肝臟青春痘 (肝膿瘍) Klebsiella pneumoniae克雷白氏桿菌3分鐘檢測 (500元) 碁米庫斯生技 (黃少穎/ 蕭樑基)

新知》這種肺炎致死率高達97％ 台團隊研發3分鐘檢測劑 2017-03-2215:13 〔記者吳亮儀／台北報導〕致死率最高達97％的肺炎克雷白氏桿菌，主要引起感染，以往檢測方式又貴又久，但三軍總醫院醫療團隊耗費多年研究，發明只要3分鐘就能測出有無感染、且成本不到500元的檢測劑。肺炎克雷白氏桿菌肺炎占全部肺炎8%，居第三名，其死率高達51%到97%；而肺炎克雷白氏桿菌菌血症的發生率在25%左右，死亡率達30%，每年發生率約4000多人。國防醫學院、三軍總醫院、台北榮總和國家衛生研究院組成的團隊研究，這項快速測定檢驗劑是全球第一個用在檢驗第1、2型「克雷白氏桿菌」的檢驗工具，只要將肝穿刺取得的菌株液或膿液滴到測試盤上，3分鐘後就能知道結果，且精準度近100%。研發團隊成員之一、三軍總醫院感染暨熱帶醫學科主任林永崇指出，這種桿菌主要存在人體腸道內，若抵抗力不好，有時會移轉到肝臟導致肝膿瘍，進而移轉到眼睛。林永崇指出，台灣人特別容易受這桿菌感染，只要出現肝膿瘍幾乎百分之百是因肺炎克雷白氏桿菌感染，而美國不到4成，推測可能和基因有關。「肝膿瘍就像長在肝臟上的青春痘」林永崇說，這只能透過穿刺引流搭配抗生素治療，若未即時處理，細菌恐跑到其它部位引發敗血症、眼內炎、腦膜炎、肺炎、髂腰肌膿瘍等。新研發的檢驗劑已由台北榮總、三軍總醫院、高醫附醫等3家醫學中心做測試，效果很好，已將此技術技轉給生技公司，預計1年內可投入市面。這項研究在去年12月刊登於《臨床微生物學雜誌》（Journal of Clinical Microbiology）。

The Antimicrobial Susceptibility of Klebsiella pneumoniae from Community Settings in Taiwan, a Trend Analysis Scientific Reports 6, Article number: 36280 (2016) Drug-resistant Klebsiella pneumoniae, especially extended-spectrum β-lactamase (ESBL)- and/or AmpC β-lactamase-producing strains, is an emerging problem worldwide. However, few data focusing on drug susceptibility of K. pneumoniae from community is available. In this study, we analyzed 1016 K. pneumoniae isolates from outpatients or those visiting emergency rooms collected during 2002–2012 from Taiwan Surveillance of Antimicrobial Resistance program. Significantly decreased susceptibilities to 3rd generation cephalosporins and ciprofloxacin were found during the study period. By 2012, susceptibility to cefotaxime and ciprofloxacin was 83.6% and 81.6%, respectively. The prevalence of ESBL-producers increased from 4.8% in 2002 to 11.9% in 2012 (P = 0.012), while that of AmpC β-lactamase-producers increased from 0% to 9.5% in the same period (P < 0.001). Phylogenic analysis of the ESBL and AmpC-β-lactamase-producers by pulsed-field gel electrophoresis and multi-locus sequence typing revealed wide genetic diversity even among the most common sequence type 11 isolates (33.0%). By multivariate analysis, later study year, elderly, and urine isolates were associated with carriage of ESBL genes, while only urine isolates were associated with carriage of AmpC β-lactamase genes. Further studies are needed to determine which antibiotics are reasonable empirical therapy options for patients presenting with severe sepsis that might be caused by K. pneumoniae.

