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1.
J Clin Microbiol ; 62(4): e0166523, 2024 Apr 10.
Article En | MEDLINE | ID: mdl-38501659

Many Legionella pneumonia patients do not produce sputum, and it is unknown whether purulent sputum is required for the identification of Legionella species. This study aimed to evaluate the identification rate of Legionella species based on sputum quality and the factors predictive of Legionella infection. This study included Legionella pneumonia patients at Kurashiki Central Hospital from November 2000 to December 2022. Sputum quality, based on gram staining, was classified as the following: Geckler 1/2, 3/6 and 4/5. Geckler 4/5 was defined as purulent sputum. The sputa of 104 of 124 Legionella pneumonia patients were cultured. Fifty-four patients (51.9%) were identified with Legionella species, most of which were Legionella pneumophila serogroup 1 (81.5%). The identification rates of Legionella species according to sputum quality were 57.1% (16/28) in Geckler 1/2 sputum, 50.0% (34/68) in Geckler 3/6 sputum, and 50.0% (4/8) in Geckler 4/5 sputum, which were not significantly different (P = 0.86). On multivariate analysis, pre-culture treatment with anti-Legionella antimicrobials (odds ratio [OR] 0.26, 95% confidence interval [CI] 0.06-0.91), Pneumonia Severity Index class ≥IV (OR 2.57 [95% CI 1.02-6.71]), and intensive care unit admission (OR 3.08, 95% CI 1.06-10.09) correlated with the ability to identify Legionella species, but sputum quality did not (OR 0.88, 95% CI 0.17-4.41). The identification rate of Legionella species in non-purulent sputum was similar to that in purulent sputum. For the diagnosis of Legionella pneumonia, sputum should be collected before administering anti-Legionella antibiotics and cultured regardless of sputum quality.


Legionella pneumophila , Legionella , Legionnaires' Disease , Pneumonia , Humans , Sputum , Legionnaires' Disease/diagnosis
3.
BMC Pulm Med ; 23(1): 487, 2023 Dec 05.
Article En | MEDLINE | ID: mdl-38053068

BACKGROUND: Human rhinoviruses (HRVs) infection is a common cause of exacerbations in pediatric patients with asthma. However, the effects of corticosteroids on HRV-induced exacerbations in pediatric asthma are unknown. We conducted a prospective observational study to determine the viral pathogens in school-age pediatric inpatients with asthma exacerbations. We assessed the effects of maintenance inhaled corticosteroids (ICS) on the detection rates of HRV species and treatment periods of systemic corticosteroids during exacerbations on pulmonary lung function after exacerbations. METHODS: Nasopharyngeal samples and clinical information were collected from 59 patients with asthma exacerbations between April 2018 and March 2020. Pulmonary function tests were carried out 3 months after exacerbations in 18 HRV-positive patients. Changes in forced expiratory volume in 1 second (FEV1)% predicted from baseline in a stable state were compared according to the treatment periods of systemic corticosteroids. RESULTS: Fifty-four samples collected from hospitalized patients were analyzed, and viral pathogens were identified in 45 patients (83.3%) using multiplex PCR assay. HRV-A, -B, and -C were detected in 16 (29.6%), one (1.9%), and 16 (29.6%) patients, respectively. The detection rates of HRV-C were lower in the ICS-treated group compared with those in the ICS-untreated group (p = 0.01), whereas maintenance ICS treatment did not affect the detection rate for viral pathogens in total and HRV-A. Changes in FEV1% predicted in patients treated with systemic corticosteroids for 6-8 days (n = 10; median, 4.90%) were higher than those in patients treated for 3-5 days (n = 8; median, - 10.25%) (p = 0.0085). CONCLUSIONS: Maintenance ICS reduced the detection rates of HRV (mainly HRV-C) in school-age inpatients with asthma exacerbations, and the treatment periods of systemic corticosteroids during exacerbations affected lung function after HRV-induced exacerbations. The protective effects of corticosteroids on virus-induced asthma exacerbations may be dependent upon the types of viral pathogen.


Anti-Asthmatic Agents , Asthma , Child , Humans , Anti-Asthmatic Agents/therapeutic use , Rhinovirus , Inpatients , Administration, Inhalation , Asthma/drug therapy , Asthma/chemically induced , Adrenal Cortex Hormones
4.
J Epidemiol ; 2023 Dec 02.
Article En | MEDLINE | ID: mdl-38044087

BACKGROUND: Studies on the association between preserved ratio impaired spirometry (PRISm) and dementia are limited. Indeed, PRISm has often been overlooked or ignored as an index of lung function impairment. Therefore, we investigated the association of PRISm with the risk for the development of dementia in an older Japanese population. METHODS: A total of 1202 community-dwelling, older Japanese participants aged ≥65 years without dementia were followed up for a median of 5.0 years. Participants were categorized by spirometry as follows: normal spirometry (FEV1/FVC ≥0.70 and FEV1 ≥80% predicted), PRISm (≥0.70 and <80%), airflow limitation (AFL) Global Initiative for Chronic Obstructive Lung Disease (GOLD) 1 (<0.70 and ≥80%), and AFL GOLD 2 to 4 (<0.70 and <80%). Hazard ratios (HRs) and their 95% confidence intervals (CIs) were computed using a Cox proportional hazards model. RESULTS: During the follow-up period, 122 participants developed dementia. The age- and sex-adjusted incidences of dementia in the participants with normal spirometry, PRISm, AFL GOLD 1, and AFL GOLD 2 to 4 were 20.5, 37.0, 18.4, and 28.6 per 1000 person-years, respectively. Participants with PRISm had a higher risk of dementia (HR 2.04 [95%CI, 1.19-3.49]) than those with normal spirometry after adjusting for confounders. Moreover, both reduced FEV1% predicted values and FVC% predicted values were associated with the risk for dementia. CONCLUSION: PRISm was associated with an increased risk of dementia in a general older Japanese population.

