area under the receiver operating characteristic curve for counting the number of risk factors was 0.79 (95% CI, 0.74-0.84).The clinical profile of HCAP was different from that of CAP. However, physicians can predict drug resistance in patients with either CAP or HCAP by taking account of the cumulative number of the risk factors. Clinical trial registered with https://upload.umin.ac.jp/cgi-open-bin/ctr/ctr.cgi?function=browsaction=browstype=summaryrecptno=R000004001language=E ; number UMIN000003306.

Plasmid-mediated AmpC β-lactamase-producing Escherichia coli (AmpC-E) bacteraemia was characterized by comparison with bacteraemia caused by extended-spectrum β-lactamase (ESBL)-producing E. coli (ESBL-E) and non-resistant E. coli (NR-E) in the era of the worldwide spread of the CTX-M-15-producing O25b-ST131-B2 clone. Of 706 bloodstream E. coli isolates collected between 2005 and 2010 in three Japanese university hospitals, 111 ESBL screening-positive isolates were analysed for AmpC and ESBL genes by PCR. A case–control study was performed in which the cases consisted of all of the patients with AmpC-E bacteraemia. Phylogenetic groups, sequence types and O25b serotype were determined. Twenty-seven AmpC-E isolates (26 of which were of the CMY-2 type) were identified, and 54 ESBL-E and 54 NR-E isolates were selected for the controls. Nineteen AmpC-E isolates were also positive for ESBL. CTX-M-14 was the most prevalent ESBL type among both the AmpC-E and ESBL-E isolates. The O25b-ST131-B2 clone was the most prevalent among the ESBL-E isolates (26%) and the second most prevalent among the NR-E isolates (13%), but only one O25b-ST131-B2 clone was found among the AmpC-E isolates. Twenty-three different sequence types were identified among the AmpC-E isolates. When compared with bacteraemia with ESBL-E, previous isolation of multidrug-resistant bacteria and intravascular catheterization were independently associated with a lower risk for AmpC-E. When compared with NR-E bacteraemia, prior use of antibiotics was the only significant risk factor for AmpC-E. Unlike the spread of the O25b-ST131-B2 clone between ESBL-E and NR-E, the AmpC-E isolates were not dominated by any specific clone.

Background The risk of infection, including surgical site infection (SSI), after spine surgery has increased due to aging and more immunocompromised hosts. An infection control team (ICT) is responsible for management of health care-associated infections at our institution. Methods The study subjects were 40 patients (18 men and 22 women with an average age of 54 years) referred to the ICT after spine surgery since 2010. Pathogenic bacteria and treatment in these cases were reviewed. Results Collaboration with the ICT involved guidance on use of antibiotics for infection in 30 patients (16 SSI and 14 non-SSI) and a search for the infection focus for fever of unknown origin in 10 patients (7 patients were found to have urinary tract infections and 2 patients were found to have pneumonia). The detection rate of causative bacteria in ICT consultation was 88% (35 out of 40 patients). SSI patients with instrumentation involved had a significantly higher rate of methicillin-resistant Staphylococcus aureus infection compared with those without instrumentation (42% vs 13%; P Discussion All cases of SSI with instrumentation involved were cured by ICT support without removal of instrumentation. Early assistance from the ICT was important for prevention of worsening of methicillin-resistant S aureus infection. Conclusions Collaboration with the ICT was helpful for detection of pathogenic bacteria and allowed appropriate use of antibiotics at an early stage.

Background Point prevalence surveys (PPSs) in Japanese hospitals have not yet been reported. The purpose of this pilot PPS study was to evaluate the epidemiology of health care–associated infections (HAIs) and antimicrobial use in a Japanese tertiary university hospital. Methods A 1-day, cross-sectional PPS was performed at a Japanese university hospital. Data on demographics, active HAIs, and antimicrobial use of all inpatients were collected using a data collection form. Results Of 841 patients, 85 (10.1%) had 90 active HAIs, and 308 patients (36.6%) were administered 494 antimicrobials. Among the 90 HAIs and 58 pathogens, the most frequent infection and isolated pathogen were pneumonia (20.0%) and Enterobacteriaceae (27.6%), respectively. Of the 118 antimicrobials used for treatment of HAIs, carbapenems were the most frequently administered category of antimicrobials (22.9%). In regard to antimicrobials for surgical prophylaxis, 37 of 119 (31.1%) were administered to patients on postoperative day 3 or later, and 48 of 119 (40.3%) were administered orally. Conclusions The incidence of HAIs is higher than in other developed countries. The social and medical situation in Japan may affect patient demographics, active HAIs, and antimicrobial use. Multicenter PPSs are necessary to uncover the real epidemiology of HAIs and antimicrobial use in Japan.

