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Background and Objective: The identification of factors associated with long-term prognosis after community-onset pneumonia in elderly patients should be considered when initiating advance care planning (ACP). We aimed to identify these factors and develop a prediction score model., Methods: Patients aged 65 years and older, who were hospitalized for pneumonia at nine collaborating institutions, were included. The prognosis of patients 180 days after the completion of antimicrobial treatment for pneumonia was prospectively collected., Results: The total number of analysable cases was 399, excluding 7 outliers and 42 cases with missing data or unknown prognosis. These cases were randomly divided in an 8:2 ratio for score development and testing. The median age was 82 years, and there were 68 (17%) deaths. A multivariate analysis showed that significant factors were performance status (PS) ≥2 (Odds ratio [OR], 11.78), hypoalbuminemia ≤2.5 g/dL (OR, 5.28) and dementia (OR, 3.15), while age and detection of antimicrobial-resistant bacteria were not associated with prognosis. A scoring model was then developed with PS ≥2, Alb ≤2.5, and dementia providing scores of 2, 1 and 1 each, respectively, for a total of 4. The area under the curve was 0.8504, and the sensitivity and specificity were 94.6% and 61.7% at the cutoff of 2, respectively. In the test cases, the sensitivity and specificity were 91.7% and 63.1%, respectively, at a cutoff value of 2., Conclusion: Patients meeting this score should be considered near the end of life, and the initiation of ACP practices should be considered., (© 2024 Asian Pacific Society of Respirology.)

Background: Aspiration pneumonia is an important condition in elderly patients and detecting dysphagia early can help clinicians identify patients with a high risk of aspiration pneumonia. We previously reported the usefulness of the Assessment of Swallowing Ability for Pneumonia (ASAP) in predicting the occurrence of and mortality from pneumonia in patients in acute care hospitals; however, there are very few reports on the utility of this screening test for patients in stable condition., Methods: Elderly patients in stable condition (n = 133) without pneumonia were prospectively enrolled. Associations between ASAP, Functional Independence Measure (FIM), Controlling Nutrition Status (CONUT), and Charlson Co-morbidity Index (CCI) scores and occurrence of/mortality from pneumonia during hospitalization were evaluated., Results: The occurrence of pneumonia was observed in 27 (20.3%) patients, and 18 (13.5%) died during hospitalization. Multivariate analysis showed that low ASAP score and low FIM motor were independent predictors for the occurrence of pneumonia, and low ASAP score was an independent predictor for mortality from pneumonia. Areas under the curve for ASAP, FIM motor, FIM cognition, and CONUT scores were 0.895 (95% confidence interval [CI], 0.829-0.960), 0.913 (95% CI, 0.860-0.968), 0.841 (95% CI, 0.761-0.921), and 0.753 (95% CI, 0.649-0.858), respectively, for occurrence, and 0.881 (95% CI, 0.807-0.955), 0.904 (95% CI, 0.860-0.949), 0.829 (95% CI, 0.727-0.931), 0.746 (95% CI, 0.617-0.874), respectively, for mortality., Conclusion: The ASAP and FIM motor are useful for predicting the occurrence of and mortality from pneumonia in elderly inpatients in long-term care hospitals., Competing Interests: Conflict of Interest The authors have no conflicts of interest., (Copyright © 2023 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

The potential antimicrobial and anti-inflammatory effectiveness of azithromycin against severe influenza is yet unclear. We retrospectively investigated the effect of intravenous azithromycin administration within 7 days of hospitalization in patients with influenza virus pneumonia and respiratory failure. Using Japan's national administrative database, we enrolled and classified 5066 patients with influenza virus pneumonia into severe, moderate, and mild groups based on their respiratory status within 7 days of hospitalization. The primary endpoints were total, 30-day, and 90-day mortality rates. The secondary endpoints were the duration of intensive-care unit management, invasive mechanical ventilation, and hospital stay. The inverse probability of the treatment weighting method with estimated propensity scores was used to minimize data collection bias. Use of intravenous azithromycin was proportional to the severity of respiratory failure (mild: 1.0%, moderate: 3.1%, severe: 14.8%). In the severe group, the 30-day mortality rate was significantly lower with azithromycin (26.49% vs. 36.65%, p = 0.038). In the moderate group, the mean duration of invasive mechanical ventilation after day 8 was shorter with azithromycin; there were no significant differences in other endpoints between the severe and moderate groups. These results suggest that intravenous azithromycin has favorable effects in patients with influenza virus pneumonia using mechanical ventilation or oxygen.

