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在penicillin resistance這個產品中，有5篇Facebook貼文，粉絲數超過2萬的網紅藥學人生 - Pharmalife，也在其Facebook貼文中提到， 近一個月前，南韓梨花女子大學附醫新生兒加護病房 (NICU)，有四名早產兒在數小時之內相繼死亡。 後續鑑識報告發現四名嬰兒中，有三名小孩的血液培養報告顯示為 Citrobacter freundii 這隻格蘭氏陰性桿菌 (Gram negative bacilli; GNB)。 進一步報告...
　同時也有10000部Youtube影片，追蹤數超過2,910的網紅コバにゃんチャンネル，也在其Youtube影片中提到，...

penicillin resistance 在 藥學人生 - Pharmalife Facebook 的精選貼文

藥學人生 - Pharmalife By 藥學人生 - Pharmalife

2017-12-27 22:13:39 有 223 人按讚
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近一個月前，南韓梨花女子大學附醫新生兒加護病房 (NICU)，有四名早產兒在數小時之內相繼死亡。

後續鑑識報告發現四名嬰兒中，有三名小孩的血液培養報告顯示為 Citrobacter freundii 這隻格蘭氏陰性桿菌 (Gram negative bacilli; GNB)。

進一步報告顯示，這些早產兒接受的全營養靜脈注射液 (TPN) 有被 C. freundii 所污染... 0rz

【強調】這四名早產兒的死亡是不是能全部歸因於 C. freundii 感染，仍需更多證據以釐清。

#rest_in_peace
　
━━━━━ 今天就來聊聊 Citrobacter sp ━━━━━

C. freundii 為腸細菌屬 (Enterobacteriaceae)，可以在土壤、汙水、食品等環境中出現，同時，也存在於人體腸道內。
　　
某種程度上來說，Citrobacter sp 是比較後線的院內菌株，他的抗藥性主要來自：
∎ 先天性惡論｜自產的 beta-lactamase
∎ 後天交到壞朋友｜從別種 GNB 的質體 (plasmid) 交換而來 Extended-spectrum beta-lactamases (ESBLs) 基因，導致 Citrobacter sp 對 cephalosporin, penicillin, aztreonam 等藥物產生抗藥性。
∎ 環境逼我走絕路｜Citrobacter sp 可被 cephalosporin 類藥物誘導出自身染色體上的 AmpC 基因，產生 AmpC cephalosporinases，並對前三代 cephalosporin 產生抗藥性。
　　　　
━━━━━

Citrobacter sp 雖為腸道菌叢之一，但臨床上對於部分免疫力較弱、經過數輪抗生素轟炸過的病人而言，依然可能造成泌尿道感染 (UTI)、院內肺炎 (nosocomial pneumonia)、腹腔內感染 (intra-abdominal infection; IAI)，以及新生兒腦膜炎或敗血症。
　　
對於 Citrobacter sp 的治療，若敏感性試驗尚未出爐之前...
☞ 非嚴重感染且院內 MDR GNB 比例 <20%：可考慮以 piperacillin/tazobactam (Tazocin) 作為首選治療
☞ "嚴重感染" 或 "院內 MDR GNB > 20%"：Meropenem
　　
☞ 待敏感性試驗出爐後，若為 ESBL/AmpC (+)，可視 MIC 調整為 imipenem, meropenem, doripenem, ceftolozane-tazobactam (Zerbaxa), ceftazidime-avibactam (Avycaz), or meropenem-vaborbactam (Vabomere)。

━━━━━

熊大讚曰：「Citrobacter sp 只是基因壞，人不壞。」

━━━━━━━━━━━━━━━

原始報導連結：https://goo.gl/nahrnK
US CDC | Antibiotic / Antimicrobial Resistance: https://goo.gl/1sGdgn

#citrobacter #enterobacteriaceae #contaminate #ICU

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penicillin resistance 在 一個平凡醫學生的日常。 Facebook 的最讚貼文

