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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.This multicenter prospective observational study included 596 patients with NHCAP from 73 centers in Japan between May 2014 and February 2016.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.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.

Accurate prognostic tools for mortality in patients with healthcare-associated pneumonia (HCAP) are needed to provide appropriate medical care. Tools like PSI, A-DROP, I-ROAD, and CURB-65, widely used for predicting mortality in community-acquired and hospital-acquired pneumonia cases, remain controversial. We identified articles evaluating either PSI, A-DROP, I-ROAD, or CURB-65 and the mortality outcome in patients with HCAP and calculated the pooled sensitivities, specificities, positive likelihood ratio (PLR), negative likelihood ratio (NLR), diagnostic odds ratios, and the overall summary area under the curves (AUCs) for mortality prediction. Additionally, the differences in prognostic power among these four assessment tools were evaluated using the mean differences of AUCs. Using a cut-off value of moderate, sensitivity, specificity, PLR, and NLR were found to be 0.91-0.97, 0.15-0.53, 1.14-1.66, and 0.18-0.33. respectively. Upon using a cut-off value of severe, sensitivity, specificity, PLR, and NLR were 0.63-0.70, 0.53-0.66, 1.49-2.03, and 0.47-0.58, respectively. Overall AUCs were 0.70 (0.68-0.72), 0.71 (0.63-0.78), 0.68 (0.63-0.73), and 0.67 (0.63-0.71), respectively, for PSI, A-DROP, I-ROAD, and CURB-65 (p=0.63). In conclusions, these severity assessment tools do not have enough power to predict mortality in HCAP patients. Furthermore, there are no significant differences in predictive performance among these four severity assessment tools.

The nationwide surveillance on antimicrobial susceptibility of bacterial respiratory pathogens from the patients in Japan was conducted by Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2014. The isolates were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections during the period between January 2014 and April 2015 by three societies. Antimicrobial susceptibility testing was conducted at the central reference laboratory according to the method recommended by Clinical Laboratory Standards Institute. Susceptibility testing was evaluated in 1534 strains (335 Staphylococcus aureus, 264 Streptococcus pneumoniae, 29 Streptococcus pyogenes, 281 Haemophilus influenzae, 164 Moraxella catarrhalis, 207 Klebsiella pneumoniae, and 254 Pseudomonas aeruginosa). Ratio of methicillin-resistant S. aureus was 43.6%, and those of penicillin-susceptible S. pneumoniae was 100%. Among H. influenzae, 8.2% of them were found to be β-lactamase-producing ampicillin-resistant strains, and 49.1% to be β-lactamase-non-producing ampicillin-resistant strains. Extended spectrum β-lactamase-producing K. pneumoniae and multi-drug resistant P. aeruginosa with metallo β-lactamase were 9.2% and 0.4%, respectively.

The nationwide surveillance on antimicrobial susceptibility of bacterial respiratory pathogens from the patients in Japan was conducted by the Japanese Society of Chemotherapy, the Japanese Association for Infectious Diseases, and the Japanese Society for Clinical Microbiology in 2016. The isolates were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections during the period between February 2016 and August 2016 by three societies. Antimicrobial susceptibility testing was conducted at the central reference laboratory according to the method recommended by Clinical Laboratory Standards Institute. Susceptibility testing was evaluated in 1062 strains (143 Staphylococcus aureus, 210 Streptococcus pneumoniae, 17 Streptococcus pyogenes, 248 Haemophilus influenzae, 151 Moraxella catarrhalis, 134 Klebsiella pneumoniae, and 159 Pseudomonas aeruginosa). Ratio of methicillin-resistant S. aureus was 48.3%, and those of penicillin-susceptible S. pneumoniae was 99.5%. Among H. influenzae, 14.1% of them were found to be β-lactamase-producing ampicillin-resistant strains, and 41.1% to be β-lactamase-non-producing ampicillin-resistant strains. Extended spectrum β-lactamase-producing K. pneumoniae and multi-drug resistant P. aeruginosa with metallo β-lactamase were 4.5% and 0.6%, respectively.

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 β-lactamase-producing ampicillin-resistant strains, and 37.2% to be β-lactamase-non-producing ampicillin-resistant strains. Extended spectrum β-lactamase-producing K. pneumoniae and multi-drug resistant P. aeruginosa with metallo β-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.

Nursing and healthcare-associated pneumonia (NHCAP) is a category of healthcare-associated pneumonia that was modified for the healthcare system of Japan. The NHCAP guidelines stated the difficulty in assessing the severity classifications, for instance, A-DROP. We compared the usefulness of different severity classifications (A-DROP, CURB-65, PSI, and I-ROAD) in predicting the prognosis of nursing and healthcare-associated pneumonia. We conducted a retrospective analysis on 303 adult patients hospitalized for nursing healthcare-associated pneumonia and community-acquired pneumonia, which were diagnosed at the Department of Respiratory Medicine of Niigata General City Hospital between January 2012 and December 2014. We evaluated 159 patients with community-acquired pneumonia and 144 with nursing and healthcare-associated pneumonia. In the nursing and healthcare-associated pneumonia group, 30-days mortality and in-hospital mortality rates were 6.5% and 8.7%, respectively, in severe cases and 16.1% and 25.0%, respectively, in the most severe cases, based on A-DROP. With I-ROAD, these rates were 11.1% and 11.1%, respectively, in group B and 14.9% and 20.7%, respectively, in group C. With PSI, the rates were 2.3% and 6.8%, respectively, in class IV and 14.3% and 19.8%, respectively, in class V. Despite some variability due to the small sample size, both the 30-days and in-hospital mortality rates increased as the severity increased. In this study, both the 30-days mortality and in-hospital mortality rates in the nursing and healthcare-associated pneumonia group tended to increase in severity with the A-DROP. We found that A-DROP was useful in predicting the prognosis of nursing and healthcare-associated pneumonia.

