Immunosuppressive therapy and humoral response to third mRNA COVID-19 vaccination with a six-month interval in rheumatic disease patients.

OBJECTIVES: To evaluate the long-term impact of immunosuppressive therapeutic agents on antibody response to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) mRNA vaccination in patients with autoimmune rheumatic diseases (AIRD) in order to propose a strategy for annual vaccination. METHODS: This prospective multicentre cohort study evaluated the humoral response to second and third BNT162b2 and/or mRNA-1273 vaccines in 382 Japanese AIRD patients classified into 12 different medication groups and in 326 healthy controls (HCs). The third vaccination was administered six months after the second vaccination. Antibody titres were measured using the Elecsys Anti-SARS-CoV-2 S assay. RESULTS: The seroconversion rate and antibody titres were lower in AIRD patients than in HCs 3-6 weeks after the second vaccination and 3-6 weeks after the third vaccination. Seroconversion rates were <90% after the third vaccination in patients receiving mycophenolate mofetil and rituximab. Antibody levels after the third vaccination were significantly lower in the groups prescribed TNF inhibitor with or without methotrexate, abatacept and rituximab or cyclophosphamide than those of HCs in a multivariate analysis adjusting for age, sex, and glucocorticoid dosage. The third vaccination induced an adequate humoral response in patients treated with sulfasalazine, bucillamine, methotrexate monotherapy, iguratimod, interleukin-6 inhibitors or calcineurin inhibitors including tacrolimus. CONCLUSIONS: Repeated vaccinations in many immunosuppressed patients produced antibody responses similar to those observed in HCs. In contrast, annual vaccination in patients receiving TNF inhibitors, abatacept, mycophenolate mofetil and rituximab may require caution.

Clinical and virological features of SARS-CoV-2 Omicron variant-infected immunocompromised patients receiving immunosuppressive medications.

BACKGROUND: The prognosis of immunocompromised individuals with COVID-19 remains a significant concern. Information regarding the clinical and virological characteristics of immunocompromised patients infected with SARS-CoV-2 during the Omicron variant period is limited. METHODS: Medical records of patients admitted to our hospital with COVID-19 during the Omicron (BA.1-5) epidemic were retrospectively reviewed. Clinical, virological (nasopharyngeal swabs and blood), and serological data were compared between immunocompromised patients receiving immunosuppressive medications (calcineurin inhibitors, mycophenolate mofetil, or steroids) and control patients not receiving immunosuppressive medications. RESULTS: Twenty-eight immunocompromised patients (25 transplant recipients) and 26 control patients were included. Fourteen of the immunocompromised patients (50%) received monoclonal antibodies. The immunocompromised group included 15 mild/moderate (53.6%), 10 severe (35.7%), and three critical (10.7%) disease severities. The mortality rate due to COVID-19 during hospitalization was 3.6% (1/28) in the immunocompromised group, with no difference between the two groups. Three cases of re-exacerbation after discharge occurred in the immunocompromised group and none in the control group. Linear regression based on nasopharyngeal real-time-PCR cycle threshold (Ct) values according to the time since symptom onset showed markedly slower viral clearance in the immunocompromised group than in the control group (Pslope = 0.078). In the immunocompromised group, patients who received monoclonal antibodies showed faster viral clearance than those who did not receive monoclonal antibodies. The convalescent anti-spike IgG titers were comparable to those in the control group in patients who received monoclonal antibodies and significantly lower than those in the control patients in patients who did not receive monoclonal antibodies (P < 0.001). The prevalence of viremia at onset was significantly higher in the immunocompromised group than in the control group (35.7%, [10/28] vs. 11.5%, [3/26]; P = 0.003). All three patients with critical disease severity in the immunocompromised group exhibited viremia, one of whom died. All three patients with viremia in the control group were critical, of whom two died. CONCLUSIONS: Immunocompromised individuals receiving immunosuppressive medications are more likely to show delayed post-infection SARS-CoV-2 viral clearance and the development of viremia, potentially resulting in worsening severity and outcomes, especially in viremic patients, even during the Omicron epidemic.

