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Mahoko Ikeda,1,2,* Miyuki Mizoguchi,1,* Yukie Oshida,3 Keita Tatsuno,1 Ryoichi Saito,4 Mitsuhiro Okazaki,5 Shu Okugawa,2 Kyoji Moriya1,2 1Department of Infection Control and Prevention, The University of Tokyo Hospital, Hongo, Bunkyo-ku, Tokyo, Japan; 2Department of Infectious Diseases, The University of Tokyo Hospital, Hongo, Bunkyo-ku, Tokyo, Japan; 3Division of Infectious Diseases, Shizuoka Cancer Center, Simonagakubo, Nagaizumi-chou, Suntou-gun, Shizuoka, Japan; 4Department of Microbiology and Immunity, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, Yushima, Bunkyo-ku, Tokyo, Japan; 5Department of Medical Technology, School of Health Sciences, Tokyo University of Technology, Kamata, Ota-ku, Tokyo, Japan *These authors contributed equally to this work Purpose: Klebsiella pneumoniae is a pathogen that causes pneumonia and urinary tract infection. Hypervirulent K. pneumoniae strains often show hypermucoviscosity, are of the K1 or K2 serotype, and harbor the rmpA and magA genes. However, the differences in the prevalence of K. pneumoniae with these hypervirulent characteristics between the infection and colonization status are not well understood. Therefore, in this study, we compared the clinical and microbiological characteristics of K. pneumoniae isolated from urine or sputum samples of cases of infection and colonization. Patients and methods: This retrospective study was conducted at a tertiary care teaching hospital in Tokyo, Japan. Patients whose sputum or urine tested positive for the presence of K. pneumoniae isolates were randomly included in the study. Clinical and microbiological data were collected from medical records. Results: Of the 130 cases investigated, 68 and 62 cases showed the presence of K. pneumoniae in the sputum and urine, respectively. There were 49 infection cases, including 21 in the sputum group and 28 in the urine group. The infections were not accompanied by liver abscess. Of the 130 K. pneumoniae isolates, 25 (19.2%) showed capsular serotype K1 or K2, whereas 33 (25.4%) showed hypermucoviscosity. The prevalence of virulence genes magA, allS, rmpA, mrkD, uge, kfu-BC, and wabG was 10% (all in K1), 13.1%, 16.9%, 85.4%, 79.2%, 36.9%, and 91.5%, respectively. In both the sputum and urine groups, there was no difference in the characteristics of patients with infection and those with colonization. Analysis of microbiological characteristics revealed that only rmpA was significantly more frequent in the infection cases than in the colonization/asymptomatic cases in both the sputum and urine groups. Conclusion: The rmpA-positive K. pneumoniae isolates were dominant in the infection cases compared with those in the colonization/asymptomatic cases, suggesting that rmpA may play a crucial role in the development of urinary tract infection and pneumonia. Keywords: Klebsiella pneumoniae, hypermucoviscosity, rmpA, capsular polysaccharide serotype, infection, colonization, pneumonia, urinary tract infection

Kazuhito Yuhashi,1 Yuka Yagihara,1 Yoshiki Misawa,1 Tomoaki Sato,1 Ryoichi Saito,2 Shu Okugawa,1 Kyoji Moriya1 1Department of Infection Control and Prevention, Faculty of Medicine, The University of Tokyo, 2Department of Microbiology and Immunity, Graduate School of Health Care Sciences, Tokyo Medical and Dental University, Bunkyo-ku, Tokyo, Japan Purpose: The enzyme immunoassay (EIA) has lower sensitivity for Clostridium difficile toxins A and B than the polymerase chain reaction in the diagnosis of C. difficile-associated diarrhea (CDAD). Furthermore, toxin positivity with EIA performed on C. difficile isolates from stool cultures may be observed even in patients with EIA glutamate dehydrogenase (GDH)-positive and toxin-negative stool specimens. It is unclear whether such patients should be treated as having CDAD.Methods: The present study retrospectively compared patient characteristics, treatment, and diarrhea duration among three groups of patients who underwent stool EIA testing for CDAD diagnosis: a toxin-positive stool group (positive stool group; n=39); a toxin-negative stool/toxin-positive isolate group (discrepant negative/positive group, n=14); and a dual toxin-negative stool and isolate group (dual negative group, n=15). All cases included were confirmed to be GDH positive on EIA test.Results: Patients’ backgrounds and comorbidities were not significantly different among three groups. No difference was observed among the three groups with regard to antimicrobial drug use before diarrhea onset. Treatment was received by 82.1% of the positive stool group compared to 7.1% of the discrepant positive/negative group and 0% of the dual negative group, while mean diarrhea duration was 10.6 days compared to 7.9 days (P=0.6006) and 3.4 days (P=0.0312), respectively.Conclusion: Even without treatment, patients with toxin-negative stool specimens had shorter diarrhea duration than those with toxin-positive stool specimens even with toxin-positive isolates. These findings may suggest a limited need for CDAD treatment for GDH-positive patients and toxin-negative stool specimens. Keywords: Clostridium difficile toxin, diarrhea duration, treatment

