Hisamichi Yuda

A New Strategy for Healthcare-Associated Pneumonia: A 2-Year Prospective Multicenter Cohort Study Using Risk Factors for Multidrug-Resistant Pathogens to Select Initial Empiric Therapy

BACKGROUND Optimal empiric therapy for hospitalized patients with healthcare-associated pneumonia (HCAP) is uncertain. METHODS We prospectively applied a therapeutic algorithm, based on the presence of risk factors for multidrug-resistant (MDR) pathogens in a multicenter cohort study of 445 pneumonia patients, including both community-acquired pneumonia (CAP; n = 124) and HCAP (n = 321). RESULTS MDR pathogens were more common (15.3% vs 0.8%, P < .001) in HCAP patients than in CAP patients, including Staphylococcus aureus (11.5% vs 0.8%, P < .001); methicillin-resistant S. aureus (6.9% vs 0%, P = .003); Enterobacteriaceae (7.8% vs 2.4%, P = .037); and Pseudomonas aeruginosa (6.9% vs 0.8%, P = .01). Using the proposed algorithm, HCAP patients with ≥2 MDR risk factors, one of which was severity of illness (n = 170), vs HCAP patients with 0-1 risk factor (n = 151) had a significantly higher frequency of MDR pathogens (27.1% vs 2%, P < .001). In total, 93.1% of HCAP patients were treated according to the therapy algorithm, with only 53% receiving broad-spectrum empiric therapy, yet 92.9% received appropriate therapy for the identified pathogen. Thirty-day mortality was significantly higher for HCAP than for CAP (13.7% vs 5.6%, P = .017), but among HCAP patients with 0-1 MDR risk factor, mortality was lower than with ≥2 MDR risk factors (8.6% vs 18.2%, P = .012). In multivariate analysis, initial treatment failure, but not inappropriate empiric antibiotic therapy, was a mortality risk factor (odds ratio, 72.0). CONCLUSIONS Basing empiric HCAP therapy on its severity and the presence of risk factors for MDR pathogens is a potentially useful approach that achieves good outcomes without excessive use of broad-spectrum antibiotic therapy. CLINICAL TRIALS REGISTRATION Japan Medical Association Center for Clinical Trials, JMA-IIA00054.

Activation of protein C pathway in the airways.

The protein C (PC) pathway plays important roles in the regulation of the coagulation system and inflammatory response. This study evaluated the degree of PC activation in the airway of patients with bronchial asthma (BA), and the expression and regulation of PC and its receptor in airway epithelial cell lines. Thirteen BA patients and 8 healthy volunteers were enrolled in the study. BEAS-2B and A549 epithelial cell lines were used in experimental assays. Expression of anticoagulant factors was evaluated by RT-PCR and Western blotting. The activated protein C (APC)/thrombin (1.65 +/- 0.35 vs 3.34 +/- 0.59) and APC/PC (8.30 +/- 2.26 vs 24.41 +/- 9.88) ratios were significantly decreased and the concentrations of soluble thrombomodulin (TM) were significantly increased in induced sputum from BA patients compared with healthy subjects. Airway epithelial cells express PC, its receptor, and TM. PC antigen prepared from epithelial cells was significantly activated in the presence of thrombin. Thrombin increased the expression of PC antigen from lung epithelial cells. However, tumor necrosis factor-alpha, eotaxin, and RANTES (regulated on activation, normal T-cell expressed and secreted) decreased the expression of PC and its receptor in bronchial epithelial cells. Overall, these results showed for the first time that reduced activation of PC pathway occurs in the airway of BA patients and that TM, PC, and its receptor, are expressed by human airway epithelial cells. The expression of these PC pathway components was found to be downregulated by inflammatory cytokines. The decrease in PC activation may contribute to exacerbation of the inflammatory response in the airway of asthmatic patients.

Community-acquired pneumonia and nursing home-acquired pneumonia in the very elderly patients

The rapid increase in the elderly population is leading to a corresponding increase in the number of people requiring medical care. To date no comparative study between community-acquired pneumonia (CAP) and nursing home-acquired pneumonia (NHAP) has been reported in the very elderly non-intubated patients. The present study was undertaken to compare the clinical characteristics and microbial etiology between CAP and NHAP in elderly patients >/=85-years old. There were 54 patients with NHAP and 47 with CAP. Performance status was significantly worse in the NHAP than in the CAP group. Among all patients, the most frequent pathogens were Chlamydophilia pneumoniae followed by Streptococcus pneumoniae, Mycoplasma pneumoniae influenza virus and Staphylococcus aureus. The frequency of S. peumoniae was significantly higher in NHAP patients than in CAP patients after adjusting for age and sex. Physical activity, nutrition status and dehydration were significant prognostic factors of pneumonia among all patients. In-hospital mortality was significantly higher in NHAP than in CAP after adjusting for age and sex. This study demonstrated that the etiology and clinical outcome differ between CAP and NHAP patients in the very elderly non-intubated population.

Decreased protein C activation is associated with abnormal collagen turnover in the intraalveolar space of patients with interstitial lung disease.

Activation of the coagulation system in the alveo lar space plays an important role in the pathogenesis of inter stitial lung disease (ILD) and pulmonary fibrosis. The protein C (PC) pathway is the main modulator of coagulation activation. This study evaluated whether dysfunction of the PC pathway is associated with increased collagen synthesis in the intraalveolar space of patients with ILD. This study comprised 22 patients with ILD; of these, five had idiopathic pulmonary fibrosis (IPF), nine had sarcoidosis-associated ILD, and eight had col lagen vascular disease-associated ILD (CVD-ILD). Thrombin— antithrombin complex (TAT) was measured as a marker of coagulation activation. As markers of the PC pathway activity, the concentration of activated PC-PC inhibitor (APC-PCI) complex and the APC-PCI/PC ratio were measured and, as a marker of collagen synthesis, the concentration of aminotermi nal propeptide of type III procollagen (PIIINP) was measured in bronchoalveolar lavage fluid (BALF) of ILD patients. TAT was significantly increased in BALF from ILD patients as com pared to control subjects. The concentrations of PIIINP were significantly elevated in patients with ILD as compared to healthy subjects. In contrast, the concentration of APC-PCI and the values of APC-PCI/PC ratio were significantly de creased in BALF from patients with ILD. BALF concentration of PIIINP was significantly and inversely correlated with the concentration of APC-PCI and with the APC-PCI/PC ratio. These findings suggest that dysfunction of the protein C path way may have important physiopathologic implications in the development of pulmonary fibrosis in ILD.

Dose-dependent differential effects of thrombin in allergic bronchial asthma

Apart from its role in the coagulation system, thrombin plays an important role in the inflammatory response through its protease‐activated receptors (PARs). However, the role of thrombin in the immune response is not clear.

Ct Scores of Emphysema and Oxygen Desaturation During Low-Grade Exercise in Patients with Emphysema

PURPOSE We evaluated the usefulness of CT for assessing oxygen desaturation during walking in patients with emphysema. MATERIAL AND METHODS The study comprised 32 patients with emphysema (mean age 67+/-6 years). Serial CT images of 5 mm were obtained from the apex to the basal regions of the lung during deep inspiration. The severity of emphysema was scored by four physicians according to a visual method. A six-minute walking test and oxygen desaturation (pSO2) measurements were performed. RESULTS AND CONCLUSION The mean CT score of the four observers was significantly correlated with the nadir pSO2 and deltapSO2, but did not correlate with the total distance walked. These results suggest that CT may be used for the assessment of oxygen desaturation during low-grade exercise in patients with emphysema.