Successful maintenance treatment of disseminated nocardiosis with cerebral abscess in a severely immunocompromised patient allergic to trimethoprim-sulfamethoxazole using moxifloxacin and high-dose minocycline: A case report.

Nocardiosis in patients after allogeneic hematopoietic stem cell transplantation (HSCT) is rare, but is associated with a significant mortality risk. Although trimethoprim-sulfamethoxazole (TMP/SMX) remains the cornerstone of nocardiosis treatment, optimal alternative therapies for patients intolerant to TMP/SMX are not well-established. Herein, we report a case of disseminated nocardiosis with bacteremia and multiple lesions in the lungs and brain caused by Nocardia farcinica, in a 60-year-old man who had previously undergone allogeneic HSCT and was receiving immunosuppressants for severe chronic graft-versus-host disease. The patient received atovaquone for the prophylaxis of Pneumocystis pneumonia because of a previous serious allergic reaction to TMP/SMX. The patient was initially treated with imipenem/cilastatin and amikacin, which were later switched to ceftriaxone and amikacin based on the results of antimicrobial susceptibility testing. After switching to oral levofloxacin and a standard dose of minocycline, the patient experienced a single recurrence of brain abscesses. However, after switching to oral moxifloxacin and high-dose minocycline, the patient did not experience any relapses during the subsequent two years and seven months of treatment. In treating nocardiosis with brain abscesses, it is crucial to select oral antibiotics based on the antimicrobial susceptibility test results and pharmacokinetics, especially when TMP/SMX is contraindicated. A combination of oral moxifloxacin and high-dose minocycline could be a promising alternative therapy.

Trajectories of the SARS-CoV-2 RNA load in patients with hematological malignancy.

OBJECTIVES: The higher risk of prolonged viral shedding in coronavirus disease (COVID-19) patients with hematological malignancies (HM) necessitates test-based de-isolation strategies. However, evidence to establish their appropriate isolation period is insufficient. This study investigated the factors affecting prolonged viral shedding and the requisite isolation period in these patients. METHODS: We retrospectively reviewed 14 COVID-19 patients with HM between January and April 2022, who were subjected to our test-based de-isolation strategy, followed by analysis of the viral load trajectory. The viral loads of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were evaluated using the cycle threshold (Ct ) of the reverse-transcription quantitative polymerase chain reaction. The trajectories were classified according to the time-interval from COVID-19 onset to the attainment of Ct values >30. RESULTS: The median interval between onset and attainment of a Ct value >30 was 22 days. Five patients with mild or moderate COVID-19 without intense treatment histories achieved Ct values >30 within 20 days. The other nine patients needed more than 20 days, including three patients who did not meet this criterion during the observation period. CONCLUSIONS: The SARS-CoV-2 viral load trajectories in patients with HM can be stratified by treatment history for the underlying HM and severity of COVID-19.

Clinical outcomes of COVID-19 caused by the Alpha variant compared with one by wild type in Kobe, Japan. A multi-center nested case-control study.

OBJECTIVES: The emergence of the Alpha variant of novel coronavirus 2019 (SARS-CoV-2) is a concerning issue but their clinical implications have not been investigated fully. METHODS: We conducted a nested case-control study to compare severity and mortality caused by the Alpha variant (B.1.1.7) with the one caused by the wild type as a control from December 2020 to March 2021, using whole-genome sequencing. 28-day mortality and other clinically important outcomes were evaluated. RESULTS: Infections caused by the Alpha variant were associated with an increase in the use of oxygen (43.4% vs 26.3%. p = 0.017), high flow nasal cannula (21.2% vs 4.0%, p = 0.0007), mechanical ventilation (16.2% vs 6.1%, p = 0.049), ICU care (30.3% vs 14.1%, p = 0.01) and the length of hospital stay (17 vs 10 days, p = 0.031). More patients with the Alpha variant received medications such as dexamethasone. However, the duration of each modality did not differ between the 2 groups. Likewise, there was no difference in 28-day mortality between the 2 groups (12% vs 8%, p = 0.48), even after multiple sensitivity analyses, including propensity score analysis. CONCLUSION: The Alpha variant was associated with a severe form of COVID-19, compared with the non-Alpha wild type, but might not be associated with higher mortality.

