Comprehensive metabolic modulations of sphingolipids are promising severity indicators in COVID-19.

The COVID-19 pandemic, caused by SARS-CoV-2, has had a significant worldwide impact, affecting millions of people. COVID-19 is characterized by a heterogenous clinical phenotype, potentially involving hyperinflammation and prolonged tissue damage, although the exact underlying mechanisms are yet to be fully understood. Sphingolipid metabolites, which govern cell survival and proliferation, have emerged as key players in inflammatory signaling and cytokine responses. Given the complex metabolic pathway of sphingolipids, this study aimed to understand their potential role in the pathogenesis of COVID-19. We conducted a comprehensive examination of sphingolipid modulations across groups classified based on disease severity, incorporating a time-course in serum and urine samples. Several sphingolipids, including sphingosine, lactosylceramide, and hexosylceramide, emerged as promising indicators of COVID-19 severity, as validated by correlation analyses conducted on both serum and urine samples. Other sphingolipids, such as sphingosine 1-phosphate, ceramides, and deoxy-dihydroceramides, decreased in both COVID-19 patients and individuals with non-COVID infectious diseases. This suggests that these sphingolipids are not specifically associated with COVID-19 but rather with pathological conditions caused by infectious diseases. Our analysis of urine samples revealed elevated levels of various sphingolipids, with changes dependent on disease severity, potentially highlighting the acute kidney injury associated with COVID-19. This study illuminates the intricate relationship between disturbed sphingolipid metabolism, COVID-19 severity, and clinical factors. These findings provide valuable insights into the broader landscape of inflammatory diseases.

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.

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.

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.

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.

Emergence of Hepatitis C Virus Genotype 2c Infection Among Human Immunodeficiency Virus-Infected Men Who Have Sex With Men in Tokyo, Japan.

ABSTRACT: We report on hepatitis C virus genotype 2c infection in 12 human immunodeficiency virus-infected men who have sex with men in Tokyo, Japan. The uncommon strains from the 12 patients were genetically clustered; they suggested an emerging outbreak in this population at high risk of sexually transmitted infections.

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.

Aureobasidium melanigenum catheter-related bloodstream infection: a case report.

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.

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.

Protothecosis in the mucosa of the pharynx mimicking pharyngeal cancer in an immunocompetent individual: a case report.

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.

Hemodialysis patients with coronavirus disease 2019: reduced antibody response.

BACKGROUND: Because patients on maintenance hemodialysis (HD) have an impaired immune response to pathogens, they are at higher risk of severe coronavirus disease 2019 (COVID-19). However, data on antibody production among HD patients with COVID-19 is scarce. Thus, we performed a retrospective cohort study evaluating severe acute respiratory syndrome coronavirus two antibody (SARS-CoV-2) production within 1 month after COVID-19 onset in hospitalized patients on HD. METHODS: SARS-CoV-2-specific immunoglobulin (Ig) G levels were quantified using an iFlash 3000 Chemiluminescence Immunoassay analyzer (Shenzhen YHLO Biotech Co., Ltd.) to detect IgG antibodies specific for the S1 subunit of the spike protein (IgG-S1). Propensity score matching was used to balance covariate distribution in HD and non-HD patients. From April 2020 to February 2021, antibody testing was performed on 161 hospitalized patients with symptomatic COVID-19. Of them, 34 HD patients were matched to 68 non-HD patients. RESULTS: After propensity score matching, the median levels of IgG-S1 in the HD patients at 7-13 days after symptom onset were significantly lower than in non-HD patients, especially in those with severe disease. Among all patients, those with severe disease produced lower levels of IgG-S1 at 7-13 days compared with non-severe patients. CONCLUSION: COVID-19 patients with severe disease, especially those undergoing HD, had lower IgG-S1 production in the second week of the disease. Thus, the increased risk of severe COVID-19 in HD patients may be, in part, due to a slow and reduced antibody response.

Neisseria meningitidis serogroup W135 in a traveler visiting Japan from Argentina, 2019.

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.

Human abdominal abscess caused by Necropsobacter rosorum and tips for its identification: A case report.

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.

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.

MRSA Transmission in Intensive Care Units: Genomic Analysis of Patients, Their Environments, and Healthcare Workers.

BACKGROUND: Methicillin-resistant Staphylococcus aureus (MRSA)-and now USA300 MRSA-is a significant intensive care unit (ICU) pathogen; healthcare worker (HCW) contamination may lead to patient cross-transmission. METHODS: From September 2015 to February 2016, to study the spread of MRSA, we enrolled HCWs in 4 adult ICUs caring for patients on MRSA contact precautions. Samples were collected from patient body sites and high-touch surfaces in patient rooms. HCW hands, gloves, and personal protective equipment were sampled pre/post-patient encounter. Whole genome sequencing (WGS) was used to compare isolates from patients, HCWs, and environment. RESULTS: There were 413 MRSA isolates sequenced (38% USA300, 52% USA100) from 66 patient encounters. Six of 66 HCWs were contaminated with MRSA prior to room entry. Isolates from a single patient encounter were typically either USA100 or USA300; in 8 (12%) encounters both USA300 and USA100 were isolated. WGS demonstrated that isolates from patients, HCWs, and environment often were genetically similar, although there was substantial between-encounter diversity. Strikingly, there were 5 USA100 and 1 USA300 clusters that contained similar strains (<22 single-nucleotide variants [SNVs], with most <10 SNVs) within the cluster despite coming from different encounters, suggesting intra- and inter-ICU spread of strains, that is, 4 of these genomic clusters were from encounters in the same ICU; 5 of 6 clusters occurred within 1 week. CONCLUSIONS: We demonstrated frequent spread of MRSA USA300 and USA100 strains among patients, environment, and HCWs. WGS identified possible spread within and even between ICUs. Future analysis with detailed contact tracing in conjunction with genomic data may further elucidate pathways of MRSA spread and points for intervention.

