Serum Procalcitonin Levels Predict Mortality Risk in Patients With Pulmonary Tuberculosis: A Single-Center Prospective Observational Study.

Globally, tuberculosis is the leading infectious cause of death; discovering biomarkers that predict a high mortality risk may improve treatment outcomes. We prospectively enrolled 252 pulmonary tuberculosis patients who were not coinfected with human immunodeficiency virus and initiated antituberculosis treatment, measured serum procalcitonin levels (PCT), and assessed mortality risk. PCT serum levels higher than 0.13 (day 0), 0.05 (day 7), 0.12 (day 14), or 0.06 (day 28) ng/mL predicted nonsurvivors with odds ratios of 7.9, 14.3, 20.0, and 7.3, respectively (P ≤ .005 for all), respectively. Therefore, serum PCT levels are a promising mortality risk indicator for patients with pulmonary tuberculosis. Main Point. For patients with pulmonary tuberculosis, a promising mortality risk indicator is the level of serum procalcitonin, which is weakly associated with sputum bacterial load and independent of radiographic findings.

Nationwide surveillance of bacterial respiratory pathogens conducted by the surveillance committee of Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2012: General view of the pathogens' antibacterial susceptibility.

The nationwide surveillance on antimicrobial susceptibility of bacterial respiratory pathogens from the patients in Japan was conducted by Japanese Society of Chemotherapy, Japanese association for infectious diseases and Japanese society for Clinical Microbiology in 2012. The isolates were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections during the period between January and December in 2012 by three societies. Antimicrobial susceptibility testing was conducted at the central reference laboratory according to the method recommended by Clinical Laboratory Standard Institutes. Susceptibility testing was evaluated in 1236 strains (232 Staphylococcus aureus, 225 Streptococcus pneumoniae, 16 Streptococcus pyogenes, 231 Haemophilus influenzae, 147 Moraxella catarrhalis, 167 Klebsiella pneumoniae and 218 Pseudomonas aeruginosa). Ratio of methicillin-resistant S. aureus was 51.3%, and those of penicillin-intermediate S. pneumoniae was 0.4%. Among H. influenzae, 5.6% of them were found to be ß-lactamase-producing ampicillin-resistant strains, and 37.2% to be ß-lactamase-non-producing ampicillin-resistant strains. Extended spectrum ß-lactamase-producing K. pneumoniae and multi-drug resistant P. aeruginosa with metallo ß-lactamase were 4.2% and 3.2%, respectively. Continuous national surveillance is important to determine the actual situation of the resistance shown by bacterial respiratory pathogens to antimicrobial agents.

IL-17A synergistically stimulates TNF-α-induced IL-8 production in human airway epithelial cells: A potential role in amplifying airway inflammation.

BACKGROUND: Recent reports have suggested an involvement of neutrophilic inflammation driven by interleukin (IL)-17 from Th17 cells, especially in severe, refractory asthma. It remains unknown about the possible interactions of this cytokine and other proinflammatory cytokines to direct neutrophilic airway inflammation. MATERIALS AND METHODS: We evaluated the effects of IL-17A, IL-17E, and IL-17F in combination with other stimuli such as tumor necrosis factor (TNF) -α on the production and expression of IL-8 in human bronchial epithelial cells. We also studied their effects on other cytokine production. The possible role of mitogen-activated protein kinase (MAPK) and nuclear factor-kappa B (NF-κB) signaling pathways was evaluated by specific inhibitors. We examined the effects of anti-asthma drugs, such as steroids or salmeterol. RESULTS: IL-17A alone induced only a minimal effect on IL-8 expression. IL-17A, but not IL-17E or IL-17F, in combination with TNF-α showed a synergistic effect on IL-8 expression. Similar findings were found when combination with IL-1ß and IL-17A were used, but such was not the case with lipopolysaccharide (LPS). In addition, we further found such synergy on GM-CSF production. The synergy with TNF-α and IL-17A was significantly inhibited by MAPKs inhibitors. Corticosteroids such as fluticasone propionate and dexamethasone, but not salmeterol, partially suppressed the IL-17A and TNF-α-induced IL-8 production. CONCLUSIONS: IL-17A in the combination with TNF-α or IL-1ß showed a synergistic augmenting effect on IL-8 and GM-CSF production in human airway epithelial cells.

Clarithromycin ameliorates pulmonary inflammation induced by short term cigarette smoke exposure in mice.