Background: Lascufloxacin hydrochloride (LSFX) is a quinolone antibiotic that inhibits DNA gyrase and topoisomerase IV of bacteria, it is anticipated to minimize antibiotic resistance in bacteria. It exhibits antibacterial activity against a relatively wide range of bacterial species, including anaerobic bacteria, and its efficacy and safety against community-acquired pneumonia have been shown; however, its efficacy and safety against nursing and healthcare associated pneumonia (NHCAP) have not been verified., Methods/design: Here, a single-arm, open-label, uncontrolled study was conducted in which LSFX was administered to patients with NHCAP at 24 facilities. The research subjects (77 cases) were orally administered 75 mg of LSFX once a day for 7 days. The primary endpoint was the clinical efficacy at the time of test of cure (TOC) (TOC; 5-10 days after the end of LSFX administration), while the secondary endpoints were the efficacy at the time of end of treatment, early clinical efficacy, microbiological efficacy at the time of TOC and end of treatment, and safety evaluation of LSFX., Discussion: NHCAP is a common pneumonia in clinical settings and a notable pneumonia whose mortality is high compared to community-acquired pneumonia. The present study showed the efficacy and safety of LSFX against NHCAP, which could lead to a larger number of therapeutic options for NHCAP., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Introduction: The culture method is the gold standard for identifying pathogenic bacteria in patients with pneumonia but often does not reflect the exact bacterial flora in pulmonary lesions of pneumonia, partly owing to easiness or difficulties in culturing certain bacterial species. We aimed to evaluate bacterial flora in bronchoalveolar lavage fluid (BALF) samples directly obtained from pneumonia lesions using 16S ribosomal RNA (rRNA) gene analysis to compare the results of the BALF culture method in each category of pneumonia., Methods: Bacterial florae were detected by a combination of the culture method, and the clone library method using the 16S rRNA gene sequencing in BALF directly obtained from pneumonia lesions in pneumonia patients from April 2010 to March 2020 at the University of Occupational and Environmental Health, Japan, and affiliated hospitals. Clinical information of these patients was also collected, and lung microbiome was evaluated for each pneumonia category., Results: Among 294 pneumonia patients (120 with community-acquired pneumonia (CAP), 101 with healthcare-associated pneumonia (HCAP), and 73 with hospital-acquired pneumonia (HAP)), significantly higher percentages of obligate anaerobes were detected in CAP than in HCAP and HAP patients by the clone library method. Corynebacterium species were significantly highly detected in HAP patients and patients with cerebrovascular diseases than in patients without, and Streptococcus pneumoniae was frequently detected in patients with diabetes mellitus., Conclusion: Obligate anaerobes may be underestimated in patients with CAP. Corynebacterium species should be regarded as the causative bacteria for pneumonia in patients with HAP and cerebrovascular diseases., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Introduction: Nursing and healthcare-associated pneumonia (NHCAP) was proposed by the Japanese Respiratory Society in 2011. However, the clinical characteristics of NHCAP are still unclear. Thus, this study aimed to clarify its clinical characteristics., Methods: This multicenter prospective observational study included 596 patients with NHCAP from 73 centers in Japan between May 2014 and February 2016., Results: Patient background was characterized by an older age (81.5 ± 10.1 years), most patients had complications (94.1%), and many patients had a high probability of aspiration pneumonia (68.6%). Among the isolates, Streptococcus pneumoniae was the most common (12.7%), while Pseudomonas aeruginosa was also isolated at 10.8%. The overall 30-day mortality rate for patients was 11.9%, and the factors affecting mortality were non-ambulatory status, high blood urea nitrogen level, impaired consciousness, and low albumin level. Sulbactam/ampicillin was the most commonly administered antibiotic, including in groups with high severity of illness and high risk of multidrug-resistant (MDR) pathogens. Both the A-DROP and I-ROAD scores were useful in predicting the prognosis of NHCAP. Confirmation of intention to provide do not attempt resuscitation (DNAR) instructions was given to 333 patients (55.9%), and 313 patients agreed to DNAR instructions., Conclusions: NHCAP tends to occur in elderly patients with underlying diseases. The risk of MDR pathogens and the mortality rate are intermediate for community-acquired pneumonia and hospital-acquired pneumonia. As NHCAP is considered an important concept in an aging society, such as in Japan, establishing a treatment strategy that considers not only prognosis but also quality of life would be beneficial., (Copyright © 2022 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: This study investigated the diagnostic utility of the BioFire FilmArray Pneumonia Panel (PN panel), an automated and multiplexed nucleic acid detection system that rapidly detects 26 pathogens (18 bacteria and eight viruses) and seven antimicrobial resistance markers in a single assay., Methods: We analyzed the targets in lower respiratory tract specimens using the PN panel and compared the detection results with those of bacterial culture methods and antimicrobial susceptibility testing., Results: Of the 57 samples analyzed, the PN panel detected 97 targets (84 bacteria, four viruses, and nine antimicrobial resistance markers). Detection of bacteria and antimicrobial resistance was three times greater than that of the bacterial culture (25 bacteria and two resistant isolates) against the targets available in the panel. The overall positive and negative percent agreements between the PN panel and culture methods for bacterial detection were 100.0% and 92.9%, respectively. Multiple pathogens were detected by the PN panel in 24 samples (42.1%), ranging from two pathogens in 11 samples (19.3%) to six pathogens in one sample (1.8%). The PN panel semiquantitatively detected higher copies (≥ 10 6  copies/mL) of bacterial targets if the bacteria were positive by the culture method. In contrast, the semiquantitative values obtained by the panel varied (10 4 to 10 7  ≤ copies/mL) among bacteria that were negative by the culture method., Conclusions: The PN panel enhanced the detection of pathogens and antimicrobial resistance markers in lower respiratory tract specimens., (© 2022. The Author(s).)