Objectives: Clostridium species are ubiquitous in nature and commonly cause infections, including bacteremia. C. perfringens is often the causative species, while the epidemiology of other clostridial species remains unclear. This study aimed to examine the epidemiology and risk factors for mortality among patients with clostridial bacteremia in Japan., Methods: This multicenter, retrospective cohort study analyzed patients with Clostridium spp. in blood cultures from four tertiary hospitals in Japan. Data on demographics, underlying conditions, clinical and laboratory values, and in-hospital mortality were included. Multivariate logistic regression analysis identified independent risk factors for in-hospital mortality., Results: Of 349 patients with Clostridium spp. in blood cultures, 278 (79.7%) had clinically significant clostridial bacteremia: C. perfringens was the most common species (52.9%), followed by C. ramosum (9.7%) and C. clostridioforme (4.3%). The median patient age was 77 years, and 61.9% were male. The in-hospital mortality rate was 25.9%, with 34.7% of deaths occurring within 3 days of the date of the positive blood culture. Independent risk factors for mortality were hepato-pancreato-biliary malignancy, chronic heart failure, acute renal failure, Pitt bacteremia score, and pneumonia., Conclusions: Mortality from clostridial bacteremia is high, particularly among patients with pneumonia, comorbidities, or severe acute conditions. To improve mortality, early-stage treatment strategies are needed., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: SH reports grants from Shionogi paid to his institution and speaker fees from MSD and Shionogi outside the submitted work. The other authors declare no conflicts of interest., (Copyright © 2024. Published by Elsevier Ltd.)

Escherichia coli is a facultative anaerobic bacterium that causes urinary tract and bloodstream infections. Generally, E. coli is easily identified in routine clinical microbiology laboratories. Herein, we report a case of pyelonephritis with bacteremia due to extended-spectrum β-lactamase (ESBL) producing E. coli, which delayed the identification of the isolate as it exhibited carbon dioxide (CO 2 )-dependent growth. The patient was a 62-year-old man who presented with nausea and an altered mental status. Contrast-enhanced computed tomography revealed multiple abscesses in the left kidney. The anaerobic bottles of the two sets of blood cultures were positive, but growth on a routine aerobic culture was weak. Identification of the isolate was delayed because it grew only on agar plates incubated in a 5 % CO 2 atmosphere. The isolate was suspected to be an ESBL-producing strain based on antimicrobial susceptibility testing, which was confirmed by polymerase chain reaction analysis. The patient was successfully treated with administering meropenem and nephrectomy. To the best-of-our-knowledge, this is the first reported case of a human infection caused by ESBL-producing carbon-dioxide-dependent E. coli., (Copyright © 2024 Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases, and Japanese Society for Infection Prevention and Control. Published by Elsevier Ltd. All rights reserved.)

Nocardia exalbida, an uncommon Nocardia, was first identified in 2006. We herein report a 70-year-old man with pulmonary nocardiosis caused by N. exalbida after living-donor liver transplantation. We also review 11 previously reported cases of N. exalbida infections. To our knowledge, there are no case reports available on nocardiosis consequent to N. exalbida infection following transplantation, thus highlighting the importance of identifying bacterial species for the successful management of infection.

