Bloodstream infections require timely and appropriate diagnosis and treatment, as inadequate management is associated with higher mortality. Previous predictive models for bloodstream infection have generally incorporated laboratory test results in addition to vital signs, although laboratory results are not always immediately available in clinical practice. This study aimed to develop and validate a machine learning model to predict positive blood cultures using only vital signs in febrile intensive care unit (ICU) patients (maximum BT ≥ 38 °C). Clinical data from ICU patients at two university hospitals were included, with 597 blood cultures used for model development and 366 for external validation. Six explanatory variables derived from body temperature, heart rate, and mean arterial pressure measured over three days were used to construct a Balanced Random Forest model. The area under the receiver operating characteristic curve was 0.700 ± 0.072 for internal validation and 0.679 ± 0.010 for external validation. SHapley Additive exPlanations value analysis indicated that a larger temperature range contributed to positive predictions, while no increase in temperature, increases in blood pressure, and a decrease in heart rate contributed to negative predictions. The model demonstrates moderate predictive performance and shows comparable results across different datasets. It can continuously monitor the need for blood cultures, thereby serving as an adjunctive tool to support clinical decision-making.

OBJECTIVES:We aimed to compare the clinical features in patients with streptococcal toxic shock syndrome (STSS) caused by the three β-hemolytic streptococci (BHS): Streptococcus pyogenes, Streptococcus agalactiae, and Streptococcus dysgalactiae subsp. equisimilis (SDSE). METHODS:Overall, 301 adult patients with STSS with S. pyogenes (32.9%), S. agalactiae (17.6%), and SDSE (49.5%) in Japan were enrolled between 2016 and 2021. Data were analyzed to identify differences in clinical characteristics among the three BHS. Bacterial isolates were examined for emm or capsular typing. RESULTS:The incidence of STSS with S. pyogenes declined during the COVID-19 pandemic, but STSS with S. agalactiae and SDSE did not. Patients with SDSE were the oldest (median age, 81 years; interquartile range, 70-88 years) followed by those with S. agalactiae (76 years; 67-85 years) and S. pyogenes (66 years; 58-78 years). The case fatality rates (CFRs) of STSS caused by the three BHS were not significantly different, ranging from 48-59%; however, the CFR significantly increased with age in patients with SDSE (P <0.05). CONCLUSIONS:The characteristics of STSS differed among the three BHS. Clinicians should be aware of poor outcomes in patients with STSS, and provide appropriate treatment at an early stage.

Objective: We aimed to investigate the impact of preceding seasonal influenza on the clinical characteristics of adult patients with invasive pneumococcal disease (IPD) in Japan. Methods: Data for 1722 adult patients with IPD were analyzed before (2017-2019) and during the COVID19 pandemic (2020-2022). Results: The seasonal influenza epidemic disappeared soon after the emergence of the pandemic. Compared with that before the pandemic (66.7%), we observed a lower bacteremic pneumonia proportion in patients with IPD during the pandemic (55.6%). The clinical presentations of IPD cases significantly differed between those with and without preceding influenza. The proportion of bacteremic pneumonia was higher in IPD patients with preceding influenza than in those without in both younger (44.9% vs 84.2%) and older adults (65.5% vs 87.0%) before the pandemic. The case fatality rate was significantly higher in IPD patients with preceding influenza (28.3%) than in those without (15.3%) in older adults before the pandemic ( P = 0.020). Male and aging are high risk factors for death in older patients with IPD who had preceding influenza. Conclusion: Our study reveals that preceding seasonal influenza plays a role in the development of bacteremic pneumococcal pneumonia, increasing the risk of death in older adults. (c) 2024 Published by Elsevier Ltd on behalf of International Society for Infectious Diseases. This is an open access article under the CC BY-NC-ND license ( http://creativecommons.org/licenses/by-nc-nd/4.0/ )

The use of extracorporeal membrane oxygenation (ECMO) increased during the COVID-19 pandemic. However, complications associated with the long-term use of ECMO are poorly understood. This case report describes the autopsy findings of a perihepatic abscess in a patient with long-term COVID-19, which could not be diagnosed before death. In cases where the source of infection remains elusive but uncontrolled infections occur, we recommend the combined use of ultrasonography and contrast-enhanced computed tomography (CT) in patients with COVID-19 undergoing prolonged ECMO support, with particular consideration given to the potential development of cholecystitis.