Introduction: Systemic corticosteroid therapy is occasionally used as an additive therapy, especially for patients with severe pneumonia. However, its recommendation for use in patients with pneumonia varies worldwide, and its efficacy is unclear., Methods: Adult Japanese patients hospitalized with community-onset pneumonia between January and December 2012 were analyzed using the Diagnostic Procedure Combination database. The patients were classified into mild-to-moderate and severe groups using the A-DROP (age, dehydration, respiration, orientation, and blood pressure) system. The 90-day survival rate was evaluated between the presence or absence of corticosteroid treatment using the Kaplan-Meier method in the overall, mild-to-moderate and severe groups, respectively. The patients' clinical characteristics were adjusted between the two groups using the inverse probability of treatment weighting method., Results: Among 123,811, 110,534 patients were classified as mild-to-moderate grade (corticosteroid group: 8,465, non-corticosteroid group: 102,069) and 13,277 patients were classified as severe grade (corticosteroid group: 1,338, non-corticosteroid group: 11,939). The 90-day survival rate was higher in the non-corticosteroid group than in the corticosteroid group in patients with pneumonia of overall grade (weighted hazard ratio [HR]: 1.36; P < 0.001) and those with mild-to-moderate grade (weighted HR: 1.46; P < 0.001). However, there were no significant differences in the outcomes between the two groups in those with severe grade (weighted HR: 1.08; P = 0.38)., Conclusions: Additive systemic corticosteroid therapy may be related to poor 90-day prognosis in patients with mild-to-moderate grade community-onset pneumonia, although it may not be positively associated with its prognosis in those with severe grade., (Copyright © 2021 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Background: Although muscle mass loss and pneumonia are common and crucial issues in hemodialysis (HD) patients, few reports have focused on their association, which remains unclear. This study assessed the association between skeletal muscle mass and the incidence of pneumonia in HD patients using the psoas muscle index (PMI)., Methods: This retrospective study included 330 patients on HD who were treated at a single center between July 2011 and June 2012. The observation period was between July 2011 and June 2021. Demographic, clinical, and HD data were collected, and the associations between PMI and hospitalization due to bacterial pneumonia were evaluated using Cox proportional hazards models adjusted for patients' background data. Additionally, the correlation between patient characteristics and PMI was evaluated using multivariable linear regression., Results: Among 330 patients (mean age, 67.3 ± 13.3; 56.7% male; median dialysis vintage 58 months, (interquartile range [IQR] 23-124), 79 were hospitalized for pneumonia during the observation period (median observation period was 4.5 years [IQR 2.0-9.1]). The multivariable Cox proportional analysis, which was adjusted for age, sex, dialysis vintage, diabetes mellitus, and stroke history and considered death as a competing risk, indicated that decreased PMI/(standard deviation) was closely associated with the development of pneumonia (hazard ratio: 0.67, 95% confidence interval: 0.47-0.95, p = 0.03)., Conclusions: Skeletal muscle mass was associated with the development of pneumonia in patients on HD and could be a useful marker for the risk of pneumonia., (© 2021. The Author(s).)

Background: Assessment of swallowing functions in elderly people with pneumonia is important. Videofluoroscopic and videoendoscopic examinations have been known as reliable assessments of swallowing functions. However, it is often difficult to use these tools in patients with pneumonia due to their poor condition and/or inadequate hospital facilities. We have previously constructed the Assessment of Swallowing Ability for Pneumonia (ASAP) as a straightforward evaluation for swallowing function. This study investigates the efficacy of the ASAP in predicting several outcomes in elderly patients with pneumonia., Methods: Elderly patients with pneumonia (n = 130) who were admitted to Tobata Kyoritsu Hospital from January to June 2016 were enrolled prospectively. Associations between their ASAP scores and in-hospital mortality, recurrence of pneumonia within 30 days, 6-month mortality, and detection of antibiotic-resistant bacteria were evaluated., Results: Lower ASAP scores were associated with higher rates of in-hospital mortality, recurrence of pneumonia, and 6-month mortality. The areas under the curve were 0.84 (95% confidence interval [CI], 0.72-0.96) for in-hospital mortality, 0.76 (95% CI, 0.67-0.85) for recurrence of pneumonia, 0.74 (95% CI, 0.64-0.84) for 6-month mortality, and 0.67 (95% CI, 0.52-0.82) for detection of antibiotic-resistant bacteria. Multivariate analysis showed that a lower ASAP score was an independent risk factor for in-hospital mortality, recurrence of pneumonia, and 6-month mortality., Conclusions: The ASAP was useful for predicting short- and long-term mortalities and recurrence of pneumonia., Competing Interests: Conflict of Interest The authors state that they have no conflict of interest., (Copyright © 2021 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Purpose: Pneumonia is a major cause of respiratory-related hospitalization and an important prognostic factor in patients with chronic interstitial lung disease (ILD). However, the relationship between the incidence of pneumonia and human leukocyte antigen (HLA) serotype has not been fully elucidated. Therefore, this study aimed to determine if there is a relationship between HLA serotype and the incidence of pneumonia in Japanese patients with ILD., Methods: The medical records of patients with ILD treated at any of three centers in Japan were reviewed to determine their HLA-A and HLA-B serotypes. The characteristics of patients with and without pneumonia were compared. Cox regression analysis was performed to identify risk factors for pneumonia and death in these patients., Results: One hundred and forty-four patients with ILD (pneumonia group, n = 27; non-pneumonia group, n = 117) and complete HLA serology data available were included. HLA-B54 positivity was significantly more common in the pneumonia group than in the non-pneumonia group (37.0% vs. 15.4%, p = 0.010). HLA-B54 positivity was also a significant risk factor for pneumonia (hazard ratio [HR] 4.166, 95% confidence interval [CI] 1.862-9.320, p = 0.001) and death (HR 4.050, 95% CI 1.581-10.374, p = 0.004) in patients with ILD. Furthermore, HLA-B54 positivity was a significant risk factor for pneumonia (HR 3.964, 95% CI 1.392-11.090, p = 0.010) and death (HR 8.131, 95% CI 1.763-37.494, p = 0.007) in patients with idiopathic pulmonary fibrosis., Conclusion: HLA-B54 positivity was a significant risk factor for pneumonia and death in patients with ILD, including those with idiopathic pulmonary fibrosis., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: Before advance care planning, it is essential to understand the differences in preferences for medical care of terminal-phase pneumonia in elderly patients among the patients, their families, and their doctors. This study aimed to clarify these differences and investigate the actual care provided to elderly patients with pneumonia in nursing hospitals., Methods: Multicenter questionnaire surveys of 179 patients admitted to nursing homes and long-term care beds in hospitals of three healthcare corporations, their families, and their physicians were conducted between January and August 2018. The questionnaires mainly assessed preferences for life-prolonging medical care procedures, including antibiotic treatments, in terminal-phase pneumonia. A follow-up survey regarding the prognosis and the actual care provided by the physicians was conducted 1 year after the first survey., Results: Only 16.2% of the patients had sufficient prior discussions with their families about their care. More families preferred cardiac massage, intubation, and tracheostomy, while fewer families preferred peripheral intravenous fluids or antibiotics than physicians. A total of 30 patients' families (16.7%) answered to withhold antibiotic treatment, while all physicians supported antibiotic administration. The only significant factor related to withholding antibiotics was high age (P = 0.0057). The follow-up survey administered to the doctors revealed that 49 patients (35.7%) had died within one year. Of the 137 patients, 54 patients (39.4%) had developed pneumonia during this observation period and all were treated with antibiotics., Conclusions: This study revealed large discrepancies between patients/families and physicians regarding preferences for care. Medical staff should make efforts to fill the gap by ensuring advance care planning., Competing Interests: Conflict of interest The authors declare no conflict of interest., (Copyright © 2020 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Background: Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that commonly has a lethal course caused by the tick-borne Huaiyangshan banyang virus [former SFTS virus (SFTSV)]. The viral load in various body fluids in SFTS patients and the best infection control measure for SFTS patients have not been fully established., Case Presentation: A 79-year-old man was bitten by a tick while working in the bamboo grove in Nagasaki Prefecture in the southwest part of Japan. Due to the occurrence of impaired consciousness, he was referred to Nagasaki University Hospital for treatment. The serum sample tested positive for SFTSV-RNA in the genome amplification assay, and he was diagnosed with SFTS. Furthermore, SFTSV-RNA was detected from the tick that had bitten the patient. He was treated with multimodal therapy, including platelet transfusion, antimicrobials, antifungals, steroids, and continuous hemodiafiltration. His respiration was assisted with mechanical ventilation. On day 5, taking the day on which he was hospitalized as day 0, serum SFTSV-RNA levels reached a peak and then decreased. However, the cerebrospinal fluid collected on day 13 was positive for SFTSV-RNA. In addition, although serum SFTSV-RNA levels decreased below the detectable level on day 16, he was diagnosed with pneumonia with computed tomography. SFTSV-RNA was detected in the bronchoalveolar lavage fluid on day 21. By day 31, he recovered consciousness completely. The pneumonia improved by day 51, but SFTSV-RNA in the sputum remained positive for approximately 4 months after disease onset. Strict countermeasures against droplet/contact infection were continuously conducted., Conclusions: Even when SFTSV genome levels become undetectable in the serum of SFTS patients in the convalescent phase, the virus genome remains in body fluids and tissues. It may be possible that body fluids such as respiratory excretions become a source of infection to others; thus, careful infection control management is needed.

