Splenomegaly Negatively Impacts Neutrophil Engraftment in Cord Blood Transplantation.

Delayed neutrophil engraftment (NE) has been reported in cord blood transplantation (CBT) compared with other stem cell transplantation methods. The numbers of total nucleated cells (TNCs), CD34+ cells (generally ≥ 1 × 105/kg), and granulocyte/macrophage colony-forming units (CFU-GM) significantly impact NE. Splenomegaly exerts negative effects on NE, but the appropriate cell dose for the patients with splenomegaly has not yet been determined, especially in CBT. We retrospectively investigated the effect of splenomegaly and number of CD34+ cells infused on NE through the analysis of outcomes of 502 consecutive patients who underwent single CBT for the first time at Toranomon Hospital between 2011 and 2018. Spleen index, Lmax × Hvert (SI Lmax × Hvert), was defined as maximal length at any transverse section, (Lmax) × vertical height (Hvert), and splenomegaly was defined as SI Lmax × Hvert ≥ 115 cm2. Our results show that splenomegaly (hazard ratio [HR], .60; P < .01) and low dose of infused CD34+ cells (HR, .58; P < .01) had significant negative impact on NE, whereas neither CFU-GM dose nor TNC dose had any impact on NE in multivariate analysis. Other factors with a significant negative impact on NE in multivariate analysis were myeloid disease (HR, .62; P < .01), nonremission status at CBT (HR, .71; P < .01), low Eastern Cooperative Oncology Group Performance Status (HR, .68; P < .01), and graft-versus-host disease prophylaxis (other than tacrolimus alone) (HR, .76; P < .01). Without splenomegaly, even patients infused with < .8 × 105/kg CD34+ cells achieved up to 94.3% NE, with the median value observed at 21 days post-CBT. This study shows that splenomegaly has a significant negative impact on NE after CBT. Cord blood units with < .8 × 105/kg CD34+ cells may still be a suitable choice for patients without splenomegaly.

Cryptococcal meningitis following umbilical cord blood transplantation, association between the occurrence of cryptococcal infection and tacrolimus discontinuation among allogeneic hematopoietic stem cell recipients.

Few cases of cryptococcal infection following umbilical cord blood transplantation (UCBT) have been reported. We report a case, where cryptococcal infection occurred soon after rapidly reducing the dose of tacrolimus in a UCBT recipient who received micafungin prophylaxis during the early phase of transplantation. The etiology of cryptococcal infection following allogeneic hematopoietic stem cell transplantation (allo-HSCT), including UCBT, might be associated with rapid dose-reduction of calcineurin inhibitors, such as tacrolimus during early phase of allo-HSCT. To our knowledge, this is the first English-language report to describe in detail a case of cryptococcal meningitis with fungemia during early phase of UCBT.

Risk Factors for Recurrent Helicobacter cinaedi Bacteremia and the Efficacy of Selective Digestive Decontamination With Kanamycin to Prevent Recurrence.

Background: Previous studies suggest that Helicobacter cinaedi can cause recurrent bacteremia. In this study, we elucidated the risk factors for recurrent H. cinaedi bacteremia and explored the efficacy of selective digestive decontamination (SDD) as a preventive measure. Methods: We retrospectively reviewed the medical records of patients with H. cinaedi bacteremia between March 2009 and December 2016 at 2 Japanese hospitals. Results: We identified 168 patients with H. cinaedi bacteremia. Bacteremia recurred in 34 patients. The 100-day cumulative incidence rate of recurrent bacteremia was 18.7%. In univariate analysis of factors associated with recurrent bacteremia, anticancer chemotherapy (hazard ratio [HR], 3.75; 95% confidence interval [CI], 1.86-7.58; P < .001), systemic steroids (HR, 3.79; 95% CI, 1.70-8.45; P = .0011), and hematological malignancy (HR, 3.18; 95% CI, 1.64-6.19; P < .001) were detected. Multivariate analysis indicated that anticancer chemotherapy (HR, 2.47; 95% CI, 1.19-5.12; P = .015) and systemic steroids (HR, 2.40; 95% CI, 1.03-5.61; P = .044) were the independent risk factors. Of the 168 patients, 47 received SDD. According to Gray's test, SDD might have reduced the rate of recurrence but this was not statistically significant (HR, 0.46; 95% CI, 0.18-1.18; P = .11). However, in a proportional hazard modeling analysis, SDD reduced the rate of recurrence (HR, 0.36; 95% CI, 0.13-1.00; P = .050). Conclusions: The 100-day cumulative incidence of recurrent H. cinaedi bacteremia was 18.7%. Anticancer chemotherapy and systemic steroids were independent risk factors for recurrent bacteremia. SDD is a potential strategy for reducing the recurrence.

