Unique characteristics of community-onset healthcare- associated bloodstream infections: a multi-centre prospective surveillance study of bloodstream infections in Japan.

BACKGROUND: Analysis of bloodstream infections (BSIs) is valuable for their diagnosis, treatment and prevention. However, limited data are available in Japan. AIM: To investigate the characteristics of patients with bacteraemia in Japan. METHODS: This study was conducted in five hospitals from October 2012 to September 2013. Clinical, demographic, microbiological and outcome data for all blood-culture-positive cases were analysed. FINDINGS: In total, 3206 cases of BSI were analysed: 551 community-onset healthcare-associated (CHA)-BSIs, 1891 hospital-acquired (HA)-BSIs and 764 community-acquired (CA)-BSIs. The seven- and 30-day mortality rates were higher in patients with CHA- and HA-BSIs than in patients with CA-BSIs. The odds ratios (ORs) for seven-day mortality were 2.56 [95% confidence interval (CI) 1.48-4.41] and 2.63 (95% CI 1.64-4.19) for CHA- and HA-BSIs, respectively. The ORs for 30-day mortality were 2.41 (95% CI 1.63-3.57) and 3.31 (95% CI 2.39-4.59) for CHA- and HA-BSIs, respectively. There were 499 cases (15.2%) of central-line-associated BSI and 163 cases (5.0%) of peripheral-line-associated BSI. Major pathogens included coagulase-negative staphylococci (N = 736, 23.0%), Escherichia coli (N = 581, 18.1%), Staphylococcus aureus (N = 294, 9.2%) and Klebsiella pneumoniae (N = 263, 8.2%). E. coli exhibited a higher 30-day mortality rate among patients with HA-BSIs (22.3%) compared with patients with CHA-BSIs (12.3%) and CA-BSIs (3.4%). K. pneumoniae exhibited higher 30-day mortality rates in patients with HA-BSIs (22.0%) and CHA-BSIs (22.7%) compared with patients with CA-BSIs (7.8%). CONCLUSION: CHA- and HA-BSIs had higher mortality rates than CA-BSIs. The prognoses of E. coli- and K. pneumonia-related BSIs differed according to the category of bacteraemia.

Relative incidences and outcomes of Clostridium difficile infection following transplantation of unrelated cord blood, unrelated bone marrow, and related peripheral blood in adult patients: a single institute study.

BACKGROUND: Clostridium difficile is a major cause of nosocomial diarrhea. The incidence and prognosis of C. difficile-associated diarrhea (CDAD) has not yet been assessed in adult patients after unrelated cord blood transplantation (uCBT). METHODS: The medical records of 135 adult unrelated cord blood transplant recipients were reviewed retrospectively to investigate the clinical features of CDAD after uCBT. These data were compared to medical records of 39 unrelated bone marrow transplant recipients and 27 related peripheral blood stem cell transplant recipients as controls. RESULTS: A total of 17 recipients developed CDAD, with onset occurring at a median of 22 days (range, 0-56 days) after transplantation. Among the unrelated cord blood transplant recipients, 11 (9%) developed CDAD. These results were comparable with those of CDAD after unrelated bone marrow transplantation (uBMT) (2/39, 6%) and related peripheral blood stem cell transplantation (rPBSCT) (4/27, 16%) (P=0.37). Fifteen of the infected recipients were successfully treated with oral metronidazole, vancomycin, or cessation of antibiotics. The remaining 2 recipients who developed CDAD after uCBT died of other causes. The development of CDAD did not negatively affect overall survival after uCBT. CONCLUSIONS: These data indicate that the incidence and prognosis of CDAD after uCBT are comparable with those after uBMT and rPBSCT.

Rapidly progressive fatal hemorrhagic pneumonia caused by Stenotrophomonas maltophilia in hematologic malignancy.