Reliability of the respiratory rate and oxygenation index for successful high-flow nasal cannula support in coronavirus disease pneumonia: a retrospective cohort study.

BACKGROUND: High-flow nasal cannula (HFNC) therapy is an important non-invasive respiratory support in acute respiratory failure, including coronavirus disease (COVID-19) pneumonia. Although the respiratory rate and oxygenation (ROX) index is a simple and useful predictor for HFNC failure and mortality, there is limited evidence for its use in patients with COVID-19 pneumonia. We aimed to evaluate the ROX index as a predictor for HFNC failure in patients with COVID-19 pneumonia. We also evaluated the ROX index as a predictor for 28-day mortality. METHODS: In this single-center, retrospective, cohort study, 248 patients older than 18 years of age with COVID-19 pneumonia received HFNC therapy for acute respiratory failure. The ROX index was evaluated within 4 h from the start of HFNC therapy. Past medical history, laboratory data, and the ROX index were evaluated as predictors for HFNC failure and 28-day mortality. RESULTS: The ROX index < 4.88 showed a significantly high risk ratio for HFNC failure (2.13 [95% confidence interval [CI]: 1.47 - 3.08], p < 0.001). The ROX index < 4.88 was significantly associated with 28-day mortality (p = 0.049) in patients with COVID-19 pneumonia receiving HFNC therapy. Age, chronic hypertension, high lactate dehydrogenase level, and low ROX index showed significantly high risk ratio for HFNC failure. C-reactive protein level and low ROX index were predictors of 28-day morality. CONCLUSION: The ROX index is a useful predictor for HFNC success and 28-day mortality in patients with COVID-19 pneumonia receiving HFNC therapy. TRIAL REGISTRATION: An independent ethics committee approved the study (Research Ethics Review Committee of Kobe City Medical Center General Hospital [number: zn220303; date: February 21, 2022]), which was performed in accordance with the Declaration of Helsinki, Guidelines for Good Clinical Practice.

Cold agglutinin anti-I antibodies in two patients with COVID-19.

BACKGROUND: Cold agglutinin syndrome (CAS) is associated with various diseases. Several studies of CAS associated with coronavirus disease 2019 (COVID-19) reported hemolytic anemia and thrombosis; however, the clinical significance of cold agglutinins (CA) in patients with COVID-19 is unclear. Here, we present two cases of CA identified in the context of COVID-19 without hemolytic anemia and clotting. CASE REPORT AND DISCUSSION: Two patients with no known risk factors for CA were diagnosed with COVID-19; peripheral blood smears reveal red blood cells (RBCs) agglutination. These patients showed a high CA titer. We confirmed retrospectively that the CA was an anti-I antibody. The two COVID-19 cases with a high CA titer showed no hemolysis or thrombosis. Mycoplasma pneumoniae is known to cause CAS, but not all patients who have a high CA titer show hemolysis. Coagulation abnormalities are documented in severe COVID-19 cases. Although CA increases the risk of thrombosis in those with lymphoproliferative diseases, the role of anti-I antibodies in COVID-19 is unclear. The impact of CAS on clinical presentations in COVID-19 remains a matter of verification. CONCLUSIONS: A high CA titer was identified in COVID-19 patients without hemolytic anemia and clotting. Anti-I antibodies were identified. Further studies are required to clarify the pathophysiology of CA in COVID-19.

Negative myoclonus as a manifestation of cefepime neurotoxicity.

Negative myoclonus may present in the early stages of cefepime neurotoxicity. Cefepime neurotoxicity typically presents as reduced consciousness, myoclonus, and seizures; however, negative myoclonus is uncommon. This video shows an older woman with cefepime neurotoxicity that presented as a negative myoclonus of the upper limbs.

A pseudo-outbreak of COVID-19 associated pulmonary aspergillosis: a microbiological investigation of both the patients and the environment.

