Search

We aimed to detect possible changes in Candida species distribution over time and to know the antifungal susceptibility profile of isolates obtained from patients with bloodstream infection (BSI) due to this pathogen. Risk factors associated with 30-day mortality were also assessed. We conducted a retrospective cohort study of patients diagnosed with Candida BSI at a Japanese university hospital from 2013 to 2021. The change in the distribution pattern of the Candida spp. isolated was examined by considering three successive sub-periods of 3 years each. Risk factors for 30-day mortality were determined using Cox regression analysis. In the entire study period, Candida albicans was the most frequent species (46.7%), followed by Candida glabrata (21.5%) and Candida parapsilosis (18.7%). There was no change in Candida species distribution comparing the three sub-periods analyzed. All isolates were susceptible to micafungin, and most were susceptible to fluconazole, except for C. glabrata. No isolates were resistant to amphotericin B or voriconazole. The overall 30-day mortality was 40.2%. Univariate analysis revealed an association between 30-day mortality and central venous catheter (CVC) removal at any time, high Pitt bacteremia score (PBS), and high Charlson comorbidity index (CCI). Multivariate Cox analysis found that high PBS was the only independent predictor of 30-day mortality; subsequent multivariate Cox regression demonstrated that early CVC removal significantly reduced 30-day mortality. Candida species distribution and antifungal susceptibility profile in our hospital remained similar from 2013 to 2021. Early CVC removal may improve candidemia outcomes.

Amenamevir has been approved for the treatment of herpes zoster (HZ); however, its therapeutic efficacy against central nervous system (CNS) infection may be insufficient due to its low spinal fluid permeability. We herein report a case of aseptic meningitis in a 91-year-old Japanese man treated with amenamevir for HZ in the trigeminal nerve region. Several cases of CNS infection have been reported in patients receiving amenamevir treatment for HZ. Patients with CNS complications often have skin rashes near the trigeminal region. Thus, we should be alert for signs of CNS infection when administering amenamevir to patients with such rashes.

The most common routes of transmission of coronavirus disease 2019 are droplet and contact infections. During dental treatment, many instruments are used that generate droplets of saliva and blood. Several droplets are generated during extraction of an impacted third molar (M3). Surgical masks are often used during tooth extraction; however, the surface structure of surgical masks against droplets is not fully understood. Therefore, we analyzed the droplets adhered to surgical masks during impacted M3 extraction using electron microscopy. A surgical mask used during impacted M3 extraction was studied. The collected surgical mask was divided into three layers and observed using electron microscopy. The outer and inner layers had a similar mesh-like structure, while the middle layer had a denser three-dimensional structure. Droplets ranging from 20-100 μm in size generated during the extraction adhered to the fibers of the outer layer of the mask. Fewer droplets adhered in the middle layer than those in the outer layer. No droplets reached the inner layer. In conclusion, it is suggested that a surgical mask can prevent droplet infection when performing impacted M3 extraction. This study is expected to contribute to the study of infection control strategies during dental treatment in the future.

Purpose The Japanese Society of Medical Oncology published a guideline (GL) on febrile neutropenia (FN) in 2017. The study’s purpose is to reveal how widely GL penetrated among physicians and surgeons providing chemotherapy. Methods A questionnaire survey was conducted with SurveyMonkey™ for members of the Japanese Association of Supportive Care in Cancer and relevant academic organizations. Each question had four options (always do, do in more than half of patients, do in less than half, do not at all) and a free description form. Responses were analyzed with statistical text-analytics. Result A total of 800 responses were retrieved. Major respondents were experts with more than 10-year experience, physicians 54%, and surgeons 46%. Eighty-seven percent of respondents knew and used GL. Forty-eight percent assessed FN with Multinational Association of Supportive Care in Cancer (MASCC) score “always” or “more than half.” Eighty-one percent chose beta-lactam monotherapy as primary treatment in high-risk patients. Seventy-seven percent did oral antibacterial therapy in low-risk patients ambulatorily. Seventy-eight percent administered primary prophylactic G-CSF (ppG-CSF) in FN frequency ≥ 20% regimen. Fifty-nine percent did ppG-CSF for high-risk patients in FN frequency 10–20% regimen. Ninety-seven percent did not use ppG-CSF in FN frequency Conclusion GL is estimated to be widely utilized, but some recommendations were not followed, presumably due to a mismatch with actual clinical practices in Japan.

