The Role of Frequent Screening or Diagnostic Testing of Serum Cryptococcal Antigen in Liver Transplant Recipients: A Descriptive Epidemiology.

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.

The effect of infectious diseases on lung transplantation in Japan.

Lung transplantation in Japan is an increasingly accessible treatment option for end-stage lung disease; however, the lack of donor organs is a persisting challenge. Five- and 10-year survival rates of lung transplant recipients in Japan are comparable, if not superior, to international standards. The outcomes of lung transplantation in Japan are likely affected by multiple factors. Infectious disease complications are a significant burden to transplant recipients and account for approximately 30% of recipient mortality in Japan, presenting a major challenge in peri-transplant management. Herein, we explore the current status of infectious disease epidemiology, available evidence surrounding infectious diseases in lung transplantation, and potentially influential factors pertinent to lung transplantation outcomes in Japan. Although infection remains the major cause of morbidity and mortality associated with lung transplantation in Japan, there is limited data and evidence. Despite some uncertainties, publicly available data suggests a low rate of antimicrobial resistance in Gram-negative bacteria and a distinct set of endemic pathogens that recipients may encounter. As a countermeasure against the burden of infectious diseases, 8 out of 10 transplant centers in Japan have a dedicated infectious diseases department. Despite these efforts, specific surveillance, prevention, and management are indispensable to improving post-transplantation infectious disease management. We accordingly lay out potential areas for improving infectious disease-related outcomes among lung transplant recipients in Japan.

Infectious Disease Physician Availability and Postgraduate Antimicrobial Stewardship Education in Japan.

This cross-sectional study evaluates resident physician perceptions of antimicrobial stewardship education in Japan in the presense of infectious disease physicians educators.

Pre-Transplant Seroprevalence, Associated Factors, and Post-Transplant Incidence of Toxoplasma gondii Infection Among Heart Transplant Recipients in Japan.

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.

A case of hypervirulent K1-ST23 Klebsiella pneumoniae endocarditis and papillary muscle rupture secondary to multiple site abscesses.

Hypervirulent Klebsiella pneumoniae (hvKP) causes multisite infections and abscesses. However, endocarditis is a rare presentation of hvKP infection. Herein, we report a case of K. pneumoniae native valve infective endocarditis secondary to community-acquired liver and prostate abscesses. The patient developed papillary muscle rupture, leading to mitral regurgitation, and underwent emergent mitral valve replacement. The diagnosis of endocarditis was confirmed microbiologically and histologically. The causative strain belonged to the hypermucoid K1 capsular genotype and possessed the rmpA gene. The genome sequence was deposited in GenBank under the accession number JAQZBZ000000000.

Antiviral effect and safety of nafamostat mesilate in patients with mild early-onset COVID-19: An exploratory multicentre randomized controlled clinical trial.

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.

Train-the-Trainers in hand hygiene facilitate the implementation of the WHO hand hygiene multimodal improvement strategy in Japan: evidence for the role of local trainers, adaptation, and sustainability.

BACKGROUND: "Train-the-Trainers in hand hygiene" (TTT) is a standardized training to train infection prevention and control (IPC) practitioners with the aim to promote hand hygiene in health care according to the World Health Organization (WHO) multimodal improvement strategy. Little is known in the literature about the sustained impact of hand hygiene and IPC trainings adapted locally. The aim of this study is to describe the impact of three TTT courses conducted annually in Japan on the adoption of the WHO multimodal improvement strategy by local IPC practitioners who became a "trainer" after their first TTT participation as a "trainee". METHODS: Three TTT courses were conducted annually from 2020 to 2022 in Japan. A team "TTT-Japan" composed of more than 20 IPC practitioners who completed their first TTT participation adapted the original TTT program to reflect the local healthcare context in Japan, and subsequently convened the 2nd and 3rd TTTs. Pre- and post-course evaluations and post-course satisfaction surveys of the course participants were conducted to assess improvement in knowledge on hand hygiene and perception towards the course, respectively. Attitude and practice surveys of the TTT-Japan trainers were conducted to assess their perception and experience in hand hygiene promotion. The Hand Hygiene Self-Assessment Framework (HHSAF), a validated tool created by WHO to monitor the capacity of hand hygiene promotion at facility level, was applied at TTT-Japan trainers' facilities to compare results before and after trainers' engagement. We applied inductive thematic analysis for qualitative analyses of open-ended survey questions of the trainers' attitude and practice surveys, and the Wilcoxon Sign Rank test for quantitive comparisons of pre- and post-data for the surveys and HHSAF. RESULTS: 158 Japanese healthcare workers participated in three TTT courses, the majority of whom (131, 82.9%) were nurses. Twenty-seven local trainers were involved in 2nd and 3rd TTTs. The scores of pre- and post-course evaluations significantly improved after the course (P < 0.001) and the improvement was consistent across all three TTTs. Post-course satisfaction survey showed that over 90% of the participants reported that the course met their expectations and that what they learned in the courses would be useful for their practice. Trainers' attitude and practice survey showed that more than three quarters (76.9%) of the trainers reported that their experience as a trainer had a positive impact on their practice at their own facilities. Qualitative analysis of the trainers' attitude and practice survey revealed that trainers appreciated continuous learning as a trainer, and group effort to promote hand hygiene as the TTT-Japan team. The HHSAF institutional climate change element at the trainers' facilities significantly improved after their engagement as a trainer (P = 0.012). CONCLUSIONS: TTTs were successfully adapted and implemented in Japan, leading to sustained hand hygiene promotion activities by local trainers over three years. Further research is warranted to assess the long-term impact on local hand hygiene promotion in different settings.

