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Bacterial meningitis is a rare but severe infectious complication after hematopoietic stem cell transplantation. However, its clinical features were previously not clear. We reviewed the cases of 7 patients diagnosed with bacterial meningitis with a positive cerebrospinal fluid culture among 1147 patients who underwent cord blood transplantation (CBT) at our institution between September 2007 and September 2020. The diagnosis was made on day + 5- + 45, and 5 patients developed bacterial meningitis before neutrophil engraftment. The causative organisms were all Gram-positive cocci: Enterococcus faecium and Enterococcus gallinarum (2 patients each), and Staphylococcus haemolyticus, Streptococcus mitis/oralis, and Rothia mucilaginosa (1 patient each). Six patients developed bacterial meningitis secondary to prior or concomitant bacteremia caused by the same bacterium. Five patients had received anti-MRSA agents at onset: vancomycin in 3, teicoplanin in 1, and daptomycin in 1. After diagnosis of bacterial meningitis, linezolid was eventually used for 6 patients. Two patients with E. gallinarum were alive at day + 1380 and + 157 after CBT, respectively, whereas 5 patients died 17-53 (median 43) days after the onset of bacterial meningitis. Breakthrough meningitis in CBT can occur even during the use of anti-MRSA drugs, and intensive antibiotic treatment is necessary.

Cyst infection is a frequent and serious complication of autosomal dominant polycystic kidney disease (ADPKD). Hematogenous spread via bacterial translocation in the intestine is considered to be the main cause, so intestinal flora may be involved. However, the exact role of the intestinal flora in cyst infection in ADPKD is unknown. We report a 66-year-old woman and a 56-year-old man with ADPKD who had severe hepatic cyst infection. We analyzed the microbiome of infected cyst content, feces, and saliva in these two patients. The microbiome of patient 1 showed various bacteria in an infected cyst, whereas that of patient 2 showed only one bacterium. In both patients, the composition of the microbiome of the cyst content was quite different from those of feces and saliva, and the main bacteria in the infected cyst content represented a small proportion of those in feces and saliva. Lactobacilli were not almost detected in the infected cyst content though some lactobacilli are endemic in the gastrointestinal tract and the saliva. The association between bacteria in cysts and those in feces or saliva remains uncertain, and further research on this topic is needed.

To evaluate the efficacy and safety of nafamostat combined with favipiravir for coronavirus disease 2019.We conducted a multicenter, randomized, single-blind, placebo-controlled parallel assignment study in hospitalized patients with mild-to-moderate coronavirus disease 2019 pneumonia. Patients were randomly assigned to receive favipiravir alone (n=24) or nafamostat with favipiravir (n=21). Outcomes included changes in the WHO Clinical Progression Scale score, time to improvement in body temperature, and improvement in oxygen saturation (SpOThere was no significant difference in changes in the Clinical Progression Scale between nafamostat with favipiravir and favipiravir alone groups (median, -0·444 vs. -0·150, respectively; least-squares mean difference, -0·294; p=0·364). Time to improvement in body temperature was significantly shorter in the combination group (5·0 days; 95% CI, 4·0-7·0) than in the favipiravir group (9·0 days; 95% CI, 7·0-18·0; p=0·009). Changes in SpOAlthough our study showed no differences in clinical progression, earlier defervescence and recovery of SpOThis study was registered in the Japan Registry of Clinical Trials (identifier: jRCTs031200026) and WHO's International Clinical Trial Registry Platform (identifier: JPRN-jRCTs031200026).