Background: In contrast to community-acquired pneumonia (CAP), no specific severity assessment tools have been developed for healthcare-associated pneumonia (HCAP) in clinical practice. Objectives: In this review, we assessed the clinical significance of severity assessment tools for HCAP. Methods: We identified related articles from the PubMed database. The eligibility criteria were original research articles evaluating severity scoring tools and reporting the outcomes of mortality in patients with HCAP. Results: Eight articles were included in the meta-analysis. The PORT score and CURB-65 were evaluated in 7 and 8 studies, respectively. Using cutoff values of ≥IV and V for the PORT score, the diagnostic odds ratios (DORs) were 5.28 (2.49-11.17) and 3.76 (2.88-4.92), respectively, and the areas under the curve (AUCs) were 0.68 (0.64-0.72) and 0.71 (0.67-0.75), respectively. Conversely, the AUCs for ≥IV and V were 0.71 (0.67-0.76) and 0.74 (0.70-0.78), respectively, when applied only to nonimmunocompromised patients. In contrast, when using cutoff values of ≥2 and ≥3 for CURB-65, the DORs were 3.35 (2.26-4.97) and 2.65 (2.05-3.43), respectively, and the AUCs were 0.65 (0.61-0.69) and 0.66 (0.62-0.70), respectively. Conversely, the AUCs for ≥2 and ≥3 were 0.65 (0.61-0.69) and 0.68 (0.64-0.72), respectively, when applied only to nonimmunocompromised patients. Conclusions: The PORT score and CURB-65 do not have substantial power compared with the tools for CAP patients, although the PORT score is more useful than CURB-65 for predicting mortality in HCAP patients. According to our results, however, these tools, especially the PORT score, can be more useful when limited to nonimmunocompromised patients.

We herein report a 58-year-old Japanese woman who survived 14 years after surgery for lung adenocarcinoma harboring an epidermal growth factor receptor (EGFR) exon 19 deletion. She developed recurrence, for which she underwent multimodal therapy, including EGFR-tyrosine kinase inhibitor (TKI) administration. She ultimately died from a rapidly progressive right lung tumor that was resistant to EGFR-TKI. According to the autopsy findings, she had combined large-cell neuroendocrine carcinoma (LCNEC) and adenocarcinoma in the right lung, which retained an EGFR exon 19 deletion in both components. Therefore, the histological transformation to LCNEC can be a mechanism of acquired EGFR-TKI resistance.

Background Although the clinical efficacy of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) in EGFR-mutant non-small cell lung cancer (NSCLC) patients has been demonstrated, their efficacy in EGFR-mutant NSCLCs with central nervous system (CNS) metastases and the role of radiotherapy remain unclear. This study aimed to determine if it is preferable to add upfront cranial radiotherapy to EGFR-TKIs in patients with EGFR-mutant NSCLC with newly diagnosed brain metastases. Methods We retrospectively analyzed the data of EGFR-mutant NSCLC patients with CNS metastases who received EGFR-TKIs as a first-line therapy. Results A total of 104 patients were enrolled and 39 patients received upfront brain radiotherapy, while 65 patients received first and second generation EGFR-TKIs first. The median time to treatment failure (TTF) was 7.8 months (95% confidence interval [CI]: 6.3-9.4). The median survival time (MST) was 24.0 months (95% CI: 20.1-30.1). The overall response rate of the CNS was 37%. The median CNS progression-free survival (PFS) was 13.2 months (95% CI: 10.0-16.2). Brain radiotherapy prior to EGFR-TKI prolonged TTF (11.2 vs. 6.8 months, P = 0.038) and tended to prolong CNS-PFS (15.6 vs. 11.1 months, P = 0.096) but was not significantly associated with overall survival (MST 26.1 vs. 24.0 months, P = 0.525). Univariate and multivariate analyses indicated that poor performance status and the presence of extracranial metastases were poor prognostic factors related to overall survival. Conclusion EGFR-TKI showed a favorable effect for EGFR-mutant NSCLC patients with CNS metastases. Prolonged TTF and CNS-PFS were observed with upfront brain radiotherapy.