Micafungin Breakthrough Fungemia in Patients with Hematological Disorders.

Limited data are available on micafungin breakthrough fungemia (MBF), fungemia that develops on administration of micafungin, in patients with hematological disorders. We reviewed medical and microbiological records of patients with hematological disorders who developed MBF between January 2008 and June 2015. A total of 39 patients with MBF were identified, and Candida (30 strains) and non-Candida (9 strains) fungal species were recognized as causative strains. Among 35 stored strains, Candida parapsilosis (14 strains), Trichosporon asahii (7 strains), Candida glabrata (5 strains), and other fungal species (9 strains) were identified by sequencing. Neutropenia was identified as an independent predictor of non-Candida fungemia (P = 0.023). T. asahii was the most common causative strain (7/19) during neutropenia. The 14-day crude mortality rate of patients treated with early micafungin change (EMC) to other antifungal agents was lower than that of the patients not treated with EMC (14% versus 43%, P = 0.044). Most of the stored causative Candida strains were susceptible (80%) or showed wild-type susceptibility (72%) to micafungin. The MICs of voriconazole for T. asahii were low (range, 0.015 to 0.12 µg/ml), whereas the MICs of amphotericin B for T. asahii were high (range, 2 to 4 µg/ml). MBF caused by non-Candida fungus should be considered, especially in patients with neutropenia. EMC could improve early mortality. Based on epidemiology and drug susceptibility profiling, empirical voriconazole-containing therapy might be suitable for treating MBF during neutropenia to cover for T. asahii.

First evidence of bacterial translocation from the intestinal tract as a route of Helicobacter cinaedi bacteremia.

BACKGROUND: The route of Helicobacter cinaedi bacteremia has not yet been clarified. Although bacterial translocation from the intestinal tract into the circulation has been suggested, it has not been demonstrated thus far. The objective of this study was to investigate the port of entry of this bacterium. MATERIAL AND METHODS: We conducted a retrospective study on patients with H. cinaedi bacteremia between March 2009 and May 2013. Records of patients in whom H. cinaedi was detected in both blood and stool cultures were extracted. H. cinaedi was identified using gyrB-targeted PCR. Pulse-field gel electrophoresis was used to investigate the consistency of the genotypes. RESULTS: Seventy-one patients were diagnosed with H. cinaedi bacteremia during the study period. H. cinaedi was detected in both blood and stool samples of 21 patients. Pulse-field gel electrophoresis was used to investigate the consistency of the genotypes in 18 evaluable strains (from 9 patients). The pulse-field gel electrophoresis patterns of the stool- and blood-derived strains of H. cinaedi were consistent among all 9 patients. Most of the 9 patients analyzed were immunocompromised and being treated with anticancer drugs or steroids, which suggests reduced intestinal immunity. CONCLUSIONS: This is the first study to demonstrate that bacterial translocation from the intestinal tract could represent one route of H. cinaedi bacteremia.

Clinical and Microbiological Characteristics of Breakthrough Candidemia in Allogeneic Hematopoietic Stem Cell Transplant Recipients in a Japanese Hospital.