夫婦でStreptococcus pyogenesによる壊死性筋膜炎を発症したが，妻のみ劇症型の経過となり死亡するという転帰の異なる2症例を経験した。妻は，病変部位の病理検査では好中球の浸潤が乏しく，血液培養から病原制御因子であるCsrSに変異のある菌株が検出された。一方，夫の病理検査では多数の好中球の浸潤を認め，菌株に病原制御因子の変異を認めなかった。菌株の病原制御因子の変異は，劇症化や病理組織所見と関連する可能性が示唆された。

Coronavirus disease 2019 (COVID-19) is associated with coagulopathy. However, the underlying mechanisms are not completely understood. We evaluated the association between COVID-19 coagulopathy and extracellular vesicle (EV) levels. We hypothesized that several EV levels would be higher in COVID-19 coagulopathy patients than in non-coagulopathy patients. This prospective observational study was conducted in four tertiary care faculties in Japan. We enrolled 99 COVID-19 patients (48 with coagulopathy and 51 without coagulopathy) aged ≥20 years who required hospitalization, and 10 healthy volunteers; we divided the patients into coagulopathy and non-coagulopathy groups according to the D-dimer levels (≥1 μg/mL and <1 μg/mL, respectively). We used flow cytometry to measure the tissue-factor-bearing, endothelium-derived, platelet-derived, monocyte-derived, and neutrophil-derived EV levels in platelet-free plasma. The EV levels were compared between the two COVID-19 groups as well as among the coagulopathy patients, non-coagulopathy patients, and healthy volunteers. No significant difference was found in EV levels between the two groups. Meanwhile, the cluster of differentiation (CD) 41 + EV levels were significantly higher in COVID-19 coagulopathy patients than in healthy volunteers (549.90 [255.05–984.65] vs. 184.3 [150.1–254.1] counts/µL, p = 0.011). Therefore, CD41+ EVs might play an essential role in COVID-19 coagulopathy development.

Cargo ships are at risk of disease outbreaks like Legionella and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) due to their cramped and shared conditions. A case of medical evacuation due to co-infection of Legionella pneumophila with SARS-CoV-2 highlights the need for international infection control guidelines, information networks and molecular epidemiological approaches for identifying infection routes.

Metallo-beta-lactamases (MBLs) are enzymes that break down carbapenem antibiotics, leading to carbapenem-resistant organisms. Carbapenemase-resistant Enterobacterales (CRE) is one of them. Outbreaks of CRE infection can occur in healthcare facilities and lead to increased deaths, illness, and medical costs. This study was conducted to detect MBLs using non-carbapenem agents and exclude MBLs among CRE isolates. A total of 3776 non-duplicate sequential Enterobacterales isolates from a single facility were screened between January 2019 and December 2022 using non-carbapenem agents, ceftazidime and cefoperazone/sulbactam. Positive 153 isolates (4.0%) were further tested using carbapenemase-confirmation tests and verified through polymerase chain reaction (PCR) testing. Fifteen imipenemase (IMP)-type MBL-producing Enterobacterales (0.4%) including one susceptible to carbapenems were identified. Moreover, 160 isolates (4.2%) meeting the criteria for CRE were directly subjected to PCR testing. All fourteen CRE isolates with MBLs identified through PCR testing were found to be the same strains screened using ceftazidime and cefoperazone/sulbactam. Screening using ceftazidime and cefoperazone/sulbactam can effectively detect MBL-producing Enterobacterales strains. This screening method showed comparable results to screening with meropenem, potentially serving as a supplementary approach and contributing to differentiating between MBL- and non-MBL-producing CRE strains. Our findings support these screening methods, particularly in regions where IMP-type MBLs are prevalent.

Background: Bloodstream infections (BSIs), including persistent bacteremia (PB), are a leading source of morbidity and mortality globally. PB has a higher mortality rate than non- PB, but the clinical aspects of PB in terms of the causative pathogens and the presence of clearance of PB are not well elucidated. Therefore, this study aimed to describe the clinical and epidemiological characteristics of PB in a real-world clinical setting. Methods: We performed a retrospective observational survey of patients who underwent blood culture between January 2012 and December 2021 at Tohoku University Hospital. Cases of PB were divided into three groups depending on the causative pathogen: gram-positive cocci (GPC), gram-negative rods (GNRs), and Candida spp. For each group, we examined the clinical and epidemiological characteristics of PB, including differences in clinical features depending on the clearance of PB. The main outcome variable was mortality, assessed as early (30-day), late (30–90 day), and 90-day mortality. Results: Overall, we identified 31,591 cases of single bacteremia; in 6709 (21.2%) cases, the first blood culture was positive, and in 3124 (46.6%) cases, a follow-up blood culture (FUBC) was performed. Of the cases with FUBCs, 414 (13.2%) were confirmed to be PB. The proportion of PB cases caused by Candida spp. was significantly higher (29.6%, 67/226 episodes) than that for GPC (11.1%, 220/1974 episodes, p < 0.001) and GNRs (12.1%, 100/824 episodes, p < 0.001). The Candida spp. group also had the highest late (30–90 day) and 90-day mortality rates. In all three pathogen groups, the subgroup without the clearance of PB tended to have a higher mortality rate than the subgroup with clearance. Conclusions: Patients with PB due to Candida spp. have a higher late (30–90 day) and 90-day mortality rate than patients with PB due to GPC or GNRs. In patients with PB, FUBCs and confirming the clearance of PB are useful to improve the survival rate.