Background: Cryptococcosis is a notable infectious complication of liver transplantation. Currently, there is no recommendation for screening serum cryptococcal antigen (CrAg) levels in solid organ transplant recipients. We aimed to explore the role of serum CrAg in liver transplant recipients at an institution where posttransplant serum CrAg has been widely tested., Methods: This retrospective study was conducted at a tertiary care center in Japan. All liver transplant recipients with serum CrAg measured either for screening or for diagnostic testing at least once after transplantation between April 2005 and March 2022 were included. For participants with either a positive CrAg test result or positive culture for Cryptococcus , we manually reviewed clinical manifestations, management, and prognosis from the medical records., Results: During the study period, 12 885 serum CrAg tests (median, 16 tests per patient) were performed in 468 liver transplant recipients. The 1-year posttransplant incidence of positive serum CrAg test results and culture-proven cryptococcosis was 1.9% (9/468) and 0.6% (3/468), respectively. No patient with persistently negative serum CrAg test results showed growth of Cryptococcus in culture. Four patients had clinical manifestations consistent with cryptococcosis, of whom 2 (50.0%) started antifungal therapy promptly based on a positive serum CrAg test result. In contrast, 5 patients had no clinical manifestations. Three of the 5 (60.0%) patients did not receive antifungal therapy and remained free of clinical manifestations., Conclusions: Serum CrAg test was more sensitive than culture among liver transplant recipients and prompted early diagnosis and antifungal therapy in symptomatic patients. However, serial screening of serum CrAg in asymptomatic patients may be of little value, with the potential for false-positive results., Competing Interests: Potential conflicts of interest. All authors: No potential conflicts., (© The Author(s) 2024. Published by Oxford University Press on behalf of Infectious Diseases Society of America.)

Bacillus cereus , which causes opportunistic infections in hospitals as well as food poisoning, is genetically similar to Bacillus anthracis . We herein report the draft genome including the capsule operon of B. cereus BCER1 isolated from the blood of a hospital patient in Japan., Competing Interests: The authors declare no conflict of interest.