The Japanese Association for Infectious Diseases (JAID) and Japanese Society of Chemotherapy (JSC) announced the “Guide for the Use of Antimicrobial Drugs” in 2001 and the “Guidelines for the Use of Antimicrobial Drugs” in 2005. Subsequently, the “The JAID/JSC guide to clinical management of infectious diseases 2011” was published. With its revision, guidelines were newly prepared. Concerning respiratory infectious diseases, in Japan, the Japanese Respiratory Society published guidelines for the management of community-acquired pneumonia, hospital-acquired pneumonia, respiratory tract infection, and -/nursing and healthcare-associated pneumonia. Furthermore, the Japanese Society of Pediatric Pulmonology and Japanese Society for Pediatric Infectious Diseases announced the “Guidelines for the Management of Respiratory Infectious Diseases in Children in Japan”. Internationally, many guidelines, including those established by the American Thoracic Society and Infectious Diseases Society of America, have been published from various countries. Thereafter, clinical research on respiratory infectious diseases has advanced, leading to the accumulation of many outcomes regarding epidemiology, clinical diagnosis, and treatment. However, the types of microorganisms that cause respiratory infectious diseases have increased with the number of resistant bacteria. In addition, conditions have also varied with causative microorganisms through the recent compromised host's severe status. The place of treatment varies: from the outpatient clinic to the ICU. Physicians responsible for treatment also vary: practitioners, hospital doctors, pulmonologists, emergency physicians, board certified member of JAID, Japanese antimicrobial chemotherapy physician. There are a large number of options of antimicrobial drugs that are available, including new drugs; therapeutic strategies are confused. On the other hand, recently, the entity of PK-PD has been commonly recognized, and the importance of scientifically using antimicrobial drugs has been emphasized. In addition, the Japanese Society of Chemotherapy established a system for antimicrobial chemotherapy-certified physicians, and promoted the widespread, adequate use of antimicrobial drugs. Based on these, the two societies prepared the JAID/JSC Guidelines for the Treatment of Respiratory Infectious Diseases. If specific treatment guidelines can be presented, this may contribute to an improvement in the treatment responses of respiratory infectious diseases, a reduction in health expenditure, and the prevention of resistant bacteria. The guidelines were prepared based on the EBM so that they reflected the management of respiratory infectious diseases in Japan and covered all such diseases in adults and children. To prepare the guidelines, a committee was established in 2012, and a draft was published on homepage based on an approval from the boards of directors at the two societies through a review-based consensus. Opinions were collected from the two societies' members. In Japan, there have been no such guidelines covering respiratory infectious diseases. In the future, with further advances in research, the contents of the guidelines must be revised. However, we successfully provided treatment guidelines that are the most advanced at present. The guidelines were prepared for all clinicians to understand the Treatment of Respiratory Infectious Diseases and manage them with antimicrobial drugs adequately. They do not limit treatment by individual physicians or affect their rights to select it. The guidelines may be commonly applied for respiratory infectious disease management/research/education in Japan, improving the quality of respiratory infectious disease management, preventing an increase in the number of resistant bacteria, and contributing to national health. We hope that the guidelines will be utilized by a large number of clinicians in respiratory infectious disease management. Lastly, we thank the committee members and secretariat staff for their cooperation. 1. Descriptions on the recommendation grade and evidence level Recommendation grade Evidence level A Strongly recommended, I Randomized comparative study B General recommendation II Non-randomized comparative study C Comprehensive evaluation by the attending physician III Case report IV Specialist's opinion Open in a separate window 2. Definition of first- and second-choice drugs First-choice drugs Drugs to be recommended for initial treatment Second-choice drugs Alternative drugs when first-choice drugs cannot be used due to allergy, organ disorder, or local factors Open in a separate window 3. Precautions - In this article, with respect to the administration method (especially doses) of antimicrobial drugs, they are recommended based on sufficient doses. Considering the products adopted at each medical institution, antibiograms, severity, underlying disease, age, and presence or absence of organ disorder, the dose should be increased or decreased if necessary. - The spectra of third-generation cephems for intravenous injection, CTX and CTRX, are similar, but CTX, which is excreted in the kidney, should be primarily used when liver dysfunction is present, and CTRX, which is excreted in bile, should be primarily used when renal dysfunction is present. - As quinolones exhibit antitubercular actions, patients with pulmonary tuberculosis should be excluded for use. 4. A list of antimicrobial drug abbreviations and doses for neonates are presented at the end of this volume.

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 β-lactamase-non-producing ampicillin (ABPC)-intermediately resistant, 33.5% to be β-lactamase-non-producing ABPC-resistant and 11.0% to be β-lactamase-producing ABPC-resistant strains. Extended spectrum β-lactamase-producing K.pneumoniae and multi-drug resistant P.aeruginosa with metallo β-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., Journal of Infection and Chemotherapy, 21(6), pp.410-420; 2015

We herein report a 58-year-old Japanese woman who survived 14 years after surgery for lung adenocarcinoma harboring an epidermal growth factor receptor (EGFR) exon 19 deletion. She developed recurrence, for which she underwent multimodal therapy, including EGFR-tyrosine kinase inhibitor (TKI) administration. She ultimately died from a rapidly progressive right lung tumor that was resistant to EGFR-TKI. According to the autopsy findings, she had combined large-cell neuroendocrine carcinoma (LCNEC) and adenocarcinoma in the right lung, which retained an EGFR exon 19 deletion in both components. Therefore, the histological transformation to LCNEC can be a mechanism of acquired EGFR-TKI resistance.

Objective: Chemotherapy with irinotecan plus cisplatin has shown promise in chemo-naïve small-cell lung cancer (SCLC) patients. However, irinotecan treatment for relapsed or refractory SCLC has not been adequately evaluated. This phase II study evaluated the appropriate treatment schedule of irinotecan as a single agent. This study was designed to determine the antitumor activity, toxicity, and survival in previously treated SCLC patients. Methods: Previously treated SCLC patients with at least one platinum-based regimen received irinotecan (100 mg/m2) on days 1 and 8, every 3 weeks, until disease progression. The assessment of the response rate was the primary endpoint. Results: Thirty patients were enrolled, with an objective response rate of 41.3% (95% confidence interval [CI] 25.5–59.3), and a disease control rate of 69%. Median progression-free and overall survival was 4.1 months (95% CI, 2.2–5.4) and 10.4 months (95% CI, 8.1–14), respectively. The grade 3/4 hematological toxicities were neutropenia (36.7%), thrombocytopenia (3.3%), anemia (13.3%), and febrile neutropenia (6.6%). There were no grade 4 nonhematological toxicities. Frequent grade 3 nonhematological toxicities included diarrhea (10%), anorexia (6.6%), and hyponatremia (6.6%). Conclusions: This phase II study showed a high objective response rate and long survival. Irinotecan monotherapy schedule used was well tolerated, and could be an active treatment option for these patients.

