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.

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.

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.

Analysis of cross-reactivity among flaviviruses using sera of patients with dengue showed the importance of neutralization tests with paired serum samples for the correct interpretations of serological test results for dengue.

Dengue is a febrile illness caused by the dengue virus (DENV) that belongs to the genus Flavivirus in the family Flaviviridae. Cross-reactivity between flaviviruses poses a challenge while interpreting serological test results. In the present study, the cross-reactivity of sera of the patients with dengue, who traveled from Japan to DENV-endemic countries, was analyzed by using an enzyme-linked immunosorbent assay (ELISA) and neutralization test (NT). Sixteen serum samples were collected from patients with dengue and were tested for: i) IgM antibodies against Zika virus (ZIKV), West Nile virus (WNV), Japanese encephalitis virus (JEV), and tick-borne encephalitis virus (TBEV) using IgM ELISA, ii) IgG antibody against TBEV using IgG ELISA, and iii) neutralizing antibody against ZIKV, WNV, TBEV, and JEV. Among the 16 samples tested using ELISA, seven samples were IgM-positive for at least one of the other flaviviruses, and nine samples were IgG-positive for TBEV. Neutralizing antibody titers (NATs) against ZIKV, WNV, and TBEV were one-fourth or lower than those against the causative DENV in all samples. The NATs against JEV were one-fourth or lower than those against the causative DENV in six convalescent-phase serum sample among the seven convalescent-phase serum samples. The NAT against DENV of the residual one convalescent-phase serum was similar to that against JEV and that against JEV of its relevant acute-phase serum sample. These results showed that NTs with paired serum samples are important to correctly interpret the serological test results for DENV.

Toxic shock like syndrome caused by Streptococcus agalactiae bacteremia during treatment for multiple myeloma.

Toxic shock-like syndrome (TSLS) is a life-threatening hyperinflammatory complication caused by Streptococcus species infections. We reported the first case of TSLS caused by primary bacteremia of Streptococcus agalactiae during chemotherapy for multiple myeloma. A 74-year-old woman, who received combination chemotherapy of elotuzumab, pomalidomide, and dexamethasone for treatment-refractory multiple myeloma, was transported to our hospital under comatose and septic shock. Her blood culture detected Streptococcus agalactiae, and considering the progressive multiorgan failure, she was diagnosed with TSLS. Empiric antibiotic treatment with meropenem and respiratory and circulatory support were quickly initiated, resulting in an almost complete recovery of organ functions. It should be noted that with the advances of chemotherapy, the risk of infection is becoming more diverse.

The association between adverse reactions and immune response against SARS-CoV-2 spike protein after vaccination with BNT162b2 among healthcare workers in a single healthcare system: a prospective observational cohort study.

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.

The First Reported Case of Bordetella pertussis Bacteremia in a Patient With Human Immunodeficiency Virus Infection.

We describe a case of bacteremia in a human immunodeficiency virus-infected patient caused by a Bordetella pertussis strain lacking 2 major virulence factors, filamentous hemagglutinin and fimbriae. Although B pertussis bacteremia is uncommon, physicians should be aware that even attenuated B pertussis strains can cause invasive infection in immunocompromised patients. Bordetella pertussis is a gram-negative coccobacillus that causes a severe paroxysmal coughing disease known as whooping cough or pertussis. Bordetella pertussis colonizes the epithelial cells of the human respiratory tract, and the organisms are typically isolated from nasopharynx. We describe a case of B pertussis bacteremia in a patient with human immunodeficiency virus (HIV) infection. Interestingly, the isolate recovered from blood culture did not produce the major virulence factors, filamentous hemagglutinin (FHA) and fimbriae (FIM). Previously, 3 cases of B pertussis bacteremia were reported in the literature. We discuss the features of B pertussis bacteremia.

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.

Extracorporeal membrane oxygenation may decrease the plasma concentration of remdesivir in a patient with severe coronavirus disease 2019.