Few data on breakthrough candidemia (BC), defined as candidemia that develops on administration of antifungal agents (AFAs), in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients are available. The medical and microbiological records of recipients of an allo-HSCT obtained between December 2008 and December 2014 were reviewed. Of 768 allo-HSCT cases, 26 developed BC. Among the 26 causative strains, 22 strains were stored and identified by sequencing. The following species were isolated: Candida parapsilosis (9 strains), C. glabrata (4 strains), C. guilliermondii (3 strains), and other Candida species (6 strains). The AFAs being used when BC developed were micafungin (17 cases), liposomal amphotericin B (5 cases), itraconazole (2 cases), and voriconazole (2 cases). All 17 cases who developed BC during micafungin administration were administered 150 mg/day of micafungin. The susceptibilities of the causative Candida species to the administered AFAs when breakthrough occurred ranged from susceptible to resistant. Especially, 85% of the Candida species that caused BC during micafungin administration were susceptible to micafungin. Additionally, 75% of the strains were wild type for susceptibility to the administered AFAs when breakthrough occurred. Systemic steroid administration and a longer severe neutropenic phase (≥5 days) were independent risk factors for BC (P = 0.016 and P = 0.015, respectively). BC developed in allo-HSCT recipients even when they received a sufficient dose of AFA, including micafungin, to which the causative Candida species were susceptible and/or had wild-type susceptibility in vitro Systemic steroid administration and a longer severe neutropenic phase were host-based factors associated with BC.

Successful Treatment of Pulmonary Mucormycosis Caused by Cunninghamella bertholletiae with High-Dose Liposomal Amphotericin B (10 mg/kg/day) Followed by a Lobectomy in Cord Blood Transplant Recipients.

Infection caused by Cunninghamella bertholletiae carries one of the highest mortality rates among mucormycosis, and there are no reported cases that survived from the infection in allogeneic hematopoietic stem cell transplantation recipients occurring before neutrophil engraftment. Here, we present two cases of pulmonary mucormycosis caused by C. bertholletiae occurring before neutrophil engraftment after cord blood transplantation. Both were successfully treated with high-dose liposomal amphotericin B (10 mg/kg/day) combined with micafungin, which was then followed by neutrophil recovery, reduction in immunosuppressive agents, and a subsequent lobectomy. The intensive antifungal therapy immediately administered upon suspicion of mucormycosis greatly suppressed the infection in its early stage and was well tolerated despite its prolonged administration and simultaneous use of nephrotoxic agents after transplantation. Although the synergic effect of micafungin remains unclear, these cases highlight the importance of prompt administration of high-dose lipid polyene when suspecting mucormycosis in highly immunocompromised patients, which enables subsequent diagnostic and therapeutic interventions, resulting in a favorable outcome.

[Investigation of the Pathophysiology and Diagnostic Methods Through a Case of Acute HIV Infection in which the Western Blot Method Remained Negative Over the Long Term and the 4th Generation Screening Assay Became Negative for a Certain Period of Time after Initiating Antiretroviral Therapy].

Confirmatory tests using Western blot (WB) and HIV-1 nucleic acid testing (HIV-1 RNA) following a positive screening test are required for the diagnosis of HIV-1 infection according to the current Japanese guidelines for HIV-1/2 diagnosis. We report herein on a rare case in a patient who remained negative for WB over 10 months in spite of being positive by fourth-generation immunoassays (4thGIA) and who subsequently seroreverted by 4thGIA for three months after initiating antiretroviral therapy. Case: A man in his early twenties previously visited a hospital because of fever in October 2012. Laboratory data revealed leukocytopenia, thrombocytopenia and increased serum ferritin, suggesting hemophagocytic syndrome (HPS). During that visit, he tested positive for a 4thGIA, but negative for HIV-1 WB and his result of HIV-1 RNA result was detected invalid because of the presence of some inhibitory material in his RNA preparation. Thereafter, he was diagnosed as having cytomegalovirus-associated HPS treatment was for which initiated. In January 2013, he developed Pneumocystis jirovecii pneumonia, and his HIV-1 RNA viral load was 7.7 × 105 copies/mL in February 2013. Acute HIV infection was suspected, because the HIV-1 WB remained negative. He was started on antiretroviral therapy in April 2013. His 4thGIA was converted to negative in May 2013 and was reconverted to positive in August 2013. HIV-1 WB, however, continued to be indeterminant until February 2014, in which it turned positive for the first time according to the CDC criteria. Methods and Results: The genetic analyses of HIV-1 were done on the gag, env, nef and pol region of the HIV-1 gene from the patient. There was no clear element to delay antibody production on the virus side. Preserved specimens of the patient were measured with eight kinds of HIV screening assay. It was thought that the fourth generation assay was positive only by the presence of the antigen until March 2013 because the antibody had not been detected. Discussion: We encountered a case of acute HIV infection in which the WB result was negative for 10 months after the first positive response of the 4thGIA. The 4thGIA is essential for the early diagnosis and early treatment of HIV infection; therefore, the 4thGIA should be strictly recommended to avoid the use of older generations of immunoassay in the diagnostic guidelines. The role of the WB test should be examined closely from various aspects for use as a confirmatory test under recent laboratory situations in which highly sensitive and specific methods, e.g. the 4th GIA, have become available. In addition, unnecessary confusion due to the diversities of antibody formation should be avoided. The antibody detection tests for HIV are still necessary and indispensable for the confirmation of the disease or the diagnosis of the acute infection stage. Therefore development of a newer antibody measuring method which could achieve an easier operation and should have a higher sensitivity and specificity for HIV confirmation is strongly expected.