Waning cellular immune responses and predictive factors in maintaining cellular immunity against SARS-CoV-2 six months after BNT162b2 mRNA vaccination.

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.

Preseptal cellulitis with Streptococcus pyogenes complicated by streptococcal toxic shock syndrome: A case report and review of literature.

Preseptal cellulitis, an infection of the eyelid and skin around the eye, can be distinguished from orbital cellulitis. It is common in children and is rarely complicated. Streptococcus pyogenes is one of the major pathogens causing preseptal cellulitis. Here, we report a case of a 46-year-old man with carcinoma of unknown primary presenting preseptal cellulitis of S. pyogenes complicated by streptococcal toxic shock syndrome and multiple metastatic abscesses involving right eyelid, subcutaneous tissue in the scalp, mediastinum, bilateral pleural spaces, pericardial space, and the left knee. Although he required a prolonged hospitalization, antibiotic therapy and multiple courses of debridement led to full recovery. A literature review revealed that there were only four cases of preseptal cellulitis with S. pyogenes in adults and two cases were complicated by streptococcal toxic shock syndrome. The cases had either trauma or immunocompromising factors similar to our patient. All patients survived with antibiotic therapy and debridement, and the functional outcome was favorable. In summary, preseptal cellulitis caused by S. pyogenes can be severe in adult cases where immunocompromising factors and type of strain may play a role in the severity of the disease. Awareness of the risk of severe complications, treatment with appropriate antibiotic therapy, and timely debridement are crucial for favorable prognoses.

Teicoplanin and vancomycin as treatment for glycopeptide-susceptible Enterococcus faecium bacteraemia: a propensity score-adjusted non-inferior comparative study.

OBJECTIVES: Limited evidence is available regarding alternative therapeutic agents to vancomycin in treating glycopeptide-susceptible Enterococcus faecium (GSEF) bacteraemia. This study assessed the effectiveness and safety of teicoplanin compared with vancomycin for treating GSEF bacteraemia. PATIENTS AND METHODS: This was a retrospective, non-inferiority cohort study. Patients aged ≥18 years who developed GSEF bacteraemia and received either teicoplanin or vancomycin were included. The primary effectiveness outcome was the clinical success at the end of treatment, with a generalized linear model using the propensity score for selecting the agent as a covariate. We used an absolute difference of 20% in clinical success as the non-inferiority margin. Using multivariable logistic regression, the primary safety outcome was the incidence of acute kidney injury (AKI). RESULTS: In total, 164 patients (74 and 90 in the teicoplanin and vancomycin groups, respectively) were included. Overall, 64.9% (48/74) and 48.9% (44/90) of patients in the teicoplanin and vancomycin groups, respectively, achieved the primary effectiveness outcome. A generalized linear analysis showed an adjusted effectiveness difference of 9.9% (95% CI, -0.9% to 20.0%; P = 0.07), indicating non-inferiority of teicoplanin versus vancomycin. The incidence of AKI was 8.1% (6/74) and 24.4% (22/90) in the teicoplanin and vancomycin groups, respectively, with an adjusted OR of 0.242 (95% CI, 0.068 to 0.864; P = 0.029), indicating significantly lower AKI risk in the teicoplanin than in the vancomycin group. CONCLUSIONS: Teicoplanin is a safe and useful alternative therapeutic agent for treating GSEF bacteraemia.

A case report of fatal COVID-19 complicated by rapidly progressive sepsis caused by Klebsiella variicola.