Autoimmune pulmonary alveolar proteinosis (aPAP) is a rare disease characterized by the excessive accumulation of surfactant proteins within the alveolar spaces and by higher titers of autoantibodies to granulocyte-macrophage colony-stimulating factor (GM-CSF) in the serum and bronchoalveolar lavage fluid. The antibodies inhibit the maturation and phagocytosis of alveolar macrophages. Although the standard therapy for aPAP has been whole-lung lavage (WLL), this procedure is invasive and needs to be repeated for several years. GM-CSF inhalation therapy is a new procedure for treating aPAP and can induce remission with less invasiveness, although it is generally less effective in severe cases. We evaluated five cases with remarkable improvement by using sequential GM-CSF inhalation therapy after WLL; however, the treatment failed when this therapy preceded WLL. Therefore, sequential GM-CSF inhalation after WLL may reinforce the efficiency of WLL in patients with severe aPAP.

Aspiration pneumonia is thought to be associated with a poor outcome in patients with community acquired pneumonia (CAP). However, there has been no systematic review regarding the impact of aspiration pneumonia on the outcomes in patients with CAP. This review was conducted using the MOOSE guidelines: Patients: patients defined CAP. Exposure: aspiration pneumonia defined as pneumonia in patients who have aspiration risk. Comparison: confirmed pneumonia in patients who were not considered to be at high risk for oral aspiration. Outcomes: mortality, hospital readmission or recurrent pneumonia. Three investigators independently identified published cohort studies from PubMed, CENTRAL database, and EMBASE. Nineteen studies were included for this systematic review. Aspiration pneumonia increased in-hospital mortality (relative risk, 3.62; 95% CI, 2.65–4.96; P

Akira Watanabe , Katsunori Yanagihara a, b, , Tetsuya Matsumoto , Shigeru Kohno a, , Nobuki Aoki a, , Toyoko Oguri , Junko Sato , Tetsuro Muratani , Morimasa Yagisawa , Kazuhiko Ogasawara , Naoto Koashi , Tsuneo Kozuki , Akira Komoto , Yoshisaburo Takahashi , Toshikatsu Tsuji , Michinori Terada , Kunio Nakanishi , Rikizo Hattori , Yukio Hirako , Akinori Maruo , Shinichi Minamitani , Kohei Morita , Tomotaro Wakamura , Keisuke Sunakawa , Hideaki Hanaki , Yoshinobu Ohsaki , Yasuhito Honda , Shoichi Sasaoka , Hiroaki Takeda , Hideki Ikeda , Atsuko Sugai , Makoto Miki , Susumu Nakanowatari , Hiroshi Takahashi , Mutsuko Utagawa , Nobuyuki Kobayashi , Jin Takasaki , Hisami Konosaki , Yasuko Aoki , Michi Shoji , Hajime Goto , Takeshi Saraya , Daisuke Kurai , Mitsuhiro Okazaki , Yoshio Kobayashi , Yasuhiro Katono , Akihiko Kawana , Katsu Saionji , Naoki Miyazawa , Yoshimi Sato , Yuji Watanuki , Makoto Kudo , Shigeru Ehara , Hiroki Tsukada , Yumiko Imai , Nobuei Watabe , Sakura Aso , Yasuo Honma , Hiroshige Mikamo , Yuka Yamagishi , Yoshio Takesue , Yasunao Wada , Tadahiro Nakamura , Noriko Mitsuno , Keiichi Mikasa , Kei Kasahara , Kenji Uno , Reiko Sano , Naoyuki Miyashita , Yukinori Kurokawa , Mariko Takaya , Masao Kuwabara , Yaeko Watanabe , Masao Doi , Satomi Shimizu , Kiyoshi Negayama , Junichi Kadota a, , Kazufumi Hiramatsu , Yoshitomo Morinaga , Junichi Honda , Masaki Fujita , Satoshi Iwata , Aikichi Iwamoto , Takayuki Ezaki , Shoichi Onodera , Shinya Kusachi , Kazuhiro Tateda , Michio Tanaka , Kyoichi Totsuka , Yoshihito Niki , Tetsuro Matsumoto a

To investigate the trends of antimicrobial resistance in pathogens isolated from surgical site infections (SSI), a Japanese surveillance committee conducted the first nationwide survey. Seven main organisms were collected from SSI at 27 medical centers in 2010 and were shipped to a central laboratory for antimicrobial susceptibility testing. A total of 702 isolates from 586 patients with SSI were included. Staphylococcus aureus (20.4 %) and Enterococcus faecalis (19.5 %) were the most common isolates, followed by Pseudomonas aeruginosa (15.4 %) and Bacteroides fragilis group (15.4 %). Methicillin-resistant S. aureus among S. aureus was 72.0 %. Vancomycin MIC 2μg/ml strains accounted for 9.7 %. In Escherichia coli, 11 of 95 strains produced extended-spectrum β-lactamase (Klebsiella pneumoniae, 0/53 strains). Of E. coli strains, 8.4 % were resistant to ceftazidime (CAZ) and 26.3 % to ciprofloxacin (CPFX). No P. aeruginosa strains produced metallo-β-lactamase. In P. aeruginosa, the resistance rates were 7.4 % to tazobactam/piperacillin (TAZ/PIPC), 10.2 % to imipenem (IPM), 2.8 % to meropenem, cefepime, and CPFX, and 0 % to gentamicin. In the B. fragilis group, the rates were 28.6 % to clindamycin, 5.7 % to cefmetazole, 2.9 % to TAZ/PIPC and IPM, and 0 % to metronidazole (Bacteroides thetaiotaomicron; 59.1, 36.4, 0, 0, 0 %). MIC90 of P. aeruginosa isolated 15 days or later after surgery rose in TAZ/PIPC, CAZ, IPM, and CPFX. In patients with American Society of Anesthesiologists (ASA) score ≥3, the resistance rates of P. aeruginosa to TAZ/PIPC and CAZ were higher than in patients with ASA ≤2. The data obtained in this study revealed the trend of the spread of resistance among common species that cause SSI. Timing of isolation from surgery and the patient’s physical status affected the selection of resistant organisms.