5.
Am J Respir Crit Care Med ; 206(5): 563-572, 2022 09 01.
Article En | MEDLINE | ID: mdl-35549659

Rationale: Several Western studies have reported that participants with preserved ratio impaired spirometry (PRISm) have higher risks of airflow limitation (AFL) and death. However, evidence in East Asian populations is limited. Objectives: To investigate the relationship between PRISm and the risks of death and incident AFL in a Japanese population. Methods: A total of 3,032 community-dwelling Japanese participants aged ⩾40 years were seen in follow-up for a median of 5.3 years by annual spirometry examinations. Participants were classified into lung function categories at baseline as follows: normal spirometry (FEV1/FVC ⩾0.70 and FEV1 ⩾80% predicted), PRISm (⩾0.70 and <80%), AFL Global Initiative for Chronic Obstructive Lung Disease 1 (<0.70 and ⩾80%), and AFL Global Initiative for Chronic Obstructive Lung Disease 2-4 (<0.70 and <80%). Hazard ratios (HRs) and their 95% confidence intervals were computed using a Cox proportional hazards model. Measurements and Main Results: During the follow-up period, 131 participants died, 22 of whom died of cardiovascular disease, and 218 participants developed AFL. When examining the prognosis of each baseline lung function category, participants with PRISm had higher risks of all-cause death (HR, 2.20; 95% confidence interval, 1.35-3.59) and cardiovascular death (HR, 4.07; 1.07-15.42) than those with normal spirometry after adjusting for confounders. Moreover, the multivariable-adjusted risk of incident AFL was greater in participants with PRISm than in those with normal spirometry (HR, 2.48; 1.83-3.36). Conclusions: PRISm was associated with higher risks of all-cause and cardiovascular death and a greater risk of the development of AFL in a Japanese community.


Lung , Pulmonary Disease, Chronic Obstructive , Aged , Forced Expiratory Volume , Humans , Japan/epidemiology , Respiratory Function Tests , Risk Factors , Spirometry , Vital Capacity
6.
J Infect Chemother ; 28(5): 623-630, 2022 May.
Article En | MEDLINE | ID: mdl-35153137

INTRODUCTION: Whether inflammatory biomarkers including procalcitonin (PCT) and C-reactive protein (CRP) are useful for predicting prognosis in nursing and healthcare-associated pneumonia (NHCAP) is unknown. The aim of the present study was to investigate the utility of serial PCT and CRP measurements for predicting prognosis and treatment efficacy for hospitalized NHCAP patients. METHODS: This prospective, observational, cohort study enrolled consecutive NHCAP patients hospitalized at Kurashiki Central Hospital from October 2010 to September 2017. PCT and CRP were measured twice, once on admission and again within 48-72 h after admission. The primary outcome was 30-day all-cause mortality, and the secondary outcome was initial treatment failure. RESULTS: A total of 299 patients were included. The 30-day mortality rate was 8.4% (25/299), and the initial treatment failure rate was 15.4% (46/299). On multivariate analysis, performance status [odds ratio (OR) (95% confidence interval (CI)): 2.25 (1.34-3.77), P = 0.002], temperature [OR (95%CI): 0.53 (0.32-0.88), P = 0.02], heart rate [OR (95%CI): 1.03 (1.01-1.06), P = 0.007], albumin [OR (95%CI): 0.42 (0.18-0.95), P = 0.04], and blood urea nitrogen [OR (95%CI): 1.02 (1.00-1.05), P = 0.04] were significant prognostic factors, and CRP D3 [OR (95%CI): 1.07 (1.02-1.11), P = 0.003] and PSI [OR (95%CI): 1.01 (1.00-1.02), P = 0.01] were the predictors of initial treatment failure. Consecutive measurements of PCT and CRP were not significant predictors of 30-day mortality. CONCLUSIONS: Inflammatory biomarkers including PCT and CRP were not useful for predicting prognosis and treatment efficacy in NHCAP patients. We should carefully evaluate the patients' vital signs and comorbidities when managing NHCAP patients.