COVID-19 and Fatal Sepsis Caused by Hypervirulent Klebsiella pneumoniae, Japan, 2020.

A patient in Japan with coronavirus disease and hypervirulent Klebsiella pneumoniae K2 sequence type 86 infection died of respiratory failure. Bacterial and fungal co-infections caused by region-endemic pathogens, including hypervirulent K. pneumoniae in eastern Asia, should be included in the differential diagnosis of coronavirus disease patients with acutely deteriorating condition.

Outcomes associated with treatment change from tenofovir disoproxil fumarate to tenofovir alafenamide in HIV-1-infected patients: a real-world study in Japan.

OBJECTIVES: To investigate the impact of switching from tenofovir disoproxil fumarate (TDF)- to tenofovir alafenamide (TAF)-containing regimens on bone, kidney, serum lipids and body weight among Asian patients. METHODS: A prospective, multicentre, observational cohort study was conducted at three centres for HIV infection in Japan during 2017-2019. HIV-infected adults previously treated with TDF-containing regimens and scheduled to switch to TAF-containing regimens were included. Bone mineral density (BMD), renal markers, lipids and weight were measured consecutively from 12 months before to 12 months after the switch. RESULTS: Among 118 patients evaluated, the mean percentage change to spine BMD during 1 year of TAF treatment was higher than that during 1 year of TDF treatment (mean difference = 1.9%; 95% confidence interval (CI): 0.8-3.1). Urine protein and ß2 -microglobulin levels decreased significantly after the switch, while low-density lipoprotein cholesterol and triglycerides increased. During the TDF and TAF periods, the mean weight gains were 0.2 and 1.9 kg, respectively (mean difference = 1.6 kg; 95% CI: 0.9-2.3). Subgroup analysis revealed a significant difference between the mean body weight change associated with an integrase inhibitor (INSTI) (+2.8 kg) and that associated with a non-INSTI (+1.2 kg) third agent treatment only during the TAF period. CONCLUSIONS: Among predominantly Japanese HIV-infected patients, BMD and renal tubular markers improved, while lipid profiles worsened significantly after the switch. Weight gain during the TAF period was larger than that during the TDF period. Concurrent use of INSTI with TAF may act synergistically to gain body weight.

Prevalence and clinical characteristics of patients with biologically false-positive reactions with serological syphilis testing in contemporary practice: 10-year experience at a tertiary academic hospital.

OBJECTIVES: Biologically false positive (BFP) reactions are well described in early literature. However, only a few recent reports described the incidence and clinical characteristics of patients with BFP reactions. We reviewed the serological test results of patients tested for syphilis in our hospital in the past decade and described the clinical characteristics of patients with BFP reactions. METHODS: This is a retrospective study of patients tested for syphilis in a tertiary academic hospital. All serological results were retrieved from the clinical laboratory database. We calculated the incidence of BFP reactions. Clinical characteristics and laboratory data of patients with BFP reactions were reviewed manually. RESULTS: Among 94 462 subjects, 588 patients had BFP reactions (0.62%). Most BFP reactions were observed in patients aged over 60 years, with a history of malignancy and autoimmune diseases. Eighty-five per cent of patients had low rapid plasma reagin (RPR) titre (≤1:4), but two patients had extremely high RPR titre (≥1:256). BFP reactions were more likely to persist beyond 6 months among patients with RPR titre of ≥1:8. There was no statistically significant correlation between RPR titre and total protein albumin gap, surrogate of immunoglobulin levels among patients with BFP reactions. CONCLUSION: There was a low incidence of BFP reactions in the last decade. A minority of BFP reactions had high non-treponemal antibody titre and persisted longer than 6 months. In the era of re-emergence of syphilis, this information could help clinicians interpret the results of well-established diagnostic tests for syphilis.

Clinical characteristics and risk factors associated with Pneumocystis jirovecii infection in patients with solid tumors: study of thirteen-year medical records of a large cancer center.

BACKGROUND: Pneumocystis jirovecii pneumonia (PCP)-related risk factors among patients with solid tumors are not completely defined. Thus, we aimed to characterize PCP cases with underlying solid tumors, to highlight the factors contributing to its development besides the prolonged use of moderate-to-high dose corticosteroids. METHODS: We retrospectively reviewed the medical records of patients with solid tumors diagnosed with PCP between 2006 and 2018 at a cancer center in Tokyo, Japan. Demographic and clinical data were collected, which included malignancy types, total lymphocyte count, coexisting pulmonary disease, chemotherapy, radiation therapy, corticosteroid use, and PCP-attributable mortality. RESULTS: Twenty cases of PCP with solid tumors were documented in 151,718 patients and 788,914 patient-years. Lung cancer (n = 6, 30%) was the most common underlying tumor, followed by breast cancer (n = 3, 15%). Only six (30%) patients were taking a dosage of ≥20 mg prednisone equivalents daily for ≥4 weeks from the onset of PCP. Among the remaining 14 patients, seven (50%) had coexisting pulmonary diseases, 10 (71%) had received chemotherapy within 90 days prior to PCP diagnosis, seven (50%) had undergone chest radiation therapy before PCP diagnosis, seven (50%) had received only intermittent corticosteroids, and one (7%) received no corticosteroids. Mortality attributable to PCP was 40%. CONCLUSIONS: More than half of the patients were not taking a dosage of ≥20 mg prednisone equivalents daily for ≥4 weeks. Multiple other factors (e.g., lymphocytopenia, radiation to chest) may have potentially contributed to PCP in patients with solid tumors in a composite manner. We need to establish a method for estimating the likelihood of PCP taking multiple factors into account in this patient population.