Potential Impact of Rapid Blood Culture Testing for Gram-Positive Bacteremia in Japan with the Verigene Gram-Positive Blood Culture Test.

Background. Early detection of Gram-positive bacteremia and timely appropriate antimicrobial therapy are required for decreasing patient mortality. The purpose of our study was to evaluate the performance of the Verigene Gram-positive blood culture assay (BC-GP) in two special healthcare settings and determine the potential impact of rapid blood culture testing for Gram-positive bacteremia within the Japanese healthcare delivery system. Furthermore, the study included simulated blood cultures, which included a library of well-characterized methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant enterococci (VRE) isolates reflecting different geographical regions in Japan. Methods. A total 347 BC-GP assays were performed on clinical and simulated blood cultures. BC-GP results were compared to results obtained by reference methods for genus/species identification and detection of resistance genes using molecular and MALDI-TOF MS methodologies. Results. For identification and detection of resistance genes at two clinical sites and simulated blood cultures, overall concordance of BC-GP with reference methods was 327/347 (94%). The time for identification and antimicrobial resistance detection by BC-GP was significantly shorter compared to routine testing especially at the cardiology hospital, which does not offer clinical microbiology services on weekends and holidays. Conclusion. BC-GP generated accurate identification and detection of resistance markers compared with routine laboratory methods for Gram-positive organisms in specialized clinical settings providing more rapid results than current routine testing.

A Novel Reduced-Toxicity Myeloablative Conditioning Regimen Using Full-Dose Busulfan, Fludarabine, and Melphalan for Single Cord Blood Transplantation Provides Durable Engraftment and Remission in Nonremission Myeloid Malignancies.

A pilot study of a novel, reduced-toxicity, myeloablative conditioning regimen using intravenous busulfan 12.8 mg/kg, fludarabine 180 mg/m(2), and melphalan 80 mg/m(2) for single cord blood transplantation (CBT) was conducted at our institution. Fifty-one patients with myeloid malignancies not in remission were included in this study. Their median age was 59 years (range, 19 to 70 years), with a median hematopoietic cell transplantation-specific comorbidity index score of 3. With a median observation period of 39.6 months (range, 24.3 to 90.8 months) among the survivors, overall survival and progression-free survival at 2 years were both 54.9%. Forty-six of 51 achieved neutrophil engraftment at a median of 19.5 days (range, 13 to 38 days) after transplantation, with a cumulative incidence of 90.2%. No patient developed graft rejection in this study. All patients who achieved engraftment showed hematological complete remission with complete donor chimerism. Eleven patients relapsed at a median of 4.9 months (range, .5 to 26.7 months). Cumulative incidences of nonrelapse mortality (NRM) at 100 days and 2 years were 11.8% and 25.5%, respectively. In conclusion, the present results show that the novel conditioning regimen for single CBT provided durable engraftment and remission with acceptable NRM leading to excellent survival, even for a relatively older population with myeloid malignancies not in remission.

Breakthrough viridans streptococcal bacteremia in allogeneic hematopoietic stem cell transplant recipients receiving levofloxacin prophylaxis in a Japanese hospital.

