Identification rate of Legionella species in non-purulent sputum culture is comparable to that in purulent sputum culture in Legionella pneumonia.

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.

Three cases of hospitalized Legionella pneumonia patients successfully treated with lascufloxacin.

Legionella pneumonia is one of the major causes of severe pneumonia, in which treatment delay might lead to a poor prognosis. Therefore, as far as possible, early diagnosis and treatment of Legionella pneumonia is essential. Regarding the antimicrobials for Legionella pneumonia, fluoroquinolones, such as levofloxacin, or macrolides, such as azithromycin (AZM), are recommended in Japan and other countries. Lascufloxacin (LSFX), the newest fluoroquinolone developed in Japan, has been in use in daily clinical practice since January 2020. However, there are only few reports of Legionella pneumonia cases treated with LSFX. Here, we report three cases of hospitalized Legionella pneumonia patients that were successfully treated using LSFX. All three patients were admitted to the medical ward on admission, although one patient was subsequently transferred to the ICU for mechanical ventilatory management due to worsening of the pneumonia on day 3. All patients improved and were discharged following LSFX treatment (the patient admitted to the ICU was treated using LSFX + AZM combination therapy) without any severe adverse events. LSFX might be considered to be the first antibiotic choice for Legionella pneumonia, similar to levofloxacin. However, further data regarding the treatment of Legionella pneumonia cases using LSFX are needed to evaluate its efficacy and safety.

Home High-Flow Nasal Cannula Oxygen Therapy for Stable Hypercapnic COPD: A Randomized Clinical Trial.

Rationale: The long-term effects of using a high-flow nasal cannula for chronic hypercapnic respiratory failure caused by chronic obstructive pulmonary disease remain unclear. Objectives: To assess whether long-term high-flow nasal cannula use reduces the number of exacerbations and improves other physiological parameters in patients with chronic hypercapnic respiratory failure caused by chronic obstructive pulmonary disease. Methods: We enrolled 104 participants (aged ⩾40 yr) with daytime hypercapnia (Global Initiative for Chronic Obstructive Lung Disease stages 2-4) receiving long-term oxygen therapy (⩾16 h/d for ⩾1 mo) and randomly assigned them to high-flow nasal cannula/long-term oxygen therapy and long-term oxygen therapy groups. The primary endpoint was the moderate or severe exacerbation rate. We compared changes from baseline in arterial blood gas values, peripheral oxygen saturation, pulmonary function, health-related quality-of-life scores, and the 6-minute-walk test. Measurements and Main Results: High-flow nasal cannula use significantly reduced the rate of moderate/severe exacerbations (unadjusted mean count 1.0 vs. 2.5, a ratio of the adjusted mean count between groups [95% confidence interval] of 2.85 [1.48-5.47]) and prolonged the duration without moderate or severe exacerbations. The median time to first moderate or severe exacerbation in the long-term oxygen therapy group was 25 (14.1-47.4) weeks; this was not reached in the high-flow nasal cannula/long-term oxygen therapy group. High-flow nasal cannula use significantly improved health-related quality of life scores, peripheral oxygen saturation, and specific pulmonary function parameters. No safety concerns were identified. Conclusions: A high-flow nasal cannula is a reasonable therapeutic option for patients with stable hypercapnic chronic obstructive pulmonary disease and a history of exacerbations. Clinical trial registered with www.umin/ac.jp (UMIN000028581) and www.clinicaltrials.gov (NCT03282019).

Inflammatory biomarkers are not useful for predicting prognosis in nursing and healthcare-associated pneumonia: A prospective, cohort study.

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.

Prospective multicenter survey for Nursing and Healthcare-associated Pneumonia in Japan.

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.

Clinical manifestations of hospitalized influenza patients without risk factors: A prospective multicenter cohort study in Japan via internet surveillance.