BACKGROUND: Pneumonia caused by Stenotrophomonas maltophilia is rare, but can be lethal in severely immunocompromised patients. However, its clinical course remains unclear. PATIENTS AND METHODS: Patients with pneumonia caused by S. maltophilia in Toranomon Hospital (890 beds, Tokyo, Japan) were reviewed retrospectively between April 2006 and March 2010. RESULTS: During the study period, 10 cases of S. maltophilia pneumonia were identified. Seven patients had acute myeloid leukemia, 2 had myelodysplastic syndrome, and 1 had malignant lymphoma. All patients developed symptoms after allogeneic hematopoietic stem cell transplantation (HSCT). Five patients received first cord blood transplantation (CBT), 4 patients received second CBT, and 1 patient received first peripheral blood stem cell transplantation (PBSCT). The overall incidence of S. maltophilia pneumonia among 508 patients who received HSCT during the period was 2.0%. The incidence was 0% (0/95) in patients after bone marrow transplantation, 0.8% (1/133) after PBSCT, and 3.2% (9/279) after CBT. Pneumonia developed a median of 13.5 days (range, 6-40) after transplantation. At onset, the median white blood cell count was 10/µL (range, 10-1900), and the median neutrophil count was 0/µL (range, 0-1720). In all patients, S. maltophilia bacteremia developed with bloody sputum or hemoptysis. The 28-day mortality rate was 100%; the median survival after onset of pneumonia was 2 days (range, 1-10). CONCLUSIONS: Hemorrhagic S. maltophilia pneumonia rapidly progresses and is fatal in patients with hematologic malignancy. Attention should be particularly paid to the neutropenic phase early after HSCT or prolonged neutropenia due to engraftment failure. A prompt trimethoprim-sulfamethoxazole-based multidrug combination regimen should be considered to rescue suspected cases of S. maltophilia pneumonia in these severely immunosuppressed patients.

Phase-contrast X-ray imaging of the gas diffusion layer of fuel cells.

The understanding of and in situ observation of the transport and distribution of water in carbon-paper gas diffusion layers (GDLs) using non-destructive imaging techniques is critical for achieving high performance in polymer electrolyte fuel cells (PEFCs). To investigate the behavior of water in GDLs of PEFCs, phase-contrast X-ray imaging via X-ray interferometric imaging (XII) and diffraction-enhanced imaging (DEI) were performed using 35 keV X-rays. The XII technique is useful for the radiographic imaging of GDLs and in situ observations of water evolution processes in operating PEFCs. DEI provides a way for tomographic imaging of GDLs in PEFCs. Because high-energy X-rays are applicable to the imaging of both carbon papers and heavy materials, which make up PEFCs, phase-contrast X-ray imaging techniques have proven to be valuable for investigation of GDLs.

Risk factors for mortality among patients with Stenotrophomonas maltophilia bacteremia in Tokyo, Japan, 1996-2009.

Stenotrophomonas maltophilia is an important nosocomial pathogen, especially among immunocompromised patients. The objective of this study was to clarify the clinical characteristics, prognosis, and prognostic factors of patients with S. maltophilia bacteremia in Japan. The microbiology records of all patients with S. maltophilia bacteremia between January 1996 and April 2009 at Toranomon Hospital, Tokyo, Japan, were retrospectively reviewed. A total of 53 cases of bacteremia were identified. Thirty patients had an underlying hematological disorder, and 23 were receiving hematopoietic transplantation. The overall mortality rate was 51%. On univariate analysis, neutropenia (p < 0.01), the presence of a central venous catheter, and mixed infection with enterococci (p < 0.05) were significantly related to the mortality. Among these variables, neutropenia (p < 0.01) and mixed infection with enterococci (p < 0.05) were independent factors associated with mortality. In contrast, all eight patients in whom S. maltophilia was the etiologic agent of catheter-related infection survived following catheter removal. S. maltophilia is an important pathogen among immunocompromised patients, especially in the neutropenic phase or mixed infection with enterococci. If a central venous catheter was present at the onset of S. maltophilia bacteremia, the prompt removal of the catheter was important.

Quantitative analysis of amyloid plaques in a mouse model of Alzheimer's disease by phase-contrast X-ray computed tomography.