Introduction: Since the SARS-CoV-2 Omicron variant became dominant, assessing COVID-19 vaccine effectiveness (VE) against severe disease using hospitalization as an outcome became more challenging due to incidental infections via admission screening and variable admission criteria, resulting in a wide range of estimates. To address this, the World Health Organization (WHO) guidance recommends the use of outcomes that are more specific to severe pneumonia such as oxygen use and mechanical ventilation., Methods: A case-control study was conducted in 24 hospitals in Japan for the Delta-dominant period (August-November 2021; "Delta") and early Omicron (BA.1/BA.2)-dominant period (January-June 2022; "Omicron"). Detailed chart review/interviews were conducted in January-May 2023. VE was measured using various outcomes including disease requiring oxygen therapy, disease requiring invasive mechanical ventilation (IMV), death, outcome restricting to "true" severe COVID-19 (where oxygen requirement is due to COVID-19 rather than another condition(s)), and progression from oxygen use to IMV or death among COVID-19 patients., Results: The analysis included 2125 individuals with respiratory failure (1608 cases [75.7%]; 99.2% of vaccinees received mRNA vaccines). During Delta, 2 doses provided high protection for up to 6 months (oxygen requirement: 95.2% [95% CI:88.7-98.0%] [restricted to "true" severe COVID-19: 95.5% {89.3-98.1%}]; IMV: 99.6% [97.3-99.9%]; fatal: 98.6% [92.3-99.7%]). During Omicron, 3 doses provided high protection for up to 6 months (oxygen requirement: 85.5% [68.8-93.3%] ["true" severe COVID-19: 88.1% {73.6-94.7%}]; IMV: 97.9% [85.9-99.7%]; fatal: 99.6% [95.2-99.97]). There was a trend towards higher VE for more severe and specific outcomes., Conclusion: Multiple outcomes pointed towards high protection of 2 doses during Delta and 3 doses during Omicron. These results demonstrate the importance of using severe and specific outcomes to accurately measure VE against severe COVID-19, as recommended in WHO guidance in settings of intense transmission as seen during Omicron., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Takeshi Arashiro is an unpaid consultant for the World Health Organization. The other authors declare no conflicts of interest., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Background: Among solid organ transplant (SOT) recipients, heart transplant (HT) recipients are at a higher risk of Toxoplasma gondii infection. As Toxoplasma seroprevalence varies by geographic location, updated local epidemiology is essential to guide preventive and therapeutic strategies. However, the Toxoplasma seroprevalence and incidence of post-transplant toxoplasmosis among SOT recipients in Japan are unknown., Methods: We performed a single-center retrospective observational study at an HT center in Tokyo, Japan. All HT recipients aged ≥18 years between 2006 and April 2019 were included. We reviewed patient charts and conducted a questionnaire survey to investigate the risk factors for infection., Results: Among 105 recipients included in the study, 11 (10.5%) were seropositive before transplant. Ninety-five recipients (90.5%), including all pre-transplant seropositive recipients, answered the questionnaire. The recipients who had lived in Okinawa (odds ratio [OR] 7.5 [95% CI 1.42-39.61]; P = .032) and who reported raw-meat eating habits (OR 4.64 [95% CI 1.04-23.3]; P = .021) were more likely to be seropositive. None of the patients developed symptoms of toxoplasmosis. The post-transplant incidence of other major adverse outcomes was not significantly different according to the pre-transplant serostatus., Conclusions: About 10% of HT recipients at an HT center in Tokyo were seropositive for Toxoplasma pre-transplant, and none developed symptomatic toxoplasmosis post-transplant on trimethoprim-sulfamethoxazole. The history of raw meat consumption was associated with seropositivity; therefore, avoiding it might be recommended for HT recipient candidates., Competing Interests: Declaration of Competing Interest All the authors declare no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Escherichia coli is a gram-negative intestinal commensal that can also cause various infections, including urinary tract infections, biliary tract infections, neonatal meningitis, and septicemia. Although the characteristics of uropathogenic E. coli and the mechanisms of urinary tract infection have been well studied, the genetic distinctions among E. coli isolates from different types of infections have not yet been determined. This study compared the phylogenetic and virulence factors of E. coli isolates from bacteremic biliary tract infections with those from bacteremic urinary tract infections. The phylogenetic B2 group was the most prevalent in both pathogenic groups (68 % in biliary pathogenic isolates and 85 % in uropathogenic isolates), but the frequency pattern of the phylogenetic group was different. Half of the uropathogenic isolates belonged to ST95 and ST131 (51 %). Among the biliary pathogenic isolates, ST131 was the most prevalent, while the remaining half belonged to other STs outside the four major STs. The frequency of some virulence factors, such as papC , papG2 , hlyA , tcpC , fyuA , kpsMT2 , sat , and traT, was lower in the biliary pathogenic isolates than in the uropathogenic isolates. The frequency of phylogenetic groups and STs in MLST differed between E. coli isolates from bacteremic biliary tract infections and urinary tract infections. Additionally, some virulence factors, including adhesion and toxin gene groups, showed lower frequencies in the biliary pathogenic group than in the uropathogenic group. Studying the differences in E. coli pathovars from different infection sites is important for developing pathovar-specific targeted therapies such as vaccine therapy., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2023 The Authors. Published by Elsevier Ltd.)

Paralytic ileus as tuberculosis-immune reconstitution inflammatory syndrome (TB-IRIS) is extremely rare. We herein report a 44-year-old man with pulmonary and renal tuberculosis who developed paralytic ileus 14 days after starting antituberculosis therapy (ATT) despite an initial favorable response to ATT. Paralytic ileus was successfully managed with conservative care. He initially required hemodialysis because of obstructive uropathy due to renal tuberculosis, but he was able to withdraw from dialysis after placement of ureteral stents. TB-IRIS can affect organs other than the original sites of tuberculosis, and the combined use of steroids may be effective for its prevention and treatment.