Background: Oral cavity is a reservoir of various respiratory pathogens, and poor oral hygiene is associated with an increase in anaerobic bacteria in oral cavity. In addition, it positively relates higher risk of developing pneumonia and increased pneumonia-related mortality. However, the association between poor oral hygiene and increase in obligate anaerobes in the lungs of pneumonia patients is unclear., Methods: A total of 39 patients with pneumonia in whom bronchoscopic examination and oral hygiene evaluation were performed were prospectively enrolled. The microbiota of the bronchoalveolar lavage fluid (BALF) directly obtained from the pneumonia lesion was analysed by the clone library analysis. In addition, oral hygiene evaluations were performed using oral hygiene index (OHI), tongue coating score, oral dryness, and community periodontal index of treatment needs (CPITN). The association between the detection of oral streptococci and obligate anaerobes and oral hygiene status was evaluated., Results: Using the clone library analysis of BALF, the phylotypes of oral streptococci and obligate anaerobes were detected in 31 (79.5%) and 26 (66.7%) patients, respectively. Increased oral dryness, OHI, and CPITN, but not the tongue coating score, significantly correlated with higher rate of detection of obligate anaerobes, although no significant associations between the detection of oral streptococci in the lungs and each oral hygiene evaluation were observed. Significantly higher number of obligate anaerobes were detected in the lungs in patients with total oral hygiene score of ≥ 5 (P = 0.008)., Conclusion: Poor oral hygiene is associated with increased obligate anaerobes in the lungs of patients with pneumonia., (© 2019 American Academy of Periodontology.)

Oral treatment for elderly outpatients with pneumonia is becoming increasingly important in this super-aged society from the perspective of cost-effectiveness and limited hospital capacities. We evaluated the efficacy and safety of two oral respiratory quinolones, sitafloxacin and garenoxacin, in elderly patients with pneumonia. This randomized, multicenter, open-label trial was conducted among patients aged ≥65 years with clinically and radiographically confirmed pneumonia in Japan. Patients were randomly assigned (1:1) to receive either sitafloxacin (100 mg/day) or garenoxacin (400 mg/day) for 3-10 days. The primary efficacy endpoint was the clinical cure rate at 5-10 days after the end of treatment. From December 2013 to November 2017, we enrolled 120 patients at 11 hospitals and randomly assigned 59 patients to the sitafloxacin group (1 patient withdrew) and 61 patients to the garenoxacin group. These included 30 patients with nursing and healthcare-associated pneumonia (NHCAP) (18 receiving sitafloxacin, 12 receiving garenoxacin) and 37 patients with aspiration pneumonia (16 receiving sitafloxacin, 21 receiving garenoxacin). The clinical cure rates in the sitafloxacin and garenoxacin groups were 88.5% (95% confidence interval: 76.6-95.6) and 88.9% (95% confidence interval: 77.4-95.8), respectively. No significant differences were observed in the incidence rates of drug-related adverse events between the sitafloxacin (20.7%; 12/58 patients) and garenoxacin (27.9%; 17/61 patients) groups. The most common adverse event was hepatic dysfunction, which occurred in seven patients in each group. We conclude that sitafloxacin and garenoxacin are comparably effective and safe for the treatment of pneumonia, including NHCAP and aspiration pneumonia, in elderly patients., (Copyright © 2019 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Aim: Pneumonia in older adults is increasingly recognized as a healthcare issue in countries with an aging population. Long-term macrolide therapy reduces exacerbations of chronic respiratory diseases, but its effects on the prevention of pneumonia have not been determined., Methods: We carried out a randomized, controlled trial to test the effect of long-term clarithromycin therapy on the prevention of pneumonia among older adults. People aged ≥65 years who had recovered from pneumonia within the previous 3 months were recruited and randomly allocated to a long-term, low-dose clarithromycin (CAM) therapy group (n = 13) or a control group (n = 15)., Results: Both groups were followed up until recurrence of pneumonia. The median follow-up period was 251 days (95% CI 171-330) in the CAM group and 132 days (95% CI 67-196) in the control group (P = 0.627). The recurrence rate of pneumonia was two out of 13 (15%) in the CAM group and five out of 15 (33%) in the control group (P = 0.268). The median time to recurrence of pneumonia was 315 days (95% CI 249-382) in the CAM group and 260 days (95% CI 184-335) in the control group (P = 0.260). None of the differences between groups were statistically significant., Conclusions: No statistically significant suppressive effects of long-term, low-dose macrolide therapy on the development of pneumonia among older people were found in this small sample. A large-scale, randomized, controlled study is required. Geriatr Gerontol Int 2019; 19: 1006-1009., (© 2019 Japan Geriatrics Society.)