INTRODUCTION: Influenza remains a clinically heavy burden worldwide. It is well known that some populations are at high risk of complications from influenza, whereas, even previously healthy people might suffer from severe influenza. The objective of this study was to clarify clinical manifestations of hospitalized patients without risk factors infected with influenza. METHODS: The clinical data for patients who were severely ill with influenza, and required hospitalization were gathered and analyzed between November 2014 and August 2020 (6 influenza seasons) using an internet-surveillance system. Among them, the patients who had no risk factors of complications from influenza were extracted. RESULTS: Finally, a total of 91 patients (9.0% of all influenza-related hospitalizations) without risk factors were analyzed. The no risk group was younger than the risk group, though other significant differences of clinical characteristics were not recognized between the groups. Pneumonia was the most common cause of hospitalization in the no risk group, and primary influenza viral pneumonia was the most common pneumonia. Antiviral drugs were administered in 96.7% of the no-risk group, and artificial ventilation was performed in 18.7%. In-hospital death was recorded for 3 patients without risk factors. CONCLUSIONS: Severe complications of influenza which required hospitalization may occur in a certain degree of patients with no risk factors. Efforts are needed to diagnose and treat influenza appropriately even in previously healthy younger patients. Continuous nationwide surveillance will be required to clarify risk factors for severe influenza even in previously healthy younger patients. (UMIN000015989).

Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents.

BACKGROUND: Baloxavir marboxil is a selective inhibitor of influenza cap-dependent endonuclease. It has shown therapeutic activity in preclinical models of influenza A and B virus infections, including strains resistant to current antiviral agents. METHODS: We conducted two randomized, double-blind, controlled trials involving otherwise healthy outpatients with acute uncomplicated influenza. After a dose-ranging (10 to 40 mg) placebo-controlled trial, we undertook a placebo- and oseltamivir-controlled trial of single, weight-based doses of baloxavir (40 or 80 mg) in patients 12 to 64 years of age during the 2016-2017 season. The dose of oseltamivir was 75 mg twice daily for 5 days. The primary efficacy end point was the time to alleviation of influenza symptoms in the intention-to-treat infected population. RESULTS: In the phase 2 trial, the median time to alleviation of influenza symptoms was 23.4 to 28.2 hours shorter in the baloxavir groups than in the placebo group (P<0.05). In the phase 3 trial, the intention-to-treat infected population included 1064 patients; 84.8 to 88.1% of patients in each group had influenza A(H3N2) infection. The median time to alleviation of symptoms was 53.7 hours (95% confidence interval [CI], 49.5 to 58.5) with baloxavir, as compared with 80.2 hours (95% CI, 72.6 to 87.1) with placebo (P<0.001). The time to alleviation of symptoms was similar with baloxavir and oseltamivir. Baloxavir was associated with greater reductions in viral load 1 day after initiation of the regimen than placebo or oseltamivir. Adverse events were reported in 20.7% of baloxavir recipients, 24.6% of placebo recipients, and 24.8% of oseltamivir recipients. The emergence of polymerase acidic protein variants with I38T/M/F substitutions conferring reduced susceptibility to baloxavir occurred in 2.2% and 9.7% of baloxavir recipients in the phase 2 trial and phase 3 trial, respectively. CONCLUSIONS: Single-dose baloxavir was without evident safety concerns, was superior to placebo in alleviating influenza symptoms, and was superior to both oseltamivir and placebo in reducing the viral load 1 day after initiation of the trial regimen in patients with uncomplicated influenza. Evidence for the development of decreased susceptibility to baloxavir after treatment was also observed. (Funded by Shionogi; JapicCTI number, 153090, and CAPSTONE-1 ClinicalTrials.gov number, NCT02954354 .).

Impact of bronchoalveolar lavage lymphocytosis on the effects of anti-inflammatory therapy in idiopathic non-specific interstitial pneumonia, idiopathic pleuroparenchymal fibroelastosis, and unclassifiable idiopathic interstitial pneumonia.