一個平凡醫學生的日常。 By 一個平凡醫學生的日常。

2017-07-27 20:57:00 有 63 人按讚
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我覺得抗生素的使用是一個很揭露人性的議題。對病人自己短期而言，他們主觀上當然覺得使用強力的big gun antibiotics有利無害。但對社會大眾長期來說卻影響深遠，後患無窮。選擇一時的方便還是盡力延長藥物的有效期；只著眼一人的病情還是關注整個社會的健康：這是醫生用藥時必須考慮的後果，也希望病人（和家屬）能夠理解。

【我們正步入「後抗生素時代」｜ 醫患連線】

「瑪嘉烈醫院一名長期病患者去年因肺炎留醫，醫生處方 Azithomycin 及 Augmentin 5日後情況沒有好轉，繼而獲處方更強力抗生素 Tazocin，惟病人4日後因肺炎去世。」病人家屬責怪醫生未能為病人處方「最強」的藥物，令病人失去最佳治療時間。可是，應否先為病人處方 Tazocin 卻值得商榷。

然而，「最強」的抗生素只會帶來「更強」的細菌，於剛發現抗生素青黴素 (Penicillin) 的年代，它就是「最強」的抗生素，直到細菌普遍出現耐藥性。於是，科學家找出耐藥性的原因，研發出更廣譜性「更強」的抗生素 Amoxicillin。之後，科學家再研發出「更強」的抗生素 Augmentin。而現在Augmentin 卻被認為是「普通」的抗生素。

原來，「沒有最強，只有更強」。 出現如此強勁的耐藥性細菌，究竟是誰的責任呢？

人往往都追求最好的，最強的。既然有特效藥能殺死細菌，為何我要服普通的藥？ 「弱肉強食，適者生存」，在細菌的世界也不外如是。不同的細菌每天在你我的身體中爭個你死我活，亦會不斷變異，務求自己能生存。然而，特效藥將絕大部份細菌殺清，連幫助對抗惡菌的益菌都殺掉。有節制地﹑有需要地及情況嚴重時使用特效藥沒問題，但假若每一次的感染，甚至是情況輕微的感染都使用，只會「逼得細菌太緊」，替變異成功的抗藥惡菌爭取領土。結果，絕大部份細菌都殺清光，取而代之就是那些特效藥殺不死的抗藥惡菌。特效藥霎時降級，變成普通藥，唯有再研發「更強」的抗生素了。

問題有多嚴重？

世界衛生組織於2014年的抗菌素耐藥性報告中指出，我們正步入「後抗生素時代」—— 意指一些原本常見或輕微的感染因耐藥性而無藥可醫，像回到了以前沒有抗生素的時代一樣。大家對抗耐甲氧西林金黃葡萄球菌 (Methicillin-resistant Staphylococcus aureus, MRSA) 相信並不陌生。近年引起更大關注的，是碳青霉烯酶腸道菌 (Carbapenem-resistant Enterobacteriaceae, CRE) 。某些克雷伯氏菌 (Klebsiella species) 和大腸桿菌 (Escherichia coli) 都屬於益菌，能在健康的人的腸道中找到。無奈因不正確使用抗生素，它們對碳青霉烯 (Carbapenem) 已出現耐藥性。健康的人有益菌這隊大軍保護，CRE難以侵入。因此，CRE襲擊的大都是長期病患者，特別是一些經常服用抗生素，而導致腸內益菌減少的人。益菌減少，令CRE這類抗藥惡菌能乘虛而入，大肆破壞。某些CRE只對市面上「最後一道防線」的粘桿菌素 (Colistin) 有反應，因此也能解釋為何感染CRE死亡的人能達50%。更甚的是，現時開始有不同國家及地區，發現對粘桿菌素產生耐藥性的腸道菌 (Colistin-resistant Enterobacteriaceae)，而本港亦在1,324 個醫院臨床樣本中，有0.4%出現其耐藥性的基因。此外，另一種引起擔憂的超級細菌是淋病奈瑟菌 (Neisseria gonorrhoeae)。現在已經有最少十個國家，包括英國﹑澳洲﹑加拿大﹑法國﹑日本等，發現牠對作為「最後一道防線」的第三代頭孢菌素 (Third-generation cephalosporin)，如頭孢曲松 (Ceftriaxone)，產生耐藥性。