Healthcare-Associated Pneumonia , Biomarkers , C-Reactive Protein/analysis , Cohort Studies , Humans , Prognosis , Prospective Studies
7.
Respir Investig ; 60(1): 129-136, 2022 Jan.
Article En | MEDLINE | ID: mdl-34580039

BACKGROUND: Viral respiratory infections are a common cause of acute exacerbations of chronic obstructive pulmonary disease (AECOPD) and asthma. We conducted a multicenter prospective study to determine the differences in the spectrum of viruses between adults with asthma exacerbations and AECOPD and assessed the prevalence and impact of human rhinovirus (HRV)-C in adults, which is more pathogenic in children with asthma than other HRV species. METHODS: Nasopharyngeal and serum samples and clinical information were collected from 64 outpatients with adult asthma exacerbations and 44 outpatients with AECOPD between April 2018 and March 2020. Viral pathogens and HRV strains were identified from nasal samples by multiplex PCR and VP4/VP2 nested PCR. RESULTS: Viral pathogens were identified in 31 patients with asthma exacerbations (48.4%) and 17 patients with AECOPD (38.6%). The most commonly detected viruses were HRV/enterovirus followed by human metapneumovirus (hMPV) in patients with asthma exacerbations, and hMPV followed by parainfluenza virus in patients with AECOPD. HRV-C was the HRV species most commonly associated with both asthma exacerbations and AECOPD. Clinical characteristics, baseline lung function, serum inflammatory chemokines, hospitalization, and systemic steroid use did not differ between HRV-C-positive patients and those positive for other HRV species. CONCLUSIONS: Exacerbation-associated spectrum of viruses differed between adults with asthma exacerbations and AECOPD. HRV-C was the HRV species most often observed in adult asthma exacerbations and AECOPD, although it did not worsen patients' clinical outcomes relative to those of patients with other HRVs. Underlying disease-specific factors may be responsible for susceptibility to respiratory viruses. TRIAL REGISTRATION: UMIN-CTR UMIN000031934.


Asthma , Enterovirus , Picornaviridae Infections , Pulmonary Disease, Chronic Obstructive , Respiratory Tract Infections , Viruses , Adult , Asthma/epidemiology , Asthma/virology , Humans , Multiplex Polymerase Chain Reaction , Picornaviridae Infections/epidemiology , Prospective Studies , Pulmonary Disease, Chronic Obstructive/epidemiology , Pulmonary Disease, Chronic Obstructive/virology , Respiratory Tract Infections/epidemiology , Respiratory Tract Infections/virology , Rhinovirus/genetics , Viruses/genetics
8.
Infect Dis Ther ; 10(4): 2309-2322, 2021 Dec.
Article En | MEDLINE | ID: mdl-34339026

INTRODUCTION: Whether the sensitivity of the BinaxNOW Streptococcus pneumoniae urinary antigen test kit (BinaxNOW), adjusted by some variables including vital signs, laboratory examinations and pneumonia severity, has been decreasing is unknown. The aim of the present study was to investigate whether BinaxNOW sensitivity has decreased recently and to identify the predictors of the BinaxNOW result, including the time trend. METHODS: This prospective cohort study enrolled consecutive patients with pneumococcal community-acquired pneumonia who were hospitalised at Kurashiki Central Hospital from January 2001 to December 2015. Pneumococcal community-acquired pneumonia was defined as positive blood or pleural effusion or sputum culture results. To evaluate the effect of the time trend for the sensitivity of BinaxNOW, time series regression analysis was performed. In addition, predictors of the BinaxNOW result were examined by multivariable analysis using variables such as sex, vital signs, blood tests such as C-reactive protein, albumin, blood urea nitrogen, creatinine, white blood cell count, haematocrit and platelets, antibiotic pre-treatment, bacteraemia, and pneumonia severity, in addition to time trend and seasonality. RESULTS: A total of 446 patients were included. BinaxNOW sensitivity showed a significant, gradual decrease from 2001 (81.3%) to 2015 (48.7%). On multivariable analysis [odds ratio (95% confidence interval)], bacteraemia [2.516 (1.387-4.561), P = 0.002] was a predictor of a positive BinaxNOW result, whereas male sex [0.467 (0.296-0.736), P = 0.001], white blood cell count [0.959 (0.930-0.989), P = 0.008] and the time trend per year [0.900 (0.859-0.943), P < 0.001] were predictors of a negative BinaxNOW result. CONCLUSIONS: The sensitivity of BinaxNOW decreased over a 15-year period. We should be careful when interpreting BinaxNOW results in daily clinical practice, and the development of a new kit with good sensitivity is anticipated. TRIAL REGISTRATION NUMBER: UMIN000004353.

9.
Diagn Microbiol Infect Dis ; 101(1): 115457, 2021 Sep.
Article En | MEDLINE | ID: mdl-34271234

The aim of the present study was to investigate the predictors of targeted therapy (TT) for pneumococcal community-acquired pneumonia (PCAP) with a positive urinary antigen test (UAT) and compare the outcomes with those of nontargeted therapy. This prospective cohort study enrolled consecutive PCAP patients with a positive UAT who were hospitalized at Kurashiki Central Hospital from October 2010 to November 2019. A total of 286 patients were included. Of them, 56 patients (19.6%) were included in the TT group. On multivariate analysis, identification of Gram-positive diplococci by Gram stain (OR [95% CI]: 2.46 [1.32-4.63]) was a positive predictor, whereas aspiration pneumonia (0.17 [0.03-0.59]) and CURB-65 score (0.59 [0.42-0.81]) were negative predictors of TT. Initial treatment failure and 30-day mortality were not significantly different. The UAT is not used enough for TT, and TT for PCAP did not have worse outcomes.