BACKGROUND: Idiopathic non-specific interstitial pneumonia (iNSIP), idiopathic pleuroparenchymal fibroelastosis (iPPFE), and unclassifiable idiopathic interstitial pneumonia (IIP) are IIPs with chronic fibrotic phenotypes, and unlike idiopathic pulmonary fibrosis, they have often been treated with anti-inflammatory drugs, including corticosteroids and immunosuppressants. However, the impact of bronchoalveolar lavage (BAL) lymphocytosis on the effects of anti-inflammatory therapy has never been evaluated. This study aimed to elucidate whether BAL lymphocytosis can be used to predict the efficacy of anti-inflammatory drugs for iNSIP, iPPFE, and unclassifiable IIP. METHODS: Japanese patients diagnosed with iNSIP, iPPFE, and unclassifiable IIP by multidisciplinary discussion were identified using the nationwide registry. Eligible patients were stratified into four groups with and without BAL lymphocytosis and anti-inflammatory therapy to compare overall survival (OS) and changes in lung function. BAL lymphocytosis was defined as a lymphocyte differential count > 15%, and the cut-off was corroborated by survival classification and regression tree analysis. RESULTS: Overall, 186 patients (37 iNSIP, 16 iPPFE, and 133 unclassifiable IIP) were analyzed. Limited to patients treated with anti-inflammatory drugs (n = 123), patients with BAL lymphocytosis had a better prognosis [hazard ratio (HR), 0.26; 95% confidence interval (CI), 0.11-0.63; P = 0.003], higher slope of forced vital capacity (FVC) % predicted for 2 years, and longer OS (log-rank test, P = 0.012) than those without BAL lymphocytosis. On multivariate analysis, BAL lymphocytosis (HR 0.31; 95% CI 0.13-0.75; P = 0.009) was a prognostic factor for OS, along with age and FVC % predicted. Conversely, for patients managed without anti-inflammatory therapy (n = 63), the presence or absence of BAL lymphocytosis had no prognostic value. CONCLUSIONS: BAL lymphocytosis is associated with good outcomes in patients treated with anti-inflammatory drugs, but has no prognostic value when anti-inflammatory drugs are not used. BAL lymphocytosis may provide a predictive biomarker for identifying patients with iNSIP, iPPFE and unclassifiable IIP who are likely to benefit from anti-inflammatory drugs.

Clinical factors associated with shorter durable response, and patterns of acquired resistance to first-line pembrolizumab monotherapy in PD-L1-positive non-small-cell lung cancer patients: a retrospective multicenter study.

BACKGROUND: Despite the wide-spread use of immune checkpoint inhibitors (ICIs) in cancer chemotherapy, reports on patients developing acquired resistance (AR) to ICI therapy are scarce. Therefore, we first investigated the characteristics associated with shorter durable responses of ICI treatment and revealed the clinical patterns of AR and prognosis of the patients involved. METHODS: We conducted a retrospective multi-center cohort study that included NSCLC patients with PD-L1 tumor proportion scores of ≥50% who received first-line pembrolizumab and showed response to the therapy. Among patients showing response, progression-free survival (PFS) was investigated based on different clinically relevant factors. AR was defined as disease progression after partial or complete response based on Response Evaluation Criteria in Solid Tumors. Among patients with AR, patterns of AR and post-progression survival (PPS) were investigated. Oligoprogression was defined as disease progression in up to 5 individual progressive lesions. RESULTS: Among 174 patients who received first-line pembrolizumab, 88 showed response and were included in the study. Among these patients, 46 (52%) developed AR. Patients with old age, poor performance status (PS), at least 3 metastatic organs, or bone metastasis showed significantly shorter PFS. Among 46 patients with AR, 32 (70%) developed AR as oligoprogression and showed significantly longer PPS than those with non-oligoprogressive AR. CONCLUSIONS: Patients with old age, poor PS, at least 3 metastatic organs, or bone metastasis showed shorter durable responses to pembrolizumab monotherapy. Oligoprogressive AR was relatively common and associated with better prognosis. Further research is required to develop optimal approaches for the treatment of these patients.

Increased risk of Legionella pneumonia as community-acquired pneumonia after heavy rainfall in 2018 in west Japan.

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.

Usefulness of ß-lactam and macrolide combination therapy for treating community-acquired pneumonia patients hospitalized in the intensive care unit: Propensity score analysis of a prospective cohort study.

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.

Molecular epidemiological characterization in mucoid-type Streptococcus pneumoniae isolates obtained from invasive pneumococcal disease patients in Japan.

