Jun-ichi Kadota

Healthcare-associated Pneumonia and Aspiration Pneumonia

Healthcare-associated pneumonia (HCAP) is a new concept of pneumonia proposed by the American Thoracic Society/Infectious Diseases Society of America in 2005. This category is located between community-acquired pneumonia and hospital-acquired pneumonia with respect to the characteristics of the causative pathogens and mortality, and primarily targets elderly patients in healthcare facilities. Aspiration among such patients is recognized to be a primary mechanism for the development of pneumonia, particularly since the HCAP guidelines were published. However, it is difficult to manage patients with aspiration pneumonia because the definition of the condition is unclear, and the treatment is associated with ethical aspects. This review focused on the definition, prevalence and role of aspiration pneumonia as a prognostic factor in published studies of HCAP and attempted to identify problems associated with the concept of aspiration pneumonia.

Antibiotic susceptibility survey of blood-borne MRSA isolates in Japan from 2008 through 2011

We conducted an antibiotic susceptibility survey of 830 blood-borne methicillin resistant Staphylococcus aureus collected from nationwide hospitals in Japan over a three-year period from January 2008 through May 2011. Antibiotic susceptibility was judged according to the criteria recommended by the Clinical Laboratory Standard Institute. Over 99% of the MRSA showed to be susceptible to teicoplanin, linezolid, sulfamethoxazole/trimethoprim and vancomycin, and over 97% of them were susceptible to daptomycin, arbekacin and rifampin. The majority of the MRSA strains showed resistant to minocycline, meropenem, imipenem, clindamycin, ciprofloxacin, cefoxitin, and oxacillin in the rates of 56.6, 72.9, 73.7, 78.7, 89.0, 99.5, and 99.9%, respectively. Among the MRSA strains, 72 showed reduced susceptibility to vancomycin, including 8 strains (0.96%) of vancomycin-intermediate S. aureus (VISA), 54 (6.51%) of heterogeneous vancomycin-intermediate S. aureus (hVISA), and 55 (5.63%) of β-lactam antibiotics-induced vancomycin resistant S. aureus (BIVR). Unexpectedly, among the 54 hVISA and 55 BIVR, 45 isolates (83.3% and 81.8%, respectively) showed both hVISA and BIVR phenotypes. A new trend of vancomycin resistance found in this study was that VISA strains were still prevalent among the bacteremic specimens. The high rates of the hVISA/BIVR two-phenotypic vancomycin resistance, and the prevalence of VISA in the bloodborne MRSA call attention in the MRSA epidemiology in Japan.

Nationwide surveillance of 6 otorhinolaryngological infectious diseases and antimicrobial susceptibility pattern in the isolated pathogens in Japan.

The Japanese Three Academic Societies Joint Antimicrobial Susceptibility Surveillance Committee has conducted a nationwide surveillance on antimicrobial susceptibility patterns and rates of isolation in 6 otolaryngological diseases. The surveillance program was conducted in the otorhinolaryngological departments of 29 universities, and their 26 affiliated hospitals. Patients suffering from acute otitis media, chronic otitis media, acute nasal sinusitis, chronic nasal sinusitis, acute tonsillitis, and peritonsillar abscess between January 2011 and June 2012 were investigated. The collected swab or incision samples were cultivated for microbial identification, and the drug susceptibility of detected bacteria was measured at the Kitasato University Research Center for Infections and Antimicrobials. The surveillance focused on three gram-positive bacteria (Streptococcus pneumoniae, Streptococcus pyogenes, and Staphylococcus aureus), three gram-negative bacteria (Haemophilus influenzae, Moraxella Catarrhalis, and Pseudomonas aeruginosa), and three anaerobic bacteria (Peptostreptococcus spp., Prevotella spp., and Fusobacterium spp.). Bacterial susceptibility to 39 antimicrobial drugs was investigated. We compared bacterial isolation ratio of each disease in this surveillance from those of past 4 times surveillance which we performed formerly, and we also compared percentage of main drug resistant strains from those of past 4 times surveillance. The age composition between this time and former surveillances was not statistically significant by student-t test. We were unable to completely resolve the rise in resistant bacteria, such as methicillin-resistant S. aureus, penicillin-resistant S. pneumoniae, penicillin-intermediate resistant S. pneumoniae, beta-lactamase non-producing ampicillin-resistant H. influenzae, beta-lactamase producing ampicillin-resistant H. influenzae, and beta-lactamase producing amoxicillin clavulanic acid-resistant H. influenzae. We suggest promoting the proper usage of antimicrobial drugs in order to avoid the spread of these bacteria.

A retrospective analysis to estimate target trough concentration of vancomycin for febrile neutropenia in patients with hematological malignancy.