Anti-Bacterial Agents/therapeutic use , Antigens, Bacterial/urine , Pneumonia, Pneumococcal/diagnosis , Pneumonia, Pneumococcal/drug therapy , Streptococcus pneumoniae/isolation & purification , Aged , Aged, 80 and over , Community-Acquired Infections/diagnosis , Community-Acquired Infections/drug therapy , Community-Acquired Infections/microbiology , Community-Acquired Infections/urine , Female , Humans , Male , Pneumonia, Pneumococcal/urine , Prospective Studies , Streptococcus pneumoniae/immunology , Treatment Outcome
10.
J Infect Chemother ; 27(10): 1447-1453, 2021 Oct.
Article En | MEDLINE | ID: mdl-34147355

INTRODUCTION: Whether ß-lactam and macrolide combination therapy reduces mortality in severe community-acquired pneumonia (SCAP) patients hospitalized in the intensive care unit (ICU) is controversial. The aim of the present study was to evaluate the usefulness of ß-lactam and macrolide combination therapy for SCAP patients hospitalized in the ICU. METHODS: A prospective, observational, cohort study of hospitalized pneumonia patients was performed. Hospitalized SCAP patients admitted to the ICU within 24 h between October 2010 and October 2017 were included for analysis. The primary outcome was 30-day mortality, and secondary outcomes were 14-day mortality and ICU mortality. Inverse probability of treatment weighting (IPTW) analysis as a propensity score analysis was used to reduce biases, including six covariates: age, sex, C-reactive protein, albumin, Pneumonia Severity Index score, and APACHE II score. RESULTS: A total of 78 patients were included, with 48 patients in the non-macrolide-containing ß-lactam therapy group and 30 patients in the macrolide combination therapy group. ß-lactam and macrolide combination therapy significantly decreased 30-day mortality (16.7% vs. 43.8%; P = 0.015) and 14-day mortality (6.7% vs. 31.3%; P = 0.020), but not ICU mortality (10% vs 27.1%, P = 0.08) compared with non-macrolide-containing ß-lactam therapy. After adjusting by IPTW, macrolide combination therapy also decreased 30-day mortality (odds ratio, 0.29; 95%CI, 0.09-0.96; P = 0.04) and 14-day mortality (odds ratio, 0.19; 95%CI, 0.04-0.92; P = 0.04), but not ICU mortality (odds ratio, 0.34; 95%CI, 0.08-1.36; P = 0.13). CONCLUSIONS: Combination therapy with ß-lactam and macrolides significantly improved the prognosis of SCAP patients hospitalized in the ICU compared with a non-macrolide-containing ß-lactam regimen.


Community-Acquired Infections , Pneumonia, Bacterial , Anti-Bacterial Agents/therapeutic use , Cohort Studies , Community-Acquired Infections/drug therapy , Drug Therapy, Combination , Humans , Intensive Care Units , Macrolides/therapeutic use , Pneumonia, Bacterial/drug therapy , Propensity Score , Prospective Studies , Treatment Outcome , beta-Lactams/therapeutic use
11.
J Infect Chemother ; 27(10): 1429-1435, 2021 Oct.
Article En | MEDLINE | ID: mdl-34088603

INTRODUCTION: Japan experienced a heavy rainfall event from June 28 to July 8, 2018, and many casualties were caused by both heavy rainfall and flooding. Few studies have investigated patients' characteristics and the causative pathogens of community-acquired pneumonia before and after heavy rainfall events. The aim of the present study was to evaluate the causative pathogens and clinical characteristics of hospitalized patients with community-acquired pneumonia before and after the heavy rainfall event using prospective cohort data. METHODS: The study was divided into two periods: July to November 2013-2017 (before heavy rainfall) and July to November 2018 (after heavy rainfall). The patients' clinical characteristics and causative pathogens before and after the heavy rainfall were investigated. Regarding the causative pathogens, adjustments were made for precipitation and seasonal patterns. RESULTS: There were no significant differences in the number and clinical characteristics of patients before and after heavy rainfall. However, the frequency of Legionella pneumonia was significantly higher after than before the heavy rainfall event (8.9% vs 3.0%, P = 0.02) and remained significant after adjusting for precipitation and season. Three of 7 Legionella pneumonia patients engaged in reconstruction work and 2 Legionella pneumonia patients had soil exposure. CONCLUSIONS: An increased risk of Legionella pneumonia after not only rainfall and serious flooding, but also following recovery work or soil exposure should be considered.


Community-Acquired Infections , Legionella , Legionnaires' Disease , Pneumonia , Community-Acquired Infections/epidemiology , Humans , Japan/epidemiology , Legionnaires' Disease/epidemiology , Pneumonia/epidemiology , Prospective Studies
12.
J Glob Antimicrob Resist ; 22: 441-447, 2020 09.
Article En | MEDLINE | ID: mdl-32339851