The humoral and cellular immune responses following booster vaccination with SARS-CoV-2 mRNA in people living with human immunodeficiency virus.

INTRODUCTION: People living with human immunodeficiency virus (PLWH) have higher mortality rates from COVID-19 than those without HIV. Additionally, the seroconversion rate of antibodies following a second dose of SARS-CoV-2 vaccine is lower in PLWH than non-infected individuals, indicating the need for booster vaccination. Here, we evaluated the humoral and cellular immune responses to booster SARS-CoV-2 vaccination in PLWH. METHODS: The dynamics of anti-spike IgG titers and antigen-specific interferon (IFN)-γ levels to SARS-CoV-2 vaccination were assessed over a 6-month period following a third vaccination of 34 PLWH. RESULTS: Antibody titers for humoral immunity were 50 % lower at 24 weeks post-vaccination than those at 12 weeks. However, those at 24 weeks after the booster vaccination were approximately eight times higher than before. Regarding cellular immunity, IFN-γ levels at 24 weeks after the third vaccination were lower than those at 12 weeks, but nearly 90 % of participants maintained a cut-off value of ≥0.15 IU/mL. A comparison between two groups with CD4+ T lymphocytes counts of <500/µL or ≥500/µL exhibited no statistically significant differences in antibody or IFN-γ levels. However, in the group with CD4+ T lymphocyte counts of <500/µL, the rate of IFN-γ above the cut-off value at 24 weeks after the booster vaccination was lower than that of ≥500/µL. CONCLUSION: An immune response is expected in PLWH given successful antiretroviral therapy with booster SARS-CoV-2 vaccination. However, caution should be exercised for cases with low CD4+ T-lymphocyte counts. (240/250 words).

A delayed diagnosis of fascioliasis: The importance of appropriate fecal diagnostic method.

Fascioliasis, a zoonotic helminthiasis, occurs sporadically in Japan. In this report, we describe a case of fascioliasis that was initially difficult to diagnose because the fecal examination method was negative for the Fasciola sp. eggs. A 64-year-old man living in Shimonoseki City, Japan, presented with fatigue and anorexia. Laboratory tests showed hepatic dysfunction and eosinophilia. Abdominal dynamic contrast-enhanced computed tomography and magnetic resonance cholangiopancreatography suggested intrahepatic biliary cysts. Thereafter, fever and night sweats persisted, and positron emission tomography and biopsy of the porta hepatis lymph node were performed on suspicion of malignancy. However, histopathological diagnosis found non-specific inflammation. As fascioliasis was suspected due to eosinophilia and the multiple hepatic masses, fecal egg examination was performed by an external private laboratory, which adopted the flotation method and reported the absence of parasite eggs. However, fecal examination was retried in our laboratory using the formalin-ether concentration method, and we detected Fasciola sp. eggs. This case suggests that misdiagnosis may occur depending on the fecal examination method; thus, it is necessary to choose a suitable method for certain parasite species.

Impact of pharmacist-driven antimicrobial stewardship interventions in a secondary care facility in Japan: A pragmatic quasi-experimental study.