INTRODUCTION: Streptococcus pneumoniae with a mucoid-type capsule is associated with invasive pneumococcal diseases (IPDs). Despite the introduction of pneumococcal vaccines, IPDs caused by mucoid-type isolates are still prevalent. The present study aimed to characterize mucoid-type S. pneumoniae isolated from IPD patients throughout Japan in 2017 (post-vaccination era). METHODS: A total of 225 mucoid-type isolates were collected. The serotype, antimicrobial susceptibility, and multilocus sequence type of these isolates were determined. RESULTS: The prevalence of IPDs caused by mucoid-type isolates was high in adults, especially in the elderly (≥65 years of age), and prognosis in these patients was significantly poor. Of the mucoid-type isolates, the predominant serotype was serotype 3 (84.4%), and the remaining were serotypes 37 (15.1%) and 8 (0.4%). Antimicrobial susceptibility showed that most mucoid isolates exhibited the penicillin-intermediate resistant S. pneumoniae genotype (gPISP). However, the serotype 3 isolate exhibited the penicillin-resistant S. pneumoniae genotype (gPRSP). This gPRSP isolate was classified into ST166, which is related to serotypes 9 V and 11 strains. Sequence analysis of the capsule-coding regions and its flanking regions indicated that recombination occurred upstream and downstream of the capsule-coding region, suggesting that gPRSP (serotype 9 V/ST166) obtaining the type-3 capsule gene cluster resulted in the emergence of gPRSP (serotype 3/ST166). CONCLUSIONS: Our findings indicated that IPDs caused by mucoid-type S. pneumoniae are still a serious concern and mucoid-type S. pneumoniae with novel phenotype could emerge via capsular switching in response to environmental changes such as introduction of vaccines and improper use of antimicrobial agents.

Clinical manifestations of adult patients requiring influenza-associated hospitalization: A prospective multicenter cohort study in Japan via internet surveillance.

INTRODUCTION: Influenza remains a clinically heavy burden worldwide. The objective of this study was to clarify clinical manifestations of severely ill patients infected with influenza. METHODS: The clinical data for patients who were severely ill with influenza, and required hospitalization were gathered and analyzed between November 2014 and August 2019 (5 influenza seasons) using an internet-surveillance system. RESULTS: A total of 924 patients were enrolled and analyzed. The median age was 78 years (IQR, 67-84), and the patients in the 2015-2016 season were significantly younger than those in other seasons. Pneumonia was the most common disease indicated as a cause for hospitalization, followed by a poor general condition and exacerbation of underlying respiratory diseases. Antiviral drugs were administered in 97.0% of the patients with peramivir being the most-frequently use antiviral. In-hospital death was recorded for 44 patients (4.8%). Multivariate analysis indicated that nursing home resident (OR: 6.554) and obesity (OR: 24.343) were independent predictors of in-hospital mortality. CONCLUSIONS: Complications of influenza infection remain a heavy burden especially among the elderly. Continuous nationwide surveillance will be required to grasp the actual situation of influenza epidemics. (UMIN000015989).

Prognostic factors in nursing and healthcare-associated pneumonia.