OBJECTIVES: Nursing and healthcare-associated pneumonia (NHCAP) was proposed by the Japanese Respiratory Society to refer to healthcare-associated pneumonia. This study aimed to investigate whether antipseudomonal antibiotic therapy improved the prognosis of NHCAP patients at high risk for antimicrobial-resistant pathogens. METHODS: Consecutive hospitalised NHCAP patients in Kurashiki Central Hospital between October 2010 and December 2016 were prospectively enrolled. NHCAP patients who were at high risk for antimicrobial resistance were defined as those who received antimicrobials in the preceding 90 days and/or were on tube feeding. The patients who received antipseudomonal antibiotics were defined as the guideline-concordant (GC) therapy group, and the others were defined as the guideline-discordant (GD) therapy group. The primary outcome was 30-day mortality. Inverse probability of treatment weighting (IPTW) analysis was used to reduce biases. RESULTS: There were 277 patients with NHCAP; a majority (78.0%) were discharged from a hospital in the preceding 90 days. There were 52 patients in the GC group and 225 patients in the GD group. The 30-day mortality rate was significantly higher in the GC group than in the GD group (17.3%, 9/52 vs. 7.1%, 16/225; P = 0.03). After IPTW analysis, the GC therapy, compared with GD therapy, did not improve the 30-day mortality (OR 1.71, 95% CI 0.65-4.47; P = 0.28). CONCLUSIONS: Not all NHCAP patients, even those at high risk for antimicrobial resistance, need antipseudomonal antimicrobial treatment. The treatment strategy for NHCAP patients should be individualised, according to the pneumonia severity, risk for antimicrobial-resistant pathogens, and antibiogram in each hospital.


Anti-Infective Agents , Cross Infection , Healthcare-Associated Pneumonia , Pneumonia, Bacterial , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Cross Infection/drug therapy , Drug Resistance, Bacterial , Healthcare-Associated Pneumonia/drug therapy , Humans , Pneumonia, Bacterial/drug therapy
13.
J Infect Chemother ; 26(4): 372-378, 2020 Apr.
Article En | MEDLINE | ID: mdl-31787528

The usefulness of existing pneumonia severity indices for predicting mortality in nursing and healthcare-associated pneumonia (NHCAP) is unclear. This study compared the usefulness of existing pneumonia severity indices for predicting mortality in NHCAP and community-acquired pneumonia (CAP). Consecutive hospitalized pneumonia patients including NHCAP and CAP patients were prospectively enrolled between October 2010 and November 2017. Admission pneumonia severity was assessed using CURB-65, Pneumonia Severity Index (PSI), A-DROP, Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) severe pneumonia criteria, and I-ROAD. The primary outcome was 30-day mortality. The discriminatory ability of each severity index was evaluated by receiver operating characteristic curve analysis. Overall, 828 patients had NHCAP, and 1330 patients had CAP. Thirty-day mortality was 12.8% and 5.6% in NHCAP and CAP patients, respectively. The area under the curve of PSI (0.717, 95% confidence interval 0.673-0.761) was the highest among all pneumonia severity indices, with significant differences compared with CURB-65 (0.651, 95% confidence interval 0.598-0.705, P = 0.02) and IDSA/ATS severe pneumonia criteria (0.659, 95% confidence interval 0.612-0.707, P = 0.03). The predictive abilities for 30-day mortality of the pneumonia severity indices, excluding PSI and I-ROAD, were significantly inferior for NHCAP than for CAP. PSI may be the most useful pneumonia severity score for predicting mortality in NHCAP. However, the predictive ability for mortality of each pneumonia severity score was worse for NHCAP than for CAP; therefore, the prognostic factors in NHCAP need to be identified for better management of NHCAP patients.


Healthcare-Associated Pneumonia/mortality , Severity of Illness Index , Aged , Aged, 80 and over , Case-Control Studies , Community-Acquired Infections/mortality , Female , Humans , Male , Middle Aged , Prospective Studies , Sensitivity and Specificity
14.
Sci Rep ; 9(1): 18406, 2019 12 05.
Article En | MEDLINE | ID: mdl-31804572

Whether macrolide combination therapy reduces the mortality of patients with severe community-acquired pneumonia (CAP) hospitalized in the non-intensive care unit (ICU) remains unclear. Therefore, we investigated the efficacy of adding azithromycin to ß-lactam antibiotics for such patients. This prospective cohort study enrolled consecutive patients with CAP hospitalized in the non-ICU between October 2010 and November 2016. The 30-day mortality between ß-lactam and azithromycin combination therapy and ß-lactam monotherapy was compared in patients classified as mild to moderate and severe according to the CURB-65, Pneumonia Severity Index (PSI), and Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) criteria. Inverse probability of treatment weighting (IPTW) analysis was used to reduce biases. Based on the CURB-65 and PSI, combination therapy did not significantly reduce the 30-day mortality in either group (179 patients in the combination group, 952 in the monotherapy group). However, based on the IDSA/ATS criteria, combination therapy significantly reduced the 30-day mortality in patients with severe (odds ratio [OR] 0.12, 95% confidence interval [CI] 0.007-0.57), but not non-severe pneumonia (OR 1.85, 95% CI 0.51-5.40); these results were similar after IPTW analysis. Azithromycin combination therapy significantly reduced the mortality of patients with severe CAP who met the IDSA/ATS criteria.