BACKGROUND: Breakthrough viridans streptococcal bacteremia (VSB) in patients with hematological malignancy receiving levofloxacin prophylaxis is a major blood stream infection (BSI) occurring during febrile neutropenia. However, clinical data focused on VSB in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients are lacking. METHODS: The medical records of allo-HSCT recipients who received oral levofloxacin prophylaxis between January 2011 and August 2013 at Toranomon Hospital were reviewed to evaluate breakthrough VSB. Stored viridans streptococcal (VGS) species were identified by using sodA gene sequencing, and were assessed for drug susceptibility. RESULTS: Among the 184 allo-HSCT recipients on levofloxacin prophylaxis, 28 (15.2 %) experienced breakthrough VSB. All of the 28 recipients with VSB were treated with a cefepime-based or piperacillin/tazobactam-based regimen. The susceptibility rates of the VGS strains for levofloxacin, cefepime, piperacillin/tazobactam, meropenem, and vancomycin were 0 %, 95 %, 100 %, 100 %, and 100 %, respectively. Both the MIC50 (minimum inhibitory concentration) and the MIC90 of ceftazidim (0.5 µg/mL and 2 µg/mL, respectively) were higher than the MIC90 of all the other anti-pseudomonal beta-lactams (APBLs). Only 1 VGS strain had a penicillin MIC ≥ 2 µg/mL by the Etest (3.6 %). There were no cases with acute respiratory distress syndrome (ARDS) that was associated with VSB, although the rate of viridans group streptococcal shock syndrome was high (26 %). The crude 30-day mortality rate in the VSB group (10.7 %) did not differ significantly from that in the BSI without VSB group (9.3 %) or non-BSI group (7.0 %) (P = 0.77). Also, VSB was not a risk factor for all-cause mortality up to 60 days following allo-HSCT (P = 0.43). CONCLUSIONS: APBL with increased anti-VGS activity (APBL-VA) monotherapy would typically be optimal for treating the VGS strains in this setting. Indication of adding an empiric anti-gram-positive agent to APBL-VA for treating VSB should depend on local factors, such as the susceptibility results. In addition, breakthrough VSB is probably not a major cause of death in allo-HSCT settings, where beta-lactam non-susceptible VGS and the ARDS are rare.

Anti-HLA antibodies other than against HLA-A, -B, -DRB1 adversely affect engraftment and nonrelapse mortality in HLA-mismatched single cord blood transplantation: possible implications of unrecognized donor-specific antibodies.

The impact of anti-HLA antibodies, except for donor-specific anti-HLA-A, -B, -DRB1 antibodies, on engraftment was retrospectively evaluated in 175 single cord blood transplantations (CBT). Patients and donors had been typed at HLA-A, -B, and -DRB1 antigens, and anti-HLA antibodies had been screened before transplantation to avoid the use of cord blood (CB) units with corresponding antigens. The median age was 59 (range, 17 to 74) years. Overall, 61% were male, 89% had high-risk disease status, 77% received myeloablative conditioning regimens, and over 80% were heavily transfused patients. Sixty-nine of the 175 (39.4%) were positive for anti-HLA antibodies. Thirty-nine patients had antibodies only against HLA-A, -B, or -DRB1, 13 had antibodies only against HLA-C, -DP, -DQ, or -DRB3/4/5, and 17 had antibodies both against HLA-C, -DP, -DQ, or -DRB3/4/5 and against HLA-A, -B, or -DRB1. Because CB units had not been typed at HLA-C, -DP, -DQ, or -DRB3/4/5, it was possible that antibodies against them were unrecognized donor-specific antibodies. Patients with antibodies only against HLA-A, -B, or -DRB1 showed comparable neutrophil engraftment rates to those without antibodies (89.7% versus 83%, P = .65), whereas patients having antibodies against C, DP, DQ, or -DRB3/4/5 showed lower engraftment rate (66.7%, P = .12), which became statistically significant in a subgroup of HLA-mismatched donor-recipient pairs (50%, P = .01). Our results demonstrated that the presence of donor nonspecific anti-HLA-A, -B, -DRB1 antibodies had no significant influence on engraftment, whereas anti-HLA-C, -DP, -DQ, or -DRB3/4/5 antibodies adversely affect engraftment, possibly because of unrecognized donor-specific anti-HLA antibodies against them, especially in HLA-mismatched CBT.

Clinical characteristics of bacteremia caused by Helicobacter cinaedi and time required for blood cultures to become positive.