Systemic inflammatory response syndrome and sepsis are considered to contribute to hypercytokinemia in both patients with severe infection and immunocompromised condition. Past research has demonstrated that antibiotics and antifungals not only have antimicrobial efficacy but also affect the immune system. We previously examined whether immune cells were modulated by antibiotics such as tetracyclines or macrolides. The modulation of lipopolysaccharide-stimulated cells by those agents was elucidated. However, few reports about the modulation of the immune system by antifungal agents were found. In this study, the production of pro-inflammatory cytokines and chemokines and signaling pathways involved were investigated in zymosan-activated THP-1 cells. The effects were examined using antifungal agents such as echinocandin including caspofungin (CAS) and micafungin. Pro-inflammatory cytokine and chemokine levels were determined using enzyme-linked immunosorbent assay. Protein phosphorylation was evaluated by western blot analysis. CAS significantly decreased zymosan-induced pro-inflammatory cytokine and chemokine release in THP-1 cells. CAS (30 µg/mL) also downregulated tumor necrosis factor alpha levels, as shown by enzyme-linked immunosorbent assay. In western blot analysis, inhibitor of nuclear factor-kappa-B alpha, p38, c-Jun N-terminal kinase, extracellular signal-regulated kinase, and nuclear factor of activated T-cells phosphorylation and activation of caspase-1 and spleen tyrosine kinase (Syk) were downregulated. The major underlying mechanism of pro-inflammatory cytokine and chemokine suppression by CAS is to inhibit activation of Syk and its downstream signaling molecules. Based on the results, it can be concluded that CAS activity possibly involves Syk signaling pathways and has potential to prevent hypercytokinemia in fungal sepsis.

Introduction Invasive fungal infections have been attracting attention as significant fatal complications in patients with febrile neutropenia (FN) who undergo intensive chemotherapy or hematopoietic stem cell transplantation to treat hematological malignancies. Although clinical trials are already underway in other countries, evidence supporting the use of caspofungin (CAS) in FN patients in Japan is still insufficient. Methods A retrospective study of patients treated with CAS for FN associated with hematological diseases between April 2015 and March 2018 was conducted to determine the treatment efficacy and safety. The study was conducted as a multicenter collaboration, and the data of 52 patients who met all of the inclusion criteria were analyzed. A five-composite-endpoint method was used, and the treatment was judged to be effective when all five endpoints (defervescence during neutropenia; no breakthrough fungal infections; resolution of baseline fungal infections; a survival for seven days or more after the completion of therapy; and no discontinuation of therapy due to side effects or invalidity) were met. Results The efficacy rate was 53.8% (28/52), which is close to the average reported efficacy rate. Adverse events included liver dysfunction and electrolyte abnormalities, but no renal dysfunction or serious events were seen. Conclusion These results suggest that the use of CAS in FN patients with hematological diseases is effective and well-tolerated, and we believe that the use of CAS could become a significant treatment in Japan.

Eosinophilic fasciitis (EF) is a rare connective tissue disease that causes inflammation and fibrosis of the fascia, inducing pain and motor dysfunction. Characteristic skin manifestations, such as edema, erythema, induration, peau d'orange appearance, and the groove sign, are of diagnostic significance and observed in the majority of patients with EF. We herein report a case of EF without these characteristic skin manifestations. A 66-year-old Japanese woman developed progressive limb pain and motor dysfunction. No skin changes were observed. We diagnosed the patient with EF based on the clinical course, magnetic resonance imaging, and en bloc biopsy containing fascia and muscle. Oral prednisolone therapy markedly attenuated limb pain and motor dysfunctions. Through a systemic search of the medical literature, we retrieved 4 juvenile cases and 8 adult cases of EF without characteristic skin manifestations during the clinical course. We herein present a systemic review on EF without skin manifestations and discuss differences between the two proposed sets of diagnostic criteria of EF.