The visual system of the brain can perceive an external scene in real-time with extremely low power dissipation, although the response speed of an individual neuron is considerably lower than that of semiconductor devices. The neurons in the visual pathway generate their receptive fields using a parallel and hierarchical architecture. This architecture of the visual cortex is interesting and important for designing a novel perception system from an engineering perspective. The aim of this study is to develop a vision system hardware, which is designed inspired by a hierarchical visual processing in V1, for real time texture segregation. The system consists of a silicon retina, orientation chip, and field programmable gate array (FPGA) circuit. The silicon retina emulates the neural circuits of the vertebrate retina and exhibits a Laplacian-Gaussian-like receptive field. The orientation chip selectively aggregates multiple pixels of the silicon retina in order to produce Gabor-like receptive fields that are tuned to various orientations by mimicking the feed-forward model proposed by Hubel and Wiesel. The FPGA circuit receives the output of the orientation chip and computes the responses of the complex cells. Using this system, the neural images of simple cells were computed in real-time for various orientations and spatial frequencies. Using the orientation-selective outputs obtained from the multi-chip system, a real-time texture segregation was conducted based on a computational model inspired by psychophysics and neurophysiology. The texture image was filtered by the two orthogonally oriented receptive fields of the multi-chip system and the filtered images were combined to segregate the area of different texture orientation with the aid of FPGA. The present system is also useful for the investigation of the functions of the higher-order cells that can be obtained by combining the simple and complex cells.

We designed a VLSI binocular vision system that emulates the disparity computation in the primary visual cortex (V1). The system consists of two silicon retinas, orientation chips, and field programmable gate array (FPGA), mimicking a hierarchical architecture of visual information processing in the disparity energy model. The silicon retinas emulate a Laplacian-Gaussian-like receptive field of the vertebrate retina. The orientation chips generate an orientation-selective receptive field by aggregating multiple pixels of the silicon retina, mimicking the Hubel-Wiesel-type feed-forward model in order to emulate a Gabor-like receptive field of simple cells. The FPGA receives outputs from the orientation chips corresponding to the left and right eyes and calculates the responses of the complex cells based on the disparity energy model. The system can provide the responses of complex cells tuned to five different disparities and a disparity map obtained by comparing these energy outputs. Owing to the combination of spatial filtering by analog parallel circuits and pixel-wise computation by hard-wired digital circuits, the present system can execute the disparity computation in real time using compact hardware.

We describe a novel real-time system that emulates the architecture and functionality of the vertebrate retina. This system reconstructs the neural images formed by the retinal neurons in real time by using a combination of analog and digital systems consisting of a neuromorphic silicon retina chip, a field-programmable gate array, and a digital computer. While the silicon retina carries out the spatial filtering of input images instantaneously, using the embedded resistive networks that emulate the receptive field structure of the outer retinal neurons, the digital computer carries out the temporal filtering of the spatially filtered images to emulate the dynamical properties of the outer retinal circuits. The emulations of the neural image, including 128 x 128 bipolar cells, are carried out at a frame rate of 62.5 Hz. The emulation of the response to the Hermann grid and a spot of light and an annulus of lights has demonstrated that the system responds as expected by previous physiological and psychophysical observations. Furthermore, the emulated dynamics of neural images in response to natural scenes revealed the complex nature of retinal neuron activity. We have concluded that the system reflects the spatiotemporal responses of bipolar cells in the vertebrate retina. The proposed emulation system is expected to aid in understanding the visual computation in the retina and the brain.