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by systemic joint inflammation and may manifest as interstitial pneumonia (IP). Methotrexate (MTX) is one of the main therapeutic drugs used for RA, but MTX could cause severe side effects, including Pneumocystis jirovecii pneumonia (PCP) and IP. Owing to similar symptoms, it is sometimes difficult to discriminate MTX therapy-associated PCP (MTX-PCP) and MTX therapy-associated IP (MTX-IP). Soluble interleukin-2 receptor (sIL-2R) is considered a marker of T-cell activation, and serum sIL-2R levels are elevated in RA and PCP. This led us to hypothesize that serum sIL-2R is a potential biomarker for discriminating MTX-PCP and MTX-IP. Accordingly, we carried out a retrospective analysis of 20 MITX-PCP cases, 30 MTX-IP cases, and as controls, 16 patients with RA-associated IP (RA-IP) and 13 patients with PCP without MTX treatment (PCP group). C-reactive protein and alveolar-arterial oxygen differences were higher in the MTX-PCP group than those in the RA-IP and MTX-IP groups. Importantly, serum levels of sIL-2R in MTX-PCP were significantly higher than those in other three groups. Based on the receiver operating characteristic curve, the cut-off level of sIL-2R resulting in the highest diagnostic accuracy for MTX-PCP was 1,311.5 U/mL, discriminating between MTX-PCP and other groups with 91.7% sensitivity and 78.6% specificity. Thus, patients with MTX-PCP show a higher degree of systemic inflammation, severe hypoxemia, and increased sIL-2R levels compared with those in MTX-IP cases. In conclusion, serum sIL-2R could be a biomarker for PCP diagnosis among patients with RA under MTX therapy.

Introduction: The clinical significance of the number of aspiration risk factors in patients with pneumonia is unknown as yet. In the present study, we clarify the significance of the number of aspiration risk factors for mortality and recurrence in pneumonia patients., Methods: This study included 322 patients hospitalized with pneumonia between December 2014 and June 2016. We investigated associations between the number of aspiration risk factors present (orientation disturbance, bedridden, chronic cerebrovascular disease, dementia, sleeping medications and gastroesophageal disease) and 30-day and 6-month mortality, and pneumonia recurrence within 30 days., Results: Patients were categorized by number of risk factors present into groups of 0-1, 2, 3, and 4 or more. Of a total of 322 patients, 93 (28.9%) had 0-1 risk factors, 112 (34.8%) had 2, 88 (27.3%) had 3, and 29 (9.0%) had 4 or more risk factors. The percentages of patients with recurrence of pneumonia were 13.0%, 33.0%, 43.2%, and 54.2% in the 0-1, 2, 3, and 4 or more risk factor groups, respectively. The percentages of patients with 30-day mortality were 2.2%, 5.4%, 11.4%, and 24.1%, and those of patients with 6-month mortality were 6.6%, 24.5%, 30.7%, and 50.0%, in the 0-1, 2, 3, and 4 or more risk factor groups, respectively., Conclusions: The number of aspiration risk factors was associated with increases in both mortality and recurrence in pneumonia patients. Therefore, in clinical practice, physicians should consider not only the presence of aspiration risks but also the number of aspiration risk factors in these patients., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

OP0595 (RG6080) is a novel diazabicyclooctane that inhibits class A and C serine beta-lactamases. Although the combination of OP0595 and cefepime (FEP) showed good in vitro activity against extended-spectrum-beta-lactamase (ESBL)-producing pathogens, the effect of the combination therapy against severe infections, such as pneumonia or bacteremia, remains unknown in vivo In this study, we investigated the efficacy and pharmacokinetics of the combination therapy of OP0595 and FEP in a mouse model of pneumonia caused by Klebsiella pneumoniae harboring SHV- and CTX-M-9-type ESBLs. The infected BALB/c mice were intraperitoneally administered saline (control), 100 mg/kg of body weight of FEP, 20 mg/kg of OP0595, or both FEP and OP0595, twice a day. The MIC of FEP against the bacteria was 8 mg/liter and markedly improved to 0.06 mg/liter with the addition of 0.5 mg/ml of OP0595. In the survival study, the combination of FEP and OP0595 significantly improved the survival rate compared with that reported with either OP0595 or FEP alone ( P < 0.001). The number of bacteria in the lungs and blood significantly decreased in the combination therapy group compared to that reported for the monotherapy groups ( P < 0.001). In addition, the in vivo effect depended on the dose of FEP. However, pharmacokinetic analysis revealed that the percentage of time above MIC remained constant when increasing the dose of FEP in combination with 20 mg/kg of OP0595. The results of our study demonstrated the in vivo effectiveness of the combination of OP0595 and FEP., (Copyright © 2017 American Society for Microbiology.)