BACKGROUND: Cigarette smoking is considered to be one of major causes of acute worsening of asthma as well as chronic obstructive pulmonary disease (COPD). Macrolide antibiotics have been reported to reduce the risk of exacerbations of COPD, and possibly neutrophilic asthma. However, the effect of clarithromycin (CAM) on pulmonary inflammation caused by short term exposure to cigarette smoke still remains to be investigated. METHODS: C57BL/6J female mice were daily exposed to tobacco smoke using a tobacco smoke exposure system, or clean air for 8 days, while simultaneously treated with either oral CAM or vehicles. Twenty four hours after the last exposure, mice were anaesthetized and sacrificed, and bronchoalveolar lavage (BAL) fluids were collected. Cellular responses in BAL fluids were evaluated. Levels of cytokine mRNA in the lung tissues were measured by quantitative RT-PCR. Paraffin-embedded lung tissues were evaluated to quantitate degree of neutrophil infiltration. RESULTS: The numbers of total cells, macrophages and neutrophils in the BAL fluid of smoke-exposed mice were significantly increased as compared to clean air group. These changes were significantly ameliorated in CAM-treated mice. The lung morphological analysis confirmed decrease of neutrophils by CAM treatment. Studies by quantitative PCR demonstrated CAM treatment significantly reduced lung expression levels of IL-17A, keratinocyte-derived chemokine (KC), granulocyte-macrophage colony stimulating factor (GM-CSF) and MMP-9 induced by cigarette smoke. CONCLUSION: We demonstrate that CAM administration resolves enhanced pulmonary inflammation induced by short term cigarette smoke exposure in mice.

Interleukin-10 modulates pulmonary neutrophilic inflammation induced by cigarette smoke exposure.

AIM OF THE STUDY: Interleukin (IL)-10 is an anti-inflammatory cytokine, but its role in cigarette smoke (CS)-induced inflammation and chronic obstructive pulmonary disease (COPD) has not been fully elucidated. The purpose of this study was to investigate the effect of IL-10 deficiency on CS-induced pulmonary inflammation in mice in vivo and in vitro. MATERIALS AND METHODS: IL-10-deficient and wild-type control mice with a C57BL6/J genetic background were exposed to CS, and inflammatory cells in bronchoalveolar lavage fluid (BALF) and mRNA of cytokines in lung were evaluated with enzyme-linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT-PCR). RESULTS: During 12 days of daily CS exposure to wild-type mice, neutrophil counts in BAL fluid and tumor necrosis factor (TNF)-α mRNA expression were increased, peaked at day 8, and then declined on day 12 when the level of IL-10 reached its peak. In IL-10-deficient mice, neutrophil recruitment and TNF-α mRNA levels induced by CS exposure were significantly greater than those in wild-type mice. Keratinocyte-derived chemokine (KC; murine ortholog of human CXCL8) and granulocyte macrophage colony-stimulating factor (GM-CSF) mRNA levels or matrix metalloproteinase(MMP)-9 protein levels were not correlated with neutrophil count. CONCLUSIONS: IL-10 had a modulatory effect on CS-induced pulmonary neutrophilic inflammation and TNF-α expression in mice in vivo and therefore appears to be an important endogenous suppressor of airway neutrophilic inflammation.

Nationwide surveillance of bacterial respiratory pathogens conducted by the surveillance committee of Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2010: General view of the pathogens' antibacterial susceptibility.

The nationwide surveillance on antimicrobial susceptibility of bacterial respiratory pathogens from patients in Japan, was conducted by Japanese Society of Chemotherapy, Japanese Association for Infectious Diseases and Japanese Society for Clinical Microbiology in 2010. The isolates were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections during the period from January and April 2010 by three societies. Antimicrobial susceptibility testing was conducted at the central reference laboratory according to the method recommended by Clinical and Laboratory Standard Institutes using maximum 45 antibacterial agents. Susceptibility testing was evaluable with 954 strains (206 Staphylococcus aureus, 189 Streptococcus pneumoniae, 4 Streptococcus pyogenes, 182 Haemophilus influenzae, 74 Moraxella catarrhalis, 139 Klebsiella pneumoniae and 160 Pseudomonas aeruginosa). Ratio of methicillin-resistant S. aureus was as high as 50.5%, and those of penicillin-intermediate and -resistant S. pneumoniae were 1.1% and 0.0%, respectively. Among H. influenzae, 17.6% of them were found to be ß-lactamase-non-producing ampicillin (ABPC)-intermediately resistant, 33.5% to be ß-lactamase-non-producing ABPC-resistant and 11.0% to be ß-lactamase-producing ABPC-resistant strains. Extended spectrum ß-lactamase-producing K. pneumoniae and multi-drug resistant P. aeruginosa with metallo ß-lactamase were 2.9% and 0.6%, respectively. Continuous national surveillance of antimicrobial susceptibility of respiratory pathogens is crucial in order to monitor changing patterns of susceptibility and to be able to update treatment recommendations on a regular basis.