Human pulmonary dirofilariasis (HPD) is a zoonotic disease caused by Dirofilaria immitis. Most HPD cases are asymptomatic and are either detected during annual health checkups or incidentally identified during the investigation of other diseases, particularly primary or metastatic pulmonary lung cancers. However, the frequency and clinical features of Japanese patients with HPD remain unclear. We analyzed data from the Japanese Medical Abstract Society database and identified 69 cases between 1978 and 2022. The incidence of HPD increased until the 2000s but declined markedly in the 2010s. The incidence is higher in the southwestern region and lower in the northeastern region of Japan. Health checkups are the primary diagnostic opportunities. The Chugoku and Shikoku regions have had high incidence rates per population. The diagnosis of HPD using a noninvasive procedure is typically difficult because of the absence of specific clinical symptoms, and approximately 70% of the cases are detected using video-assisted thoracoscopic surgery. Climate change may increase the incidence of HPD in the northeastern region of Japan, and travel to countries with poor vector control may be a risk factor for HPD transmission. Physicians should consider this parasitic infectious disease when examining patients presenting with solitary lung nodules.

An 88-year-old woman with untreated type 2 diabetes was transferred to our hospital's emergency intensive care unit after a cardiopulmonary arrest associated with a pulmonary thromboembolism, caused by the treatment for a left femoral neck fracture at another hospital. 2 days after transfer, she developed acute respiratory distress syndrome due to hospital-acquired pneumonia. 2 weeks after transfer, she vomited despite nasogastric feeding and 2 days later, presented with laboured breathing, hypoxia, and hypotension. Blood cultures were taken, and she was diagnosed with Gram-negative rod sepsis with septic shock and a lactate concentration of 7·1 mmol/L (normal range: 0·4–1·6 mmol/L). A treatment of intravenous meropenem (1 g every 8 h) was started.

Here, we report a 60-year-old chronically bedridden man with cerebral palsy who had septic shock following a history of urinary tract infection with extended spectrum β-lactamase-producing and auxotrophic Proteus mirabilis detected on blood and urine cultures. This auxotroph formed small colonies only on the blood agar at 24 h in 5% CO2, but not in the conditions without CO2, and lacked motility and some biochemical activities. The five-year history of stones in the right renal pelvis suggests chronic urinary tract infection with P. mirabilis requiring a 28-day antibiotic treatment. This paper highlights that the CO2-dependent P. mirabilis small colony variant may cause sepsis, probably due to chronic infection in uroliths, which should warrant immediate identification.

Tuberculosis remains a major public health concern. Millions of tuberculosis cases and associated deaths have been reported worldwide. The Indo-Oceanic lineage Mycobacterium tuberculosis is common in Southeast Asia and causes extrapulmonary lesions. Only a few case studies on this lineage with genetic analysis using whole-genome sequencing have been reported in the literature. We present a case of disseminated tuberculosis, characterized by a variety of extrapulmonary lesions and paradoxical reactions, caused by the Indo-Oceanic lineage M. tuberculosis in a woman in Myanmar. A 22-year-old Burmese woman had arthritis in the right knee, with unknown aetiology, and was referred to our hospital. Computed tomography of the trunk revealed multiple nodular shadows in both lungs; swollen mediastinal lymph nodes; and small, low-density areas in the spleen. M. tuberculosis was detected in the sputum sample, joint aspirate, subcutaneous tumor, and exudate. She experienced a variety of paradoxical reactions together with aggressive tuberculosis dissemination in all areas of the body. Whole-genome sequencing of the DNA of MTB obtained from sputum and the right cervical subcutaneous abscess confirmed the Indo-Oceanic lineage of M. tuberculosis, the predominant strain in Myanmar. The Indo-Oceanic lineage M. tuberculosis causes disseminated tuberculosis all over the body including the periungual region. When patients show unusual symptoms, physicians should consider the introduction of new strains from foreign countries. Genetic analyses of the strains are recommended to define and confirm the lineages.