Remdesivir is an antiviral drug that results in clinical improvement after five days of treatment and accelerates recovery by 31%. No studies have discussed the pharmacokinetic analysis of remdesivir in patients with severe COVID-19 requiring extracorporeal membrane oxygenation (ECMO). A 63-year-old American man who underwent mechanical ventilation and ECMO for severe COVID-19 was administered remdesivir for ten days. The loading dosage was 200 mg at 7 PM on day 12 and 100 mg daily at 0:00 PM from day 13-21, administered within 1 h. The pharmacokinetic analysis was performed. The serum creatinine concentration was within the normal range of 0.5-0.7 mg/dL during treatment. According to the pharmacokinetic analysis, the plasma concentrations of remdesivir and GS-441524 4 h after administration (C4) were 662 ng/mL and 58 ng/mL, respectively, and the concentrations 18 h after administration (C18) were 32 ng/mL and 44 ng/mL, respectively. Therefore, the half-life of remdesivir and GS-441524 was 3.2 and 35.1 h, respectively. Monitoring the plasma concentrations of remdesivir and GS-441524 in patients undergoing ECMO may be necessary.

Plesiomonas shigelloides Septic Shock Following Ingestion of Dojo Nabe (Loach Hotpot).

Plesiomonas shigelloides is a gram-negative bacillus that commonly causes self-limited diarrhea in humans. We present the case of P shigelloides bacteremia in a 49-year-old man with alcoholic cirrhosis who developed septic shock a day after eating Dojo nabe (loach hotpot), a Japanese traditional dish.

Dynamic changes in fibrinogen and D-dimer levels in COVID-19 patients on nafamostat mesylate.

Critical illnesses associated with coronavirus disease 2019 (COVID-19) are attributable to a hypercoagulable status. There is limited knowledge regarding the dynamic changes in coagulation factors among COVID-19 patients on nafamostat mesylate, a potential therapeutic anticoagulant for COVID-19. First, we retrospectively conducted a cluster analysis based on clinical characteristics on admission to identify latent subgroups among fifteen patients with COVID-19 on nafamostat mesylate at the University of Tokyo Hospital, Japan, between April 6 and May 31, 2020. Next, we delineated the characteristics of all patients as well as COVID-19-patient subgroups and compared dynamic changes in coagulation factors among each subgroup. The subsequent dynamic changes in fibrinogen and D-dimer levels were presented graphically. All COVID-19 patients　were classified into three subgroups: clusters A, B, and C, representing low, intermediate, and high risk of poor outcomes, respectively. All patients were alive 30 days from symptom onset. No patient in cluster A required mechanical ventilation; however, all patients in cluster C required mechanical ventilation, and half of them were treated with venovenous extracorporeal membrane oxygenation. All patients in cluster A maintained low D-dimer levels, but some critical patients in clusters B and C showed dynamic changes in fibrinogen and D-dimer levels. Although the potential of nafamostat mesylate needs to be evaluated in randomized clinical trials, admission characteristics of patients with COVID-19 could predict subsequent coagulopathy.

Effectiveness of personal protective equipment in preventing severe acute respiratory syndrome coronavirus 2 infection among healthcare workers.

INTRODUCTION: Information on the effectiveness of personal protective equipment (PPE) for preventing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection among healthcare workers (HCWs), especially among HCWs with frequent contact with patients with SARS-CoV-2, is limited. METHODS: We conducted a prospective cohort study on 49 HCWs who worked in close contact with patients with SARS-CoV-2 infection. HCWs had blood samples taken every 2 weeks to test for SARS-CoV-2 antibodies using two different types of assay. RESULTS: Forty-nine participants (31 nurses, 15 doctors, 3 other workers) were enrolled. In total, 112 blood samples are obtained from participants. The median work days in 2 weeks was 9 (interquartile range (IQR): 5-10) days. In a single work day, 30 of the 49 participants (61.5%) had contact with patients with suspected or conformed SARS-CoV-2 at least 8 times, and approximately 60% of participants had more than 10 min of contact with a single patient. The median self-reported compliance to PPE was 90% (IQR: 80-100%). Seven participants tested positive for SARS-CoV-2 antibody using enzyme-linked immunosorbent assay (ELISA); however, none were seropositive for SARS-CoV-2 neutralizing antibody, so the positive ELISA results were assumed to be false-positive. CONCLUSIONS: The study provides evidence that appropriate PPE is sufficient to prevent infection amongHCWs. It is necessary to establish a system that provides a stable supply of PPE for HCWs to perform their duties.