[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibacterial agents (2010)].

From October 2010 to September 2011, we collected the specimen from 361 patients with lower respiratory tract infections in 16 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various antibacterial agents and patients' characteristics. All of 399 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in infection, were examined. The isolated bacteria were: Staphylococcus aureus 70, Streptococcus pneumoniae 65, Haemophilus influenzae 72, Pseudomonas aeruginosa (non-mucoid) 47, P. aeruginosa (mucoid) 14, Klebsiella pneumoniae 30, and Moraxella catarrhalis 39. Of 70 S. aureus strains, those with 2 µg/mL or less of MIC of oxacillin (methicillin-susceptible S. aureus: MSSA) and those with 4 µg/mL or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) were 45 (64.3%) and 25 (35.7%) strains, respectively. Against MSSA, imipenem had the most potent antibacterial activity and inhibited the growth of all strains at 0.063 µg/mL or less. Against MRSA, vancomycin and arbekacin showed the potent activity and inhibited the growth of all the strains at 2 µg/mL. Linezolid also showed the great activity and inhibited the growth of all the strains at 2 µg/mL. Carbapenems and penems showed the most potent activities against S. pneumoniae and panipenem inhibited the growth of all the strains at 0.125 µg/mL. Imipenem and faropenem also had a preferable activity and inhibited the growth of all the strains at 0.5 and 1 µg/mL, respectively. In contrast, there were high-resistant strains (MIC: > 128 µg/mL) for erythromycin (44.6%) and clindamycin (24.6%). Against H. influenzae, levofloxacin showed the most potent activity and its MIC90 was 0.063 µg/mL or less. Meropenem showed the most potent activity against P. aeruginosa (mucoid) and its MIC90 was 0.5 µg/mL. Against the non-mucoid type of P. aeruginosa, tobramycin had the most potent activity and its MIC90 was 2 µg/mL. Against K. pneumoniae, cefozopran had the most potent activity and inhibited the growth of all the strains at 0.063 µg/mL or less. All the antibacterial agents except ampicillin generally showed a potent activity against M. catarrhalis and the MIC90 of them were 2 µg/mL or less. The majority number (54.8%) of the patients with respiratory infection was aged 70 years or older. Bacterial pneumonia and chronic bronchitis accounted for 58.7% and 24.4% of all the respiratory infection, respectively. The bacteria frequently isolated from the patients with bacterial pneumonia were S. aureus (20.6%), S. pneumoniae (18.0%), H. influenzae (13.6%), and P. aeruginosa (13.6%). S. aureus (17.2%), H. influenzae (20.2%), and P. aeruginosa (17.2%) also were frequently isolated from the patients with chronic bronchitis. The bacteria frequently isolated from the patients were S. pneumoniae (20.0%) and H. influenzae (20.0%) before administration of the antibacterial agents. The bacteria frequently isolated from the patients previously treated with cephems were S. aureus and H. influenzae, and the isolation frequencies were 25.0% and 20.0%, respectively. The bacteria frequently isolated from the patients previously treated with macrolides were P. aeruginosa and H. influenzae, the isolation frequencies were 25.9% and 22.2%, respectively.

[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibacterial agents (2011)].