We describe the epidemiology of invasive Haemophilus influenzae disease (IHD) among adults in Japan. Data for 200 adult IHD patients in 2014–2018 were analyzed. The capsular type of H. influenzae was determined by bacterial agglutination and polymerase chain reaction (PCR), and non-typeable Haemophilus influenzae (NTHi) was identified by PCR. The annual incidence of IHD (cases per 100,000 population) was 0.12 for age 15–64 years and 0.88 for age ≥ 65 years in 2018. The median age was 77 years, and 73.5

A series of plasmid DNA constructs containing the 45W antigen gene from Taenia ovis were used to investigate the impact of antigen dimerisation on the humoral immune response to genetic immunisation. Genes encoding dimeric 45W were generated via fusion to the hinge region of human IgG3 (hIg). This region was selected because it is compact and contains 11 inter-chain disulphide-bridges. The DNA encoding the IgG3 hinge contains four exons, with the last three exons being repeats and possibly superfluous. Plasmids containing the 45W gene linked to exons 1-2, 1-3 or 1-4 of the hIgG3 hinge, were compared to a control plasmid containing a form of the 45W gene which encodes secreted, monomeric 45W protein. Western blot analysis was used to investigate the formation of the fusion-proteins in transfected Cos-7 cells. The full-length fusion construct expressed predominantly dimeric forms of the fusion-protein, while truncation of the hinge region decreased the abundance of dimeric fusion-protein and increased the proportion monomeric fusion antigen. In immunised BALB/c mice, 45W-specific antibody titres were increased 3 to 4-fold via fusion to the full-length hinge region, whereas the truncated constructs were similar to the control. IgG subclass analysis indicated that all mice generated predominantly IgG1, IgG2a and IgG2b antibodies. Therefore, these results suggest that the efficient formation of dimeric antigen, via fusion to the full-length hinge of human IgG3, can increase the immunogenicity of expressed antigens without altering the form of the immune response elicited by DNA immunisation.

We assessed the impact of the pediatric 13-valent pneumococcal conjugate vaccine (PCV13) on pneumococcal meningitis in adults in Japan in 2014–2018 by comparing epidemiological characteristics of adults with invasive pneumococcal disease with (n = 222) and without (n = 1258) meningitis. The annual incidence of pneumococcal meningitis in 2016–2018 was 0.20–0.26 cases/100,000 population. Age (p < 0.001) and case fatality rate (p = 0.003) were significantly lower in patients with meningitis than in those without meningitis. The odds of developing meningitis were higher in asplenic/hyposplenic or splenectomized patients (adjusted odds ratio [aOR] 2.29, 95% CI 1.27–4.14), for serotypes 10A (aOR 3.26, 95% CI 2.10–5.06) or 23A (aOR 3.91, 95% CI 2.47–6.19), but lower for those aged ≥ 65 years (aOR 0.59, 95% CI 0.44–0.81). PCV13 had an indirect effect on nonmeningitis, but its impact on meningitis was limited because of an increase in non-PCV13 serotypes. Of meningitis isolates, 78 (35.1%) and 3 (1.4%) were penicillin G- or ceftriaxone-resistant, respectively. We also confirmed an association of the pbp1bA641C mutation with meningitis (aOR 2.92, 95% CI 1.51–5.65).

We report on 2 Japanese patients in their 50s with mild to moderate COVID-19 pneumonia and maculopapular rash.The rash was pink to slightly violaceous with clear edges on lighter skin, but was difficult to see on tattooed and suntanned skin (PictureA-D).In both cases, the maculopapular rash was treated with topical steroids and resolved within a week.Histopathological findings of the rash indicated mild to moderate lymphocyte inflammation around vessels, without occlusion (PictureE-F).In both cases, on admission the results of SARS-CoV-2 polymerase chain reaction (PCR) tests of blood specimens and maculopapular samples obtained by punch biopsy were negative, suggesting that the rash was caused by a systemic immune response originating from localized lung inflammation.Physicians should suspect COVID-19 on the basis of cutaneous manifestations (e.g., maculopapular,