Background: We experienced a pseudo-outbreak of aspergillosis in a newly constructed COVID-19 ward. Within the first 3 months from the commencement of the ward, six intubated patients of COVID-19 developed probable or possible pulmonary aspergillosis. We suspected an outbreak of pulmonary aspergillosis associated with ward construction and launched air sampling for the investigation of the relationship between these. Methods: The samples were collected at 13 locations in the prefabricated ward and three in the general wards, not under construction, as a control. Results: The results from samples revealed different species of Aspergillus from those detected by the patients. Aspergillus sp. was detected not only from the air samples in the prefabricated ward but also in the general ward. Discussion: In this investigation, we could not find evidence of the outbreak that links the construction of the prefabricated ward with the occurrence of pulmonary aspergillosis. It might suggest that this series of aspergillosis was more likely occurred from fungi that inherently colonized patients, and was associated with patient factors such as severe COVID-19 rather than environmental factors. Once an outbreak originating from building construction is suspected, it is important to conduct an environmental investigation including an air sampling.

Predictive factors and clinical impact of ICU-acquired weakness on functional disability in mechanically ventilated patients with COVID-19.

BACKGROUND: Patients with critical COVID-19 often require invasive mechanical ventilation (IMV) and admission to the intensive care unit (ICU), resulting in a higher incidence of ICU-acquired weakness (ICU-AW) and functional decline. OBJECTIVE: This study aimed to examine the causes of ICU-AW and functional outcomes in critically ill patients with COVID-19 who required IMV. METHODS: This prospective, single-center, observational study included COVID-19 patients who required IMV for ≥48 h in the ICU between July 2020 and July 2021. ICU-AW was defined as a Medical Research Council sum score <48 points. The primary outcome was functional independence during hospitalization, defined as an ICU mobility score ≥9 points. RESULTS: A total of 157 patients (age: 68 [59-73] years, men: 72.6%) were divided into two groups (ICU-AW group; n = 80 versus non-ICU-AW; n = 77). Older age (adjusted odds ratio [95% confidence interval]: 1.05 [1.01-1.11], p = 0.036), administration of neuromuscular blocking agents (7.79 [2.87-23.3], p < 0.001), pulse steroid therapy (3.78 [1.49-10.1], p = 0.006), and sepsis (7.79 [2.87-24.0], p < 0.001) were significantly associated with ICU-AW development. In addition, patients with ICU-AW had significantly longer time to functional independence than those without ICU-AW (41 [30-54] vs 19 [17-23] days, p < 0.001). The development of ICU-AW was associated with delayed time to functional independence (adjusted hazard ratio: 6.08; 95% CI: 3.05-12.1; p < 0.001). CONCLUSIONS: Approximately half of the patients with COVID-19 requiring IMV developed ICU-AW, which was associated with delayed functional independence during hospitalization.

A cross-sectional follow up study to estimate seroprevalence of coronavirus disease 2019 in Kobe, Japan.

ABSTRACT: We conducted a study to estimate the seroprevalence of coronavirus disease 2019 (COVID-19) in Kobe, Japan with positive immunoglobulin G (IgG) rate of 3.3% (95% confidence interval [CI] 2.3%-4.6%) in April 2020. Because there were large concerns about the spread of COVID-19 among citizens thereafter, we conduct a follow-up cross-sectional study to estimate the seroprevalence, and we also added a validation study using a different assay.We conducted cross-sectional serologic testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) antibody using 1000 samples from patients at outpatient settings who visited the clinic from May 26 to June 7, 2020, stratified by the decade of age and sex. We used both Kurabo and Abbott serology assays to identify IgG against SARS-CoV-2.There were 18 and 2 positive IgG among 1000 serum samples using Kurabo and Abbott serology assays, respectively (1.8%, 95% CI 1.1%-2.8%, and 0.2%, 95% CI 0.02%-0.7% respectively). By applying the latter figure to the census of Kobe City (population: 1,518,870), it is estimated that the number of people with positive IgG is 3038 (95% CI: 304-10,632) while a total of 285 patients were identified by polymerase chain reaction (PCR) testing at the end of the study period. Assuming Abbott assay as the reference, Kurabo assay had calculated sensitivity and specificity of 100% and 98.4% respectively. Age and sex adjusted prevalence of positivity was calculated to be 0.17%.We found a lower seroprevalence than 2 months before in Kobe city although the figures were still higher than those detected by PCR. Kurabo assay showed more false positives than true positives despite reasonable sensitivity and specificity, due to low prevalence in Kobe.

Estimation of seroprevalence of novel coronavirus disease (COVID-19) using preserved serum at an outpatient setting in Kobe, Japan: A cross-sectional study.