From October 2011 to September 2012, we collected the specimen from 316 patients with lower respiratory tract infections in 16 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various antibacterial agents and patients' characteristics. All of 357 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in infection, were examined. The isolated bacteria were: Staphylococcus aureus 51, Streptococcus pneumoniae 73, Haemophilus influenzae 88, Pseudomonas aeruginosa (non-mucoid) 34, P. aeruginosa (mucoid) 9, Klebsiella pneumoniae 21, and Moraxella catarrhalis 33. Of 51 S. aureus strains, those with 2 µg/mL or less of MIC of oxacillin (methicillin-susceptible S. aureus: MSSA) and those with 4 µg/mL or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) were 31 (60.8%) and 20 (39.2%) strains, respectively. Against MSSA, imipenem had the most potent antibacterial activity and inhibited the growth of all strains at 0.063 µg/mL or less. Against MRSA, vancomycin showed the potent activity and inhibited the growth of all the strains at 1 µg/mL. Linezolid also showed the great activity and inhibited the growth of all the strains at 2 µg/mL. Carbapenems and penems showed the most potent activities against S. pneumoniae and panipenem inhibited the growth of all the strains at 0.125 µg/mL. Imipenem and faropenem also had a preferable activity and inhibited the growth of all the strains at 0.5 and 1 µg/mL, respectively. In contrast, there were high-resistant strains (MIC: > 128 µg/mL) for erythromycin (53.4%) and clindamycin (3 5.6%). Against H. influenzae, levofloxacin showed the most potent activity and its MIC90 was 0.063 µg/mL or less. Ciprofloxacin showed the most potent activity against P. aeruginosa (mucoid) and inhibited the growth of all the strains at 2 µg/mL or less. Against the non-mucoid type of P. aeruginosa, tobramycin had the most potent activity and its MIC90 was 2 µg/mL. Against K. pneumoniae, imipenem had the most potent activity and inhibited the growth of all the strains at 0.125 µg/mL. All the antibacterial agents except ampicillin generally showed a potent activity against M catarrhalis and the MIC90 of them were 2 µg/mL or less. The majority number (52.9%) of the patients with respiratory infection was aged 70 years or older. Bacterial pneumonia and chronic bronchitis accounted for 59.2% and 19.3% of all the respiratory infection, respectively. The bacteria frequently isolated from the patients with bacterial pneumonia were S. aureus (17.8%), S. pneumoniae (21.6%), and H. influenzae (16.9%). H. influenzae (36.8%) and S. pneumoniae (22.1%) also were frequently isolated from the patients with chronic bronchitis. The bacteria frequently isolated from the patients were S. pneumoniae (23.2%) and H. influenzae (27.3%) before administration of the antibacterial agents. The bacteria frequently isolated from the patients previously treated with cephems were H. influenzae and P. aeruginosa, and the isolation frequencies were 38.5% and 23.1%, respectively. The bacteria frequently isolated from the patients previously treated with macrolides were H. influenzae, the isolation frequencies were 30.0%.

[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibacterial agents (2007)].

From October 2007 to September 2008, we collected the specimen from 362 patients with lower respiratory tract infections in 14 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various antibacterial agents and patients' characteristics. Of 413 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in infection, 412 strains were examined. The isolated bacteria were: Staphylococcus aureus 65, Streptococcus pneumoniae 90, Haemophilus influenzae 88, Pseudomonas aeruginosa (non-mucoid) 53, P. aeruginosa (mucoid) 13, Klebsiella pneumoniae 19, and Moraxella catarrhalis 41. Of 65 S. aureus strains, those with 2 µg/mL or less of MIC of oxacillin (methicillin-susceptible S. aureus: MSSA) and those with 4 µg/mL or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) were 38 (58.5%) and 27 (41.5%) strains, respectively. Against MSSA, imipenem had the most potent antibacterial activity and inhibited the growth of all strains at 0.063 µg/mL or less. Against MRSA, vancomycin and arbekacin showed the most potent activity and inhibited the growth of all the strains at 2 µg/mL. Linezolid also showed the same activity as them. Carbapenems and penems showed the most potent activities against S. pneumoniae and in particular, panipenem inhibited the growth of all the strains at 0.063 µg/mL or less. Imipenem and faropenem also had a preferable activity and inhibited the growth of all the strains at 0.25 and 1 µg/mL, respectively. In contrast, there were high-resistant strains (MIC: over 128 µg/mL) for erythromycin (38.2%) and clindamycin (18.0%). Against H. influenzae, levofloxacin showed the most potent activity and its MIC90 was 0.063 µg/mL or less. Meropenem showed the most potent activity against P. aeruginosa (mucoid) and its MIC90 was 0.5 µg/mL. Against P. aeruginosa (non-mucoid), tobramycin had the most potent activity and its MIC90 was 2 µg/mL. Against K. pneumoniae, cefozopran had the most potent activity and inhibited the growth of all the strains at 0.063 µg/mL or less. Also, all the antibacterial agents except ampicillin generally showed a potent activity against M. catarrhalis and the MIC90 of them were 2 µg/mL or less. The approximately half the number (45.9%) of the patients with respiratory infection were aged 70 years or older. Bacterial pneumonia and chronic bronchitis accounted for 44.8% and 31.5% of all the respiratory infection, respectively. The bacteria frequently isolated from the patients with bacterial pneumonia were S. aureus (21.9%), S. pneumoniae (20.8%), and H. influenzae (18.6%). S. pneumoniae (27.1%), H. influenzae (24.0%) and P. aeruginosa (17.8%) also were frequently isolated from the patients with chronic bronchitis. Before the drug administration, the bacteria frequently isolated from the patients were S. pneumoniae (23.9%) and H. influenzae (23.6%). The bacteria frequently isolated from the patients treated with macrolides were S. pneumoniae, and their isolation frequencies were 34.8%.

[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibacterial agents (2008)].