Rational Corticosteroid therapy plays a key role in the treatment of COVID-19 patients with respiratory failure. However, a rebound phenomenon after steroid cessation rarely occurs. Here, we investigated the clinical features of patients with rebound after steroid therapy. Methods In total, 84 patients with COVID-19 treated with corticosteroids were enrolled and analysed retrospectively. A rebound was defined as when a patient’s respiratory status deteriorated after the cessation of corticosteroid therapy, without secondary bacterial infection. Results Subjects in the rebound group were more likely to having severe respiratory failure than those in the non-rebound group. While the duration of steroid therapy was longer in the rebound group (8 days vs 10 days, p=0.0009), the dosage of steroid and the timing of the start or termination of steroid therapy did not show any differences between the two groups (p=0.17 and 0.68, respectively). The values of soluble interleukin-2 receptor (sIL-2R) at the baseline and the values of C reactive protein (CRP) or lactate dehydrogenase (LDH) at the end of steroid therapy were significantly higher in the rebound group (937 vs 1336 U/mL; p=0.002, 0.63 vs 3.96 mg/dL; p=0.01 and 278 vs 451 IU/mL; p=0.01, respectively). No patient in the rebound group suffered from thromboses, and the causes of death were exacerbation of COVID-19, ventilator-associated pneumonia or sepsis. The prediction model using baseline features for the rebound phenomenon included four variables of age >68 years, required supplemental oxygen >5 L/min, lymphocyte counts <792 /µL and sIL-2R >1146 U/mL. The discrimination ability of this model was 0.906 (0.755–0.968). Conclusion These findings suggest that severe respiratory failure has a higher risk for the rebound phenomenon after the cessation of corticosteroids, and the values of sIL-2R, LDH and CRP are useful to assess the probability of developing rebound. A multivariate model was developed to predict rebound risk, which showed acceptable discrimination ability.

Background:TAFRO syndrome, a subtype of idiopathic multicentric Castleman disease, is an acute or subacute systemic inflammatory disease that causes fever, generalized oedema (pleural effusion or ascites), and thrombocytopenia and is associated with renal impairment, anaemia, and organomegaly (hepatosplenomegaly and lymph node enlargement). Coronavirus disease 2019 (COVID-19)-associated hyperinflammation is caused by dysregulation of proinflammatory cytokines. Cytokine storm syndrome is common to both COVID-19 and TAFRO syndrome.Case report.A 66-year-old man with TAFRO syndrome was admitted because of worsening renal function, right pleural effusion, and ascites. He was taking 20 mg prednisolone orally and 25 mg cyclosporin A orally twice daily. Despite administration of maximum oxygenation and remdesivir, the patient developed acute respiratory distress syndrome (ARDS) and was transferred to the intensive care unit.Results:Chest radiography showed bilateral lung infiltration. COVID-19 was confirmed with a positive polymerase chain reaction test for severe acute respiratory syndrome coronavirus 2. Chest and abdominal computed tomography showed massive ground-glass opacities in both lungs, slight right pleural effusion, hepatomegaly, splenomegaly, and ascites.Conclusion:To the best of our knowledge, this is the first report of COVID-19 in a patient with TAFRO syndrome. Despite receiving a moderate dose of a corticosteroid and a monoclonal antibody against the IL-6 receptor, our patient developed severe pneumonia, suggesting that strong immunomodulatory therapy in the antiviral phase of COVID-19 may promote viral growth and induce ARDS.

Patients with severe Coronavirus disease 2019 (COVID-19) are at high risk for secondary infection with multidrug-resistant organisms (MDROs). Secondary infections contribute to a more severe clinical course and longer intensive care unit (ICU) stays in patients with COVID-19. A man in his 60s was admitted to the ICU at a university hospital for severe COVID-19 pneumonia requiring mechanical ventilation. His respiratory condition worsened further due to persistent bacteremia caused by imipenem-non-susceptible Klebsiella aerogenes and he required VV-ECMO. Subsequently, he developed a catheter-related bloodstream infection (CRBSI) due to Candida albicans, ventilator-associated pneumonia (VAP) due to multidrug-resistant Pseudomonas aeruginosa (MDRP), and a perianal abscess due to carbapenem-resistant K. aerogenes despite infection control procedures that maximized contact precautions and the absence of MDRO contamination in the patient's room environment. He was decannulated from VV-ECMO after a total of 72 days of ECMO support, and was eventually weaned off ventilator support and discharged from the ICU on day 138. This case highlights the challenges of preventing, diagnosing, and treating multidrug-resistant organisms and healthcare-associated infections (HAIs) in the critical care management of severe COVID-19. In addition to the stringent implementation of infection prevention measures, a high index of suspicion and a careful evaluation of HAIs are required in such patients.