Obtaining precise etiological information regarding causative bacteria is important for the proper use of antimicrobials in hospital-acquired pneumonia (HAP), which is associated with a high rate of mortality. The aim of this study was to comparatively investigate the bacterial diversity in bronchoalveolar lavage fluid (BALF) in Japanese patients with HAP by the clone library method using the 16S rRNA gene. This study included Japanese patients with HAP who were treated at our hospital and referring hospitals. BALF specimens were obtained from pneumonia lesions identified on chest radiographs and/or computed tomography. Sputum specimens were also evaluated in patients with sputum production. Sixty-eight patients were ultimately enrolled. BALF cultivation revealed bacterial positivity in 53 of 68 (77.9%) patients, and Staphylococcus aureus (30.9%) was the most frequently isolated, followed by Pseudomonas aeruginosa (16.2%), and Escherichia coli (10.3%). In contrast, the clone library analysis identified the presence of some bacterial phenotype in 65 of 68 (95.6%) patients, and streptococci (16.2%), Corynebacterium species (11.8%), anaerobes (10.3%) were frequently detected as the predominant phylotypes. Both methods tended to detect S. aureus, Klebsiella pneumoniae, and E. coli in patients with late-onset pneumonia. In addition, the cases that phylotypes of S. aureus and P. aeruginosa were found to account for > 5% of the bacterial flora of each case were 42.9% and 72.7%, respectively. These results indicate that attention should be paid to the roles of gram-positive bacilli such as streptococci, Corynebacterium species and anaerobes, in addition to Gram-negative bacilli, in the pathogenesis of HAP.

Background: In contrast to community-acquired pneumonia (CAP), no specific severity assessment tools have been developed for healthcare-associated pneumonia (HCAP) in clinical practice., Objectives: In this review, we assessed the clinical significance of severity assessment tools for HCAP., Methods: We identified related articles from the PubMed database. The eligibility criteria were original research articles evaluating severity scoring tools and reporting the outcomes of mortality in patients with HCAP., Results: Eight articles were included in the meta-analysis. The PORT score and CURB-65 were evaluated in 7 and 8 studies, respectively. Using cutoff values of ≥IV and V for the PORT score, the diagnostic odds ratios (DORs) were 5.28 (2.49-11.17) and 3.76 (2.88-4.92), respectively, and the areas under the curve (AUCs) were 0.68 (0.64-0.72) and 0.71 (0.67-0.75), respectively. Conversely, the AUCs for ≥IV and V were 0.71 (0.67-0.76) and 0.74 (0.70-0.78), respectively, when applied only to nonimmunocompromised patients. In contrast, when using cutoff values of ≥2 and ≥3 for CURB-65, the DORs were 3.35 (2.26-4.97) and 2.65 (2.05-3.43), respectively, and the AUCs were 0.65 (0.61-0.69) and 0.66 (0.62-0.70), respectively. Conversely, the AUCs for ≥2 and ≥3 were 0.65 (0.61-0.69) and 0.68 (0.64-0.72), respectively, when applied only to nonimmunocompromised patients., Conclusions: The PORT score and CURB-65 do not have substantial power compared with the tools for CAP patients, although the PORT score is more useful than CURB-65 for predicting mortality in HCAP patients. According to our results, however, these tools, especially the PORT score, can be more useful when limited to nonimmunocompromised patients., (© 2017 S. Karger AG, Basel.)

Background: Determining whether methicillin-resistant Staphylococcus aureus (MRSA) is a true causative pathogen or reflective of colonization when MRSA is cultured from the respiratory tract remains important in treating patients with pneumonia., Methods: We evaluated the bacterial microbiota in bronchoalveolar lavage fluid (BALF) using the clone library method with a 16S ribosomal RNA (rRNA) gene analysis in 42 patients from a pneumonia registry who had MRSA cultured from their sputum or BALF samples. Patients were divided into two groups: those treated with (Group A) or without (Group B) anti-MRSA agents, and their clinical features were compared., Results: Among 248 patients with pneumonia, 42 patients who had MRSA cultured from the respiratory tract were analyzed (Group A: 13 patients, Group B: 29 patients). No clones of S. aureus were detected in the BALF of 20 out of 42 patients. Twenty-eight of 29 patients in Group B showed favorable clinical outcomes, indicating that these patients had non-MRSA pneumonia. Using a microflora analysis of the BALF, the S. aureus phylotype was predominant in 5 of 28 (17.9%) patients among the detected bacterial phylotypes, but a minor population (the percentage of clones ≤ 10%) in 19 (67.9%) of 28 patients. A statistical analysis revealed no positive relationship between the percentage of clones of the S. aureus phylotype and risk factors of MRSA pneumonia., Conclusions: The molecular method using BALF specimens suggests that conventional cultivation method results may mislead true causative pathogens, especially in patients with MRSA pneumonia. Further studies are necessary to elucidate these clinically important issues.

The balance of "Host-Pathogen-Antimicrobials" is crucial for the establishment of infectious diseases. Recently the ineffective cases, even though the appropriate antibiotics use, have been increasing since the several ineludible problems are rising, such as varied patient's background and the epidemic of the drug resistant pathogens, etc. Despite of the medical progression and the development of novel antimicrobials, the mortality of pneumonia has increased gradually and been the third cause of death in Japan. The conventional treatment depended on only bactericidal effect of antimicrobials faces a limit and the alternative strategies are required to overcome the current situation. This review addresses the potency of non-antibiotic antimicrobial agents as an alternative therapeutic strategy, especially focused on the activation of the innate host immunity induced by the macrolides and toll-like receptor agonist.