For the purpose of nationwide surveillance of the antimicrobial susceptibility of bacterial respiratory pathogens collected from patients in Japan, the Japanese Society of Chemotherapy conducted a third year of nationwide surveillance during the period from January to April 2008. A total of 1,097 strains were collected from clinical specimens obtained from well-diagnosed adult patients with respiratory tract infections. Susceptibility testing was evaluable with 987 strains (189 Staphylococcus aureus, 211 Streptococcus pneumoniae, 6 Streptococcus pyogenes, 187 Haemophilus influenzae, 106 Moraxella catarrhalis, 126 Klebsiella pneumoniae, and 162 Pseudomonas aeruginosa). A total of 44 antibacterial agents, including 26 β-lactams (four penicillins, three penicillins in combination with β-lactamase inhibitors, four oral cephems, eight parenteral cephems, one monobactam, five carbapenems, and one penem), three aminoglycosides, four macrolides (including a ketolide), one lincosamide, one tetracycline, two glycopeptides, six fluoroquinolones, and one oxazolidinone were used for the study. Analysis was conducted at the central reference laboratory according to the method recommended by the Clinical and Laboratory Standard Institute (CLSI). The incidence of methicillin-resistant S. aureus (MRSA) was as high as 59.8%, and those of penicillin-intermediate and penicillin-resistant S. pneumoniae (PISP and PRSP) were 35.5 and 11.8%, respectively. Among H. influenzae, 13.9% of them were found to be β-lactamase-non-producing ampicillin (ABPC)-intermediately resistant (BLNAI), 26.7% to be β-lactamase-non-producing ABPC-resistant (BLNAR), and 5.3% to be β-lactamase-producing ABPC-resistant (BLPAR) strains. A high frequency (76.5%) of β-lactamase-producing strains was suspected in Moraxella catarrhalis isolates. Four (3.2%) extended-spectrum β-lactamase-producing K. pneumoniae were found among 126 strains. Four isolates (2.5%) of P.aeruginosa were found to be metallo β-lactamase-producing strains, including three (1.9%) suspected multidrug-resistant strains showing resistance to imipenem, amikacin, and ciprofloxacin. Continual national surveillance of the 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.

A 58-year-old woman with an 18-year history of primary biliary cirrhosis was admitted because of pneumococcal pneumonia. She was treated with antibiotics and mechanical ventilation. After the pneumonia improved, she developed severe watery diarrhea. Although vancomycin was administered enterally, the diarrhea persisted. She died of multiple organ failure within 16 days of the onset of diarrhea. An autopsy showed intracapillary cryptococci in the systemic organs, especially in the intestinal tract. The cause of diarrhea was considered to be extensive intestinal mucosal necrosis due to disseminated cryptococcosis. This is a rare case of cryptococcal infection manifesting as acute diarrhea.

Oseltamivir has been used for treatment of influenza A and B infections, but recent reports documented that it was less active against the latter. We compared the effectiveness of oseltamivir in children between laboratory confirmed influenza A and B over 4 influenza seasons from 2001 to 2005 in a pediatric clinic in Japan. Among 1,848 patients screened, 299 influenza A and 209 influenza B patients were administered oseltamivir (treated groups), and 28 influenza A and 66 influenza B patients were assigned as non-treated groups. The duration of fever, defined as period when patients had the maximum temperature higher than 37.5 degrees C in three-time measurements in a day after the clinic visit, was evaluated among the four groups. In uni-variate analysis, the duration of fever was shorter for treated group than non-treated for influenza A (1.8 +/- 0.9 days vs 2.6 +/- 1.3 days, p0.01), but it was not significant for influenza B (2.4 +/- 1.3 days vs 2.8 +/- 1.2 days, p = 0.9). The fever duration was longer in treated influenza B than A patients (p0.01). Multi-variate analysis indicated younger age (6 years old) and higher body temperature at the clinic visit prolonged the duration of fever. Adjusted average duration of fever indicated that oseltamivir was effective for both types, but more effective on influenza A, and the benefit increased for younger children. Our data provide evidence that oseltamivir is beneficial for influenza infections, but the effectiveness is differed by type and age.

Background Efavirenz (EFV) is metabolized primarily by cytochrome P450 2B6 (CYP2B6), and high plasma concentrations of the drug are associated with a G-->T polymorphism at position 516 (516G-->T) of CYP2B6 and frequent central nervous system (CNS)-related side effects. Here, we tested the feasibility of genotype-based dose reduction of EFV. Methods CYP2B6 genotypes were determined in 456 human immunodeficiency virus type 1 (HIV-1)-infected patients who were receiving EFV treatment or were scheduled to receive EFV-containing treatment. EFV dose was reduced in CYP2B6 516G-->T carriers who had high plasma EFV concentrations while receiving the standard dosage (600 mg). EFV-naive homozygous CYP2B6 516G-->T carriers were treated with low-dose EFV. In both groups, the dose was further reduced when plasma EFV concentration remained high. Results CYP2B6 516G-->T was identified in the *6 allele (found in 17.9% of our subjects) and a novel allele, *26 (found in 1.3% of our patients). All EFV-treated CYP2B6 *6/*6 and *6/*26 carriers had extremely high plasma EFV concentrations (>6000 ng/mL) while receiving the standard dosage. EFV dose was reduced to 400 mg for 11 patients and to 200 mg for 7 patients with persistently suppressed HIV-1 loads. EFV-containing treatment was initiated at 400 mg in 4 CYP2B6 *6/*6 carriers and one *6/*26 carrier. Two of them still had a high plasma EFV concentration while receiving that dose, and the dose was further reduced to 200 mg, with successful HIV-1 suppression. CNS-related symptoms improved with dose reduction in 10 of the 14 patients, although some had not been aware of the symptoms at initial dosage. Conclusions Genotype-based EFV dose reduction is feasible in CYP2B6 *6/*6 and *6/*26 carriers, which can reduce EFV-associated CNS symptoms.