The aim of this study was to clarify the clinical and microbiological characteristics of Corynebacterium bacteremia in hematological patients. We retrospectively reviewed the medical records of patients with Corynebacterium bacteremia from April 2013 to June 2018. The causative Corynebacterium species were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Drug susceptibility tests were performed using the broth microdilution method recommended by the Clinical and Laboratory Standards Institute. In total, 147 cases of Corynebacterium bacteremia were identified during the study period. Corynebacterium striatum was the most frequent pathogen. Catheter-related bloodstream infection was diagnosed in 19.7% of all patients, and moderate/severe oral or severe gastrointestinal mucosal impairment was detected in 19.7%. Polymicrobial infection was found in about 20% of cases, with Enterococcus faecium being the most frequent isolate. The overall 30-day mortality was 34.7% (51/147). Multivariate analysis showed that E. faecium co-infection (odds ratio (OR) 9.3; 95% confidence interval (CI) 2.1-40), systemic corticosteroids (OR 3.6; 95% CI 1.4-8.9), other immunosuppressive drugs (OR 0.32; 95% CI 0.13-0.76), and a Pitt bacteremia score ≥4 (OR 12; 95% CI 3.9-40) were significant risk factors for overall 30-day mortality. The drug susceptibility rates for beta-lactam antimicrobial agents were quite low. All isolates were susceptible to glycopeptides and linezolid. However, some C. striatum isolates were resistant to daptomycin. Corynebacterium bacteremia can occur in the presence of several types of mucosal impairment. Our drug susceptibility data indicate that Corynebacterium bacteremia in hematological patients could be treated by glycopeptides or linezolid.

The aim of this study is to clarify the characteristics of gram-negative bacteremia (GNB), including extended-spectrum β-lactamase (ESBL)-producing pathogens, among allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients on levofloxacin (LVFX) prophylaxis. A retrospective analysis on GNB at the first episode of febrile neutropenia (FN) was conducted among allo-HSCT recipients (age ≥ 20 years) on 500 mg/day of oral LVFX prophylaxis. Epidemiological and microbiological features of GNB were investigated and compared between the inappropriate and appropriate empiric therapy groups. In total, FN occurred in 414 allo-HSCT cases, and bacteremia at the first episode of FN occurred in 169 cases. Overall, 29 GNB cases were documented, and the causative organisms identified were Escherichia coli in 21 cases (including 10 ESBLs), Klebsiella pneumoniae in 2, Pseudomonas aeruginosa in 2, and other in 4. The crude 30-day mortality rate was not significantly different among cases of GNB (6.9%), gram-positive bacteremia (GPB) (7.1%), or non-bacteremia (5.4%; P = 0.78). Cefepime (CFPM) was administered in all cases in the inappropriate empiric therapy group, and all causative organisms were ESBL-producing E. coli (ESBL-EC). All patients in the inappropriate empiric therapy group had a low Pitt bacteremia score (≤ 2). Thirty-day mortality did not differ significantly between the inappropriate and appropriate empiric therapy groups (1/10 vs. 1/15, P = 0.61). In conclusion, GNB was not a significant cause of death. In LVFX breakthrough ESBL-EC bacteremia among allo-HSCT recipients, the administration of CFPM as empiric therapy did not lead to significantly poor prognosis. Empiric CFPM administration might be an acceptable strategy.

Limited data are available on breakthrough fungemia, defined as fungemia that develops on administration of antifungal agents, in patients with hematological disorders. We reviewed the medical and microbiological records of adult patients with hematological diseases who had breakthrough fungemia between January 2008 and July 2019 at Toranomon Hospital and Toranomon Hospital Kajigaya in Japan.