We assess the usefulness of F-18-fluoro-deoxyglucose (FDG) positron emission tomography (PET) in the evaluation of gastrointestinal metastases. Four cases (five lesions) in which metastases from three lung cancers and one malignant fibrous histiocytoma (MFH) of the femur were found in the gastrointestinal tract were reviewed (men/women 3 : 1, age 63-78 years, mean 72 years). The five lesions were duodenal, jejunal metastasis, and two stomach metastases from lung carcinoma, and rectal metastasis from MFH of the femur. FDG-PET was unable to detect small masses, but it was able to detect unforeseen lesions such as gastrointestinal metastases because FDG-PET is a whole-body scan in a single-operation examination. FDG-PET imaging provided valuable information for the diagnosis of gastrointestinal metastasis.

Mycobacterium avium complex (MAC) causes mainly two types of disease. The first is disseminated disease in immunocompromised hosts, such as individuals infected by human immunodeficiency virus (HIV). The second is pulmonary disease in individuals without systemic immunosuppression, and the incidence of this type is increasing worldwide. M. avium subsp. hominissuis, a component of MAC, causes infection in pigs as well as in humans. Many aspects of the different modes of M. avium infection and its host specificity remain unclear. Here, we report the characteristics and complete sequence of a novel plasmid, designated pMAH135, derived from M. avium strain TH135 in an HIV-negative patient with pulmonary MAC disease. The pMAH135 plasmid consists of 194,711 nucleotides with an average G + C content of 66.5% and encodes 164 coding sequences (CDSs). This plasmid was unique in terms of its homology to other mycobacterial plasmids. Interestingly, it contains CDSs with sequence homology to mycobactin biosynthesis proteins and type VII secretion system-related proteins, which are involved in the pathogenicity of mycobacteria. It also contains putative conserved domains of the multidrug efflux transporter. Screening of isolates from humans and pigs for genes located on pMAH135 revealed that the detection rate of these genes was higher in clinical isolates from pulmonary MAC disease patients than in those from HIV-positive patients, whereas the genes were almost entirely absent in isolates from pigs. Moreover, variable number tandem repeats typing analysis showed that isolates carrying pMAH135 genes are grouped in a specific cluster. Collectively, the pMAH135 plasmid contains genes associated with M. avium's pathogenicity and resistance to antimicrobial agents. The results of this study suggest that pMAH135 influence not only the pathological manifestations of MAC disease, but also the host specificity of MAC infection.

Some important virulence factors have been elucidated in Klebsiella pneumoniae infections. We investigated the relationship between virulence factors and multilocus sequence types (STs) and assessed the risk factors for bacteremia in patients with pneumonia due to K. pneumoniae . From April 2004 through April 2012, a total of 120 K. pneumoniae isolates from patients with pneumonia (23 with bacteremia and 97 without bacteremia) were collected from 10 medical institutions in Japan. Additionally, 10 strains of K. pneumoniae serotype K2 that were isolated >30 years ago were included in this study. These isolates were characterized using multilocus sequence typing (MLST), and the characteristics of their virulence factors, such as hypermucoviscosity phenotype and RmpA and aerobactin production between patients with and without bacteremia, were examined. MLST analysis was performed on the 120 isolates from patients with pneumonia, and some sequence type groups were defined as genetic lineages (GLs). GL65 was more prevalent among patients with bacteremia (21.7%) than in those without bacteremia (7.2%). The majority of the strains with serotype K2 were classified into GL14 or GL65, and rmpA and the gene for aerobactin were present in all GL65-K2 strains but absent in all GL14-K2 strains. In a multivariate analysis, the independent risk factors for bacteremia included GL65 (adjusted odds ratio [AOR], 9.46; 95% confidence interval [CI], 1.81 to 49.31), as well as neoplastic disease (AOR, 9.94; 95% CI, 2.61 to 37.92), immunosuppression (AOR, 17.85; 95% CI, 1.49 to 214.17), and hypoalbuminemia (AOR, 4.76; 95% CI, 1.29 to 17.61). GL65 was more prevalent among patients with bacteremia and was associated with the virulence factors of K. pneumoniae .