SARS-CoV-2 infection among returnees on charter flights to Japan from Hubei, China: a report from National Center for Global Health and Medicine.

Due to the significant spread of a new type of coronavirus (SARS-CoV-2) infection (COVID-19) in China, the Chinese government blockaded several cities in Hubei Province. Japanese citizens lost a means of transportation to return back to Japan. The National Center for Global Health and Medicine (NCGM) helped the operation of charter flights for evacuation of Japanese residents from Hubei Province, and this article outlines our experiences. A total of five charter flights were dispatched, and the majority of returnees (793/829 [95.7%]) were handled at NCGM. A large number of personnel from various departments participated in this operation; 107 physicians, 115 nurses, 110 clerical staff, and 45 laboratory technicians in total. Several medical translators were also involved. In this operation, we conducted airborne precautions in addition to contact precautions. Eye shields were also used. The doctors collecting the pharyngeal swab used a coverall to minimize the risk of body surface contamination from secretions and droplets. Enhanced hand hygiene using alcohol hand sanitizer was performed. Forty-eight persons were ultimately hospitalized after the triage at NCGM operation, which was more than the number of persons triaged at the airport (n = 34). Of those hospitalized after NCGM triage, 8.3% (4/48 patients) ultimately tested positive for SARS-CoV-2, significantly higher than the positive rate among subjects not triaged (4/48 [8.3%] vs. 9/745 [1.2%]: p = 0.0057). NCGM participated in a large-scale operation to evacuate Japanese nationals from the COVID-19 epidemic area. We were able to establish a scheme through this experience that can be used in the future.

COVID-19 can suddenly become severe: a case series from Tokyo, Japan.

Since the initial report of coronavirus disease (COVID-19) from the City of Wuhan, China in December 2019, there have been multiple cases globally. Reported here are 11 cases of COVID-19 at this hospital; all of the patients in question presented with relative bradycardia. The severity of the disease was classified into four grades. Of the patients studied, 3 with mild COVID-19 and 3 with moderate COVID-19 improved spontaneously. Lopinavir/ ritonavir was administered to 3 patients with severe COVID-19 and 2 with critical COVID-19. Both patients with critical COVID-19 required mechanical ventilation and extracorporeal membrane oxygenation. Both patients with critical COVID-19 had a higher fever that persisted for longer than patients with milder COVID-19. The respiratory status of patients with critical COVID-19 worsened rapidly 7 days after the onset of symptoms. Relative bradycardia may be useful in distinguishing between COVID-19 and bacterial community-acquired pneumonia. In patients who have had a fever for > 7 days, the condition might worsen suddenly.

Non-COVID-19 Patients with Life-threatening Diseases Who Visited a Fever Clinic: A Single-center, Observational Study in Tokyo, Japan.

Objective In fever clinics screening coronavirus disease (COVID-19), there could be patients with life-threatening diseases that physicians should not overlook. We exploratorily investigated the final diagnosis among non-COVID-19 hospitalized patients who visited the fever clinic. Methods This was a retrospective, observational, and single-centered study conducted in the National Center for Global Health and Medicine (NCGM), Tokyo, Japan. We conducted a retrospective chart review of patients who visited the fever clinic in the NCGM from 11 March 2020 to 24 April 2020. Patients Patients who met the following clinical criteria visited the fever clinic in the NCGM: (1) body temperature >37.5°C, (2) any symptoms consistent with COVID-19 or (3) referral from local healthcare facilities. In the fever clinic, all patients who met the above criteria had severe acute respiratory syndrome coronavirus 2 polymerase chain reaction test with nasopharyngeal swab specimens. Patients with severe symptoms or an unstable condition were sent to an outpatient clinic for infectious diseases for further evaluation and treatment. Results Among 1,470 patients who visited the fever clinic, 84 patients were hospitalized, and 45 of them were diagnosed as having COVID-19. Among the remaining 39 non-COVID-19 patients, there were nine patients with life-threatening diseases. The life-threatening diseases included acute heart failure, septic shock, pneumocystis pneumonia, peritonsillar abscess, and necrotizing fasciitis. Conclusion Physicians should evaluate each patient carefully while considering other life-threatening conditions even in such a COVID-19 pandemic era.