BACKGROUND: Efforts to promote antimicrobial stewardship aimed at reducing antimicrobial resistance are necessary regardless of hospital scale owing to delays in new antimicrobial development. We aimed to evaluate the effects of pharmacist-driven interventions on broad-spectrum antimicrobial usage and the prognosis of patients with bacteremia in a medium-sized hospital lacking infectious disease physicians and a microbiology laboratory. METHODS: This single-center, retrospective, pragmatic, quasi-experimental study was conducted to compare pre- and post-intervention effects at Saiseikai Futsukaichi Hospital. We analyzed the days of therapy (DOT) for carbapenems and days of antibiotic spectrum coverage (DASC) for antimicrobials using an interrupted time series analysis. Cox proportional hazards analysis was performed to assess 30-day mortality using propensity score and inverse probability of treatment weighting in patients with bacteremia. RESULTS: Pharmacist-driven interventions significantly reduced the DOT (incidence rate ratio [IRR]: 0.53, 95 % confidence intervals [CI]: 0.33-0.81, p = 0.003) and DASC (IRR: 0.87, 95 % CI: 0.78-0.97, p = 0.016). The 30-day mortality due to bacteremia did not significantly differ between pre- and post-intervention in all patients (adjusted hazard ratio [HR]: 0.92, 95 % CI: 0.56-1.51, p = 0.74). Conversely, pharmacist-driven interventions significantly reduced the 30-day mortality owing to bacteremia with Pitt bacteremia score (PBS) ≥4 (adjusted HR: 0.52, 95 % CI: 0.28-0.99, p = 0.047). CONCLUSIONS: Pharmacist-driven interventions may represent a valuable approach for optimizing antimicrobial treatment and improving prognosis, especially in patients with PBS ≥4, which will potentially benefit patients in similar healthcare environments facing challenges related to antimicrobial stewardship and patient prognosis.

Breakthrough candidemia with hematological disease: Results from a single-center retrospective study in Japan, 2009-2020.

Breakthrough candidemia (BrC) is a significant problem in immunocompromised patients, particularly those with hematological disorders. To assess the characteristics of BrC in patients with hematologic disease treated with novel antifungal agents, we collected clinical and microbiological information on said patients from 2009 to 2020 in our institution. Forty cases were identified, of which 29 (72.5%) received hematopoietic stem cell transplant (HSCT)-related therapy. At BrC onset, the most administered class of antifungal agents were echinocandins, administered to 70% of patients. Candida guilliermondii complex was the most frequently isolated species (32.5%), followed by C. parapsilosis (30%). These two isolates were echinocandin-susceptible in vitro but had naturally occurring FKS gene polymorphisms that reduced echinocandin susceptibility. Frequent isolation of these echinocandin-reduced-susceptible strains in BrC may be associated with the widespread use of echinocandins. In this study, the 30-day crude mortality rate in the group receiving HSCT-related therapy was significantly higher than in the group not receiving it (55.2% versus 18.2%, P = .0297). Most patients affected by C. guilliermondii complex BrC (92.3%) received HSCT-related therapy and had a 30-day mortality rate of 53.8%; despite treatment administration, 3 of 13 patients had persistent candidemia. Based on our results, C. guilliermondii complex BrC is a potentially fatal condition in patients receiving HSCT-related therapy with echinocandin administration.

This retrospective study was conducted at a Japanese center specializing in hematopoietic stem cell transplants and found that the rare pathogen Candida guilliermondii complex was the most common cause of breakthrough candidemia, with high mortality rate, which is a concern for transplant patients.

A case of mediastinal abscess and infected aortic aneurysm caused by dissemination of Mycobacterium abscessus subsp. massiliense pulmonary disease.

An 81-year-old man was admitted to our hospital because of fever and malaise that had persisted for 3 months. The patient had undergone two aortic valve replacements, 10 and 5 years previously, because of aortic valve regurgitation and infectious endocarditis. He also had had asymptomatic Mycobacterium abscessus complex (MABC) pulmonary disease for the two previous years. Contrast-enhanced computed tomography showed a mediastinal abscess and an ascending aortic aneurysm. Mycobacterium abscessus subsp. massiliense was cultured from his blood, suggesting the aortic aneurysm was secondary to infection of an implanted device. After enlargement over only a few days, a leakage of contrast medium to the mediastinal abscess was found on computed tomography. The patient was diagnosed with rupture of an infectious aortic aneurysm, and emergency aortic replacement and drainage of the mediastinal abscess were successful. The patient was treated with several antibiotics, including meropenem, amikacin, and clarithromycin, and his general condition improved. Cultures from both the mediastinal abscess and a pericardial patch that was placed at the time of surgery 5 years previously revealed MABC. In our case, the infected aortic aneurysm most likely resulted from MABC pulmonary disease rather than from previous intraoperative contamination. This route of infection is rare. Physicians should be aware of the possibility of dissemination and subsequent infection of implants related to MABC pulmonary disease.