There are few reports on the clinical course of proven invasive aspergillosis (IA) due to rare/cryptic species in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. We retrospectively reviewed the electronic medical records of patients who underwent allo-HSCT between January 2012 and December 2018. Of 934 allo-HSCT recipients, 10 were diagnosed with proven IA and 61 were diagnosed with probable IA. DNA sequencing was performed in cases of proven IA, and Aspergillus could be identified to the species level in 8 of the 10 cases. Three were due to A. fumigatus, and 5 were due to rare/cryptic Aspergillus species, namely, A. turcosus, A. felis, A. viridinutans, A. nidulans, and A. calidoustus. In these 8 patients, no patients with IA due to A. fumigatus died, whereas 3 of the 5 with IA due to rare/cryptic species died within 12 weeks. The 2 surviving cases of IA due to rare/cryptic species were treated with surgical resection and antifungal treatment. Susceptibility testing for cryptic species in 4 cases showed an amphotericin B minimum inhibitory concentration (MIC) > 1 mg/L in 3 cases, itraconazole MIC > 1 mg/L in 2 cases, and voriconazole MIC > 1 mg/L in 2 cases. In conclusion, more than half of the causative pathogens of proven IA were rare/cryptic species, so it is important to accurately identify the Aspergillus species. In addition, surgical treatment might be an important option in cases of proven IA, given the possibility that the causative organisms are azole-resistant A. fumigatus or rare/cryptic species.

Background In this study, we investigated diagnostic accuracy of quantitative severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antigen testing and whether universal screening was effective to prevent a nosocomial outbreak of coronavirus disease 2019 (COVID-19). Methods All adult patients admitted to an acute-care hospital in Tokyo, Japan, after receiving LUMIPULSE SARS-CoV-2 Ag using a nasopharyngeal swab and a brief questionnaire to evaluate symptoms and exposures from December 3, 2020 to March 20, 2021 were included. Results Of the 5191 patients, 53 were antigen-positive, 19 were inconclusive and 5119 were negative. The sensitivity and specificity (positive or inconclusive results) of the quantitative antigen test for COVID-19 diagnosis at admission was 0.957 (95% confidence interval [CI]: 0.855–0.995) and 0.995 (95% CI: 0.992–0.997), respectively. Six asymptomatic patients were identified on admission. Two patients were antigen-negative and diagnosed with COVID-19 later; however, they had been isolated prior to diagnosis because both had symptoms of COVID-19 and exposure. No nosocomial infections occurred during the period. Conclusion Quantitative SARS-CoV-2 antigen testing was found to be valid for the early detection of asymptomatic COVID-19 patients as a universal screening test on admission.

Background: Cyst infection is a frequent and serious complication of autosomal dominant polycystic kidney disease (ADPKD). It is often difficult to treat and can be fatal, but much is still unknown about this type of infection. Hematogenous spread via bacterial translocation in the intestine is considered to be the main cause, so intestinal flora may be involved. However, the exact role of the intestinal flora in cyst infection in ADPKD is unknown.Case presentation: We report a 66-year-old woman and a 56-year-old man with ADPKD who had severe hepatic cyst infection. We analyzed the microbiome of infected cyst content, feces, and saliva in these two patients. The microbiome of patient 1 showed various bacteria in an infected cyst, whereas that of patient 2 showed only one bacterium. In both patients, the composition of the microbiome of the cyst content was quite different from those of feces and saliva, and the main bacteria in the infected cyst content represented a small proportion of those in feces and saliva.Conclusions: Cyst infection in ADPKD can be caused by a single bacterium or multiple bacteria, and cyst content culture or blood culture may identify only some of the causative bacteria. The association between bacteria in cysts and those in feces or saliva remains uncertain, and further research on this topic is needed.

Studies describing reverse transcription loop-mediated isothermal amplification (RT-LAMP) assay-based infection control strategies (LAMP-based ICSs) for coronavirus disease 2019 (COVID-19) are limited. We reviewed the medical records of cases in which RT-LAMP was performed. Standard ICSs and LAMP-based ICSs were implemented during the study period. The strategies were intended to impose longer periods of infection control precautions (ICPs) for specific patients, such as those with a history of exposure to COVID-19 patients and/or bilateral ground glass opacities (bGGO) on chest computed tomography (CT). Of 212 patients, which included 13 confirmed COVID-19 patients in the diagnostic cohort, exposure to COVID-19 patients (P