Background: Postoperative pulmonary complications (PPCs) greatly contribute to the risks for various surgeries. Prevention of PPCs is an important issue in the perioperative management. We previously reported usefulness of respiratory failure risk index (RFRI) for prediction of PPCs after digestive surgeries. Aims: This study investigated whether preoperative screening with RFRI was effective in preventing PPCs after esophagectomy. Methods: The patients who were scheduled to have esophagectomy from July 2013 to June 2014 were enrolled. The risk for PPCs was preoperatively assessed by RFRI calculated from surgical site, serum albumin, blood urea nitrogen, functional status, pulmonary function, and age. We defined those who scored over 27 out of 57 points of RFRI as high-risk patients for PPCs and applied preoperative pulmonary rehabilitation to them. The patients who underwent esophagectomy in the previous year were set as a control group. Results: 26 (male/female 25/1, mean age 70.5±7.9) and 27 patients (male/female 26/1, mean age 69.6±8.3) were enrolled in the preoperative screening and in the control group, respectively. There was no significant difference in the patient characteristics or surgical procedures between the two groups. In the preoperative screening and in the control group, 9 and 11 patients respectively satisfied the high-risk criteria. The incidence of PPCs in the preoperative screening group (7.7%) was significantly lower than that of the control group (37%, p =0.02). Conclusions: This study suggests that perioperative interventions to the patients selected by preoperative screening with RFRI may reduce PPCs after esophagectomy.

Staphylococcus aureus, including methicillin-resistant S. aureus (MRSA), produces superantigenictoxins, such as toxic shock syndrome toxin-1 (TSST-1). TSST-1 abnormally activates T cells to overproduce inflammatory cytokines (such as tumor necrosis factor-alpha, interleukin-2, and interferon-gamma) leading to shock. In this study, we investigated the inhibitory effect of antimicrobial agents and anisodamine (a Chinese herbal extract) on TSST-1-induced cytokine production. Among the macrolides and related agents examined, azithromycin and rokitamycin showed the greatest inhibitory activity against the TSST-1-induced cytokine production. This inhibitory effect was similar to that of anisodamine, which, however, had no inhibitory activity against bacterial growth. Vancomycin, teicoplanin, arbekacin, and linezolid (anti-MRSA and related agents) had no significant inhibitory effect on cytokine production. The inhibitory effect of the drugs on cell proliferation was not significant. These data indicate that some antimicrobial agents, e.g., azithromycin and rokitamycin, manifest anti-superantigenic toxin activity through the inhibition of cytokine production, just like anisodamine.

We encountered a 49-year-old HIV-infected man with chronic renal insufficiency who developed rhabdomyolysis after treatment with simvastatin. He recovered after initiating hemodialysis and discontinuing oral medications. Rhabdomyolysis most likely resulted from an excessive blood concentration of simvastatin caused by concomitant use of fluconazole in the presence of renal insufficiency.

This article describes a method for simultaneously displaying several images on a screen during an online multimedia presentation. Users with 'REALPLAYER' software and Web browsers can view images with synchronous audio on their personal computers via the Internet. Medical researchers and physicians often find it useful to compare images after treatment with those before treatment, by displaying several arranged images simultaneously. Medical care providers can browse this type of multimedia content in their offices and universities at their convenience. There presently exist two methods for creating multimedia content with voice and images using RealSystem technology. Electronic lectures of otorhinolaryngology explaining new surgical procedures for patients with chronic otitis media were created with this method and made available to otorhinolaryngologists through the Internet.

OBJECTIVE Blood (1 --> 3)-beta-D-glucan (betaG) measurement is widely used as an effective sero-diagnostic method for deep-seated mycosis. Antitumor betaG (lentinan, schizophyllan) administration is known as one of the false-positive factors of blood betaG measurement. To understand the influence of administered betaG preparation to betaG measurement in blood, we compared the interfering effect of betaG administration in different betaG measuring methods. METHODS betaG concentration in plasma was measured by three different methods. MATERIALS betaG concentration was measured in plasma of 18 samples of 7 cases with betaG administration and 86 samples without betaG administration. The period after last betaG administration was three days to three years. RESULTS In the cases for which betaG was administered, blood betaG level drastically increased using the method which employs alkaline pretreatment. Even in the cases for which betaG was administered three years previously; betaG value measured by alkaline pretreatment was significantly high. Thus, interference of betaG administration in blood betaG measurement continued for years after the last administration. CONCLUSION Disparity in betaG values measured by different methods for betaG administered cases is due to differences among sample pretreatment methods. Conformation of administered betaG seemed to be transformed into a sensitive form to factor G by alkaline pretreatment. Especially in the case of the alkaline pretreatment method, betaG administration disturbance was much stronger than for dilution-heating pretreatment. Therefore, in suspected cases, it is important to pay attention to betaG administration during the previous few years.

beta-Glucan Test MARUHA for high sensitive diagnosis of deep mycosis which was developed recently detects (1-->3)-beta-D-glucan, a component of the cell wall. The performance of beta-Glucan Test MARUHA is evaluated in this report. Although existing methods to detect (1-->3)-beta-D-glucan have trouble with sulfa drugs, hemolysis, and immunoglobulin G (IgG), these problems were overcome by the beta-Glucan Test MARUHA: No effect was observed for beta-Glucan Test MARUHA at lower than 200 micrograms/ml, 500 mg/dl, and 6,000 mg/dl of sulfa drugs, hemoglobin, and IgG, respectively. The effect of drugs administrated on the measurement value of beta-glucan Test MARUHA was checked at several concentrations. However, almost no effect of drugs, such as, 5 kinds of antifungals, 8 kinds of antibiotics, a kind of antibacterial, 2 kinds of infusions, and a kind of contrast media was observed at the practical concentrations.