BACKGROUND The target trough concentration of vancomycin in patients with febrile neutropenia has not been reported. The aim of this study was to estimate the target trough concentration for febrile neutropenia in patients with hematological malignancy. METHODS In this retrospective, single-center, observational cohort study, 63 hospitalized patients with hematological malignancy who were treated with vancomycin for febrile neutropenia due to bacteriologically documented or presumptive Gram-positive infections were analyzed. RESULTS A significant difference in the first trough concentration of vancomycin was observed between the response and non-response groups, and between the nephrotoxicity and non-nephrotoxicity groups. Multiple logistic regression analyses identified the first trough concentration as the only independent variable associated with clinical efficacy and nephrotoxicity of vancomycin. The areas under the ROC curves were 0.72 and 0.83 for clinical efficacy and nephrotoxicity, respectively. The cut-off values of the first trough concentration were 11.1 μg/ml for clinical efficacy (sensitivity 60%, specificity 87%) and 11.9 μg/ml for nephrotoxicity (sensitivity 77%, specificity 82%). CONCLUSIONS These results suggest a relationship of trough vancomycin concentration with clinical efficacy and incidence of nephrotoxicity. We propose a target trough vancomycin concentration of around 11.5 μg/ml for febrile neutropenia in patients with hematological malignancy.

Long-term, low-dose erythromycin monotherapy for Mycobacterium avium complex lung disease: A propensity score analysis

Multidrug regimens are initially withheld in mild cases of pulmonary Mycobacterium avium complex (MAC) disease. Based on the anti-inflammatory effects of macrolides, some patients are treated with erythromycin, which does not appear to exhibit cross-resistance with clarithromycin in MAC. The aim of this study was to evaluate the effects and adverse events of erythromycin monotherapy in patients with pulmonary MAC disease. This was a retrospective propensity score analysis consisting of 31 patients treated with erythromycin alone and 72 patients on conservative therapy, all of whom met the ATS/IDSA criteria for pulmonary MAC disease. The primary outcome was exacerbation requiring administration of a multidrug regimen. The secondary outcome was the rate of response to the multidrug regimens after exacerbation as a surrogate variable for cross-resistance to clarithromycin. As a result, erythromycin monotherapy was found to be likely to suppress exacerbation throughout the 7-year observation period after the diagnosis of pulmonary MAC disease (P=0.045, Breslow test). Multivariate analysis showed that erythromycin tended to prevent exacerbation, albeit statistically insignificantly (hazard ratio=0.495, 95% confidence interval 0.198-1.235; P=0.132). In addition, the rate of response to the multidrug regimens after exacerbation in the erythromycin group (56%; 5/9) was similar to that observed in the control group (62%; 13/21) (P=0.528). Erythromycin monotherapy for patients with pulmonary MAC disease may have the potential to suppress exacerbation without inducing cross-resistance to clarithromycin. However, further prospective studies are needed to microbiologically verify the effectiveness and potential for cross-resistance of these drugs.

Exophiala dermatitidis pneumonia successfully treated with long-term itraconazole therapy

Exophiala dermatitidis pneumonia is extremely rare. Here we report a case of E. dermatitidis pneumonia successfully treated with long-term itraconazole therapy. A 63-year-old woman without a remarkable medical history developed a dry and chest pain. Chest radiographs revealed consolidation in the middle lobe of the lung. Cytologic examination by bronchoscopy showed filamentous fungi and E. dermatitidis was detected in the bronchoalveolar lavage fluid. After 5 months of itraconazole therapy, her symptoms improved and the area of consolidation diminished. Two weeks after discontinuing the itraconazole therapy, the area of consolidation reappeared. Itraconazole therapy was restarted and continued for 7 months. The abnormal shadow observed on the chest X-ray gradually diminished. Over a 27-month follow-up with periodic examination, there was no relapse and the patient had a favorable clinical course.

Poor pharmacological adherence to inhaled medicines compared with oral medicines in Japanese patients with asthma and chronic obstructive pulmonary disease

Poor pharmacological adherence (adherence) is a problem that reduces quality of life in patients with chronic diseases and leads to wastage of health care resources.1,2 Few comparative studies of adherence to inhaled and oral medicines have been performed in Japanese patients with asthma and chronic obstructive pulmonary disease (COPD).3,4 To investigate adherence levels to inhaled medicines, a multicenter, cross-sectional non-interventional trial was conducted in Japanese patients who had regular use of both inhaled and oral medicines for asthma or COPD by the Kyushu Asthma Seminar Investigator Group, which was approved by each local ethics board (UMIN No. R000015329) (Supplementary Material: Table 1). To investigate adherence in consecutive outpatients with asthma (aged 20 and <80 years) and COPD (aged 40 and <80 years) who were taking at least one regular prescribed inhaled and oral medication without changes in regimens for >6 months (Supplementary Material: Table 2), one inhaled and one oral medicine were selected as the most important among all regular prescribed medicines [mean (±standard deviation) was the number of different inhaled devices and oral medicines (range) 1⁄4 1.1 ± 0.4 (1e3) and 4.3 ± 3.0 (1e18) available to patients with asthma; 1.5 ± 0.5 (1e3) and 5.0 ± 4.1 (1e22) in patients with COPD, respectively] by each physician without consultation with the patient (Supplementary Material). Adherence levels were examined by questionnaire and prescription refill method. The characteristics and lung function data within 6 months of patients were obtained after written consent (see Supplementary Material for definition and control levels of asthma and COPD). Poor adherence to medicines was defined on the basis of <80% adherence to selected inhaled or oral medicines by either the questionnaire or prescription refill method.5,6 We statistically compared the populations of patients with poor adherence to selected inhaled and oral medicines, and calculated the odds ratios [95% confidential interval (CI)] of poor adherence to inhaled medicines in total patients (asthma and COPD), patients with asthma, and patients with COPD by using a Fishers exact tests. By univariate and multivariate analyses, we investigated the risk factors as patient-, social-, and treatment-related factors [odds ratios (95% CI)] for poor adherence to inhaled medicines to compare patients with and without poor