Background: No mortality prediction rule is suited for non-elderly patients with community-acquired pneumonia. Therefore, we tried to create a mortality prediction rule that is simple and suitable for non-elderly patients with community-acquired pneumonia., Methods: Because of low mortality at young age, we used information from an administrative database that included A-DROP data. We analysed the rate and risk factors for in-hospital community-acquired pneumonia-associated death among non-elderly patients and created a mortality prediction rule based on those risk factors., Results: We examined 49,370 hospitalisations for patients aged 18-64 years with community-acquired pneumonia. The 30-day fatality rate was 1.5%. Using regression analysis, five risk factors were selected: patient requires help for feeding, the existence of malignancy, confusion, low blood pressure, and age 40-64 years. Each risk factor of our proposed mortality risk scoring system received one point. A total point score for each patient was obtained by summing the points. The negative likelihood ratio for the score 0 group was 0.01, and the positive likelihood ratio for the score ≥4 group was 19.9. The area under the curve of the risk score for non-elderly (0.86, 95% confidence interval: 0.84-0.87) was higher than that of the A-DROP score (0.72, 95% confidence interval: 0.70-0.74) (P < 0.0001)., Conclusions: Our newly proposed mortality risk scoring system may be appropriate for predicting mortality in non-elderly patients with community-acquired pneumonia. It showed a possibility of a better prediction value than the A-DROP and is easy to use in various clinical settings.

Background: Streptococcus pneumoniae is one of the main causative bacteria in patients with pneumonia; however, there are no data regarding serotype changes in adult patients with pneumonia after the introduction of the pneumococcal vaccine (PCV7) for childhood immunization in Japan. We herein evaluated the serotype distribution in adult patients with pneumonia., Methods: This retrospective epidemiological study was performed at the University of Occupational and Environmental Health, Japan from January 2011 to December 2013. The serotypes of pneumococcal isolates obtained from patients with pneumonia were evaluated along with the patients' clinical information., Results: A total of 81 patients with pneumococcal pneumonia (89 episodes) from whom S. pneumoniae was isolated were included. The numbers (percentages) of sample types were as follows: sputum 55 (61.8%), intratracheal tube suction 15 (16.9%), intrabronchial sampling 5 (5.6%) and bronchoalveolar lavage fluid 14 (15.7%). The PCV7 serotypes decreased significantly among the patients with pneumococcal pneumonia from 46.4% in 2011 to 20.0% in 2013 (p < 0.05). Conversely, PCV13 and 23-valent pneumococcal polysaccharide vaccination (PPSV23) serotypes other than PCV7 serotypes mildly increased during this period. In addition, the frequency of serotypes 19F, 23F and 4 (which are covered by PCV7) decreased annually; however, the changes in the frequencies of the other serotypes were not significant., Discussion: This study demonstrated the yearly decrease of PCV7 serotypes in adult pneumococcal pneumonia patients after introducing PCV7 into the childhood immunization schedule in Japan. Continued surveillance of pneumococcal serotype changes is important for the proper use of different pneumococcal vaccines., (Copyright © 2015 Japanese Society of Chemotherapy and The Japanese Association for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.)

Levofloxacin (LVFX) is one of respiratory quinolones with wide spectrum of antimicrobial efficacy for Gram-positive and -negative bacteria and also atypical bacteria, and 500 mg of intravenous LVFX infusion has recently been able to use once daily based on pharmacokinetics-pharmacodynamics in Japan. So far, there had been no reports of the prospective studies evaluating efficacy and safety of LVFX in patients with nursing and healthcare-associated pneumonia (NHCAP). This study was conducted to evaluate prospectively the efficacy and safety of LVFX in patients with NHCAP categories B and C (other antibacterial agents were allowed to use with LVFX) according to Japanese guideline for NHCAP by the Japanese Respiratory Society (JRS). LVFX 500 mg was intravenously administered once daily, and the clinical efficacy and safety were evaluated by clinical symptoms, peripheral blood laboratory findings and chest X-rays. Sixty-two patients (average age was 81.2 years old, female/male was 22/40) were firstly registered and evaluated for the safety of LVFX, and eventually 54 patients were enrolled for the evaluation of clinical efficacy of LVFX. The percentage of these 54 patients aged over 65 years old was 96.3%, NHCAP category B/C was 33/21. The efficacy of LVFX in all 54 patients evaluated was 85.2% (categories B/C of NHCAP was 81.8/90.5%). In addition, the efficacies of LVFX in each pneumonia severity category by A-DROP system by JRS in NHCAP patients were 100% in mild, 86.7% in moderate, 77.8% in severe/very severe. Nine patients (2 with liver dysfunction, 6 with renal dysfunction and 1 with thrombocytopenia) out of 62 patients were reported to have possible adverse effects of LVFX. All of the patients with liver and renal dysfunctions after starting LVFX administration demonstrated mild dysfunctions and continued LVFX treatment, and these dysfunctions normalized soon after cessation of LVFX. LVFX was changed to other antibacterial agent in one patient with thrombocytopenia, and also thrombocytopenia was normalized thereafter. In conclusion, LVFX is effective and relatively safe for categories B and C in patients with NHCAP.