BACKGROUND AND OBJECTIVE: Nursing and healthcare-associated pneumonia (NHCAP) is a category of healthcare-associated pneumonia modified for the healthcare system in Japan. To date, only a few studies have examined the prognostic factors of NHCAP in a prospective cohort. This study aimed to investigate the prognostic factors related to 30-day mortality in patients with NHCAP by analyzing prospective data. METHODS: We analyzed patients hospitalized for NHCAP who were enrolled between October 2010 and February 2017. Age, sex, comorbidities, vital signs and laboratory findings were used as prognostic variables. The primary outcome was 30-day mortality. RESULTS: Of 817 NHCAP patients identified, the mean age was 78.0 ± 11.1 years, 580 (71.0%) were men and 30-day mortality was 13.1% (107/817). On multivariate analysis, male sex (odds ratio [OR]: 2.07, 95% confidence interval [CI]: 1.18-3.63), malignancy (OR: 2.35, 95%CI: 1.38-4.01), performance status (PS) (OR: 1.55, 95%CI: 1.23-1.96), body temperature (OR: 0.77, 95%CI: 0.61-0.97), heart rate (OR: 1.02, 95%CI: 1.01-1.03), respiratory rate (OR: 1.04, 95%CI: 1.01-1.08), serum albumin (Alb) (OR: 0.45, 95%CI: 0.30-0.66) and blood urea nitrogen (BUN) (OR: 1.02, 95%CI: 1.01-1.03) were significantly related to 30-day mortality. On the other hand, the risk factors for involvement by drug-resistant pathogens predicted a better prognosis (OR: 0.39, 95%CI: 0.19-0.82). CONCLUSIONS: Male sex, malignancy, poor PS, hypothermia, tachycardia, tachypnea, low serum Alb and high BUN are worse prognostic factors. Thus, the risk of drug-resistant pathogens is not necessarily related to poor prognosis.

Evaluation of pneumonia severity scoring systems in nursing and healthcare-associated pneumonia for predicting prognosis: A prospective, cohort study.

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.

Daily practice and prognostic factors for pneumonia caused by methicillin-resistant Staphylococcus aureus in Japan: A multicenter prospective observational cohort study.

Pneumonia caused by methicillin-resistant Staphylococcus aureus (MRSA) is associated with poor clinical outcomes. We surveyed clinical outcomes of MRSA pneumonia in daily practice to identify risk factors for the clinical failure and mortality in patients with MRSA pneumonia. This multicenter prospective observational study was performed across 48 Japanese medical institutions. Adult patients with culture-positive MRSA pneumonia were recruited and treated with anti-MRSA antibiotics. The relationships between clinical and microbiological characteristics and clinical outcomes at test of cure (TOC) or 30-day all-cause mortality were analyzed. In total, 199 eligible patients, including nursing and healthcare-associated pneumonia (n = 95), hospital-acquired pneumonia (n = 76), and community-acquired pneumonia (n = 25), received initial treatment with anti-MRSA agents such as vancomycin (n = 135), linezolid (n = 36), or teicoplanin (n = 22). Overall clinical failure rate at TOC and the 30-day mortality rate were 51.1% (48/94 patients) and 33.7% (66/196 patients), respectively. Multivariable logistic regression analyses for vancomycin-treated populations revealed that abnormal white blood cell count (odds ratio [OR] 4.34, 95% confidence interval [CI] 1.31-14.39) was a risk factor for clinical failure and that no therapeutic drug monitoring (OR 3.10, 95% CI 1.35-7.12) and abnormally high C-reactive protein level (OR 3.54, 95% CI 1.26-9.92) were risk factors for mortality. In conclusion, this study provides evidence that majority of MRSA pneumonia patients are initially treated with vancomycin in Japan, and the absence of therapeutic drug monitoring for vancomycin is significantly associated with the mortality in patients with MRSA pneumonia.

Therapeutic plasma exchange for clinically amyopathic dermatomyositis (CADM) associated with rapidly progressive interstitial pneumonia.

BACKGROUND: Patients with clinically amyopathic dermatomyositis (CADM) with anti-melanoma differentiation-associated gene 5 antibody (anti-MDA5 Ab) frequently develop rapidly progressive interstitial pneumonia (RPIP), often with fatal outcomes. Therapeutic plasma exchange (TPE) has been reported as effective against CADM-RPIP refractory to conventional immunosuppressive therapy. However, the detailed mechanisms by which TPE improves disease activity of CADM-RPIP remain unclear. AIM: To elucidate the clinical and demographic characteristics of patients with anti-MDA5 Ab-positive CADM-RPIP treated with TPE and to analyze changes in laboratory findings before, during, and after TPE. MATERIALS & METHODS: Patients hospitalized for CADM-RPIP and treated with TPE in 2017 and 2018 were analyzed retrospectively. RESULTS: Three patients were successfully treated with TPE, with good tolerance. Anti-MDA5 Ab titers decreased significantly over the course of TPE. CONCLUSION: We emphasize that TPE could represent an effective treatment option for CADM-RPIP refractory to traditional therapy. Removal of anti-MDA5 Ab and other pathogenic factors may facilitate favorable outcomes.