Evaluation of Coronavirus Disease 2019 Severity Using Urine Biomarkers.

SUBJECTS: Early detection of coronavirus disease 2019 in patients likely to develop severe manifestations enables appropriate interventions, including rapid ICU admission. This study was conducted to determine whether noninvasive urine biomarkers can predict the clinical severity of coronavirus disease 2019. INTERVENTIONS: Not applicable. MEASUREMENTS AND MAIN RESULTS: This is single-center study, national center hospital designated for infectious disease. Fifty-eight patients who tested positive for severe acute respiratory syndrome coronavirus 2 in respiratory specimens through real-time reverse transcription-polymerase chain reaction were retrospectively studied. Urinary ß2-microglobulin, liver-type fatty acid-binding protein were serially measured. Serum interferon-γ and monocyte chemotactic protein-1 were also evaluated. The 58 patients were assigned into three groups. Patients requiring intensive care were assigned to the severe group (n = 12). Patients treated with oxygen were assigned to the moderate group (n = 13). Other patients were assigned to the mild group (n = 33). Urine tests revealed that low ß2-microglobulin and liver-type fatty acid-binding protein levels were associated with mild disease, whereas high levels were associated with severe disease. In severe cases, liver-type fatty acid-binding protein tended to be persistently high. The resulting cutoff values were ß2-microglobulin; severe versus moderate + mild: 2,457 µg/dL (specificity 76.9% and sensitivity 90.0%, area under the receiver operating characteristic curve 85.9%), liver-type fatty acid-binding protein; severe versus moderate + mild: 22.0 µg/gCre (specificity 84.6% and sensitivity 90%, area under the receiver operating characteristic curve 91.8%). Urinary ß2-microglobulin and serum interferon-γ/monocyte chemotactic protein-1 showed a similar trend. CONCLUSIONS: Evaluating urinary biomarkers such as ß2-microglobulin and liver-type fatty acid-binding protein may allow determination of coronavirus disease 2019 patients with active cytokines and recognition of patients likely to become critically ill and requiring careful observation and early intervention.

Leuconostoc lactis and Staphylococcus nepalensis Bacteremia, Japan.

Leuconostoc lactis is a glycopeptide-resistant, gram-positive, facultative anaerobic coccus isolated from dairy products, whereas Staphylococcus nepalensis is coagulase-negative coccus that has not been identified as human pathogen. We report an instructive case of L. lactis and S. nepalensis bacteremia in a 71-year-old man who experienced Boerhaave syndrome after a meal.

Environmental surface and air contamination in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) patient rooms by disease severity.

BACKGROUND: The coronavirus disease 2019 (COVID-19) continues to spread around the world. In addition to community-acquired infections, nosocomial infections are also a major social concern. The likelihood of environmental contamination and transmission of the virus based on disease severity is unknown. METHODS: We collected nasopharyngeal, environmental and air samples from patients with COVID-19 admitted to the National Centre for Global Health and Medicine between January 29th and February 29th, 2020. The patients were classified by severity of disease. The collected samples were tested using severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) real-time reverse transcription polymerase chain reaction (real-time RT-PCR). RESULTS: SARS-CoV-2 was not detected in a subset of 11 air samples. Of the 141 environmental samples collected from three patient bays and two single rooms, four samples tested positive for SARS-CoV-2 by real-time RT-PCR. Detections were made on the surface of a stethoscope used in the care of a patient with severe disease, on the intubation tube of a patient classified as critical (and on ventilator management), and on the surface of a gown worn by the nurse providing care. CONCLUSIONS: Regardless of the patients' disease severity, SARS-CoV-2 was detected on very few environmental surfaces. However, detection of SARS-CoV-2 on stethoscopes used in the care of multiple patients and on the surface of gowns worn by clinical staff indicates that medical devices may be linked to the spread of infection.