Anti-Bacterial Agents/therapeutic use , Azithromycin/therapeutic use , Bacteremia/drug therapy , Pneumonia, Bacterial/drug therapy , beta-Lactams/therapeutic use , Aged , Aged, 80 and over , Bacteremia/microbiology , Bacteremia/mortality , Bacteremia/pathology , Community-Acquired Infections , Drug Therapy, Combination , Female , Humans , Male , Pneumonia, Bacterial/microbiology , Pneumonia, Bacterial/mortality , Pneumonia, Bacterial/pathology , Prospective Studies , Severity of Illness Index , Survival Analysis
15.
Lung Cancer ; 135: 175-180, 2019 09.
Article En | MEDLINE | ID: mdl-31446992

OBJECTIVES: Afatinib is an effective treatment in patients who have epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC), but its toxicities often require dose adjustment. Exploratory analyses of previous trials have suggested that reducing the dose of afatinib can decrease treatment-related adverse events without negatively affecting effectiveness. The aim of this study was to assess the efficacy and safety of low starting dose of afatinib with dose modification according to its toxicity in patients with EGFR mutation-positive NSCLC. MATERIALS AND METHODS: This study was a multicenter, single-arm, open-label phase II trial. Treatment-naïve patients with advanced NSCLC positive for common EGFR mutations received afatinib starting in a dose of 20 mg/day. If tolerated, the dose was increased in 10-mg increments up to 50 mg/day. The primary endpoint was progression-free survival (PFS). RESULTS: From February 2015 through March 2016, 46 patients were enrolled. The median age was 73 years (range, 43-86), and 35 patients (72%) were women.EGFR mutation subtypes included exon 19 deletion (54%) and Leu858Arg point mutation (46%). Most patients had a performance status of 0 or 1 (91%) and a histological diagnosis of adenocarcinoma (98%). As of the data cut-off date of June 2017, the median follow-up was 18.9 months. The median PFS was 15.2 months (95% CI: 13.2-not estimable). The 1-year overall survival rate was 95.6% (95% CI: 89.7%-100%). The objective response rate was 81.8% (95% CI, 81.3%-98.6%). Adverse events of grade 3 or higher occurred in 14 patients (30.4%) and included rash/acne in 4 patients (8.7%), paronychia in 4 patients (8.7%), diarrhea in 2 patients (4.3%). There was no treatment-related death. CONCLUSIONS: Low starting dose of afatinib therapy showed promising clinical efficacy and good tolerability. Further investigations are warranted.


Afatinib/therapeutic use , Carcinoma, Non-Small-Cell Lung/drug therapy , Carcinoma, Non-Small-Cell Lung/genetics , Lung Neoplasms/drug therapy , Lung Neoplasms/genetics , Mutation , Adult , Afatinib/administration & dosage , Afatinib/adverse effects , Aged , Antineoplastic Agents/administration & dosage , Antineoplastic Agents/adverse effects , Antineoplastic Agents/therapeutic use , Carcinoma, Non-Small-Cell Lung/diagnosis , Carcinoma, Non-Small-Cell Lung/mortality , ErbB Receptors/genetics , Female , Humans , Kaplan-Meier Estimate , Lung Neoplasms/diagnosis , Lung Neoplasms/mortality , Male , Middle Aged , Prognosis , Protein Kinase Inhibitors/administration & dosage , Protein Kinase Inhibitors/adverse effects , Protein Kinase Inhibitors/therapeutic use , Treatment Outcome
16.
Respir Investig ; 57(6): 574-581, 2019 Nov.
Article En | MEDLINE | ID: mdl-31427269

BACKGROUND: Empyema is an important and serious disease with high morbidity and mortality worldwide. However, the bacteriology and prognostic factors of empyema remain poorly understood, and data on the relationships among these parameters are scant. METHODS: We retrospectively analyzed a prospectively collected database of patients with empyema admitted to Kurashiki Central Hospital, Japan, between May 2007 and September 2015. Only patients who had positive results on pleural fluid bacterial culture were included. We collected patient characteristics, bacteriology findings, treatments, and outcomes, and we assessed the prognostic factors for in-hospital mortality. RESULTS: We included 71 patients in this study. The most commonly isolated bacteria were members of the Streptococcus anginosus group (37%), followed by anaerobes (30%). In-hospital mortality was 11%. On multivariate analysis, polymicrobial empyema (odds ratio [OR], 8.25; 95% confidence interval [CI], 1.08-62.90) and RAPID (renal, age, purulence, infection source, and dietary factors) score (OR, 6.89; 95% CI, 1.73-27.40) were significant risk factors for in-hospital mortality. The most common etiology of polymicrobial empyema was a combination of the members of the S. anginosus group and anaerobes, but no relationship was observed between the combination of microorganisms and outcomes. Although no significant difference was observed in treatment between the survivor and non-survivor groups, all patients who underwent surgery survived. CONCLUSIONS: Members of the S. anginosus group and anaerobes were frequent pathogens in empyema, and polymicrobial etiology was independently associated with mortality in addition to the RAPID score. Surgery may be one option for preventing mortality.


Empyema, Pleural/microbiology , Hospital Mortality , Humans , Prognosis , Retrospective Studies , Streptococcus anginosus/pathogenicity
17.
Clin Chem Lab Med ; 57(10): 1632-1637, 2019 Sep 25.
Article En | MEDLINE | ID: mdl-31120857