Moxifloxacin (MFLX) is a respiratory quinolone, and is effective against not only Gram-positive and negative bacteria but also anaerobes. There has been no prospective studies evaluating the efficacy and safety of MFLX in patients with nursing and healthcare-associated pneumonia (NHCAP). Therefore, we assessed the efficacy and safety of MFLX in patients with NHCAP. NHCAP patients with mild and moderate severity assessed by the A-DROP system in community-acquired pneumonia guideline proposed by Japan Respiratory Society visited our hospitals from April 2011 to March 2012. Clinical symptoms, chest X-ray films and/or computed tomography, peripheral white and red blood cell and platelet counts, serum CRP, AST, ALT, BUN, creatinine were evaluated. Forty patients were eventually evaluated, and average age was 74.1 years old, male/female were 21/19, 92.5% (37/40) of them had one or more comorbidities. Median duration of MFLX administration was 7.1 days (4-15 days). The efficacy of MFLX in all patients was 87.5% (35/40). The efficacies in each age group were 87.9% (aged over 65 years old), 85.7% (aged under 64 years old), and in each pneumonia severity group by the A-DROP system were 91.7% (mild), 85.7% (moderate). Diarrhea and swelling of the breast were observed in one patient (2.5%) after starting MFLX administration. Mild elevated transaminases were observed in three patients (7.5%), and mild renal dysfunction was observed in two patients (5.0%). All abnormally increased levels of transaminases and serum creatinine were recovered after a cessation of MFLX. MFLX is effective and safe in patients with NHCAP.

Platelet-activating factor (PAF) is a critical mediator of severe inflammatory diseases such as pneumonia, and the PAF-receptor (PAFR) is known to be an anchor for Streptococcus pneumoniae attachment to lung epithelial cells. We conducted a DNA microarray analysis to detect critical factors that mediate fulminant pneumonia due to influenza virus and S. pneumoniae co-infection in mice. Among the factors detected, levels of PAF-acetyl hydrolase (PAF-AH), which functions as inactivated PAF, were significantly increased, and PAFR was expressed in co-infected mouse lungs, as compared to the respective levels in mice infected with either S. pneumoniae or virus alone. Significantly elevated PAF-AH enzymatic activity was observed in the co-infected mouse lung, suggesting that co-infection activated PAF-related factors. These findings suggest that PAF and related molecules play important roles in fulminant pneumonia due to influenza virus infection, especially when severe bacterial pneumonia is complicated by co-infection with influenza virus.

SELAPINA is generic product of PL granule which is one of the most common forms of combination remedies for the common cold in Japan, and includes acetaminophen. We report a case of SELAPINA-induced pneumonia successfully treated with glucocorticoid pulse therapy followed by orally administered prednisolone. A 68-year-old woman, who had been treated for rheumatoid arthiritis with pulmonary involvement, took SELAPINA with an antibiotic for 6 days because of her cold symptoms. She then suffered a high fever, cough, dyspnea, vomiting and diarrhea. Chest radiograph and high-resolution computed tomography (HRCT) scan revealed diffuse interstitial shadows. SELAPINA-induced pneumonia was diagnosed because the blastoid transformation test using her peripheral blood lymphocytes was positive on stimulation with SELAPINA, but negative for other medicines.

Human beta-defensin (hBD)-3, a 45 amino acid antimicrobial peptide, was originally isolated from human skin. hBD-3 mRNA has also been detected in the airways by RT-PCR. While hBD-3 may be involved in antimicrobial defences within the respiratory tract, the presence of hBD-3 peptide in the respiratory system has not yet been confirmed. The antimicrobial activity of the synthesised hBD-3 peptide was measured by a radial diffusion assay and a colony count assay. The present authors confirmed the presence of hBD-3 peptide in homogenates of human lung and serum using reverse-phase HPLC coupled with a highly sensitive RIA. The localisation of the hBD-3 peptide was investigated by immunohistochemistry. In addition, the serum concentrations of hBD-3 were measured by RIA. hBD-3 exhibited a strong antimicrobial activity, which was unaffected by increasing salt concentrations. Immunohistochemically, the current authors observed the expression of hBD-3 in bronchial and bronchiolar epithelial cells. The mean+/-sd serum concentration of hBD-3 in patients with bacterial pneumonia was 239.4+/-17.8 pg x mL(-1) in the acute phase and, decreased to 159.3+/-20.1 pg x mL(-1) after the completion of therapy. In conclusion, these findings will help elucidate the role of human beta-defensin-3 in host immune responses and identify the pathophysiological significance of this molecule in respiratory infections.

Clinical and bacteriological studies were carried out to investigate the isolation of MRSA from sputa and 13 cases with bronchopulmonary infections due to MRSA, during 4 years from 1985 to 1988 at the Hokusyo Central Hospital. The isolation rate of MRSA in Staphylococcus aureus from sputum increased from 0% in 1985 to 51.4% in 1988, and especially from patients in wards for aged people. Most of the MRSA strains were isolated from patients with underlying diseases, or bed sores. The roentgenographic appearances in bronchopulmonary infection patients due to MRSA, showed infiltration and cavitation. Seven out of 13 cases of bronchopulmonary infection due to MRSA died, in spite of therapy with current antibiotics, suggesting poor prognosis of this infection.

AbstractInfiltration of antigen-specific CD4+ T cells and production of interleukin (IL)-5 in inflammatory regions play a central role in antigen-induced pulmonary eosinophilia. Genetically IL-5-deficient mice lack antigen-induced airway eosinophilia, but little is known about the role of IL-5 in accumulation and activation of CD4+ T cells in the lung and in airway hyperresponsiveness (AHR). Ascaris suum extract (Asc) has been used to induce airway eosinophilia and analyze airway inflammation in IL-5 receptor α-chain-deficient (IL-5RKO) mice. We examined the role of IL-5 in CD4+ T cell activation, cytokine production, and AHR upon Asc sensitization. Pulmonary CD4+ T cells in Asc-immunized mice were activated and produced IL-5 upon local exposure to Asc in both wild-type (WT) and IL-5RKO mice. IL-2, IL-4, IL-5, IL-10 and eotaxin were detected in bronchoalveolar lavage fluid of both WT and IL-5RKO mice following exposure to Asc. Airway eosinophilia and AHR were seen only in WT mice, but not in IL-5RKO mice. We conclude that IL-5 appears to be required for the accumulation of eosinophils and AHR in the inflammatory lung. However, IL-5 does not play a critical role in the accumulation of activated CD4+ T cells in the inflammatory lung.Copyright © 2003 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]