We treated a case of adult-onset severe-form anaphylactoid purpura. This case had been diagnosed as anaphylactoid purpura pathologically by skin biopsy. However, his clinical manifestations were atypical in view of complicated massive gastrointestinal hemorrhage. Intensive therapy including corticosteroid and cyclophosphamide transiently improved his condition. Nevertheless, the beta-D-glucan value in peripheral blood was gradually elevated. Prophylactic use of fluconazole failed to prevent contraction of invasive mycosis. Finally, he suddenly suffered from diffuse cerebral hemorrhage. Postmortem examination revealed systemic invasive aspergillosis as the cause of death.

Using Amebocyte lysate of horseshoe crab to measure (1-->3)-beta-D-glucan specifically, a component of the cell wall, several kinds of diagnostic methods for deep mycosis are in practical use in Japan. However, the most important problem is that the judgment of positive or negative is method dependent. To elucidate the cause of the problem, each measurement value of the identical sample by four methods, beta-Glucan Test Maruha (MARUHA), beta-Glucan Test Wako (WAKO). FUNGITEC G Test (FUNGITEC-G) and FUNGITEC G Test MK (FUNGITEC-MK) was compared with the clinical data using 119 cases and 289 tests. Each case was divided into three groups; proven fungal infection, probable fungal infection and non-fungal infection. The negative cases for all the methods tested in the groups of proven fungal infection and probable fungal infection were allergic bronchopulmonary aspergillosis and cryptococcosis, and that for all the methods tested except FUNGITEC-MK method in the group was pulmonary aspergilloma. It seems that these cases cannot be detected correctly by only measuring (1-->3)-beta-D-glucan. On the other hand, the ratio of false positive, positive for non-fungal infection group was high in the case of FUNGITEC-MK. About 23% against the total case was positive for FUNGITEC-MK method, but negative for MARUHA, WAKO, and FUNGITEC-G methods. Although the difference of the sensitivity among four methods was not observed, the specificity, the diagnostic efficiency, and the positive predictive value of FUNGITEC-MK method were remarkably lower than those of the other methods due to false positive measurement. In conclusion, MARUHA, WAKO and FUNGITEC-G except FUNGITEC-MK is not method dependent. It is suggested that FUNGITEC-MK detects non-specific reaction resulted in false positive.

Ceftazidime-resistant Enterobacter aerogenes was isolated from blood cultures of three patients with fever. DNA analysis using pulsed-field gel electrophoresis and ribosomal RNA gene restriction digest pattern analysis revealed that the strains were clonally similar to each other with a 79.3-96.0% homology. The same strain of E. aerogenes was isolated from a three-way stopcock connected to the indwelling catheter in one of the patients at a concentration of 45 cfu/mL. A similar strain was also isolated from the urine of one other patient on the same floor. The data suggest that E. aerogenes caused septicaemia via low bacterial contamination of a three-way stopcock in a peripheral drip intravenous infusion system in at least one patient, and that the outbreak of E. aerogenes infections was due to clonally-related strains.

Lipopolysaccharide (LPS) is a potent chemotactic component for polymorphonuclear leukocytes (PMN, neutrophils). Since LPS tolerance was first described, many studies have been reported about the hyporesponsiveness in vitro corresponding to attenuating production of proinflammatory cytokines. We hypothesized that in vivo daily exposure to LPS stimuli impairs neutrophil accumulation in the rat airway. Interleukin 8 (IL-8) and/or CXC-chemokine, a neutrophil chemoattractant and activating cytokine, have been implicated as proinflammatory mediators in gram-negative respiratory tract infections. It is possible that the tolerance to LPS has occurred in relation to this chemoattractant cytokine production. To settle this issue, we examined whether the neutrophil count in bronchoalveolar lavage fluid (BALF) decreases after daily inhalation of Pseudomonas aeruginosa LPS into the rat airway. Repeated inhalation of LPS into the airway resulted in reduction in neutrophil recruitment. We measured rat CXC-chemokine (rat GRO/CINC1) levels in recovered BALF. There were noted reductions of rat GRO corresponding to the diminished neutrophil trafficking. We also confirmed that the HLA-DR positive lymphocyte number in BALF gradually increased after daily inhalation of LPS. These results suggest that continuous stimuli of LPS mitigate the accumulation of inflammatory cells in the airway by reducing chemokine production with a consequent change in the appearance of local inflammation to a chronic state.

Objective: Interstitial lung disease (ILD) is a complication occurring in 10–30% of patients with polymyositis/dermatomyositis (PM/DM) as well as in those with progressive systemic sclerosis (PSS). Clinical features are different between these two disease states, notably with respect to the duration of manifestations, pathological findings, response to steroid therapy etc. However, dissimilarities in pulmonary inflammatory cell characteristics, which, if present at all, would be of critical importance, remain as yet to be clarified. Methodology: The phenotypes of lymphocytes and alveolar macrophages in bronchoalveolar lavage fluid (BALF) were analysed to elucidate phenotypic peculiarity of pulmonary inflammatory cells of ILD in PM/DM. Eight PM/DM patients with ILD (mean age 47.9 years) were examined by bronchofibrescopy under local anaesthesia. Bronchoalveolar lavage was performed from the right middle lobe using four 50 mL aliquots of normal saline and the recovered fluid was compared with BALF of ILD in PSS. Results: Bronchoalveolar lavage fluid cells of PM/DM patients with ILD showed an increased percentage of CD8+ lymphocytes, in particular CD8+ histocompatibility leucocyte antigen-DR positive lymphocytes and CD8+ CD11b-lymphocytes, both of which represent cytotoxic T cells. However, phenotypic differences in these lymphocytes were not found between PM and DM. The percentage of alveolar macrophages with expression of histocompatibility leucocyte antigen-DQ was significantly different among the three groups (PM/DM, PSS, healthy volunteers). Conclusions: Cytotoxic T cells may be major pulmonary inflammatory cells of ILD in PM/DM with no apparent difference between PM and DM. In contrast, ILD in PSS was suggested as being likely to be characterized by activated macrophage.