Characteristics of preventive intervention acceptance for international travel among clients aged 60 years and older from a Japanese multicenter pretravel consultation registry.

OBJECTIVES: Pretravel consultation (PTC) is important for older adults owing to health problems associated with overseas travel. Although older adults in Japan, their PTC characteristics are less known. This study aimed to investigate the epidemiology of clients aged ≥ 60 years based on data from the Japan Pre-travel Consultation Registry (J-PRECOR). METHODS: Clients aged ≥ 60 years who visited J-PRECOR cooperative hospitals from February 1, 2018, to May 31, 2022, were included. The primary endpoint was a comparison of prescriptions for vaccines for hepatitis A, tetanus toxoid, and malaria prophylaxis in travelers to high-risk malaria countries in yellow fever vaccination (YFV)-available facilities with and without YFV. RESULTS: In total, 1000 clients (median age: 67 years) were included. Although 523 clients were immunized with YFV, only 38.6% of the 961 unimmunized clients were vaccinated with the tetanus toxoid-containing vaccine. Malaria chemoprophylaxis was prescribed to 25.7% of clients traveling for ≤55 days. At YFV-capable institutes, 557 clients traveling to yellow fever risk countries took PTC, 474 of whom received YFV and 83 were unvaccinated. Lower age (odds rate 0.85 per 1 year; 95% CI 0.80-0.90) and lower hepatitis A vaccination rate (0.29; 95% CI 0.14-0.63) were significantly associated with YFV. CONCLUSIONS: Preventive interventions other than YFV should be offered to older adults.

Study of the effects of in-person attendance at academic conferences on the health of the attendees under COVID-19 pandemic.

OBJECTIVE: To analyze the effects of in-person attendance at an academic conference held during the Covid-19 pandemic on the health of the attendees, as assessed based on symptoms such as fever and cough attributed to infection with the Covid-19 virus. METHODS: A questionnaire was used to survey the members of the Japan Society of Obstetrics and Gynecology (JSOG) about their health during the period from August 7 to August 12, 2022, after the 74th Annual Congress of the JSOG, which was held August 5 to 7. RESULTS: Our survey yielded responses from 3054 members (1566 of whom had attended the congress in person and 1488 of whom had not attended in person); 102 (6.5%) of the in-person attendees and 93 (6.2%) of the people who did not attend in person reported problems with their health. No statistically significant difference was found between these two groups (p = 0.766). In a univariate analysis of factors affecting the presence of health problems, attendees with age ≥60 years had significantly fewer health problems than attendees who were in their 20s (odds ratio: 0.366 [0.167-0.802; p = 0.0120]). In a multivariate analysis, attendees who had received four vaccine shots had significantly fewer health problems than attendees who had received three shots (odds ratio: 0.397 [0.229-0.690, p = 0.0010]). CONCLUSION: Congress attendees who took precautions at the congress to avoid being infected and who had a high vaccination rate did not develop significantly more health problems associated with in-person attendance at the congress.

Dynamics of anti-Spike IgG antibody level after the second BNT162b2 COVID-19 vaccination in health care workers.

INTRODUCTION: Many countries are administering a third dose of COVID-19 vaccines, but the evaluation of vaccine-induced immunity is insufficient. In addition, there are few reports of long-term observation of anti-spike IgG antibody titers after the vaccination in the Japanese population. This study aimed to evaluate anti-spike IgG levels in the Japanese health care workers six months after the BNT162b2 vaccination. METHODS: Dynamics of anti-spike IgG levels were assessed over a six-month period following the second vaccination in 49 participants (Analysis-1). A cross-sectional assessment of anti-spike IgG levels six months after the second vaccination was performed in 373 participants (Analysis-2). RESULTS: In Analysis-1, the geometric mean titer of anti-spike IgG was lower in the older age group and decreased consistently after the second vaccination regardless of age. In Analysis-2, the anti-spike IgG level was significantly negatively associated with age (r = -0.35, p < 0.01). This correlation remained statistically significant (r = -0.28, p < 0.01) after adjustment for sex, BMI, smoking habits, alcohol drinking habits, allergies, and fever or other adverse reactions at the time of vaccination. Additionally, participants who drank alcohol daily had significantly lower anti-spike IgG levels than participants who had never drunk alcohol. Sex, smoking habits, allergy, and fever and other side effects after vaccination did not show a significant association with anti-spike IgG levels. CONCLUSIONS: Six months post-vaccination, the anti-spike IgG level was substantially lower in older persons and daily alcohol drinkers. This may be an indication for an additional vaccine dose for these at-risk categories.