Densely aggregated beta-amyloid peptides are believed to play a key role in the pathogenesis of Alzheimer's disease. Amyloid plaques are a potential target for molecular imaging to determine the clinical status of Alzheimer's disease. Phase-contrast X-ray imaging combined with computed tomography is a promising technique that can be used to visualize the physical density of structures in biological tissues non-invasively, and without the use of imaging agents. Using brain tissue isolated from a mouse model of Alzheimer's disease, we show that beta-amyloid 40-positive/beta-amyloid 42-positive amyloid plaques, but not beta-amyloid 40-negative/beta-amyloid 42-positive amyloid plaques, exist as high-density aggregates that can be specifically detected by phase-contrast X-ray computed tomography. The phase-contrast X-ray computed tomography detected beta-amyloid 40-positive/beta-amyloid 42-positive amyloid plaques in three-dimensions with an extremely high sensitivity comparable to that of histological analysis, and also enabled the load of amyloid plaques to be quantified. Furthermore, the use of phase-contrast X-ray computed tomography reveals that the physical density of beta-amyloid 40-positive/beta-amyloid 42-positive amyloid plaques increases with age, and that the large volume, high-density, amyloid plaques that are specifically observed in aged Alzheimer's disease mice are closely associated with neuritic dystrophy. These results demonstrate that phase-contrast X-ray computed tomography is a highly sensitive imaging technique for analyzing dense-cored amyloid plaques in postmortem samples, and is beneficial in elucidating amyloid pathophysiology in Alzheimer's disease.

Intestinal thrombotic microangiopathy following reduced-intensity umbilical cord blood transplantation.

Thrombotic microangiopathy (TMA) is a significant complication after hematopoietic stem-cell transplantation (HSCT); however, there is little information on it following reduced-intensity cord blood transplantation (RI-CBT). We reviewed the medical records of 123 adult patients who received RI-CBT at Toranomon Hospital between January 2002 and August 2004. TMA was diagnosed in seven patients based on intestinal biopsy (n = 6) or autopsy results (n = 1). While these patients showed some clinical symptoms such as diarrhea and/or abdominal pain, mental status alterations or neurological disorders were not observed in any of them. Laboratory results were mostly normal at the onset of TMA; >2% fragmented erythrocytes (n = 1), <10 mg/dl haptoglobin (n = 1), and >200 IU/dl lactic dehydrogenase (LD) (n = 4). On endoscopic examination, TMA lesions, consisting of ulcers, erosions, and diffuse exfoliation, were distributed spottily from terminal ileum to rectum. Intestinal graft-versus-host disease (GVHD) and cytomegalovirus (CMV) colitis were confirmed in five and four patients, respectively. With therapeutic measures including supportive care (n = 4), fresh frozen plasma (n = 1), and a reduction of immunosuppressive agents (n = 1), TMA improved in four patients. The present study demonstrates that intestinal TMA is a significant complication after RI-CBT. Since conventional diagnostic criteria can overlook TMA, its diagnosis requires careful examination of the gastrointestinal tract using endoscopy with biopsy.

In vitro antiseptic susceptibility of clinical isolates from nosocomial infections.

To evaluate the susceptibility of a large number of strains to various antiseptics, we elaborated a simple, qualitative broth turbidity method in which we could quickly judge the efficacy visually. For this method, we prepared a modified neutralizer broth, consisting of trypticase soy broth containing 15% Tween 80, 1% soybean lecithin and 0.5% sodium thiosulfate. The susceptibilities of Serratia marcescens No. 26 to 4 antiseptics obtained from the turbidity method showed a good agreement with those obtained from the colony-counting method; the 4 antiseptics tested were povidone-iodine (PVP-I), chlorhexidine gluconate (CHG), benzalkonium chloride (BAC) and alkyldiaminoethylglycine hydrochloride (AEG). Both PVP-I and BAC had complete efficacy in 0.5 min against all isolates tested [100 isolates of S. marcescens, 103 of Klebsiella pneumoniae, 99 of Pseudomonas aeruginosa, 19 of Alcaligenes faecalis and 30 of A. xylosoxidans subsp. xylosoxydans (A. xylosoxydans)]. In contrast, the effectiveness of CHG was weak compared with PVP-I, BAC and AEG. Strong resistance against AEG was noted even after 3-min exposure in 1 isolate each of A. faecalis and A. xylosoxydans. It is concluded that the turbidity test is a simple and accurate method to evaluate susceptibility to various antiseptics and that it is suitable for a screening of a large number of strains. Among the 4 antiseptics tested, PVP-I and BAC showed a consistently high activity against all isolates, confirming PVP-I and BAC to be clinically useful antiseptics.