BACKGROUND: There is a growing interest in Klebsiella variicola as a causative pathogen in humans, though its clinical features and the impact of co-infection or secondary infection with COVID-19 remain unknown. CASE PRESENTATION: A 71-year-old man presented with fever, altered mental status and generalized weakness and was admitted to ICU due to severe COVID-19 pneumonia. He was newly diagnosed with type II diabetes mellitus upon admission. On hospital day 3, his respiratory status deteriorated, requiring invasive mechanical ventilation. On hospital day 10, superimposed bacterial pneumonia was suspected and subsequently, broad-spectrum antibiotics were administered for the associated bloodstream infection. On hospital day 13, despite administration of active antibiotics and appropriate source control, he decompensated and died. The causative organism isolated from blood cultures was initially reported as K. pneumoniae, but it was identified as K. variicola by a genetic analysis. A representative isolate (FUJ01370) had a novel multilocus sequence typing allelic profile (gapA-infB-mdh-pgi-phoE-rpoB-tonB: 16-24-21-27-52-17-152), to which sequence type 5794 was assigned (GenBank assembly accession: GCA_019042755.1). CONCLUSIONS: We report a fatal case of respiratory and bloodstream infection due to K. variicola complicating severe COVID-19. Co-infection or secondary infection of K. variicola in COVID-19 is likely under-recognized and can be fulminant as in this case.

Successful Treatment with Letermovir in a Heart Transplant Recipient with UL97 Mutation Ganciclovir-Resistant Cytomegalovirus Colitis and Viremia.

Currently available anti-cytomegalovirus (CMV) agents are sometimes poorly tolerated, owing to their side effects. Letermovir is a novel anti-CMV drug that is only approved for CMV prophylaxis in hematopoietic stem cell transplant recipients, with fewer side effects. We report the case of a heart transplant recipient with UL97 mutation (L595F) ganciclovir-resistant cytomegalovirus colitis who was successfully treated with off-label use of letermovir. In treating CMV infection or disease with letermovir, a transient rise or lag in the clearance of CMV-DNA polymerase chain reaction levels has been observed. Our case suggests that CMV-pp65 antigenemia can be an additional marker of treatment efficacy.

Multicenter, single-blind, randomized controlled study of the efficacy and safety of favipiravir and nafamostat mesilate in patients with COVID-19 pneumonia.

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 (SpO2). 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 SpO2 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 SpO2 were observed in the combination group.

Intracranial aspergilloma mimicking metachronous meningioma following transsphenoidal removal of a tuberculum sellae meningioma: illustrative case.

BACKGROUND: Endoscopic transsphenoidal surgery (eTSS) is a well-established approach for resection of skull-based pathologies such as tuberculum sellae meningiomas; however, central nervous system (CNS) fungal infection is a potential complication, particularly in a patient with concomitant sinusitis. OBSERVATIONS: A 58-year-old woman with a tuberculum sellae meningioma causing progressive visual disturbance and concurrent asymptomatic chronic maxillary sinusitis underwent eTSS. Six months later, a de novo dura-based mass with peripheral edema, which was assumed to be an aggressive metachronous meningioma, developed in the middle cranial fossa. The patient underwent frontotemporal craniotomy for complete resection of the lesion, and subsequent histological examination revealed an aspergilloma. She was then treated with an antifungal agent and endoscopic sinus surgery to clear the sinusitis, and no recurrent fungal infection occurred thereafter. LESSONS: CNS fungal infections may appear as a dura-based mass mimicking meningioma. The current case reiterates the importance of the appropriate management of sinusitis prior to eTSS.

Impact of targeted intervention using a collaborative approach for oral third-generation cephalosporins: An interrupted time-series analysis.

Objectives: To assess the effectiveness of a targeted intervention using a collaborative approach, added to a comprehensive educational intervention, to facilitate the appropriate use of oral third-generation cephalosporins (3GCs). Design: Quasi-experimental study. Setting: The University of Tokyo Hospital, a tertiary-care teaching hospital. Participants: Approximately 2,000,000 outpatients and 80,000 inpatients at the hospital between April 2017 and March 2020. Intervention: The targeted intervention using the collaborative approach was implemented in the departments with the highest use of oral 3GCs (ophthalmology and dermatology departments). Interrupted time-series analysis was applied to assess the change in days of therapy (DOT) of oral 3GCs between the preintervention period (April 2017-April 2019) and the postintervention period (May 2019-March 2020) for both inpatients and outpatients. Results: After the introduction of the targeted intervention with oral 3GCs, a significant immediate reduction of 13.48 DOT per 1,000 patient days was detected in inpatients (P < .001). However, no significant change in slope was observed before and after the intervention (-0.02 DOT per 1,000 patient days per month; P = .94). Although a temporary increase was observed after the targeted intervention in outpatients, the slope significantly decreased (-0.69 DOT per 1,000 outpatient visits per month; P = .044). No differences were observed in the use of other oral antibiotics after the intervention. Conclusions: The targeted intervention contributed to a reduction in DOT of oral 3GCs in both inpatients and outpatients. Targeted interventions using a collaborative approach might be helpful in further decreasing the inappropriate use of antibiotics.