A case of severe COVID-19 with pulmonary thromboembolism related to heparin-induced thrombocytopenia during prophylactic anticoagulation therapy.

A 53-year-old male Japanese patient with COVID-19 was admitted to our hospital after his respiratory condition worsened on day 9 of the disease. With the diagnosis of severe COVID-19, treatment with remdesivir, dexamethasone, and unfractionated heparin was started for the prevention of thrombosis. Although the patient's respiratory status data improved after treatment, severe respiratory failure persisted. Thrombocytopenia and D-dimer elevation were observed on day 8 after heparin therapy initiation. Heparin-induced thrombocytopenia (HIT) antibody measured by immunological assay was positive, and contrast computed tomography showed pulmonary artery thrombus. The patient was diagnosed with HIT because the pre-test probability score (4Ts score) for HIT was 7 points. Heparin was changed to apixaban, a direct oral anticoagulant, which resulted in a reduction of the pulmonary thrombus and improvement of the respiratory failure. In patients with COVID-19, anticoagulant therapy with heparin requires careful monitoring of thrombocytopenia and elevated D-dimer as possible complications related to HIT. (151/250 words).

Genetic testing and serological screening for SARS-CoV-2 infection in a COVID-19 outbreak in a nursing facility in Japan.

BACKGROUND: The Pandemic of coronavirus disease (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has critically impacted the spread of infection within nursing facilities. We evaluated the usefulness of genetic and serological tests conducted during a COVID-19 outbreak in a nursing facility in Japan. METHODS: After the first identification of SARS-CoV-2 infection, a comprehensive, facility- and/or unit-wide PCR testing from nasopharyngeal swabs was repeatedly performed in a three-unit facility including 99 residents with dementia and 53 healthcare personnel. Additionally, PCR testing was conducted separately for residents and staff with fever of ≥37.5 °C. Facility-wide serological testing, including rapid kit testing and quantitative assay, was conducted twice over 1 month apart. RESULTS: A total of 322 PCR and 257 antibody tests were performed. 37 (24.3%) of the 152 individuals (25/99 residents, 25.3%; 12/53 staff, 22.6%) were identified as PCR-positive. Seven residents died with a mortality of 7.1% (7/99). Among the 37 individuals, 10 (27.0%) were asymptomatic at the time of testing. PCR positivity was concentrated on one unit (Unit 1) (20/30 residents, 66.7%; 9/14 staff, 64.3%). The other units showed a limited spread of infection. In unit-wide and separate tests, PCR positivity detection was highly prevalent (22.9 and 44.4%, respectively) in Unit 1, compared with that in the other units. Serological testing identified two additional infected residents with a negative PCR result and showed that no staff was newly identified as infected. CONCLUSIONS: Thorough PCR testing, in combination with comprehensive and separate tests, is critical for managing COVID-19 outbreaks in nursing facilities, particularly, in units considered an epicenter. Serological testing is also beneficial for tracing contacts, confirming the number of infected individuals, and authorizing the termination of the outbreak.

Clinical improvement in a patient with severe coronavirus disease 2019 after administration of hydroxychloroquine and continuous hemodiafiltlation with nafamostat mesylate.