Taiwan Develops a New Molecular Diagnostic Method to Rapidly and Accurately Identify Hypervirulent Klebsiella pneumoniae Strains/ March 10, 2016/ Klebsiella pneumoniae is an encapsulated gram-negative bacillus that frequently causes outbreaks of nosocomial infections in hospitalized patients. It can also afflict ambulatory persons and cause community-acquired invasive diseases—including pyogenic liver abscess, endophthalmitis, meningitis, empyema, lung abscess, and necrotizing fasciitis. The worldwide emergence of multidrug-resistant strains and hypervirulent strains of K. pneumoniae has become an increasing clinical challenge and public health concern. A new molecular diagnostic method, based on detection of the two genetic determinants of O1 lipopolysaccharides, has been developed by Dr. Chi-Tai Fang of National Taiwan University to rapidly and accurately identify hypervirulent K. pneumoniae strains. This study has been published in March on Journal of Clinical Microbiology, a distinguished journal of the American Society for Microbiology./Dr. Chi-Tai Fang, two students, Ms. Yun-Jui Shih and Ms. Cheng-Man Cheong, and their parents in 2011 College of Public Health Graduation Ceremony/The research was conducted by Dr. Chi-Tai Fang, associate professor at the Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan, and two Master students, Ms. Yun-Jui Shih and Ms. Cheng-Man Cheong./ K. pneumoniae strains can be distinguished by their capsular polysaccharide (CPS) K-antigen types (77 serotypes) and lipopolysaccharide (LPS) O-antigen types (9 serotype). Strains with K1 capsular polysaccharide are extremely virulent, causing metastatic endophthalmitis, meningitis from pyogenic liver abscess. However, only 60 percent of strains causing pyogenic liver abscess are K1 strains. The remaining are of K2, K5, K20, K54, K57, and other K types. On the other hand, more than 90 percent of strains causing pyogenic liver abscess have O1 lipopolysaccharides. Therefore, O1 is a better marker for virulent K. pneumoniae strains capable of causing pyogenic liver abscess. However, there was a lack of simple and reliable method for detecting O1 in clinical and epidemiological samples, because K. pneumoniae O-serotyping is cumbersome and the reagents are not commercially available./To develops a new molecular diagnostic method to quickly and accurately identify O1 K pneumoniae, Dr. Fang and his students sequenced the genetic determinants of LPS O-antigen from O1, O2a, O2ac, O3, O4, O5, O8, O9, and O12. They identified the two genetic determinants of O1 lipopolysaccharides. They then successfully develop PCR primers that detects the O1-specific genes. They further tested the sensitivity and specificity of the new molecular detection method against the O and K reference strains provided by World Health Organization Collaborative Center for Escherichia coli and Klebsiella at Statens Serum Institut (Copenhagen, Denmark). The sensitivity and specificity were found to be 100 percent and 100 percent, respectively./Given the high accuracy and the great convenience, the new PCR detection method represents an important breakthrough in the molecular diagnosis of hypervirulent K. pneumoniae. This new technology provides a highly useful tool for the clinical and epidemiological investigations of K. pneumoniae and its associated diseases.

Development of a Colloidal Gold-Based Immunochromatographic Strip for Rapid Detection of Klebsiella pneumoniae Serotypes K1 and K2 In this study, a novel colloidal gold-based immunochromatographic strip (ICS) containing anti-Klebsiella pneumoniae capsular polysaccharide polyclonal antibodies was developed to specifically detect K. pneumoniae serotypes K1 and K2. Capsular polysaccharide K1 and K2 antigens were first used to produce polyclonal anti-K1 and anti-K2 antibodies. Reference strains with different serotypes, nontypeable K. pneumoniae strains, and other bacterial species were then used to assess the sensitivity and specificity of these test strips. The detection limit was found to be 105 CFU, and the ICSs were stable for 6 months when stored at room temperature. No false-positive or false-negative results were observed, and equivalent results were obtained compared to those of more conventional test methods, such as PCR or serum agglutination. In conclusion, the ICS developed here requires no technical expertise and allows for the specific, rapid, and simultaneous detection of K. pneumoniae serotypes K1 and K2./

碁米庫斯生物科技股份有限公司 成立於西元2015年7月，本公司主要從事抵禦細菌感染的相關研究，目前的三個主要專案為：克雷伯氏肺炎桿菌K1/K2血清分型快篩卡、抗生素的測試及篩選平台、B型腦膜炎重組次單元疫苗。其應用範圍分別為細菌感染症的檢測、治療及預防。碁米庫斯生技公司的董事長黃少穎先生具有多年的生技產業經驗，總經理蕭樑基博士從事細菌感染相關研究多年，加上多位醫生及細菌感染研究專業人員，大家一同為人類的健康而努力。

預防/B型腦膜炎重組次單元疫苗 腦膜炎雙球菌主要是藉由飛沫與接觸感染，感染後進展快且死亡率高，可引起腦膜炎與敗血症等，是一種可怕的病菌。本公司已獲得台灣國家衛生研究院「B型腦膜炎重組次單位疫苗」技術之專屬授權，此候選疫苗已申請新藥人體試驗（IND），並經台灣衛福部食品藥物管理署（FDA）核准，目前正準備在台灣進行第一階段的人體臨床試驗。

張峰義（科學諮詢委員）學歷 國防醫學院 醫學系 醫學士 國防醫學院 醫學科學研究所 博士/ 現任 三軍總醫院 感染及熱帶醫學科 主治醫師 國防醫學院 醫學系內科學科 教授/曾任 衛生福利部 疾病管制署 署長 三軍總醫院 副院長; 馮長風（科學諮詢委員）學歷 國立台灣大學 醫學系 醫學士 英國倫敦大學 醫用微生物研究所 碩士/現任 臺北榮民總醫院 特約醫師/ 曾任 臺北榮民總醫院 內科部感染科 主任 國立陽明大學 急重症醫學研究所 教授 中華民國感染症醫學會 秘書長 竹東榮民醫院 副院長; 黃少穎（董事長）學歷/國立中山大學 生命科學研究所 碩士現任 茂晶生物科技股份有限公司 執行董事 倍晶生物科技股份有限公司 執行董事/ 曾任 尚上儀器股份有限公司 經理 尚偉股份有限公司 經理 中國化學製藥生技研究所 副研究員; 蕭樑基（總經理）學歷 香港大學 臨床微生物學 博士/ 專長 臨床微生物學 抗生素抗藥機制與流行病學/現任 國家衛生研究院 感染症與疫苗研究所 研究員 國防醫學院 醫學系內科學科 合聘教授; 蔡昱果（資深研究員）學歷 國立清華大學 生命科學系 博士/ 專長 分子生物學 抗生素抗藥機制/曾任 國家衛生研究院 感染症與疫苗研究所 博士後研究員