Oxygen supplementation is commonly given to the patients with severe pneumonia including Legionella disease. Recent data suggested that apoptosis may play an important role, not only in the ...pathogenesis of Legionella pneumonia, but also in oxygen-induced tissue damage. In the present study, the lethal sensitivity to Legionella pneumonia were compared in the setting of hyperoxia between wild-type and Fas-deficient mice.
C57BL/6 mice and B6.MRL-Faslpr mice characterized with Fas-deficiency were used in this study. After intratracheal administration of L. pneumophila, mice were kept in hyperoxic conditions (85-90% O2 conc.) in an airtight chamber for 3 days. Bone-marrow derived macrophages infected with L. pneumophila were also kept in hyperoxic conditions. Caspase activity and cytokine production were determined by using commercially available kits. Smaller increases of several apoptosis markers, such as caspase-3 and -8, were demonstrated in Fas-deficient mice, even though the bacterial burdens in Fas-deficient and wild type mice were similar. Bone-marrow derived macrophages from Fas-deficient mice were shown to be more resistant to Legionella-induced cytotoxicity than those from wild-type mice under hyperoxia.
These results demonstrated that Fas-mediated signaling and apoptosis may be a crucial factor in the pathogenesis of Legionella pneumonia in the setting of hyperoxia.
Abstract Pseudomonas aeruginosa is an opportunistic pathogen that causes disease in patients with impaired host defenses; it is often a cause of life-threatening nosocomial infection in critically ...ill and immunocompromised patients. An increase in the prevalence of multiple-drug-resistant Pseudomonas aeruginosa (MDRP) in hospitals is thus a worldwide problem. These increases are frequently related to the high selective pressure of antimicrobials commonly used in hospitalized patients, particularly extendedspectrum cephalosporins, β-lactamase-inhibitor combinations, carbapenems, fluoroquinolones, and aminoglycosides. We evaluated the clinical and microbiological characteristics of drug-resistant P. aeruginosa and MDRP strains that were isolated at Niigata University Hospital, Japan, from 2000 to 2004. We experienced an outbreak of MDRP in 2000, but colonization only was the main feature of the outbreak. Also, the isolation rate of MDRP has decreased since 2004; this reduction in the isolation rate seems to be a result of a move to newly built ward sections in 2001 and the establishment of an infection control team (ICT) in 2003.
Pasteurellosis is a common zoonosis caused by bacteria in the genus Pasteurella, which form part of the oral flora of dogs and cats. Pasteurella multocida is the most common pathogen for ...pasteurellosis. Skin and soft tissue infections resulting from animal injuries, such as bites and scratches, are prevalent. Still, severe infections, such as sepsis, can present in elderly patients with comorbidities and immunocompromised individuals. The recent rise in pet ownership has been reported to increase the prevalence of pasteurellosis. In our hospital, a higher incidence of pasteurellosis was reported after 2020 than in the years preceding 2020. Therefore, we conducted a 10-year retrospective study and found that 29 cases of pasteurellosis (with duplicates) were reported. Seventeen cases, forming more than half of the total number of cases, were reported after 2020. Diabetes mellitus, which was detected in 10 cases, was the most common comorbidity. Additionally, autoimmune diseases, such as rheumatoid arthritis and vasculitis syndrome, were reported in eight cases. Only two patients had no comorbidities. Notably, the number of patients with dog bite injuries and respiratory tract infections has increased since 2020. The year 2020 coincides with the start of the novel coronavirus disease 2019 (COVID-19) pandemic, which possibly may have contributed to the increasing incidence of pasteurellosis.
Purpose
We describe the epidemiology of invasive
Haemophilus influenzae
disease (IHD) among adults in Japan.
Methods
Data for 200 adult IHD patients in 2014–2018 were analyzed. The capsular type of
...H. influenzae
was determined by bacterial agglutination and polymerase chain reaction (PCR), and non-typeable
Haemophilus influenzae
(NTHi) was identified by PCR
.
Results
The annual incidence of IHD (cases per 100,000 population) was 0.12 for age 15–64 years and 0.88 for age ≥ 65 years in 2018. The median age was 77 years, and 73.5% were aged ≥ 65 years. About one-fourth of patients were associated with immunocompromising condition. The major presentations were pneumonia, followed by bacteremia, meningitis and other than pneumonia or meningitis (other diseases). The case fatality rate (CFR) was 21.2% for all cases, and was significantly higher in the ≥ 65-year group (26.1%) than in the 15–64-year group (7.5%) (
p
= 0.013). The percentage of cases with pneumonia was significantly higher in the ≥ 65-year group than in the 15–64-year group (
p
< 0.001). The percentage of cases with bacteremia was significantly higher in the 15–64-year group than in the ≥ 65-year group (
p
= 0.027). Of 200 isolates, 190 (95.0%) were NTHi strains, and the other strains were encapsulated strains. 71 (35.5%) were resistant to ampicillin, but all were susceptible to ceftriaxone.