Objective Methicillin-resistant (MR) Staphylococcus aureus bacteremia (SAB) is associated with higher mortality rates than methicillin-susceptible (MS) SAB. This study assessed potential predictors of mortality and evaluated the association of methicillin resistance with mortality in patients with SAB. Methods We conducted a retrospective cohort study in patients with hospital-acquired SAB, from 2009 to 2018. Clinical features of patients with MR-SAB were compared with those of patients with MS-SAB and predictors of 30-day mortality were determined using Cox regression analysis. Results Among 162 patients, 56.8% had MR-SAB. Overall 30-day mortality was 19.1%; MR-SAB had higher mortality (25.0%) than MS-SAB (11.4%). Univariate analysis highlighted long-term hospitalization, prior antibiotics use, and delayed initiation of appropriate antibiotics as risk factors. Cox regression analysis showed that respiratory tract source, Pitt bacteremia score, Charlson comorbidity index, and appropriate antibiotic therapy within 24 hours were independently and significantly associated with 30-day mortality outcome. Conclusions Methicillin resistance was not an independent risk factor for mortality in patients with SAB. Early, appropriate antibiotic treatment is an important prognostic factor.

Purpose The Japanese Society of Medical Oncology (JSMO) published a guideline (GL) on febrile neutropenia (FN) in 2017. This study aims to identify promoting factors and disincentives for complying with GL recommendations according to attributes of doctors providing chemotherapy. Methods A questionnaire survey was conducted with SurveyMonkey™ for physician members of the Japanese Association of Supportive Care in Cancer and relevant academic organizations. Each question had four options (always do, do in more than half of patients, do in less than half, do not at all) and a free description form. Responses were analyzed according to the respondents’ attributes. Result Seven hundred eighty-eight out of retrieved 801 responses were available for analysis. Multivariable analysis demonstrated that the percentage of GL users was higher among women and Japanese Society of Clinical Oncology members. The overall compliance rate was higher among women, JSMO members, and board-certified medical oncologists. Internists emphasized the significance of collecting blood cultures at FN onset, and surgeons stressed the importance of G-CSF prophylaxis. Hematologists were less likely to adhere to recommendations on risk assessment of FN by the Multinational Association of Supportive Care in Cancer score and administration of gammaglobulin products. However, those are acceptable due to the characteristics of their practice. Eight recommendations had no difference in compliance rates between users and non-users, some of whose statements were ambiguous and discretionary. Conclusion Women were more likely to use and adhere to GL. The recommendations should be developed considering the characteristics of specialty and subspecialty and avoiding ambiguity and discretionary statements.

Sepsis is a systemic reaction to infection and excessive production of inflammatory cytokines and chemokines. It sometimes results in septic shock. The present study was designated to find out which quinolone antibiotic reduces TNFα production the most and to elucidate its mechanisms. We examined which quinolone antibiotic reduced TNFα production from THP-1 cells stimulated by lipopolysaccharide (LPS). Then, we examined the mechanism of inhibition of TNFα production by the antibiotic. STFX most effectively reduced TNFα concentrations within LPS-stimulated THP-1 cells supernatant. STFX suppressed TNFα production in a dose-dependent manner. We found that STFX did not inhibit the NF-kB, ERK, or p38 pathways, nor did it inhibit the production of TNFα mRNA. The percentage of intracellular TNFα was increased in cells stimulated by LPS and with STFX compared to that of cells stimulated by LPS alone. In conclusion, one of the mechanisms reducing TNFα production from LPS-stimulated THP-1 cells treated with STFX involves inhibition of TNFα release from these cells. STFX has a broad antimicrobial spectrum for gram-positive, gram-negative, and anaerobic bacteria, and may be effective for treating sepsis by both killing bacteria and suppressing inflammation.