OBJECTIVES: Coronavirus disease 2019 (COVID-19) pandemic caused by SARS-CoV-2 has been affecting many people on earth and our society. Japan is known to have relatively smaller number of its infections as well as deaths among developed nations. However, accurate prevalence of COVID-19 in Japan remains unknown. Therefore, we conducted a cross-sectional study to estimate seroprevalence of SARS-CoV-2 infection. METHODS: We conducted a cross-sectional serologic testing for SARS-CoV-2 antibody using 1000 samples from patients at outpatient settings who visited the clinic from March 31 to April 7, 2020, stratified by the decade of age and sex. RESULTS: There were 33 positive IgG among 1000 serum samples (3.3%, 95%CI: 2.3-4.6%). By applying this figure to the census of Kobe City (population: 1,518,870), it is estimated that the number of people with positive IgG be 50,123 (95%CI: 34,934-69,868). Age and sex adjusted prevalence of positivity was calculated 2.7% (95%CI: 1.8-3.9%), and the estimated number of people with positive IgG was 40,999 (95%CI: 27,333-59,221). These numbers were 396 to 858-fold more than confirmed cases with PCR testing in Kobe City. CONCLUSIONS: Our cross-sectional serological study suggests that the number of people with seropositive for SARS-CoV-2 infection in Kobe, Japan is far more than the confirmed cases by PCR testing.

Leuconostoc lactis- A Rare Cause of Bacterial Meningitis in an Immunocompromised Host.

Leuconostoc lactis, often found in fermented dairy products, although considered to have a low pathogenic potential, can cause life-threatening infections in immunocompromised hosts. We herein report a 62-year-old man with a history of alcoholic liver cirrhosis, hepatocellular carcinoma, and diabetes mellitus who developed a very rare case of bacterial meningitis caused by this organism. After we administered antibiotics including ampicillin, he recovered completely within two weeks. This gram-positive coccus (GPC) is sensitive to ampicillin but naturally resistant to vancomycin, while its susceptibility to ceftriaxone has not yet been established. In acute GPC meningitis in immunocompromised hosts, Leuconostoc lactis should therefore be considered as a possible pathogen.

Gram-ghost bacilli.

A 76-year-old man presented with a 3-day history of a productive cough and right chest pain on inspiration. The Gram stain of the sputum showed unstained bacilli and polynuclear leukocytes, suggesting a diagnosis of pulmonary acid-fast bacillus infection. Mycobacteria can be identified by Gram staining and are reported to be Gram-neutral or Gram-ghost, and recognition of Gram-ghost bacilli in the initial specimen may assist in distinguishing mycobacterial infection from community-acquired pneumonia.

Fluorous solvent as a new phase-screen medium between reagents and reactants in the bromination and chlorination of alcohols.

[reaction: see text] A perfluorohexane layer regulates the rate of reagent transport in the bromination and chlorination of alcohols. A fluorous triphasic U-tube method is effective for lighter reagents; the thionyl chloride layer (yellow) vanishes, and the chlorides are obtained from the right top organic layer in the chlorination of alcohols.

Synthesis and biological evaluation of boronic acid containing cis-stilbenes as apoptotic tubulin polymerization inhibitors.

A series of boronic acid containing cis-stilbenes as potent inhibitors of tubulin polymerization was synthesized by the introduction of boronic acid as an acceptor-type functional group into the aromatic ring B of the combretastatin framework. High cell-growth inhibition was observed with boron compounds 13 c and 13 d, in which a hydroxy group on the aromatic ring B of combretastatin A-4 was replaced with boronic acid; IC50 values toward B-16 and 1-87 cell lines are 0.48-2.1 microM. Compounds 13 c and 13 d exhibited significant inhibitory activity toward tubulin polymerization (IC50=21-22 microM). The carboxylic acid derivative 17, which can be considered as a mimic of boronic acid 13 c, did not show significant inhibition of cell growth or tubulin polymerization. According to the FACScan analysis using Jurkat cells, apoptosis was induced after incubation for 8 h with 13 c at a concentration of >10(-8) M. Growth inhibitory experiments against a panel of 39 human cancer cell lines revealed 13 c to inhibit growth differently than combretastatin A-4; the correlation coefficient (r) between the two compounds was 0.553 in the COMPARE analysis.