A Therapeutic Strategy for All Pneumonia Patients: A 3-Year Prospective Multicenter Cohort Study Using Risk Factors for Multidrug-resistant Pathogens to Select Initial Empiric Therapy.

BACKGROUND: Empiric therapy of pneumonia is currently based on the site of acquisition (community or hospital), but could be chosen, based on risk factors for multidrug-resistant (MDR) pathogens, independent of site of acquisition. METHODS: We prospectively applied a therapeutic algorithm based on MDR risks, in a multicenter cohort study of 1089 patients with 656 community-acquired pneumonia (CAP), 238 healthcare-associated pneumonia (HCAP), 140 hospital-acquired pneumonia (HAP), or 55 ventilator-associated pneumonia (VAP). RESULTS: Approximately 83% of patients were treated according to the algorithm, with 4.3% receiving inappropriate therapy. The frequency of MDR pathogens varied, respectively, with VAP (50.9%), HAP (27.9%), HCAP (10.9%), and CAP (5.2%). Those with ≥2 MDR risks had MDR pathogens more often than those with 0-1 MDR risk (25.8% vs 5.3%, P < .001). The 30-day mortality rates were as follows: VAP (18.2%), HAP (13.6%), HCAP (6.7%), and CAP (4.7%), and were lower in patients with 0-1 MDR risks than in those with ≥2 MDR risks (4.5% vs 12.5%, P < .001). In multivariate logistic regression analysis, 5 risk factors (advanced age, hematocrit <30%, malnutrition, dehydration, and chronic liver disease), as well as hypotension and inappropriate therapy were significantly correlated with 30-day mortality, whereas the classification of pneumonia type (VAP, HAP, HCAP, CAP) was not. CONCLUSIONS: Individual MDR risk factors can be used in a unified algorithm to guide and simplify empiric therapy for all pneumonia patients, and were more important than the classification of site of pneumonia acquisition in determining 30-day mortality. CLINICAL TRIALS REGISTRATION: JMA-IIA00146.

A Phase II Study of Cisplatin Plus Gemcitabine followed by Maintenance Gemcitabine for Advanced Squamous Non-Small-Cell Lung Cancer: Kyoto Thoracic Oncology Research Group 1302.

BACKGROUND: There has been no study so far on gemcitabine continuous maintenance therapy targeting only squamous non-small-cell lung cancer (NSCLC) patients. This study aimed to assess the efficacy and safety of cisplatin plus gemcitabine followed by maintenance gemcitabine for chemotherapy- naïve Japanese patients with advanced squamous NSCLC. METHODS: The patients received 4 cycles of gemcitabine (1,000 mg/m2, days 1 and 8) and cisplatin (80 mg/m2, day 1) every 3 weeks, followed by gemcitabine alone as maintenance therapy every 3 weeks until disease progression or unacceptable toxicity. The primary end point of the study was progression-free survival (PFS) from the date of registration. RESULTS: From May 2013 to October 2018, 26 patients were enrolled, and 25 patients received ≥1 cycle of planned treatment. Eighteen patients (69.2%) received 4 cycles of cisplatin plus gemcitabine, and 16 patients (61.5%) received ≥1 cycle of maintenance gemcitabine. The median PFS from the date of registration was 5.3 months (95% CI 2.9-7.3 months). In 16 patients who received ≥1 cycle of maintenance gemcitabine, the median PFS from the date of maintenance gemcitabine initiation was 3.8 months (95% CI 2.3-5.2 months). Their median overall survival from the date of registration was 11.9 months (95% CI 7.5-26.5 months). During the maintenance therapy, adverse events (AEs) were mostly Common Terminology Criteria for AE grade 1. CONCLUSIONS: While this trial did not meet the primary endpoint, the sufficient efficacy and feasibility of gemcitabine maintenance therapy were suggested.

Utility of procalcitonin for differentiating cryptogenic organising pneumonia from community-acquired pneumonia.

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.