Background This study aimed to investigate the usefulness of inflammatory biomarkers such as white blood cell (WBC) count, C-reactive protein (CRP) and procalcitonin (PCT) for differentiating cryptogenic organising pneumonia (COP) from community-acquired pneumonia (CAP). Methods COP patients hospitalised in Kurashiki Central Hospital between January 2010 and December 2017 whose WBC counts and CRP and PCT levels were measured were investigated retrospectively, and their results were compared with those of hospitalised CAP patients who were prospectively enrolled between October 2010 and November 2017. Definite COP was defined by specific histopathological findings, and possible COP was defined as a consolidation shadow on chest computed tomography and lymphocyte dominance in bronchoalveolar lavage fluid in the absence of specific histopathological findings or lung specimens. The discriminatory abilities of WBC counts, CRP and PCT were evaluated by receiver operating characteristic (ROC) curve analysis. Results There were 56 patients in the entire COP group, 35 (61.4%) with definite COP, and 914 CAP patients. All three biomarkers were significantly lower in COP than in CAP. The AUC value of PCT in all COP patients was 0.79, significantly higher than of both CRP (AUC 0.59, p < 0.001) and WBC (AUC 0.69, p = 0.048). In definite COP patients, the AUC value of PCT was 0.79, which was also significantly higher than of both WBC (AUC 0.64, p = 0.006) and CRP (AUC 0.64, p = 0.001). Conclusions PCT is a more useful biomarker for differentiating COP from CAP than WBC count or CRP. However, PCT should be used as an adjunct to clinical presentation and radiological findings.


Cryptogenic Organizing Pneumonia/diagnosis , Pneumonia/diagnosis , Procalcitonin/analysis , Aged , Aged, 80 and over , Biomarkers/blood , C-Reactive Protein/analysis , Calcitonin/blood , Community-Acquired Infections/diagnosis , Comorbidity , Female , Hospitalization , Humans , Leukocyte Count/methods , Lymphocytes/metabolism , Male , Procalcitonin/blood , Protein Precursors/blood , ROC Curve , Retrospective Studies , Severity of Illness Index
18.
BMC Pulm Med ; 18(1): 24, 2018 Jan 30.
Article En | MEDLINE | ID: mdl-29382316

BACKGROUND: Pneumococcal pneumonia causes high morbidity and mortality among adults. This study aimed to identify risk factors for bacteremic pneumococcal pneumonia, and to construct a prediction model for the development of bacteremia in patients with community-acquired pneumococcal pneumonia. METHODS: We retrospectively analyzed data from patients hospitalized with community-acquired pneumococcal pneumonia between April 2007 and August 2015. Logistic regression models were applied to detect risk factors for pneumococcal bacteremia, and a receiver operating characteristic curve was used to devise a prediction model. RESULTS: Based on the results of sputum cultures, urine antigen tests, and/or blood cultures, 389 patients were diagnosed with pneumococcal pneumonia, 46 of whom had bacteremia. In the multivariate analysis, age < 65 years, serum albumin level < 3.0 g/dL, need for intensive respiratory or vasopressor support (IRVS), and C-reactive protein level > 20 mg/dL were identified as independent risk factors for the development of pneumococcal bacteremia. The bacteremia prediction score based on receiver operating characteristic curve analysis had a sensitivity of 0.74 and a specificity of 0.78 in patients with two risk factors. The area under the receiver operating characteristic curve was 0.77 (95% confidence interval (CI), 0.70-0.85). CONCLUSIONS: Age < 65 years, hypoalbuminemia, IRVS, and high C-reactive protein level on admission are independent risk factors for the development of bacteremia in patients with community-acquired pneumococcal pneumonia. A prediction model based on these four risk factors could help to identify patients with community-acquired pneumococcal pneumonia at high risk of developing bacteremia; this can be used to guide antibiotic choices. TRIAL REGISTRATION: UMIN-CTR UMIN 000004353 . Registered 7 October 2010. Retrospectively registered.


Bacteremia/epidemiology , Community-Acquired Infections/epidemiology , Hypoalbuminemia/epidemiology , Pneumonia, Pneumococcal/epidemiology , Adult , Age Factors , Aged , Aged, 80 and over , Bacteremia/metabolism , C-Reactive Protein/metabolism , Case-Control Studies , Community-Acquired Infections/metabolism , Female , Humans , Logistic Models , Male , Middle Aged , Pneumococcal Infections/epidemiology , Pneumococcal Infections/metabolism , Pneumonia, Pneumococcal/metabolism , ROC Curve , Retrospective Studies , Risk Assessment , Risk Factors , Serum Albumin/metabolism , Vasoconstrictor Agents/therapeutic use , Young Adult
19.
BMC Pulm Med ; 17(1): 211, 2017 Dec 16.
Article En | MEDLINE | ID: mdl-29246145