Limited data are available on Stenotrophomonas maltophilia bloodstream infections (SM-BSIs) and the therapeutic efficacy of trimethoprim–sulfamethoxazole (SXT) against SM-BSI in umbilical cord blood transplant (uCBT) recipients. Medical and microbiological records of adult patients who received uCBTs between December 2008 and December 2015 at Toranomon Hospital (Tokyo, Japan) were reviewed. The efficacy and safety of SXT were evaluated only for recipients who were treated with ≥7 days of intravenous SXT for SM-BSI (evaluation cohort). Of 561 uCBT recipients, 34 developed SM-BSI. Diabetes mellitus (P = .005) and age ≥ 60 years (P = .013) were significant independent risk factors for SM-BSI. Moreover, SM-BSI was identified as an independent risk factor for all-cause mortality up to 100 days following uCBT (P = .025). Of the 34 recipients with SM-BSI, 24 were treated with an intravenous SXT-containing regimen (iSXT-CR). Septic shock (P = .0021), pneumonia (P = .011), neutropenia (P = .0015), and systemic steroid administration (P = .018) were identified as significant independent risk factors for 7-day crude mortality. The evaluation cohort included nine recipients. Doses of SXT were 2.4 to 6.9 mg/kg/day of the trimethoprim component. Of the nine recipients, five developed SM-BSI during the pre-engraftment phase. The 30-day crude-mortality rate and clinical cure rate of the cohort were 22% and 67%, respectively. Only one of the nine recipients experienced significant neutrophil toxicity. In this study, the epidemiology of SM-BSI in uCBT recipients was determined and its negative impact on survival was demonstrated. A low- to moderate-dose iSXT-CR appeared to be a tolerable and important therapeutic option for SM-BSI in the uCBT setting, including during the pre-engraftment phase.

Background Factors affecting the safety of bronchoscopy in patients with malignant hematologic disorders have not been well described. We evaluated the safety of bronchoscopy and describe factors affecting its complication rate in such patients. Methods Between January 2009 and December 2018, 316 bronchoscopies in 282 patients with malignant hematologic disorders and pulmonary infiltrates were performed at our institution. The bronchoscopic procedure used and its complications were evaluated. Results The most common underlying disease was acute myeloid leukemia (134/282 patients, 47.5%). Platelet transfusion was performed the day before or the day of bronchoscopy in 42.4%, supplemental oxygen was administered before the procedure in 23.1%, and midazolam was used in 74.4%. Thirty-five bronchoscopies (11.1%) were complicated by hemoptysis and 7 patients developed pneumothorax, 4 of whom required thoracic drainage. Two patients (0.6%) were intubated within 48 h of the procedure and prolonged oxygen desaturation (> 48 h) occurred in 3.8%. Multivariate analysis showed that only use of midazolam significantly reduced the risk of prolonged oxygen desaturation (hazard ratio 0.28, 95% confidence interval 0.09–0.85, p = 0.03). Transbronchial lung biopsy significantly increased the risk of hemoptysis (hazard ratio 10.40, 95% confidence interval 4.18–25.90, p = 0.00), while use of midazolam significantly reduced the risk (hazard ratio 0.31, 95% confidence interval 0.14–0.73, p = 0.01). Conclusions Bronchoscopy is relatively safe in patients with malignant hematologic disorders. Caution and judicious use of sedatives may improve the patient’s procedural tolerance and lower complications.

Bloodstream infection (BSI) is a major infectious complication after allogeneic hematopoietic cell transplantation (HCT). To clarify the impact of graft cell source on the incidence of BSI after transplantation, we retrospectively examined 782 adult patients receiving their first allogeneic HCT: 122 recipients of related peripheral blood stem cells or bone marrow, 215 recipients of unrelated bone marrow, and 445 recipients of unrelated umbilical cord blood (U-CB). The cumulative incidence of BSI was 42.5% at 100 days after transplantation (95% confidence interval, 39.0-46.0). Gram-positive cocci were present in 64.2% of detected isolates. Among the pre-transplant factors including age, performance status, primary disease, disease status, graft cell source, sex and ABO blood type matching, and the intensity of conditioning regimen, U-CB use was identified as the most significant risk factor for BSI by multivariate analysis (hazard ratio, 1.76; 95% confidence interval, 1.40-2.22; p < 0.00001). Among the U-CB recipients, those who are not in remission at the time of transplantation were at the greatest risk of BSI (hazard ratio, 1.69; 95% confidence interval, 1.14-2.50; p < 0.01). The study makes it clear that graft cell source has an impact on BSI development after allogeneic HCT.