Pseudomonas aeruginosa, an opportunistic pathogen, can cause life threatening infections in patients compromised by underlying respiratory disease like bronchiectasis, cystic fibrosis and diffuse panbronchiolitis. Most strains of P. aeruginosa produce some kind of protease with broad substrate specificities during the infectious state in the host. P. aeruginosa elastase, one of the strongest exotoxins, has a tissue-damaging proteolytic activity and is capable of degrading such plasma proteins as immunoglobulins, complement factor and cytokines. The present study focused on the effect of P. aeruginosa elastase and was designed to evaluate the neutrophil accumulation at the inflammation site mediated by P. aeruginosa elastase in the inflammatory response in the host. An air pouch model in rats, considered as a useful model of inflammation, was used to analyze the number of leukocytes, the volume of exudate and the concentration of interleukin-8 after the injection of P. aeruginosa elastase into the pouch cavity. The number of neutrophils and the volume of exudate in the pouch cavity increased significantly at 4 h, peaked at 8 h in a dose-dependent manner and then decreased at 24 h. The concentration of interleukine-8 in pouch fluid peaked 4 h earlier than the peak of the neutrophil number. The enzymatic activity of P. aeruginosa elastase seemed to reinforce the inflammation process. The influence of lipopolysaccharide contamination was negligible. Although these observations were made in the subcutaneous cavity, they indicate that P. aeruginosa elastase plays a role as an immunoprovocative factor in the inflammatory response in cases of infection with P. aeruginosa.

IgA nephropathy may be associated with colonisation with Haemophilus parainfluenzae. In patients with glomerular diseases, we examined renal-biopsy specimens for presence of bacterial antigen by immunofluorescence microscopy with rabbit antiserum against H parainfluenzae, and by enzyme-linked immunosorbent assay looked for IgA antibody against H parainfluenzae in patient sera. The rabbit antiserum recognised by immunoblotting four components of H parainfluenzae outer membranes (OMHP) of molecular weights 19.5, 30, 33, and 40.5 kDa. All 44 patients with IgA nephropathy and 2 of 39 patients with other glomerular diseases showed mesangial deposition of OMHP antigens (p < 0.001). Patients with IgA nephropathy had significantly more IgA antibody against H parainfluenzae than did patients with other glomerular diseases. IgA antibody in the sera of patients with IgA nephropathy recognised by immunoblotting the same four components of OMHP as recognised by rabbit antiserum. Glomerular deposition of OMHP antigens and the presence of IgA antibody against OMHP in patients with IgA nephropathy suggest that H parainfluenzae has a role in the aetiology of this disease.

Postmortem infectious lesions were analyzed in 63 patients with bacteremia and fungemia. Bacterial infection was found in 36 patients, deep mycoses in 27 and cytomegalovirus infection in 7. Among deep mycoses patients, yeast was noticed in 17, Aspergillus in 13 and Mucor in one. Infectious lesions were not observed in 10 cases. Fifteen cases of 23 leukopenic patients were complicated with deep mycoses. Deep mycoses was noticed in 43% of bacteremia and fungemia patients, but not in candicemia patients. Fungemia due to Candida was related to blood access, however, not to deep mycoses. On the other hand, disseminated mycoses was found in 4 of 5 cases with Trichosporon beigelii fungemia. T. beigelii infection is noticeably life-threatening to the immunocompromised host.

Klebsiella pneumoniae is an important causative bacterium of aspiration pneumonia in many elderly patients. We retrospectively investigated the clinical effects of the early treatment of aspiration pneumonia and background factors in 24 patients from whom Klebsiella pneumoniae was isolated. Sulbactam/ampicillin (SBT/ABPC) was selected for early treatment in 12 of the 24 patients diagnosed with aspiration pneumonia, and tazobactam/piperacillin (TAZ/PIPC) was selected for the other patients. The effective rates and success rates of early treatment were significantly higher in the TAZ/PIPC group than in the SBT/ABPC group (p = 0.003 and 0.027, respectively). Although no significant difference was noted because of the limited number of cases, the survival rates after 30 days were 91.7 and 58.3 % in the TAZ/PIPC and SBT/ABPC groups, respectively. Several bacteria isolated with Klebsiella pneumoniae were resistant bacteria, such as methicillin-resistant Staphylococcus aureus or Pseudomonas aeruginosa, and no anaerobe or extended-spectrum β-lactamase-producing Klebsiella pneumoniae was isolated. Thirteen and 11 of the 24 cases were classified as healthcare-associated pneumonia (HCAP) and hospital-acquired pneumonia (HAP), respectively, with no case classified as community-acquired pneumonia (CAP). As population aging progresses, the frequency of aspiration pneumonia classified as HCAP will increase. To cover anaerobes, it is necessary to select antibacterial drugs, such as TAZ/PIPC, for early treatment in consideration of resistant gram-negative bacteria to improve the outcome, and not drugs with weak activity against these bacteria.