From October 2008 to September 2009, we collected the specimen from 374 patients with lower respiratory tract infections in 15 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various antibacterial agents and patients' characteristics. Of 423 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in infection, 421 strains were examined. The isolated bacteria were: Staphylococcus aureus 78, Streptococcus pneumoniae 78, Haemophilus influenzae 89, Pseudomonas aeruginosa (non-mucoid) 61, P. aeruginosa (mucoid) 19, Klebsiella pneumoniae 28, and Moraxella catarrhalis 32. Of 78 S. aureus strains, those with 2 µg/mL or less of MIC of oxacillin (methicillin-susceptible S. aureus: MSSA) and those with 4 µg/mL or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) were 34 (43.6%) and 44 (56.4%) strains, respectively. Against MSSA, imipenem had the most potent antibacterial activity and inhibited the growth of all strains at 0.063 µg/mL or less. Against MRSA vancomycin and arbekacin showed the potent activity and inhibited the growth of all the strains at 1 and 2 µg/mL, respectively. Linezolid also showed the great activity and inhibited the growth of all the strains at 1 µg/mL. Carbapenems and penems showed the most potent activities against S. pneumoniae and panipenem inhibited the growth of all the strains at 0.125 µg/mL. Imipenem and faropenem also had a preferable activity and inhibited the growth of all the strains at 0.25 and 1 µg/mL, respectively. In contrast, there were high-resistant strains (MIC: > 128 µg/mL) for erythromycin (43.6%) and clindamycin (19.2%). Against H. influenzae, levofloxacin showed the most potent activity and its MIC90 was 0.063 µg/mL or less. Tobramycin showed the most potent activity against P. aeruginosa (mucoid) and its MIC90 was 2 µg/mL. Against the non-mucoid type of P. aeruginosa, tobramycin and ciprofloxacin had the most potent activity and its MIC90 was 2 µg/mL. Against K. pneumoniae, cefozopran had the most potent activity and inhibited the growth of all the strains at 0.063 µg/mL or less. All the antibacterial agents except ampicillin generally showed a potent activity against M. catarrhalis and the MIC90 of them were 2 µg/mL or less. The majority number (57.7%) of the patients with respiratory infection were aged 70 years or older. Bacterial pneumonia and chronic bronchitis accounted for 40.9% and 32.9% of all the respiratory infection, respectively. The bacteria frequently isolated from the patients with bacterial pneumonia were S. aureus (20.5%), S. pneumoniae (21.1%), and H. influenzae (22.8%). S. aureus (21.7%) and P. aeruginosa (24.6%) also were frequently isolated from the patients with chronic bronchitis. The bacteria frequently isolated from the patients were S. pneumoniae (23.4%) and H. influenzae (25.1%) before administration of the antibacterial agents. The bacteria frequently isolated from the patients previously treated with cephems and macrolides were P. aeruginosa, and the isolation frequencies were 41.4% and 40.0%, respectively.

[Susceptibilities of bacteria isolated from patients with lower respiratory infectious diseases to antibacterial agents (2009)].

From October 2009 to September 2010, we collected the specimen from 432 patients with lower respiratory tract infections in 16 institutions in Japan, and investigated the susceptibilities of isolated bacteria to various antibacterial agents and patients' characteristics. All of 479 strains that were isolated from specimen (mainly from sputum) and assumed to be bacteria causing in infection, were examined. The isolated bacteria were: Staphylococcus aureus 90, Streptococcus pneumoniae 74, Haemophilus influenzae 82, Pseudomonas aeruginosa (non-mucoid) 60, P. aeruginosa (mucoid) 31, Klebsiella pneumoniae 41, and Moraxella catarrhalis 34. Of 90 S. aureus strains, those with 2 µg/mL or less of MIC of oxacillin (methicillin-susceptible S. aureus: MSSA) and those with 4 µg/mL or more of MIC of oxacillin (methicillin-resistant S. aureus: MRSA) were 43 (47.8%) and 47 (52.2%) strains, respectively. Against MSSA, imipenem had the most potent antibacterial activity and inhibited the growth of all strains at 0.063 µg/mL or less. Against MRSA, vancomycin and arbekacin showed the potent activity and inhibited the growth of all the strains at 2 and 4 µg/mL, respectively. Linezolid also showed the great activity and inhibited the growth of all the strains at 2 µg/mL. Carbapenems and penems showed the most potent activities against S. pneumoniae and panipenem inhibited the growth of all the strains at 0.125 µg/mL. Imipenem and faropenem also had a preferable activity and inhibited the growth of all the strains at 0.25 and 0.5 µg/mL, respectively. In contrast, there were high-resistant strains (MIC: > 128 µg/mL) for erythromycin (51.4%) and clindamycin (35.1%). Against H. influenzae, levofloxacin showed the most potent activity and its MIC90 was 0.063 µg/mL or less. Meropenem showed the most potent activity against P. aeruginosa (mucoid) and its MIC90 was 1 µg/mL. Against the non-mucoid type of P. aeruginosa, tobramycin had the most potent activity and its MIC90 was 2 µg/mL. Against K. pneumoniae, cefozopran had the most potent activity and inhibited the growth of all the strains at 0.125 µg/mL or less. All the antibacterial agents except ampicillin generally showed a potent activity against M. catarrhalis and the MIC90 of them were 2 µg/mL or less. The majority number (60.0%) of the patients with respiratory infection was aged 70 years or older. Bacterial pneumonia and chronic bronchitis accounted for 48.8% and 31.7% of all the respiratory infection, respectively. The bacteria frequently isolated from the patients with bacterial pneumonia were S. aureus (21.5%), S. pneumoniae (20.2%), and H. influenzae (16.7%). S. aureus (21.9%) and P. aeruginosa (20.0%) also were frequently isolated from the patients with chronic bronchitis. The bacteria frequently isolated from the patients were S. pneumoniae (21.5%) and H. influenzae (20.5%) before administration of the antibacterial agents. The bacteria frequently isolated from the patients previously treated with cephems and macrolides were P. aeruginosa, and the isolation frequencies were 28.6% and 47.2%, respectively.