The aim of this study was to clarify the clinical characteristics of patients with Helicobacter cinaedi bacteremia and the time required for blood cultures to become positive. The medical records of all patients with H. cinaedi bacteremia at Toranomon Hospital and Toranomon Hospital Kajigaya between March 2009 and March 2013 were retrospectively reviewed. Sixty-three patients, 34 men and 29 women with a median age of 67 years (range, 37 to 88 years), were diagnosed with H. cinaedi bacteremia. A total of 51,272 sets of blood cultures were obtained during the study period, of which 5,769 sets of blood cultures were positive for some organism and 126 sets were H. cinaedi positive. The time required for blood cultures to become positive for H. cinaedi was ≤5 days in 69 sets (55%) and >5 days in 57 sets (45%). Most patients had an underlying disease, including chronic kidney disease (21 cases), solid tumor (19 cases), hematological malignancy (13 cases), diabetes mellitus (8 cases), chronic liver disease (6 cases), and postorthopedic surgery (3 cases). Only 1 patient had no apparent underlying disease. The clinical symptoms included cellulitis in 24 cases, colitis in 7 cases, and fever only in 27 cases, including 7 cases of febrile neutropenia. The 30-day mortality rate of H. cinaedi bacteremia was 6.3%. In conclusion, most cases of H. cinaedi bacteremia occurred in immunocompromised patients. We might have overlooked nearly half of the H. cinaedi bacteremia cases if the duration of monitored blood culture samples had been within 5 days. Therefore, when clinicians suspect H. cinaedi bacteremia, the observation period for blood cultures should be extended.

Serum (1,3)-beta-D-glucan is an inefficient marker of breakthrough candidemia.

The aim of this study was to evaluate the usefulness of serum (1,3)-beta-D-glucan (BDG) for earlier detection of breakthrough candidemia. We reviewed the medical records of patients with candidemia from January 2008 to March 2013. Serum BDG was measured by Wako turbidimetric assay. During the study period, a total of 147 cases of candidemia were identified, and 31 patients met the criteria for breakthrough candidemia. Serum BDG levels were measured in 25 patients with breakthrough candidemia and 67 patients with nonbreakthrough candidemia. Almost all of the patients with breakthrough candidemia had hematological malignancies. More candidemia were caused by non-C. albicans Candida in the breakthrough group than in the nonbreakthrough group (92.0% vs. 61.8%, p = .005). The median BDG value was significantly lower in breakthrough episodes than in non-breakthrough episodes (18.5 pg/ml vs. 90.4 pg/ml, p = .01). Moreover, BDG values under the cutoff was significantly higher in patients with breakthrough candidemia than in those with nonbreakthrough candidemia (44% vs. 19%, p = .03). In summary, BDG alone was insufficient to detect breakthrough candidemia, and candidemia could occur in patients being treated with antifungal agents, even when the BDG value was under the cutoff value.

[Laboratory Medicine and Medical Team Approaches--Opening Remarks from the Chair].

Recently, medical team approaches were pointed out to be important in the field of laboratory medicine. The staff working in laboratory medicine needs to participate in various kinds of medical team such as ICT or NST. With such a background, the working group for medical teams was established in the Japanese Society of Laboratory Medicine in January 2012. Special program II was organized by this group at the 60th annual meeting held in Kobe in 2013. People gathered from representative societies related to laboratory medicine and discussed how we should participate in team approaches. Based on the results of meaningful discussions, we have reached a strong consensus to pursue team approaches in the future.

[Introducing International State-of-the-Art Clinical Microbiologic Technologies to Japanese Clinical Laboratories--Opening Remarks].

Internationally, recent progress in clinical microbiology has involved adapting for multi-drug-resistant organisms (MDROs) such as carbapenemase-producing Enterobacteriaceae (CRE) using selective culture media and the active surveillance test using real-time PCR, matrix-assisted laser desorption-ionization time-of-flight mass spectrometry (MALDI-TOF MS) technology for bacterial identification, and molecular epidemiological tools such as multi-locus sequence typing (MLST). In this symposium, we discussed updating to state-of-the-art clinical microbiologic technologies in Japanese clinical laboratories.

Successful sustained engraftment after reduced-intensity umbilical cord blood transplantation for adult patients with severe aplastic anemia.