The aim of this study was to investigate the efficacy and safety of minocycline (MIN) and favipiravir combination therapy in patients with coronavirus disease 2019 (COVID-19) admitted to our hospital in Fukui Prefecture, Japan, in March and April of 2020. In this retrospective study, a favipiravir monotherapy group (Control group, n = 9) was compared with a combined favipiravir plus MIN therapy group (MIN group, n = 12). No severe cases were present. The primary comparative endpoints evaluated were duration of fever, duration of hospitalization, duration from treatment initiation to severe acute respiratory syndrome coronavirus 2 polymerase chain reaction (PCR)-negative results, and changes in cytokine and chemokine production. Median duration from start of treatment to negative PCR test was significantly shorter in the MIN group than in the Control group. Mean rates of cytokine and chemokine reduction were significantly greater for interleukin-6 and interleukin-8 in the MIN group. No difference in adverse event rates were seen between groups, and only minor adverse events were encountered. MIN has been reported to have not only broad antibacterial activity, but also antiviral and anti-inflammatory activity. The present results support the efficacy and safety of MIN plus favipiravir therapy for the treatment of COVID-19.

Fungal co-infections of coronavirus disease 2019 (COVID-19) are generally infrequent, but are more common among patients with hematological diseases or severe cases in the intensive care unit (ICU). As fungal infections often carry a high mortality rate, preventing their development is considered important for patients with COVID-19. Caspofungin covers

Summary Since the outbreak of Coronavirus disease 2019 (COVID‐19) in China, many researchers have reported the chest CT manifestations of COVID‐19 pneumonia. High‐resolution CT (HRCT) of the lung can provide important clues to understand the progressive behaviour of COVID‐19 pneumonia. This pictorial essay discusses the early features and potential progressive behaviour of COVID‐19 on HRCT of the lung.

Nursing activities are complex in nature: in the real scenario, when nurses perform caregiving activities, they can perform concurrent activities or multiple activities at a time. With traditional supervised learning, it is very difficult to classify them, especially when there is no proper information on sequence and duration of activities performed. In this paper, we used a new nursing dataset collected in a complete natural setting. As our observer could not enter the room of patient to record the duration of each activity, we utilized multilabel classification in this scenario. We considered our work both as multiclass classification and multilabel classification. We applied (1) Random Forest for multiclass classification, (2) Binary Relevance, and (3) Random Forest SRC (Survival, Regression, and Classification) for multilabel classification. By evaluating the result, we found out that Random Forest SRC achieved the highest performance that is around 86% precision, 62% recall, and 63% F1 score, whereas Random Forest achieved around 10% precision, 11% recall, and 10% F1 score and Binary Relevance achieved around 28% precision, 13% recall, and 17% F1 score. We also explained why multilabel classification is necessary to recognize activities in real scenario problems.

Invasive trichosporonosis is a rare and lethal fungal infection that occurs in immunocompromised patients. Breakthrough trichosporonosis can occur in patients treated with echinocandins since Trichosporon spp. are resistant to these antifungal agents. We report a case of breakthrough Trichosporon asahii fungemia. A 62-year-old Japanese woman with relapsed follicular lymphoma was treated empirically with broad-spectrum antibiotics and micafungin due to an intermittent fever during reinduction chemotherapy. After four cycles of anti-cancer chemotherapy, she experienced a high neutropenic fever and T. asahii was subsequently detected from a blood culture. The patient was not given voriconazole due to the contraindication for use with carbamazepine, and she was successfully treated with fluconazole plus liposomal amphotericin B without any serious complications. The combined therapy of fluconazole and liposomal amphotericin B may therefore be useful in treating T. asahii fungemia, especially in patients receiving antiepileptic agents.

Although spiral bacteria are uncommon, they cause bacteremia. We evaluated their characteristics, in particular, the time from the start of blood culture to the first report of a positive result to physicians, using the BACTEC blood culture system. In cases of spiral bacteremia, an extended treatment period should be considered.