Breakthrough invasive Candida glabrata in patients on micafungin: a novel FKS gene conversion correlated with sequential elevation of MIC.

Candida glabrata strains sequentially isolated from blood developed resistance to micafungin (MICs from <0.015 to 4 µg/ml). A novel mutation identified in micafungin-resistant strains at bp 262 of FKS2 (containing a deletion of F659 [F659del]) was inserted into the homologous region in FKS1.

Serial quantification of procalcitonin (PCT) predicts clinical outcome and prognosis in patients with community-acquired pneumonia (CAP).

Procalcitonin (PCT), a calcitonin precursor, is commonly measured in the setting of community-acquired pneumonia (CAP). However, the clinical significance of serial PCT changes has not been established. We conducted a prospective observational study of 122 patients with CAP. Thirty-day mortality was the primary endpoint. Secondary endpoints included: (1) initial treatment failure, (2) 30-day mortality and/or initial treatment failure, and (3) intensive care unit (ICU) admission. In subgroup analysis, we classified patients into pneumococcal pneumonia and non-pneumococcal pneumonia groups. The baseline frequency of 30-day mortality was 10.7%. Increases in serum PCT levels from admission to Day 3 were observed with statistically higher frequency in patients with 30-day mortality (P = 0.002). For secondary endpoints, only the 30-day mortality and/or initial treatment failure group was statistically significant (P = 0.007). Subgroup analysis revealed statistically significant changes in the non-pneumococcal pneumonia group (N = 85) across several endpoints, including 30-day mortality (P = 0.001), initial treatment failure (P = 0.013), and 30-day mortality and/or initial treatment failure (P < 0.001). No significant changes in endpoint measurements were found in the pneumococcal pneumonia group (N = 28). Interestingly, serum PCT levels at the time of diagnosis were higher in patients with pneumococcal pneumonia than those with non-pneumococcal pneumonia (P = 0.006), and this positively correlated with disease severity scores for all patients (PCT vs. PSI: R = 0.380, P < 0.001; PCT vs. A-DROP: R = 0.422, P < 0.001) and for non-pneumococcal pneumonia (PCT vs. PSI: R = 0.468, P < 0.001; PCT vs. A-DROP: R = 0.448, P < 0.001), but not for pneumococcal pneumonia. In conclusion, serial quantification of PCT can predict clinical outcomes for patients with CAP.

Secondary pulmonary alveolar proteinosis complicating myelodysplastic syndrome results in worsening of prognosis: a retrospective cohort study in Japan.