We retrospectively analyzed 12 consecutive adult severe aplastic anemia patients who received unrelated umbilical cord blood transplantation after a reduced-intensity conditioning regimen (RI-UCBT). The conditioning regimen consisted of 125 mg/m² fludarabine, 80 mg/m² melphalan, and 4 Gy of total body irradiation. The median infused total nucleated cell number and CD34(+) cell number were 2.50 × 107/kg and 0.76 × 105/kg, respectively. Eleven of the 12 patients achieved primary neutrophil and platelet engraftment. All patients who achieved engraftment had complete hematologic recovery with complete donor chimerism, except for one patient who developed late graft failure 3 years after RI-UCBT. Two of the 12 patients died of idiopathic pneumonia syndrome, and the remaining 10 patients are alive, having survived for a median of 36 months. Our encouraging results indicate that RI-UCBT may become a viable therapeutic option for adult severe aplastic anemia patients who lack suitable human leukocyte antigen-matched donors and fail immunosuppressive therapy.

Aeromonas caviae is the most frequent pathogen amongst cases of Aeromonas bacteremia in Japan.

BACKGROUND: Aeromonas species can cause various infections including bacteremia, gastroenteritis, cholangitis, and wound infections. To date, most studies on Aeromonas species have been reported from countries other than Japan. The aim of this study, therefore, was to evaluate Aeromonas bacteremia in Japan. METHODS: We reviewed the medical records of patients with Aeromonas bacteremia from January 1994 to December 2010 in Toranomon Hospital, Tokyo, and Toranomon Hospital Kajigaya, Kanagawa, Japan. RESULTS: Thirty-six cases of Aeromonas bacteremia were identified. Of these 36 strains, 18 were Aeromonas caviae, 13 were Aeromonas hydrophila, and 5 were Aeromonas veronii biovar sobria. The underlying diseases were solid tumor (21 cases), chronic hepatic disease (13 cases), diabetes mellitus (9 cases), hematological malignancies (4 cases), autosomal dominant polycystic kidney disease (2 cases), and aplastic anemia (2 cases). Patients with a solid tumor more frequently presented with A. caviae bacteremia than non-A. caviae bacteremia (14/18 vs 7/18; p = 0.041). Additionally, 16 of the 36 episodes were polymicrobial, and of these, 12 had stenosis or stasis of the bile duct or pancreatic duct (75%). The overall 30-day mortality was 19%. CONCLUSIONS: To the best of our knowledge, this is the first report to identify A. caviae as the most frequent causative pathogen of Aeromonas bacteremia in Japan. Additionally, compared with previous studies, most patients in our study had solid tumors. These findings suggest that the characteristics of Aeromonas bacteremia vary among study populations.

Cunninghamella bertholletiae pneumonia showing a reversed halo sign on chest computed tomography scan following cord blood transplantation.

This is the first reported case of a patient who developed fungal pneumonia caused by Cunninghamella bertholletiae (= C. elegans) following cord blood transplantation and who showed a reversed halo sign on a chest computed tomography scan (CT). In addition, the pathological findings related to the reversed halo sign are described in detail for the first time. The patient died due to respiratory failure and at autopsy, a consolidation corresponding to the reversed halo sign noted on CT was found histologically to be composed of a central infarct with some retained air spaces surrounded by a peripheral ring-like hemorrhagic band. Pulmonary vasculatures were occluded by thrombi containing numerous Zygomycetes hyphae within the central infarct and less frequently along the surrounding hemorrhagic band. A reversed halo sign may be an early marker to initiate preemptive therapy against Zygomycetes including C. bertholletiae.

A surveillance of high-level gentamicin-resistant enterococcal bacteremia.

Enterococci have recently been recognized as a causative organism of intractable infections, including severe sepsis and infective endocarditis, in immunocompromised patients. This study investigated the epidemiological, microbiological, and prognostic characteristics of high-level gentamicin-resistant (HLGR) enterococcal bacteremia, including severe cases of infective endocarditis, in Japan. A total of 155 enterococcal bacteremia episodes were identified between July 2007 and December 2009. HLGR strains accounted for 28% of all enterococcal strains: HLGR Enterococcus faecalis/Enterococcus faecium strains accounted for 32%/24%. The 30-day mortality rate was 31%. There was no significant difference in the 30-day mortality rates between HLGR and non-HLGR enterococcal bacteremia. There were two cases of HLGR enterococcal endocarditis, which were successfully treated with ampicillin plus ceftriaxone. We consider it important to examine the presence or absence of HLGR strains in all cases of intractable enterococcal infection, especially infective endocarditis.