Dynamic modulations of urinary sphingolipid and glycerophospholipid levels in COVID-19 and correlations with COVID-19-associated kidney injuries.

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.

Decrease in serum levels of autotaxin in COVID-19 patients.

INTRODUCTION: In order to identify therapeutic targets in Coronavirus disease 2019 (COVID-19), it is important to identify molecules involved in the biological responses that are modulated in COVID-19. Lysophosphatidic acids (LPAs) are involved in the pulmonary inflammation and fibrosis are one of the candidate molecules. The aim of this study was to evaluate the association between the serum levels of autotaxin (ATX), which are enzymes involved in the synthesis of lysophosphatidic acids. MATERIAL AND METHODS: We enrolled 134 subjects with COVID-19 and 58 normal healthy subjects for the study. We measured serum ATX levels longitudinally in COVID-19 patients and investigated the time course and the association with severity and clinical parameters. RESULTS: The serum ATX levels were reduced in all patients with COVID-19, irrespective of the disease severity, and were negatively associated with the serum CRP, D-dimer, and anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody levels. DISCUSSION: Considering the biological properties of LPAs in the pulmonary inflammation and fibrosis, modulation of ATX might be compensatory biological responses to suppress immunological overreaction especially in the lung, which is an important underlying mechanism for the mortality of the disease. CONCLUSIONS: COVID-19 patients showed a decrease in the serum levels of ATX, irrespective of the disease severity. Key MessagesAutotaxin (ATX) is an enzyme involved in the synthesis of lysophosphatidic acid (LPA), which has been reported to be involved in pulmonary inflammation and fibrosis. Patients with COVID-19 show decrease in the serum levels of ATX. Modulation of ATX might be compensatory biological responses to suppress immunological overreaction.

Identification of Odoribacter splanchnicus bacteremia using MALDI-TOF mass spectrometry and 16S rRNA sequencing: A case report.

Odoribacter splanchnicus was recently reclassified from the genus Bacteroides. We present the first case of Odoribacter splanchnicus bacteremia following appendicitis. The species was identified using MALDI-TOF mass spectrometry and later confirmed with 16S rRNA sequencing. The patient was successfully managed with surgery and antibiotic administration for two weeks.

Dynamic modulations of sphingolipids and glycerophospholipids in COVID-19.

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.

Japan perspective on antimicrobial stewardship and solid organ transplantation.

BACKGROUND: The current situation, challenges, and opportunities related to antimicrobial stewardship for solid organ transplantations (SOTs) patients in Japan are not well known. METHODS: We searched English and Japanese literature using Pubmed and Ichushi-Web (the Japanese medical literature search system provided by the Japan Medical Abstract Society) with relevant keywords including solid organ transplant, antimicrobial stewardship, and Japan. Hand searches of the references from the retrieved literature, including conference proceedings of The Japanese Association for Infectious Diseases, were conducted. RESULTS: The Japanese National Action Plan for antimicrobial resistance has brought attention to the importance of antimicrobial stewardship programs (ASPs) in Japan. According to national surveillance, the proportion of methicillin resistance among Staphylococcus aureus was 48%, while the proportion of vancomycin-resistance among Enterococcus faecium was 1.5% in 2019. Resistance against imipenem in Escherichia coli and Klebsiella pneumoniae in 2019 were 0.1% and 0.2%, respectively. Exploration of SOT-specific data on antimicrobial usage and drug resistance are warranted. A large questionnaire survey revealed a low proportion of hospitals with >500 beds implementing ASP toward immunocompromised patients. While the annual number of SOT in Japan has increased, the implementation of SOT-specific ASP varies among institutions. CONCLUSION: A coordinated ASP and exploration of the burden of antimicrobial resistance are needed for SOT patients in Japan. Promoting both intrainstitutional and interinstitutional collaboration is vital to the advancement of SOT-specific ASP in Japan.