Objectives: This study aimed to evaluate the antiviral effects and safety of nafamostat in early-onset patients with coronavirus disease 2019 (COVID-19)., Methods: In this exploratory multicentre randomized controlled trial, patients were assigned to three groups within 5 days of symptom onset, with 10 participants in each group: nafamostat at either 0.2 mg/kg/h or 0.1 mg/kg/h or a standard-of-care group. The primary endpoint was area under the curve for decrease in SARS-CoV-2 viral load in nasopharyngeal samples from baseline to day 6., Results: Of the 30 randomized patients, 19 received nafamostat. Overall, 10 patients received low-dose nafamostat, 9 patients received high-dose nafamostat, and 10 received standard-of-care. The detected viruses were Omicron strains. The regression coefficient for area under the curve for decrease in viral load as the response variable and nafamostat dose per body weight as the explanatory variable showed a significant relationship of -40.1 (95% confidence interval, -74.1 to -6.2; P = 0.022). Serious adverse events were not observed in either group. Phlebitis occurred in ca. 50% of patients treated with nafamostat., Conclusions: Nafamostat exerts virus load-reducing effects in patients with early-onset COVID-19., (Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Several clinical trials have shown that the humoral response produced by anti-spike antibodies elicited by coronavirus disease 2019 (COVID-19) vaccines gradually declines. The kinetics, durability and influence of epidemiological and clinical factors on cellular immunity have not been fully elucidated. We analyzed cellular immune responses elicited by BNT162b2 mRNA vaccines in 321 health care workers using whole blood interferon-gamma (IFN-γ) release assays. IFN-γ, induced by CD4 + and CD8 + T cells stimulated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike epitopes (Ag2), levels were highest at 3 weeks after the second vaccination (6 W) and decreased by 37.4% at 3 months (4 M) and 60.0% at 6 months (7 M), the decline of which seemed slower than that of anti-spike antibody levels. Multiple regression analysis revealed that the levels of IFN-γ induced by Ag2 at 7 M were significantly correlated with age, dyslipidemia, focal adverse reactions to full vaccination, lymphocyte and monocyte counts in whole blood, Ag2 levels before the second vaccination, and Ag2 levels at 6 W. We clarified the dynamics and predictive factors for the long-lasting effects of cellular immune responses. The results emphasize the need for a booster vaccine from the perspective of SARS-CoV-2 vaccine-elicited cellular immunity., (© 2023. The Author(s).)

Objectives: To evaluate the efficacy and safety of nafamostat combined with favipiravir for the treatment of COVID-19., Methods: We conducted a multicenter, randomized, single-blind, placebo-controlled, parallel assignment study in hospitalized patients with mild-to-moderate COVID-19 pneumonia. Patients were randomly assigned to receive favipiravir alone (n = 24) or nafamostat with favipiravir (n = 21). The outcomes included changes in the World Health Organization clinical progression scale score, time to improvement in body temperature, and improvement in oxygen saturation (SpO 2 )., Results: There was no significant difference in the 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). The time to improvement in body temperature was significantly shorter in the combination group (5.0 days; 95% confidence interval, 4.0-7.0) than in the favipiravir group (9.0 days; 95% confidence interval, 7.0-18.0; P =0.009). The changes in SpO 2 were greater in the combination group than in the favipiravir group (0.526% vs -1.304%, respectively; least-squares mean difference, 1.831; P = 0.022). No serious adverse events or deaths were reported, but phlebitis occurred in 57.1% of the patients in the combination group., Conclusion: Although our study showed no differences in clinical progression, earlier defervescence, and recovery of SpO 2 were observed in the combination group., Competing Interests: Declaration of competing interest JI, YS, and KM are co-inventors on patent applications of nafamostat as an antiviral agent (PCT/JP2021/9968, patent applicant: the University of Tokyo). All other authors declare no competing interests. FUJIFILM Toyama Chemical and Nichi-Iko supplied the favipiravir and nafamostat mesilate, respectively., (Copyright © 2022. Published by Elsevier Ltd.)