Conclusion
The clinical presentations of adult IHD patients varied widely; about three-fourths of patients were age ≥ 65 years and their CFR was high. Our findings support preventing strategies for IHD among older adults, including the development of NTHi vaccine.
Abstract
Background
Recent studies have reported that immune-checkpoint inhibitors (ICIs) cause various immune-related adverse events (irAEs) and irAEs are associated with antitumor effects of ICIs. ...However, it remains unclear whether the incidence of irAEs was associated with types of PD-1 inhibitors and treatment lines.
Methods
We retrospectively evaluated data of advanced or recurrent NSCLC patients treated in 1st to 3rd line with PD-1 inhibitors at Niigata Lung Cancer Treatment Group between January 2016 and October 2017.
Results
Of 231 patients who received anti-PD-1 therapies, 176 patients received nivolumab and 55 patients received pembrolizumab, and 63 patients (36%) developed irAEs in nivolumab therapy and 30 patients (55%) developed irAEs in pembrolizumab therapy. In the univariate analysis, male (Odd Ratio: OR 2.38, p = 0.01), smoker (OR 3.29, p = 0.002), squamous cell carcinoma (OR 2.99, p = 0.0001), pembrolizumab therapy (OR 2.15, p = 0.01), 1st line anti-PD-1 treatment (OR 2.07, p = 0.04), EGFR gene mutation negative (OR 8.77, p = 0.03) were significant predictors of irAEs. Multivariate analysis identified younger age (<75) (OR 2.46, p = 0.02), squamous cell carcinoma (OR 2.94, p = 0.0006) as independent positive predictors of irAEs. In patients treated with nivolumab, irAEs were associated with better survival (not reached vs. 15.4 months, p < 0.0005); however, in patients treated with pembrolizumab, irAEs were not correlated with overall survival (20 months vs. not reached p = 0.338). MST in patients with steroid treatment was significantly shorter than that in those without steroid treatment (not reached vs. 20.6 months, p < 0.01). The proportion of patients who received systemic steroid therapy for irAEs was not significantly different between nivolumab and pembrolizumab (46.0% vs. 46.6%, p = 0.954).
Conclusion
In the current study, pembrolizumab therapy and 1st line treatment were predictors of irAE onset in univariate analysis, but not in multivariate analysis.
Objectives Multidrug-resistant Pseudomonas aeruginosa (MDRP) is becoming a serious problem in hospitals, especially in patients on ventilators. Recent data demonstrate that colistin may be effective ...for these patients, although limited in vitro and in vivo data are available. Our aim was to identify further characteristics of colistin for the therapy of pneumonia caused by MDRP. Methods The effects of colistin on clinical strains of MDRP were examined by susceptibility test, time–kill assay, lipopolysaccharide (LPS)-blocking assay and a mouse pneumonia model, alone or in combination with other antibiotics. For the pneumonia model, mice were intranasally infected with bacteria and kept in hyperoxic conditions to mimic ventilator-associated pneumonia. Results As a single agent, colistin exhibited the strongest activity of the antimicrobial agents tested. In combination, maximum synergy was observed with colistin plus rifampicin. As expected, co-incubation of bacterial culture supernatants with colistin significantly reduced LPS activities with an associated decrease in cellular cytotoxicity. In the pneumonia model, intranasal, but not intravenous, colistin combined with rifampicin produced maximum survival protection. Pharmacokinetic analysis of colistin demonstrated the superiority of intranasal administration, judging from the compartmentalized high concentration and the long half-life in the lungs. Moreover, colistin therapy significantly decreased both production of inflammatory cytokines and LPS activity, even at a dose effecting no change in the bacterial burden in the lung. Conclusions These data strongly suggest that colistin may be an important option for combination therapy against critical MDRP infections. For pneumonia especially, intranasal colistin with rifampicin may be beneficial not only for synergistic antibacterial activity, but also for blocking LPS.
Type I and II interferons (IFNs) exert opposing effects on the progression of multiple sclerosis, even though both IFNs use the signal transducer and activator of transcription 1 (STAT1) as a ...signaling mediator. Here we report that STAT1-deficient mice expressing a transgenic T cell receptor against myelin basic protein spontaneously develop experimental autoimmune encephalomyelitis with dramatically increased frequency. The heightened susceptibility to this autoimmune disease appears to be triggered by a reduced number as well as a functional impairment of the CD4+ CD25+ regulatory T cells in STAT1-deficient animals. Adoptive transfer of wild-type regulatory T cells into STAT1-deficient hosts is sufficient to prevent the development of autoimmune disease. These results demonstrate an essential role of STAT1 in the maintenance of immunological self-tolerance.
PDF