Excessive activation and proliferation of inflammatory cell and uncontrolled release of cytokines and chemokines, also known as cytokine storm, is considered to be the main cause of sepsis. Accumulating evidence has indicated that autophagy may play an important role in regulating immune response and controlling excessive inflammation. Recent studies have showed that minocycline has immunomodulatory effects on cytokine and chemokine production. It has also been reported that minocycline can induce autophagy, suggesting that autophagy may be involved in the process of minocycline regulating inflammation and immune response. However, the precise mechanism is unclear. In the present study, we used enzyme-linked immunosorbent assays (ELISA) to measure the production of cytokines following minocycline treatment of lipopolysaccharide- (LPS-) stimulated THP-1 cells. Western blotting analysis was performed to confirm autophagy and the mTOR signal pathway. Cell proliferation was measured by WST-1 cell proliferation assay. We demonstrated that LPS induced autophagy in a tumor necrosis factor- (TNF-) α-mediated manner, and simultaneously, LPS induced the release of TNF-α to trigger inflammation and activated mammalian target of rapamycin (mTOR) to potentiate cell proliferation. Minocycline, which induces autophagy by inhibiting mTOR, suppresses cytokine production and cell proliferation and protects THP-1 cells from LPS toxicity. Further study demonstrated that there might be an intimate crosstalk between the inhibitor kappa B kinase (IKK)/nuclear factor-kappa B (NF-κB) signaling pathway and autophagy flux in modification of inflammatory responses. In addition, rapamycin, the mTOR inhibitor, has cooperative effect with minocycline on suppression of TNF-α release and induction of autophagy by repressing mTOR. Our data brought a novel clue to evaluate minocycline using as a potential therapeutic medicine for sepsis.

Enterococci is one of a major cause of bloodstream infection (BSI). Because of its intrinsic drug-resistant nature, empiric antibiotic treatment tends to be inappropriate. We conducted a single-center retrospective cohort study to evaluate the impact of Matrix-assisted laser desorption and ionization time-of-flight mass spectrometry (MALDI-TOFMS) on the improvement of early antibiotic treatment for enterococcal infection. We also investigated the 28-day mortality, length of hospitalization and duration of antibiotic treatment for enterococcal bacteremia. A total of 173 BSI episodes (172 patients) between June 2012 and June 2019 were enrolled. Patients were divided into 2 groups before (n = 82) and after (n = 91) the implementation of MALDI-TOFMS (Control group and MALDI-TOF group, respectively). Almost an equal number of Enterococcus faecalis and Enterococcus faecium cases were identified in each group (51.2% and 48.8%, and 47.3% and 52.7% in each group). By implementing MALDI-TOFMS, the time to definitive antibiotic treatment was significantly improved (median 3 vs 1 days, p 0.001). The 28-day mortality (29.3% vs 26.4%, p = 0.63) and length of hospitalization (median 16 vs 19 days, p = 0.58) were not significantly different. The duration of antibiotic treatment did not significantly differ between the two groups (median 11 vs 11 days, p = 0.78), but the duration was often shorter in older patients (74 years old) in MALDI-TOF group, excluding those in the terminal phase of malignancy. By implementing MALDI-TOFMS, the time to definitive antibiotic treatment was significantly shortened. Although associated outcomes did not significantly differ, the duration of antibiotic treatment may be shortened.

A 36-year-old man with human immunodeficiency virus (HIV) infection was admitted to our hospital due to progressive ataxia. Brain MRI demonstrated high-signal intensity in the white matter of the right parietal lobe and left cerebellar hemisphere on T2-weighted images. Despite antiretroviral therapy, as his clinical symptoms worsened and MRI lesions gradually increased with the appearance of gadolinium-enhanced lesions, immune reconstitution inflammatory syndrome by progressive multifocal leukoencephalopathy (PML) associated with HIV infection was suspected. However, JC virus (JCV) in the cerebrospinal fluid (CSF) was undetectable by DNA PCR twice. Therefore, biopsy of the right parietal lobe was performed. JCV DNA was detected by PCR using the biopsy sample. JC viral protein was also identified by immunohistochemistry. Brain biopsy should be considered for the clinical diagnosis of PML when CSF JCV is negative on repeated DNA PCR. (Received September 20, 2019; Accepted January 14, 2020; Published May 1, 2020).