Background: To evaluate the safety of bronchoscopy and describe factors affecting its complication rate in patients with hematologic disorders. Methods: Between January 2009 and December 2018, 316 bronchoscopies in 282 patients with hematologic disorders and pulmonary lesions were performed at our institution. The bronchoscopic procedure used and its complications were evaluated. Results: The most common underlying disease was acute myeloid leukemia (134/282 patients, 47.5%). Platelet transfusion was performed the day before or the day of bronchoscopy in 42.4%, supplemental oxygen was administered before the procedure in 23.1%, and midazolam was used in 74.4%. Two patients (0.6%) were intubated within 48 hour of the procedure and prolonged oxygen desaturation (>48 hour) occurred in 3.8%. Multivariate analysis showed that only use of midazolam significantly reduced the risk of prolonged oxygen desaturation ( p = 0.01, hazard ratio 0.23, 95% confidence interval 0.07–0.75). Conclusions: Bronchoscopy is relatively safe in patients with hematologic disorders. Sedation with midazolam may reduce the risk of prolonged oxygen desaturation.

A 60-year-old man developed pneumonia after undergoing autologous peripheral blood stem cell transplantation for diffuse large-B cell lymphoma. A urinary antigen test and sputum culture were both negative for Legionella pneumophila; however, a sputum sample that was examined by loop-mediated isothermal amplification (LAMP) was positive for Legionella spp. On admission, the results of blood culturing using a BACTEC system were negative for 7 days. However, L. pneumophila serogroup 5 was detected in a blood subculture using WYOα medium. The patient was successfully treated with a fluoroquinolone-based regimen. LAMP is useful for the diagnosis of Legionella spp.

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.

Objectives The aim of this study was to evaluate the in vitro effects and clinical efficacies of trimethoprim-sulfamethoxazole (SXT) combined with other antimicrobial agents against Stenotrophomonas maltophilia . Methods In vitro analysis was conducted on 89 S. maltophilia strains isolated from blood and the respiratory tract between June 2012 and October 2014. Levofloxacin (LVX), ticarcillin-clavulanic acid (TIM), and minocycline (MIN) were selected for an examination of their effects when individually combined with SXT by the checkerboard method. In addition, 29 S. maltophilia bacteremia cases were reviewed and the clinical efficacies of SXT-based combination therapies were analyzed. Results SXT+LVX showed synergy in 21, no interactions in 61, and antagonism in 7. SXT+TIM showed synergy in 71, and no interactions in 18. SXT+MIN showed synergy in 10, and no interactions in 79. The review of clinical data indicated that a combination of SXT+fluoroquinolone was not associated with improved prognosis compared with monotherapy. Conclusions The in vitro data indicated that SXT+TIM had beneficial microbiological effects and was not antagonistic. Our in vitro and clinical data analyses do not support the routine use of SXT+fluoroquinolone combination therapy for S. maltophilia infection.