Adverse reactions after vaccination with COVID-19 mRNA vaccines are common; however, the association between adverse reactions and humoral responses is uncertain. To determine whether humoral immune responses after BNT162b2 vaccine administration were associated with local and systemic adverse reactions, we conducted a prospective observational cohort study in a single tertiary referral center. Healthcare workers who received the first dose of BNT162b2 vaccine were recruited. SARS-CoV-2 anti-spike IgG antibody titers were measured three weeks after the second dose and information about adverse reactions after vaccination was collected. Among the 887 participants, 641 (72.3%) were women. The median age was 38 (range, 22-74) years. All but one showed anti-spike IgG levels well above the cutoff, with a median level of 13,600 arbitrary units/mL. Overall, 800 (92.2%) participants reported some reactions after the first dose and 822 (96.3%) after the second dose. Significantly more participants reported systemic reactions after the second dose than after the first dose (P < .01), and 625 (73.6%) reported that reactions were stronger after the second dose. Factors positively associated with elevation of anti-spike IgG levels were history of asthma (24% higher if present, P = .01) and stronger reactions after the second dose (19% higher if experienced, P = .02). The majority of participants showed good humoral responses and reported some adverse reactions after vaccination. Anti-spike IgG levels were significantly higher if adverse reactions after the second dose were stronger than those after the first dose. These findings may help inform current and future vaccine recipients.

Background: Among various complications of coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), renal complications, namely COVID-19-associated kidney injuries, are related to the mortality of COVID-19., Methods: In this retrospective cross-sectional study, we measured the sphingolipids and glycerophospholipids, which have been shown to possess potent biological properties, using liquid chromatography-mass spectrometry in 272 urine samples collected longitudinally from 91 COVID-19 subjects and 95 control subjects without infectious diseases, to elucidate the pathogenesis of COVID-19-associated kidney injuries., Results: The urinary levels of C18:0, C18:1, C22:0, and C24:0 ceramides, sphingosine, dihydrosphingosine, phosphatidylcholine, lysophosphatidylcholine, lysophosphatidic acid, and phosphatidylglycerol decreased, while those of phosphatidylserine, lysophosphatidylserine, phosphatidylethanolamine, and lysophosphatidylethanolamine increased in patients with mild COVID-19, especially during the early phase (day 1-3), suggesting that these modulations might reflect the direct effects of infection with SARS-CoV-2. Generally, the urinary levels of sphingomyelin, ceramides, sphingosine, dihydrosphingosine, dihydrosphingosine L-phosphate, phosphatidylcholine, lysophosphatidic acid, phosphatidylserine, lysophosphatidylserine, phosphatidylethanolamine, lysophosphatidylethanolamine, phosphatidylglycerol, lysophosphatidylglycerol, phosphatidylinositol, and lysophosphatidylinositol increased, especially in patients with severe COVID-19 during the later phase, suggesting that their modulations might result from kidney injuries accompanying severe COVID-19., Conclusions: Considering the biological properties of sphingolipids and glycerophospholipids, an understanding of their urinary modulations in COVID-19 will help us to understand the mechanisms causing COVID-19-associated kidney injuries as well as general acute kidney injuries and may prompt researchers to develop laboratory tests for predicting maximum severity and/or novel reagents to suppress the renal complications of COVID-19., (© 2022. The Author(s).)

Background: A heterogeneous clinical phenotype is a characteristic of coronavirus disease 2019 (COVID-19). Therefore, investigating biomarkers associated with disease severity is important for understanding the mechanisms responsible for this heterogeneity and for developing novel agents to prevent critical conditions. This study aimed to elucidate the modulations of sphingolipids and glycerophospholipids, which have been shown to possess potent biological properties., Methods: We measured the serum sphingolipid and glycerophospholipid levels in a total of 887 samples from 215 COVID-19 subjects, plus 115 control subjects without infectious diseases and 109 subjects with infectious diseases other than COVID-19., Results: We observed the dynamic modulations of sphingolipids and glycerophospholipids in the serum of COVID-19 subjects, depending on the time course and severity. The elevation of C16:0 ceramide and lysophosphatidylinositol and decreases in C18:1 ceramide, dihydrosphingosine, lysophosphatidylglycerol, phosphatidylglycerol and phosphatidylinositol were specific to COVID-19. Regarding the association with maximum severity, phosphatidylinositol and phosphatidylcholine species with long unsaturated acyl chains were negatively associated, while lysophosphatidylethanolamine and phosphatidylethanolamine were positively associated with maximum severity during the early phase. Lysophosphatidylcholine and phosphatidylcholine had strong negative correlations with CRP, while phosphatidylethanolamine had strong positive ones. C16:0 ceramide, lysophosphatidylcholine, phosphatidylcholine and phosphatidylethanolamine species with long unsaturated acyl chains had negative correlations with D-dimer, while phosphatidylethanolamine species with short acyl chains and phosphatidylinositol had positive ones. Several species of phosphatidylcholine, phosphatidylethanolamine and sphingomyelin might serve as better biomarkers for predicting severe COVID-19 during the early phase than CRP and D-dimer. Compared with the lipid modulations seen in mice treated with lipopolysaccharide, tissue factor, or histone, the lipid modulations observed in severe COVID-19 were most akin to those in mice administered lipopolysaccharide., Conclusion: A better understanding of the disturbances in sphingolipids and glycerophospholipids observed in this study will prompt further investigation to develop laboratory testing for predicting maximum severity and/or novel agents to suppress the aggravation of COVID-19., (© 2022 The Authors. Clinical and Translational Medicine published by John Wiley & Sons Australia, Ltd on behalf of Shanghai Institute of Clinical Bioinformatics.)