Update and recent advances on the management of invasive and chronic pulmonary aspergillosis

A large amount of information on deep-seated mycosis, including pulmonary aspergillosis, has been recently accumulated, and the guidelines for its management have been published in many countries, including Europe, the United States of America, and Japan. Although various types of pulmonary aspergillosis were recognized in the past, they have recently been categorized as invasive pulmonary aspergillosis (IPA), chronic pulmonary aspergillosis (CPA), and allergic bronchopulmonary aspergillosis. However, studies regarding deep-seated mycosis are limited and its management remains controversial. Therefore, reviews regarding invasive fungal diseases, especially the review on aspergillosis by Geltner [1] and chronic pulmonary aspergillosis (CPA) by Izumikawa [2], would provide us with new information based on recent evidences. The review by Geltner focuses on IPA, typically occurring in patients undergoing stem cell and organ transplantations. Organ transplantations have been increasing worldwide, with no exception in Japan, and the patients most commonly affected by fungal infections are the ones undergoing lung transplantation. Since the typical manifestation of fungal infection is lung involvement, which has a high mortality rate, it is important for pulmonologist to recognize invasive pulmonary mycosis, especially IPA. This review summarized the incidence and frequency of filamentous fungal infection, site of lung involvement, diagnostic methods, usefulness of antifungal prophylaxis, and therapeutic strategies including the emergence of drug resistance. Interestingly, bronchoscopic examination, as shown in the figures of the bronchoscopic views in this review, has been useful in diagnosing bronchial aspergillosis and fungal invasions such as tracheobronchial aspergillosis and anastomositis after lung transplantation. Additionally, immune reconstitution syndrome as a new pathogenetic mechanism of lung disease would be worthy of special mention. A published review by Izumikawa provides the latest information on CPA mainly based on studies conducted in Japan, and it includes information stated in the revised Japanese Guidelines for management of deep-seated mycosis published in 2014. The focus of this review was to describe a new entity of CPA. As observed in the last decade, the entities of chronic forms of aspergillosis have been extremely complicated involving several subtypes such as chronic necrotizing pulmonary

Angiopoietin-2 expression in patients with an acute exacerbation of idiopathic interstitial pneumonias

BACKGROUND AND OBJECTIVE We hypothesized that increased pulmonary vascular permeability may play a role in the pathogenesis of an acute exacerbation of the idiopathic interstitial pneumonias (AE-IIPs). Angiopoietin-2 (Ang-2) promotes endothelial activation, destabilization, and inflammation. The purpose of this study was to examine whether Ang-2 expression was associated with the pathogenesis of AE-IIPs. METHODS Twenty-three patients with AE-IIP patients, 18 acute lung injury/acute respiratory distress syndrome (ALI/ARDS) patients, 37 idiopathic pulmonary fibrosis (IPF) patients, and 33 healthy volunteers (HVs) were enrolled. The serum level of Ang-2 was measured by an enzyme-linked immunosorbent assay. RESULTS The serum levels of Ang-2 were higher in AE-IIPs and ALI/ARDS patients than in IPF patients and HVs; the BALF levels of Ang-2 were also higher than in IPF patients. There was a positive correlation between the serum level of Ang-2 and the CRP in patients with AE-IIP patients, whereas a significant positive correlation was found between the serum Ang-2 level and the CRP or SOFA scores of the ALI/ARDS patients. Although the baseline Ang-2 level was not related to survival, the Ang-2 levels significantly declined in survivors during treatment, while they did not change in non-survivors. CONCLUSIONS Increased pulmonary vascular permeability and inflammation due to Ang-2 may play a role in the pathogenesis of AE-IIPs.

Evaluation of prognostic differences in elderly patients with pneumonia treated by between pulmonologists and non-pulmonologists: a propensity score analysis.

The incidence of pneumonia among elderly people is increasing in aged countries, and both pulmonologists and non‐pulmonologists treat such patients.