BACKGROUND: Because of a limited number of reports, we aimed to investigate the clinical characteristics of patients with Legionella pneumonia due to non-Legionella pneumophila serogroup 1 and the diagnostic usefulness of the six-point scoring system for such patients compared with patients with pneumonia caused by L. pneumophila serogroup 1. METHODS: We retrospectively analysed patients diagnosed with Legionella pneumonia due to non-L. pneumophila serogroup 1 between March 2001 and June 2016. We examined the clinical characteristics, including symptoms, laboratory findings, radiologic findings, pneumonia severity, initial treatment and prognosis. We also calculated scores using the six-point scoring system in these patients. Furthermore, we compared the clinical characteristics and six-point scores between non-L. pneumophila serogroup 1 patients and L. pneumophila serogroup 1 patients among hospitalized community-acquired pneumonia patients enrolled prospectively between October 2010 and July 2016. RESULTS: Eleven patients had pneumonia due to non-L. pneumophila serogroup 1; their median age was 66 years and 8 patients (72.7%) were male. The most common pathogen was L. pneumophila serogroup 3 (6/11), followed by L. pneumophila serogroup 9 (3/11), L. pneumophila serogroup 6 (1/11) and L. longbeachae (1/11). Non-specific symptoms, such as fever and cough, were common. Six patients (54.5%) had liver enzyme elevation, but no patient developed hyponatraemia at <130 mEq/L. Nine patients (81.8%) showed lobar pneumonia and 7 patients (63.6%) manifested with consolidation and ground-glass opacity. Patients with mild to moderate severity comprised 10 (90.9%) by CURB-65 and 5 (45.5%) by the Pneumonia Severity Index. Of all patients, 4 were admitted to the intensive care unit and 3 died despite appropriate empiric therapy. The clinical characteristics were not significantly different between non-L. pneumophila serogroup 1 patients and L. pneumophila serogroup 1 patients (n = 23). At a cut-off value of ≥ 2 points, the sensitivity of the six-point scoring system was 54.5% (6/11) for non-L. pneumophila serogroup 1 patients and 95.7% (22/23) for L. pneumophila serogroup 1 patients. CONCLUSIONS: Cases of non-L. pneumophila serogroup 1 pneumonia varied in severity from mild to severe and the clinical characteristics were often non-specific. The six-point scoring system was not useful in predicting such Legionella pneumonia cases.


Community-Acquired Infections/diagnosis , Legionella pneumophila/isolation & purification , Legionnaires' Disease/diagnosis , Legionnaires' Disease/physiopathology , Aged , Aged, 80 and over , Anti-Bacterial Agents/therapeutic use , Community-Acquired Infections/microbiology , Female , Humans , Legionnaires' Disease/drug therapy , Male , Middle Aged , Retrospective Studies , Serogroup , Severity of Illness Index
20.
BMC Pulm Med ; 17(1): 78, 2017 May 02.
Article En | MEDLINE | ID: mdl-28464807

BACKGROUND: To date, only few studies have examined the prognostic factors of community-acquired pneumonia (CAP) defined according to the latest criteria, which excludes healthcare-associated pneumonia (HCAP). Therefore, we aimed to investigate the factors that affect prognosis, and evaluate the usefulness of existing pneumonia severity scores for predicting the prognosis of CAP. METHODS: We retrospectively analyzed patients with CAP, excluding HCAP, who were enrolled prospectively between April 2007 and February 2016. Four patients who used macrolides other than azithromycin (AZM) were excluded. We used age, sex, comorbidities, laboratory findings and antimicrobial therapy as prognostic variables. The primary outcome was 30-day mortality and secondary outcome was ICU admission. We also performed receiver operating characteristic curve analysis of Pneumonia Severity Index (PSI), Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) severe criteria, CURB-65 and A-DROP pneumonia severity scores. RESULTS: Among 1834 CAP patients, mean age was 73.5 ± 14.3 years; 1281 (69.8%) were men; and 30-day mortality was 6.7% (122/1834). In total, 1830 patients were analyzed. Multivariate analysis identified age [Odds Ratio (OR): 1.04, 95% Confidence Interval (CI): 1.02-1.07], chronic obstructive pulmonary disease (COPD) [OR: 1.77, 95% CI: 1.13-2.76], malignancy (OR: 2.25, 95% CI: 1.25-4.06), body temperature (OR: 0.81, 95% CI: 0.67-0.99), respiratory rate (OR: 1.04, 95% CI: 1.01-1.07), PaO2/FiO2 ≤ 250 (OR: 3.15, 95% CI: 1.93-5.14), Alb (OR: 0.27, 95% CI: 0.19-0.39), BUN (OR: 1.01, 95% CI: 1.00-1.02), and mechanical ventilation (OR: 2.99, 95% CI: 1.75-5.12) as prognostic factors. AZM and ß-lactam combination therapy significantly reduced 30-day mortality (OR: 0.50, 95% CI: 0.26-0.97). Areas under the curve of PSI, IDSA/ATS severe criteria, CURB-65 and A-DROP were 0.759, 0.746, 0.754 and 0.764, respectively. CONCLUSIONS: Increasing age, presence of COPD and malignancy as comorbidities, hypothermia, tachypnea, PaO2/FiO2 ratio ≤250 mmHg, low Alb level, high BUN level and mechanical ventilatory support predict a worse prognosis; AZM combination therapy should be considered for CAP, excluding HCAP. All four pneumonia severity scores are useful for assessing the severity of CAP defined by the latest criteria. TRIAL REGISTRATION: UMIN-CTR UMIN000004353 . Registered 7 October 2010. Retrospectively registered.


Anti-Bacterial Agents/therapeutic use , Community-Acquired Infections/mortality , Hospitalization/statistics & numerical data , Intensive Care Units/statistics & numerical data , Pneumonia, Bacterial/mortality , Aged , Aged, 80 and over , Anti-Bacterial Agents/classification , Community-Acquired Infections/drug therapy , Female , Hospital Mortality/trends , Humans , Japan/epidemiology , Logistic Models , Male , Middle Aged , Multivariate Analysis , Neoplasms/complications , Pneumonia, Bacterial/drug therapy , Prognosis , Prospective Studies , Pulmonary Disease, Chronic Obstructive/complications , ROC Curve , Respiration, Artificial/adverse effects , Retrospective Studies , Severity of Illness Index
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