Cladophialophora bantiana (C. bantiana) is a life-threatening melanized mycelial fungus causing brain abscess. C. bantiana is usually observed in tropical countries, including India. We report a Japanese case of C. bantiana presenting with myelitis mimicking neuromyelitis optica (NMO) and brain abscess. A 73-year-old man was administered prednisolone (30 mg/day) for antineutrophil cytoplasmic antibody (ANCA)-related vasculitis 100 days before admission. He had right side-dominant paraplegia and sensory loss in the right leg. T2-weighted spinal cord MRI revealed longitudinal high-intensity signals at the T7 to T12 levels. A ring-enhancing lesion at the T10 level was detected on gadolinium (Gd)-enhanced MRI. He was tentatively diagnosed with NMO, and steroid pulse therapy was performed. One month later, an abscess at the right cerebropontine angle was noted on Gd-enhanced brain MRI. Two months later, several subcutaneous intramuscular tumors were detected. Based on the morphological study of the cultured organelle obtained by tumor enucleation and the internal transcribed spacer sequence of ribosomal RNA, the pathogen was identified as C. bantiana. Although he received liposomal amphotericin B treatment, the patient died of respiratory insufficiency. C. bantiana infection should be considered in patients with myelitis presenting with longitudinal lesions and CNS abscess in an immunocompromised state.

The coronavirus disease 2019 (COVID-19) pandemic has affected various aspects, including socioeconomic status and health. This retrospective study aimed to investigate the influence of the COVID-19 pandemic on oral health based on the number of teeth that contribute to mastication, and the nutritional status of elderly patients with digestive cancers. The authors defined the before and during COVID-19 periods in this study as January 2019 to December 2019 and January 2020 to December 2020, respectively. Patients with digestive cancer who underwent general, laboratory, and orthopantomograph examinations for preoperative oral health assessment before general anesthesia participated in this study. The authors investigated the following general characteristics: (1) sex, (2) age, and (3) the organ affected by disease and scheduled for surgery under general anesthesia. The authors collected information about (4) the number of teeth that could contribute to mastication as a clinical oral health parameter. The parameters: (5) body mass index, (6) serum total protein levels, and (7) serum albumin levels were used to indicate the nutritional status. A total of 233 elderly patients with digestive cancer participated in this study. There was no significant difference between the age of the patients with digestive cancer. There was also no significant difference in the number of teeth that could contribute to mastication. Additionally, there was no significant difference in nutritional status as indicated by the body mass index, serum total protein levels, and serum albumin levels. This study showed that the COVID-19 pandemic during 2020 did not have a significant influence on the oral health and nutritional status of elderly patients with digestive cancer. However, the influence of COVID-19 on community oral health may become apparent in the future. Thus, dental professionals should continue further research regarding the effects of COVID-19 on oral health.

Oral antibiotic therapy is routinely administered when a third molar (M3) is extracted to prevent infectious complications after surgery. Oral third-generation cephalosporins are frequently used after M3 extraction in Japan but at the expense of an increased risk of antimicrobial resistance. Therefore, the infection control team (ICT) at our institution recommended a reduction in use of these agents after M3 extraction. In this study, we compared the types of antibiotic agents prescribed for patients undergoing M3 extraction before and after this recommendation. We investigated the relationship between type of antibiotic used and the likelihood of infectious complications as well as cost savings in patients who underwent M3 extraction in the 6 months before and after the ICT recommendation in July 2018. There was a marked reduction in use of oral third-generation cephalosporins after M3 extraction (P 0.0001) and increased use of oral penicillins and first-generation cephalosporins after the ICT recommendation. Moreover, surgical site infection (SSIs) were significantly less common after the ICT recommendation (P = 0.0099); however, the SSI rate was higher in patients who received a third-generation cephalosporin than in those who received penicillin (8.8% vs 0.5%). There was also a significant saving in per-patient antibiotic costs after the ICT recommendation (269.5 ± 282.0 JPY vs 454.7 ± 376.6 JPY; P 0.0001). These findings suggest that collaboration with an ICT promotes appropriate antibiotic use, decreases the risk of an SSI, and improves the cost-benefit ratio in patients undergoing M3 extraction.