BACKGROUND: Secondary pulmonary alveolar proteinosis (sPAP) is a very rare lung disorder comprising approximately 10% of cases of acquired PAP. Hematological disorders are the most common underlying conditions of sPAP, of which 74% of cases demonstrate myelodysplastic syndrome (MDS). However, the impact of sPAP on the prognosis of underlying MDS remains unknown. The purpose of this study was to evaluate whether development of sPAP worsens the prognosis of MDS. METHODS: Thirty-one cases of sPAP and underlying MDS were retrospectively classified into mild and severe cases consisting of very low-/low-risk groups and intermediate-/high-/very high-risk groups at the time of diagnosis of MDS, according to the prognostic scoring system based on the World Health Organization classification. Next, we compared the characteristics, disease duration, cumulative survival, and prognostic factors of the groups. RESULTS: In contrast to previous reports on the prognosis of MDS, we found that the cumulative survival probability for mild MDS patients was similar to that in severe MDS patients. This is likely due to the poor prognosis of patients with mild MDS, whose 2-year survival rate was 46.2%. Notably, 75% and 62.5% of patients who died developed fatal infectious diseases and exacerbation of PAP, respectively, suggesting that the progression of PAP per se and/or PAP-associated infection contributed to poor prognosis. The use of corticosteroid therapy and a diffusing capacity of the lung for carbon monoxide of less than 44% were predictive of poor prognosis. CONCLUSION: Development of sPAP during the course of MDS may be an important adverse risk factor in prognosis of patients with mild MDS.

Objective evaluation of whiteness of cooked rice and rice cakes using a portable spectrophotometer.

The whiteness of cooked rice and rice cakes was evaluated using a portable spectrophotometer with a whiteness index (WI). Also, by using boiled rice for measurement of Mido values by Mido Meter, it was possible to infer the whiteness of cooked rice without rice cooking. In the analysis of varietal differences of cooked rice, 'Tsuyahime', 'Koshihikari' and 'Koshinokaori' showed high whiteness, while 'Satonoyuki' had inferior whiteness. The whiteness of rice cakes made from 'Koyukimochi' and 'Dewanomochi' was higher than the whiteness of those made from 'Himenomochi' and 'Koganemochi'. While there was a significant correlation (r = 0.84) between WI values and whiteness scores of cooked rice by the sensory test, no correlation was detected between the whiteness scores and Mido values, indicating that the values obtained by a spectrophotometer differ from those obtained by a Mido Meter. Thus, a spectrophotometer may be a novel device for measurement of rice eating quality.

Activities of Daily Living, Hypoxemia, and Lymphocytes Score for Predicting Mortality Risk in Patients With Pulmonary TB.

BACKGROUND: A clinically applicable mortality risk prediction system for pulmonary TB may improve treatment outcomes, but no easy-to-calculate and accurate score has yet been reported. The aim of this study was to construct a simple and objective disease severity score for patients with pulmonary TB. RESEARCH QUESTION: Does a clinical score consisting of simple objective factors predict the mortality risk of patients with pulmonary TB? STUDY DESIGN AND METHODS: The data set from our previous prospective study that recruited patients newly diagnosed with pulmonary TB was used for the development cohort. Patients for the validation cohort were prospectively recruited between March 2021 and September 2022. The primary end point was all-cause in-hospital mortality. Using Cox proportional hazards regression, a mortality risk prediction model was optimized in the development cohort. The disease severity score was developed by assigning integral points to each variate. RESULTS: The data from 252 patients in the development cohort and 165 patients in the validation cohort were analyzed, of whom 39 (15.5%) and 17 (10.3%), respectively, died in the hospital. The disease severity score (named the AHL score) included three clinical parameters: activities of daily living (semi-dependent, 1 point; totally dependent, 2 points); hypoxemia (1 point), and lymphocytes (< 720/µL, 1 point). This score showed good discrimination with a C statistic of 0.902 in the development cohort and 0.842 in the validation cohort. We stratified the score into three groups (scores of 0, 1-2, and 3-4), which clearly corresponded to low (0% and 1.3%), intermediate (13.5% and 8.9%), and high (55.8% and 39.3%) mortality risk in the development and validation cohorts. INTERPRETATION: The easy-to-calculate AHL disease severity score for patients with pulmonary TB was able to categorize patients into three mortality risk groups with great accuracy. CLINICAL TRIAL REGISTRATION: University Hospital Medical Information Network Center; No. UMIN000012727 and No. UMIN000043849; URL: www.umin.ac.jp.

High-resolution computed tomography findings for patients with drug-induced pulmonary toxicity, with special reference to hypersensitivity pneumonitis-like patterns in gemcitabine-induced cases.