Two cases of long lasting bacteremia due to Mycobacterium avium complex despite new macrolides-containing regimens in patients with acquired immunodeficiency syndrome.

The prognosis of Mycobacterium avium complex (MAC) infection has been improved by new macrolides-containing regimens and the use of highly active antiretroviral therapy (HAART) in the treatment of acquired immunodeficiency syndrome (AIDS). We report on two AIDS cases with long lasting bacteremia due to MAC under this regimen. Both patients experienced problems due to side effects from the anti-MAC regimen and from an immune-reconstitution syndrome related to HAART. MAC infection persisted despite treatment, however, no anti-MAC drug-resistant isolates emerged throughout the clinical course in either case. These cases demonstrate that therapy for disseminated MAC infection is sometimes difficult even with HAART and macrolides-containing regimens.

[Infectious mononucleosis].

Infectious mononucleosis(IM) is a primary Epstein-Barr virus (EBV)infection. Since heterophil antibody negative IM is common in Japan, EBV antibody(presence of VCA-IgM or anti-EA, high titers of VCA-IgG in the absence of anti-EBNA) is useful for serologic diagnosis of IM. Although EBV causes the continuous growth of lymphoid cell lines in vitro and causes malignant diseases such as Burkitt lymphoma, nasopharyngeal cancer and malignant lymphomas in immunocompromised patients, IM is usually self-limiting, and after primary infection EBV persists in B cells throughout life without producing symptoms. In the present study, we studied CD8+ lymphocytes of patients with IM and demonstrate an increase in lymphocytes expressing HLA-DR and CD45RO, increase of intracellular pH, elevated plasma levels of sCD8, indicating activation of the subset. We also demonstrate activation of CD4+ T lymphocytes and gamma delta T lymphocytes. Activation of these immune systems in response to EBV is supposed to play an important role in assuring the benign course of IM.

[Hypokalemic periodic paralysis during treatment of acute promyelocytic leukemia].

A 40-year-old man was admitted with fever and purpura. He was diagnosed as having acute promyelocytic leukemia, and treated with all-trans retinoic acid. After achieving complete remission, he received consolidation therapy. During the chemotherapy, quadriplegia occurred three times. This was diagnosed as hypokalemic periodic paralysis because of the patient's low serum potassium level. Results of hormone and urine examinations showed no indication of secondary hypokalemia. However, the patient had a history of quadriplegia of unknown etiology at the age of 36. We speculated that in addition to the patient's predisposition to hypokalemic periodic paralysis, chemotherapy including prednisolone, and excessive ingestion of carbohydrate had induced his quadriplegia.

Susceptibility to vancomycin of methicillin-resistant Staphylococcus aureus isolated in a university hospital in Japan.

Intravenous vancomycin was approved in 1991 in Japan and has been widely used for treatment of infections caused by methicillin-resistant Staphylococcus aureus (MRSA). Consequently, ever since the initial discovery of vancomycin intermediate-resistant S. aureus in Japan, the vancomycin resistance of this organism has been a great concern in clinical settings. We investigated whether vancomycin resistance had emerged in MRSA isolated in our hospital since the approval of the use of intravenous vancomycin. Vancomycin susceptibility was evaluated on the basis of minimum inhibitory concentrations determined by the agar dilution method and a heterogeneous resistance examination. The median minimum inhibitory concentration of the 69 MRSA strains isolated in 1988 and the 74 isolated in 1998 was 0.75 microgram/ml and 1.0 microgram/ml, respectively (p < 0.001), however, all of the strains were classified in the susceptible group. None of them was an MRSA heterogeneously resistant to vancomycin (hetero-VRSA), which has been defined as a strain having a 1/10(6) or greater heterogeneously resistant subpopulation to vancomycin. In another set of investigations, no hetero-VRSA were found among 12 other MRSA strains isolated after intravenous administration of vancomycin for 14 or more days (range: 14 to 77 days). We conclude that while the use of intravenous vancomycin may have slightly lowered the vancomycin susceptibility of MRSA in our hospital, the decrease in so small that it may not be significant clinically. In addition, no hetero-VRSA were found in our hospial.