The number of people infected with severe acute respiratory syndrome coronavirus 2 is increasing globally, and some patients have a fatal clinical course. In light of this situation, the World Health Organization (WHO) declared coronavirus disease 2019 (COVID-19) a pandemic on March 11, 2020. While clinical studies and basic research on a treatment for COVID-19 are ongoing around the world, no treatment has yet been proven to be effective. Several clinical studies have demonstrated the efficacy of chloroquine phosphate and nafamostat mesylate with COVID-19. Here, we report the case of a Japanese patient with COVID-19 with severe respiratory failure who improved following the administration of hydroxychloroquine and continuous hemodiafiltlation with nafamostat mesylate. Hence, hydroxychloroquine with nafamostat mesylate might be a treatment option for severe COVID-19.

Guidelines for standardizing cleansing and disinfection of gastrointestinal endoscopes.

As part of the activities toward standardizing endoscopy procedures, the Japan Gastroenterological Endoscopy Society has prepared guidelines for cleansing and disinfection of gastrointestinal endoscopes. The environment of gastrointestinal endoscopy differs between Japan and advanced Western countries. In advanced Western countries, gastrointestinal endoscopy is performed almost exclusively at specialized facilities, where strict provisions are observed for cleansing and disinfecting endoscopes. In Japan, however, gastrointestinal endoscopy is performed even in small clinics, and the annual number of gastrointestinal endoscopy cases is enormous. In addition, the method for cleansing and disinfecting endoscopes differs among hospitals. Although there is a distinct lack of evidence for how gastrointestinal endoscopes are cleaned and disinfected, it is necessary to standardize the method for doing so to advance the field of endoscopic medicine.

Gastrointestinal Graft-versus-Host Disease Is a Risk Factor for Postengraftment Bloodstream Infection in Allogeneic Hematopoietic Stem Cell Transplant Recipients.

Bloodstream infection (BSI) is a well-known cause of morbidity and mortality in allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients. Here, we conducted a retrospective study to assess the morbidity, etiology, risk factors, and outcomes of BSI in the postengraftment period (PE-BSI) after allo-HSCT. Forty-three of 316 patients (13.6%) developed 57 PE-BSI episodes, in which 62 pathogens were isolated: Gram-positive bacteria, gram-negative bacteria, and fungi, respectively, accounted for 54.8%, 35.5%, and 9.7% of the isolates. Multivariate analysis revealed methylprednisolone use for graft-versus-host disease (GVHD) prophylaxis (odds ratio [OR], 6.49; 95% confidence interval [CI], 1.49 to 28.2; P = .013) and acute gastrointestinal GVHD (GI-GVHD) (OR, 8.82; 95% CI, 3.99 to 19.5; P < .0001) as risk factors for developing PE-BSI. This finding suggested that GI-GVHD increases the risk of bacterial translocation and subsequent septicemia. Moreover, among patients with GI-GVHD, insufficient response to corticosteroids, presumably related to an intestinal dysbiosis, significantly correlated with this complication. Patients with PE-BSI presented worse outcome compared with those without (3-year overall survival, 47.0% versus 18.6%; P < .001). Close microbiologic monitoring for BSIs and minimizing intestinal dysbiosis may be crucial to break the vicious cycle between GI-GVHD and bacteremia and to improve transplant outcomes especially in patients who require additional immunosuppressants.

Invasive meningococcal disease due to a non-capsulated Neisseria meningitidis strain in a patient with IgG4-related disease.

BACKGROUND: Invasive Meningococcal Disease (IMD) is a rare and critical disease in Japan. Most of these cases are caused by capsulated Neisseria meningitidis strains. Non-capsulated (non-typable) strains are considered relatively low-pathogenic and can colonize in the nasopharynx of healthy children and young adults. As far as could be ascertained, only twelve IMD cases due to non-capsulated strains have been reported in the literature. No clear risk factors could be identified in a literature review (unknown or immunocompetent, seven cases; C6 deficiency, three cases). CASE PRESENTATION: We report a Japanese male taxi driver with bacteremia and meningitis due to non-capsulated N. meningitidis. He had a fever and shaking chills. Ceftriaxone was administered, and the patient finally recovered. During the clinical course, relative adrenal insufficiency occurred and was treated with hydrocortisone. A hidden co-morbidity, immunoglobulin G4 (IgG4)-related disease, was revealed in the past surgical history (a resection of bilateral orbital tumors), which included symptoms (swelling lachrymal glands and lymph nodes), elevated IgG4, immunoglobulin E, and hypocomplementemia. He recovered finally and no recurrence was observed. CONCLUSIONS: Our IMD case is the first reported in Japan, where IMD is not considered pandemic. The patient had a history of IgG4-related disease, although we could not establish a clear relationship between the patient's IMD and co-morbidity. A collection of further clinical cases might establish the risk factors and characteristics of IMD that could be caused by this neglected pathogen, non-capsulated N. meningitidis.