A 63-year-old woman was admitted to our hospital to receive a fourth course of modified rituximab-ESHAP chemotherapy for relapsed primary breast diffuse large B-cell lymphoma. She developed hemophagocytic lymphohistiocytosis (HLH) 20 days after admission. Polymerase chain reaction (PCR) detected cytomegalovirus (CMV) DNA in her peripheral blood; therefore, she was diagnosed with CMV-associated HLH and consequently treated with foscarnet (FCN). Her general condition and pancytopenia soon improved, and the antiviral drug was stopped for 1 week. However, she suddenly became disoriented 10 days later, and this condition rapidly worsened. Cerebrospinal fluid (CSF) examination revealed an elevated white blood cell count with lymphocytic predominance and a high CMV DNA load, prompting a final diagnosis of CMV meningoencephalitis. We began intravenous combination therapy with FCN and ganciclovir (GCV), and her conscious state gradually improved. CMV DNA sequencing did not reveal drug resistance associated with mutations, and intravenous GCV was stopped for 1 week. FCN treatment was then continued until CMV DNA was no longer detected in her CSF samples via PCR. CMV meningoencephalitis is a rare neurological infection complicated with hematological malignancy in non-transplant patients and can be serious and life-threatening with a high mortality rate. This infection requires a differential diagnosis of consciousness impairment that develops in a patient with lymphoid malignancy during chemotherapy.

We examined the applicability of Matrix-assisted laser desorption ionization-time of flight mass spectrometry using 54 Helicobacter cinaedi isolates from humans. In all 54 isolates, MALDI-TOF MS detected H. cinaedi as the best match organism. Our findings suggest that MALDI TOF-MS can be used effectively to identify H. cinaedi.

A total of 46 clinical isolates of Candida guilliermondii and Candida famata were reidentified genetically, resulting in 27 C. guilliermondii and 12 Candida fermentati strains. The majority of C. guilliermondii strains, but not C. fermentati strains, were isolated from blood cultures. C. fermentati was more sensitive to antifungals, hydrogen peroxide, and killing by murine macrophages than was C. guilliermondii . The C. guilliermondii isolates were echinocandin susceptible in vitro but resistant to micafungin in a murine model of invasive candidiasis.

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 .

Tuberculosis screening was performed for a healthy asymptomatic woman to determine whether she had been infected with active genital tuberculosis via sexual intercourse with her husband who had epididymal tuberculosis. Vaginal swab culture yielded Mycobacterium tuberculosis. Furthermore, whole genome sequencing revealed that the two causative isolates were genetically identical. This appears to be the first report on the sexual transmission of genital tuberculosis from a man to an asymptomatic woman, detected by active screening for genital tuberculosis and molecular analysis, including whole genome sequencing. Active screening for genital tuberculosis in the female partner should be considered soon after diagnosis of male genital tuberculosis, even when the female partner is asymptomatic.

Staphylococcus lugdunensis (SL) is a bacterium with a highly pathogenicity than most other coagulase-negative Staphylococcus spp. (CoNS). In Japan, data on this pathogen are sparse, and the current prevalence of SL bacteremia is unknown. Therefore, we investigated the prevalence of SL in blood culture specimens in a prospective multicenter study across 5 facilities. A total of 3,284 patients had positive blood cultures, and 2,478 patients had bacteremia. Among the patients with bacteremia, 7 patients (0.28%) had SL bacteremia. A total of 281 patients had CoNS bacteremia, with SL accounting for 2.49% of these cases. Of the 7 patients with SL bacteremia, 1 patient (14.3%) had infective endocarditis, and 1 patient (14.3%) died within 30 days. In this study, SL resulted in the development of bacteremia in select patients. Clinicians in Japan should be aware of the prevalence of SL and the complications of SL bacteremia.

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.

Summary 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.

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.

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.