[Comparison of the newly developed MB redox system with mycobacteria growth indicator tube (MGIT) and 2% Ogawa egg media for recovery of mycobacteria in clinical specimens].

The rate of recovery and the mean time to detection of mycobacteria in clinical specimens were determined in a newly-developed MB Redox system based on liquid medium, and the results were compared with those of MGIT and 2% Ogawa egg media. From 587 sputum specimens processed, totally 203 mycobacterial isolates were detected, of which 177 (87.2%) with MB Redox, 185 (91.1%) with MGIT and 133 (65.6%) with 2% Ogawa medium. The difference in the percentages of positive cultures between either of the two liquid media and 2% Ogawa medium was significant (p < 0.0001). The mean time to detection of the Mycobacterium tuberculosis complex was 17.5 days with MB Redox, 18.7 days with MGIT, and 26.2 days with 2% Ogawa medium. The contamination rates were 1.5, 1.7, and 4.1% for MB Redox, MGIT, and 2% Ogawa medium, respectively. In conclusion, both MB Redox and MGIT systems, based on liquid medium, are more efficient than 2% Ogawa medium for the recovery of mycobacteria in clinical specimens.

Effects of dehydroepiandrosterone on mitogen-activated protein kinase in human aortic smooth muscle cells.

The objective of the present study was to determine whether dehydroepiandrosterone (DHEA) modifies growth factor-induced mitogen-activated protein kinase (MAPK) activation, based on our previous study demonstrating that DHEA attenuates fetal calf serum-induced proliferation in human male aortic smooth muscle cells (human male aortic SMCs). Human male aortic SMCs were used for this study. Platelet-derived growth factor-BB (PDGF-BB), epidermal growth factor (EGF), and basic fibroblast growth factor (bFGF), but not insulin-like growth factor-1 (IGF-1), stimulated MAPK activity. Only MAPK activation induced by PDGF-BB was reduced by pretreatment with DHEA, although DHEA did not affect the MAPK activation induced by EGF or bFGF. The basal and PDGF-stimulated MAPK activity were decreased by two types of cyclic AMP (cAMP) elevating agents and increased by cAMP-dependent protein kinase (PKA) inhibitor in human male aortic SMCs, suggesting that cAMP regulates MAPK negatively. The intracellular cAMP was increased by PDGF-BB. The increase of cAMP by PDGF-BB was augmented by pretreatment with DHEA, although DHEA alone did not affect cAMP. Neither EGF nor bFGF affected cAMP with and without DHEA pretreatment. Secretion of PGE2 induced by PDGF was augmented by pretreatment with DHEA. Stimulatory effects of DHEA on the production of PGE2 and cAMP were partially canceled by aromatase inhibitor and completely canceled by indomethacin or selective inhibitor of cyclooxygenase-2. These results suggest that DHEA inhibited MAPK activation induced by PDGF-BB via PGE2 overproduction and subsequent cAMP-dependent pathway in human male aortic SMCs.

Takayasu's arteritis accompanied with massive pericardial effusion--a case report.

A 40-year-old woman who had been treated for Takayasu's arteritis was admitted to the hospital with fever, fatigue, malaise, and severe chest pain. Computed tomography of the chest demonstrated massive pericardial effusion and bilateral pleural effusion. In laboratory data, the C-reactive protein was high at 22.0 mg/dL, and erythrocyte sedimentation rate was also high at 80 mm/hr. The diagnosis was pericarditis with a recurrence of the systemic inflammatory process of Takayasu's arteritis. The patient was treated with methylprednisolone pulse therapy. Her massive pericardial effusion disappeared without pericardiocentesis.