Mycobacterium abscessus and massiliense lung infection during macrolide treatment for bronchiolitis obliterans after allogeneic hematopoietic stem cell transplantation.

In patients undergoing allogeneic hematopoietic stem cell transplantation (allo-SCT), post-transplant lung infection is critical for their prognosis. Mycobacterium abscessus complex is not fully recognized as a nontuberculous mycobacteria (NTM) pathogen of post-SCT lung infection. Here, we present three post-allogeneic SCT patients who developed pulmonary infection caused by M. abscessus complex including M. abscessus and M. massiliense. In all three cases, macrolide antibiotics had been administered for bronchiolitis obliterans syndrome (BOS) before the confirmation of their infection, and macrolide resistance was noted in the M. abscessus isolates, one of which resulted in an unfavorable treatment outcome. It is important to consider M. abscessus lung infection as well as other NTM in patients receiving allo-SCT, particularly those receiving macrolide therapy for BOS.

[Disseminated Cryptococcosis with Eosinophilia and Elevated IgE in a Non-HIV-infected Patient].

In general, disseminated cryptococcosis usually occurs among immunocompromised patients, especially those with cell-mediated immunodeficiency, such as HIV-infected patients. We present herein a rare case of an apparently immunocompetent 33-year-old woman who developed disseminated cryptococcal diseases, which included meningitis and pneumonia with eosinophilia, and pulmonary tuberculosis during her disease course. Pneumonia with a diffuse micronodular pattern, immediately followed by meningitis, was diagnosed as disseminated cryptococcosis, because of the presence of yeast-like-fungi demonstrated by transbronchial lung biopsy and a positive cerebrospinal fluid (CSF) culture. In addition, the pneumonia exhibited eosinophilia in the peripheral blood and bronchoalveolar lavage fluid. Re-exacerbation of the pneumonia occurred approximately 3 weeks after onset, along with a sputum culture positive for Mycobacterium tuberculosis. Administration of anti-tuberculosis drugs resulted in recovery from the pulmonary tuberculosis. The treatment of cryptococcal meningitis was initiated using a standard induction regimen;however, an unrecovered status, highlighted by elevated CSF pressure, persisted. Finally, full recovery was induced by the addition of flucytosine treatment (100 mg/kg/day) and repeated daily via lumbar puncture. The allergic condition of this patient may have contributed to the onset of disseminated cryptococcosis.

Influence of the bacterial phenotypes on the clinical manifestations in Klebsiella pneumoniae bacteremia patients: A retrospective cohort study.

Ninety-four episodes of Klebsiella pneumoniae bloodstream infection were identified at a university hospital in Japan. After excluding extended-spectrum beta lactamase-producing strains, 83 blood isolates from these patients were assayed in terms of their bacterial phenotypes such as the mucoid and hypermucoviscosity phenotypes. Bacterial phenotypes were correlated with the patients' clinical manifestations. The hypermucoviscosity phenotype was significantly associated with septic shock at the onset of infections (odds ratio, 15.92; 95% confidence interval, 1.27-468.12), but was not associated with liver abscess formation. Mortality was determined by the presence of septic shock. RmpA gene was associated with the induction of the hypermucoviscosity phenotype. These results reveal unique roles of bacterial phenotypes on the patient's clinical condition in K. pneumoniae bacteremia.