BACKGROUND: Gemcitabine (GEM) is widely used as a chemotherapeutic agent. However, pulmonary toxicity has been rarely observed with GEM use. This article aims to determine the incidence and causes of drug-induced pulmonary toxicity, and to classify the high-resolution computed tomography (HRCT) findings for antitumor therapy-associated pulmonary toxicity based on characteristic patterns and pathological considerations, with a special focus on GEM-associated pulmonary toxicity (GAPT). METHODS: Medical records of all patients with drug-induced pulmonary toxicity seen at Kyorin University hospital between April 2006 and December 2011 were retrospectively reviewed. The study examined correlations between HRCT and the assessed pathological or clinical findings, with a specific focus on antitumor drugs. RESULTS: We identified 66 patients with drug-induced pulmonary toxicity. Among the antitumor drugs, GEM was the primary offending agent (n = 8) for pulmonary toxicity followed by docetaxel and gefitinib. HRCT patterns for the eight GAPT patients included the non-specific interstitial pneumonia (NSIP; n = 5) and the hypersensitivity pneumonitis (HP)-like pattern (n = 3). In contrast, four patients in the study were found to have the HP-like pattern, with three cases associated with GEM and one case associated with imatinib mesylate. The transbronchial lung biopsy or video-assisted thoracic surgery specimens for these patients showed granuloma or organizing tissue with a random distribution that was independent of the respiratory bronchiole. These results appeared to correspond to the HRCT-determined centrilobular nodules. CONCLUSION: GEM was the leading cause of drug-induced pulmonary toxicity in the patients examined in this study. This toxicity appears as NSIP or an HP-like pattern during HRCT examinations. This HP-like pattern may be useful for diagnosing GEM-induced pulmonary toxicity, as well as demonstrating granuloma or organizing tissue during lung pathology examinations.

Evidence for reactivation of human herpesvirus 6 in generalized lymphadenopathy in a patient with drug-induced hypersensitivity syndrome.

The present case provides direct evidence of human herpesvirus 6 reactivation in resected lymph node tissue in a patient with drug-induced hypersensitivity syndrome. This case clearly demonstrates that appropriate pathological evaluation of lymphadenopathy for drug-induced hypersensitivity syndrome, which mimics malignant lymphoma in clinical, radiological, and pathological findings, is required.

A novel macrolide solithromycin exerts superior anti-inflammatory effect via NF-κB inhibition.

Macrolides are reported to reduce exacerbation of chronic inflammatory respiratory disease, such as chronic obstructive pulmonary disease (COPD), and also show anti-inflammatory effects in vitro and in vivo. However the anti-inflammatory efficacies of current macrolides are relatively weak. Here we found that a novel macrolide/fluoroketolide solithromycin (CEM-101) showed superior anti-inflammatory effects to macrolides in current clinical use. The effects of solithromycin (SOL) on lipopolysaccharide-induced TNFα (tumor necrosis factor α) and/or CXCL8 (C-X-C motif chemokine ligand 8; interleukin-8) release, phorbol 12-myristate 13-acetate-induced MMP9 (matrix metalloproteinase 9) activity and NF-κB (nuclear factor-κB) activity under conditions of oxidative stress have been evaluated and compared with the effects of erythromycin, clarithromycin, azithromycin, and telithromycin in macrophage-like PMA-differentiated U937 cells and peripheral blood mononuclear cells (PBMC) obtained from COPD patients. We also examined effect of SOL on cigarette smoke-induced airway inflammation in mice. SOL exerted superior inhibitory effects on TNFα/CXCL8 production and MMP9 activity in monocytic U937 cells. In addition, SOL suppressed TNFα release and MMP9 activity in PBMC from COPD patients at 10 µM, which is 10 times more potent than the other macrolides tested. Activated NF-κB by oxidative stress was completely reversed by SOL. SOL also inhibited cigarette smoke-induced neutrophilia and pro-MMP9 production in vivo, although erythromycin did not inhibit them. Thus, SOL showed better anti-inflammatory profiles compared with macrolides currently used in the clinic and may be a promising anti-inflammatory and antimicrobial macrolide for the treatment of COPD in future.

Fluorodeoxyglucose (FDG) uptake in pulmonary rheumatoid nodules diagnosed by video-assisted thoracic surgery lung biopsy: two case reports and a review of the literature.

Two cases of rheumatoid nodules evaluated by fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) and video-assisted thoracic surgery (VATS) biopsy are reported. The first case was that of a 44-year-old woman who presented with a cavitated nodule with intense standardized uptake values (SUVs) both in the early (max 3.4) and delayed (max 4.4) phases, suggesting malignancy. However, after VATS biopsy, she was diagnosed as having a rheumatoid nodule with vasculitis. The second case was that of a 74-year-old woman admitted with bilateral lung nodules, two of which showed intense early (max 2.2) and delayed (max 6.0) phase SUVs, and mild early (max 0.6) and delayed (max 0.9) phase SUVs. These two nodules were finally proven to be a lung cancer and rheumatoid nodule without vasculitis, respectively. These cases show that rheumatoid nodules with an enhanced inflammatory process, such as vasculitis, can appear false-positive for malignancy on FDG-PET/CT scan images.