Invasive meningococcal disease (IMD) can occur in travelers returning from mass-gathering events or endemic regions. We present a 60-year-old Argentine traveler to Tokyo who developed IMD by Neisseria meningitidis Serogroup W135 during her stay in Japan. N. meningitidis serogroup W135 infection has become common in Argentina, whereas IMD less commonly occurs in Japan. Considering the prevalence, the patient most likely acquired the infection in Argentina, and it developed in Japan. Air travel enables passengers to reach the four corners of the world within a few days. IMD should be considered in travelers due to its potential to induce rapid clinical deterioration and transmission., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Prospective audit and feedback (PAF) is considered an effective procedure for appropriate antibiotic use. However, its effect on the time to de-escalation is unclear. We aimed to evaluate the effect of daily PAF implementation, focusing on the time to de-escalation of anti-methicillin-resistant Staphylococcus aureus (MRSA) agents as an outcome measure. To this end, a single-center, retrospective, quasi-experimental study including patients treated with intravenous anti-MRSA agents during pre-PAF (April 1, 2014 to March 31, 2015) and post-PAF (April 1, 2015 to March 31, 2016) periods was conducted. The time to de-escalation was estimated using the Kaplan-Meier method, and Cox proportional hazard analysis was performed to assess the effect of daily PAF implementation on the time to de-escalation. Interrupted time series analysis was used to evaluate the relationship between daily PAF implementation and anti-MRSA agent utilization data converted to defined daily dose (DDD) and days of therapy (DOT) per 1,000 patient days. The median time to de-escalation was significantly shorter in the post-PAF period than in the pre-PAF period (6 days vs. 7 days, P < 0.001). According to multivariate analysis, PAF implementation was independently associated with a shorter time to de-escalation (hazard ratio [HR], 1.18; 95% confidence interval [CI], 1.02 to 1.35). There were no significant differences in hospital mortality, 30-day mortality, and length of stay between the two periods. Interrupted time series analysis showed significant reductions in the trends of DDD (trend change, -0.65; 95% CI, -1.20 to -0.11) and DOT (trend change, -0.74; 95% CI, -1.33 to -0.15) between the pre-PAF and post-PAF periods. Daily PAF implementation for patients treated with intravenous anti-MRSA agents led to a shorter time to de-escalation and lower consumption of anti-MRSA agents without worsening the clinically important outcomes., Competing Interests: This work was supported by Japan Society for the Promotion of Science (JSPS) KAKENHI Grant Number 17K08437 (to TY) and 20K07127 (to TY) (https://www.jsps.go.jp/english/index.html). The funders had no role in study design, data collection, and analysis, decision to publish, or preparation of the manuscript. The authors have declared that no competing interests exist including any employment and personal financial interests.