Infections caused by multidrug-resistant (MDR) Pseudomonas aeruginosa are very difficult to treat. The aim of this study was to develop more effective treatments by investigating in vitro the effects of combinations of antibiotics against 47 MDR P. aeruginosa isolates harbouring various resistance factors. The isolates included 41 (87%) metallo-β-lactamase (MBL)-positive strains, 37 (79%) strains with mutations in OprD and 46 (98%) strains carrying the genes encoding aminoglycoside-modifying enzymes (AMEs). The quinolone resistance-determining region was mutated in all of the strains. These strains were classified into 16 groups according to amplified fragment length polymorphism and resistance factors. The effects of combinations of antibiotics on 16 representative strains were determined using a ‘Break-point Checkerboard Plate’ assay. Combinations of amikacin + aztreonam (coverage rate, 81.3%) and arbekacin + aztreonam (93.8%) inhibited growth. In contrast, combinations of ciprofloxacin + meropenem (6.3%) and ciprofloxacin + ceftazidime (12.5%) were much less effective. Aztreonam and arbekacin (or amikacin) are not substrates for MBLs and AMEs, respectively. We conclude that the combined effects of these drugs were possibly because of resistance factors.

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-resistantStaphylococcus 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.

Staphylococcus lugdunensis (SL) is a bacterium with a highly pathogenicity than most other coagulase-negative Staphylococcus spp. (CoNS). In Japan, data on this pathogen are sparse, and the current prevalence of SL bacteremia is unknown. Therefore, we investigated the prevalence of SL in blood culture specimens in a prospective multicenter study across 5 facilities. A total of 3,284 patients had positive blood cultures, and 2,478 patients had bacteremia. Among the patients with bacteremia, 7 patients (0.28%) had SL bacteremia. A total of 281 patients had CoNS bacteremia, with SL accounting for 2.49% of these cases. Of the 7 patients with SL bacteremia, 1 patient (14.3%) had infective endocarditis, and 1 patient (14.3%) died within 30 days. In this study, SL resulted in the development of bacteremia in select patients. Clinicians in Japan should be aware of the prevalence of SL and the complications of SL bacteremia.

It is difficult to determine whether anticancer treatment should be started for cancer patients with chronic infections. If an anticancer drug is administered to cancer patients with chronic infections, it is difficult to determine when anticancer therapy should be started. It is important to evaluate the current status of each patient's cancer and infections for decision-making. There is limited evidence in this area; therefore, we have to individualize our approach for each patient. Oncologists are expected to treat cancer patients in collaboration with infectious disease doctors.

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.

I.v. BU/fludarabine plus melphalan or TBI in unrelated cord blood transplantation for high-risk hematological diseases

Varicella zoster virus (VZV) infection usually manifests with a skin rash. To the best of our knowledge, this is the first report of a case of VZV meningoencephalitis presenting with Elsberg syndrome without a rash in an immunocompetent patient. Clinicians should consider the potential for VZV infection as well as herpes simplex virus infection in cases of aseptic meningitis accompanied by bladder and rectal disturbances, even in patients without any rash symptoms.

Background The optimal graft-versus-host disease (GVHD) prophylaxis after umbilical cord blood transplantation has not been established. Our previous observation using single calcineurin inhibitors revealed a high incidence and severity of early immune-mediated complications, especially for older patients or those with poor performance status. Methods We conducted a single institute pilot study assessing the safety and effectiveness of mycophenolate mofetil (MMF) and tacrolimus (FK) combination as a GVHD prophylaxis for 29 patients (FK+MMF), and the results were compared with matched-pairs extracted from our historical database who received FK alone as GVHD prophylaxis (control). Results FK+MMF group showed superior engraftment rate compared with control group (cumulative incidence until day 60 posttransplant; 90%±0% vs. 69%±1%, P=0.02). A cumulative incidence of severe type preengraftment immune reactions was significantly decreased in FK+MMF group (16%±1%) compared with that of control group (52%±2%, P=0.03), and, remarkably, there was no nonrelapse mortality (NRM) observed up to day 30 posttransplant in FK+MMF group, whereas 21%±1% of NRM was observed in the control group. However, the incidences of acute and chronic GVHD, estimated overall and progression-free survivals were comparable between two groups. Conclusions MMF and FK in combination was well tolerated and decreased early NRM possibly by better control of preengraftment immune reactions. Subsequent NRM or disease progression needs to be overcome to further improve survival.

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.