Necropsobacter rosorum is a gram-negative facultative anaerobe, which was reclassified from the family Pasteurellaceae in 2011. It has been detected in the gastrointestinal and respiratory tracts of mammals; however, reports of infection in humans are scarce. We report a case of an abdominal abscess in which N. rosorum was detected; it was successfully treated with drainage and antimicrobial therapy. Routine laboratory testing such as matrix-assisted laser desorption/ionization time-of-flight mass spectrometry and an identification system using biochemical phenotypes could not identify N. rosorum. Instead, it was misidentified as other Pasteurellaceae species, including Aggregatibacter spp. or Pasteurella spp. Sequencing of 16S rRNA was required to identify N. rosorum. We suggest the application of simple methods, such as indole production, oxidase, and catalase tests, to differentiate N. rosorum from genetically similar species., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Aureobasidium melanigenum is a ubiquitous dematiaceous fungus that rarely causes invasive human infections. Here, we present a case of Aureobasidium melanigenum bloodstream infection in a 20-year-old man with long-term catheter use., Case Presentation: A 20-year-old man receiving home care with severe disabilities due to cerebral palsy and short bowel syndrome, resulting in long-term central venous catheter use, was referred to our hospital with a fever. After the detection of yeast-like cells in blood cultures on day 3, antifungal therapy was initiated. Two identification tests performed at a clinical microbiological laboratory showed different identification results: Aureobasidium pullulans from matrix-assisted laser desorption/ionization time-of-flight mass spectrometry, and Cryptococcus albidus from a VITEK2 system. Therefore, we changed the antifungal drug to liposomal amphotericin B. The fungus was identified as A. melanigenum by DNA sequence-based analysis. The patient recovered with antifungal therapy and long-term catheter removal., Conclusion: It is difficult to correctly identify A. melanigenum by routine microbiological testing. Clinicians must pay attention to the process of identification of yeast-like cells and retain A. melanigenum in cases of refractory fungal infection., (© 2022. The Author(s).)

Background: Acute renal injury is an important complication of coronavirus disease 2019 (COVID-19). Both COVID-19-specific mechanisms, such as damage to the renal parenchyma by direct infection, and non-specific mechanisms, such as the pre-renal injury factors, have been proposed to be involved in COVID-19-associated renal injuries. In this study, we aimed to elucidate the characteristics of COVID-19-associated renal injuries, focusing mainly on urine sediment findings., Methods: We compared the urine sediment findings and their associations with renal functions or urinary clinical parameters between subjects with COVID-19 and subjects without COVID-19 with acute renal injuries., Results: We found that the number of urine sediment particles and the levels of N-acetyl-β-D-glucosaminidase, α1-microglobulin, liver type fatty acid-binding protein, and neutrophil gelatinase-associated lipocalin were associated with the severity of COVID-19. In addition, we observed that the number of granular casts, epithelial casts, waxy casts, and urinary chemical marker levels were lower in the subjects with COVID-19 than subjects without COVID-19 with acute renal injuries when the subjects were classified according to their renal function., Conclusions: These results suggest that pre-renal injury factors might be largely involved in the pathogenesis of COVID-19-associated renal injuries compared with non-COVID-19-associated renal injuries arising from surgery or sepsis., (Copyright © 2022. Published by Elsevier Ltd.)

Background: Protothecosis is a rare infection in humans and animals caused by the achlorophyllic algae Prototheca species. More than half of the protothecosis cases are cutaneous infections, and most cases are observed in immunocompromised individuals., Case Presentation: We report a case of Prototheca wickerhamii infection in the mucosa of the pharynx in a 53-year-old immunocompetent woman with an incidentally found mass lesion at the left tongue base. Histopathological findings of the mass lesion suggested cryptococcosis, but P. wickerhamii was identified from the oropharynx scrape culture based on DNA sequencing. After surgical resection, fosfluconazole treatment was initiated, and subsequently, treatment was switched to topical amphotericin B. The residual mass lesion did not deteriorate during the 4-month antifungal treatment and 1-year observational period., Conclusions: Prototheca species can be easily misdiagnosed as yeasts because of their morphological and pathological similarities. Prototheca, in addition to Cryptococcus should be considered if slow-growing, large Gram-positive organisms are encountered. Lactophenol cotton blue staining of the colony helps distinguish these organisms. Further study is needed to determine the appropriate treatment according to the infection focus., (© 2022. The Author(s).)