香港情況如何？

醫管局及衛生防護中心均有監察細菌耐藥性。醫管局的超級細菌報告（2011-2016）指出，監察的鮑氏不動桿菌 (Acinetobacter species) 中，約50%對碳青霉烯 (Carbapenem) 有耐藥性，金黃葡萄球菌 (Staphylococcus aureus) 中，約40%對甲氧西林 (Methicillin) 有耐藥性，及有20%的大腸桿菌 (Escherichia coli) 製造廣譜β-內酰胺酶 (Extended-spectrum β-lactamase, ESBL)。更甚的是，醫管局亦發現了耐碳青霉烯酶腸道桿菌 (CRE) 個案在近年有所增加，由2011年的19名病人增加至2015年的340名病人。另一方面，衞生署亦有監察淋病奈瑟菌 (Neisseria gonorrhoeae) 耐藥性的興起，該細菌對頭孢菌素 (Ciprofloxacin) 及青黴素 (Penicillin) 有耐藥性的分別佔總數的95%及50%，幸好對頭孢曲松 (Ceftriaxone) 的耐藥性還處於接近0%的低水平，但我們絕不能對此掉以輕心。

新的抗生素在那裡？

雖然一直有科研人員致力研發新的抗生素，但是成效始終不大。一份2016年初出版的抗生素回顧文獻指出，由2000年至2015年新核准 (Approved) 的抗生素有三十款，另有兩款為新的 β-lactam/β-lactamase inhibitor 組合，當中只有六款為市場首見新藥 (First-in-class)，其餘為新一代的藥物 (New generation of existing class)。然而，單計算美國食品藥物管理局 (FDA)　在2016年新核准的藥物的七十八款中，卻沒有一款為抗生素，只有兩款為針對細菌毒素的單株抗體，而對比抗癌藥則有十款，可見每年能成功推出市場的抗生素廖廖可數。

截至現時的臨床實驗 (Clinical trial) 中，單針對肺癌的有1648項紀錄，而針對細菌感染的只有145項紀錄（註：每項紀錄以單一地方進行的單個實驗去計算），數據顯示出藥廠亦不願去研發抗生素。其中一個可能的原因為細菌變異速度快，而全球濫用抗生素的情況嚴重，以致細菌容易產生耐藥性，令新研發的抗生素很快失效。另外，抗生素療程有限，相比起需長期服用的藥物，如降膽固醇藥，所賺取的利潤未必太多，亦不持久。

假若你是藥廠的老闆，你會投資相對高風險的抗生素，或是能賺大錢的抗癌藥呢？

事實上，要成功研發更多抗生素，政府的角色十分重要。若果單靠藥廠自行研發，結果只會遠遠追不上不斷變異的惡菌。因此，政府應立刻投放更多資源，支持科研人員研發新的抗生素，才能及早未雨綢繆。當然，在公共衛生層面上，政府亦應靠一系列的措施去減慢細菌產生耐藥性的速度。

也許，這名瑪嘉烈醫院患者去世一事告訴我們「後抗生素時代」已漸漸逼近。

如何應對？下回再談。

事件來源：http://hk.apple.nextmedia.com/news/art/20170724/20099693

參考資料：
Medeiros, A. (1997). Evolution and Dissemination of β-Lactamases Accelerated by Generations of β-Lactam Antibiotics. Clinical Infectious Diseases, 24(Supplement 1), pp.S19-S45.

Centers for Disease Control and Prevention. (2017). Carbapenem-resistant Enterobacteriaceae in Healthcare Settings | HAI | CDC. [online] Available at: https://www.cdc.gov/hai/organisms/cre/ [Accessed 24 Jul. 2017].

Centre for Health Protection. (2017). Bacterial pathogen isolation and percentage of antimicrobial resistance - out-patient setting. [online] Available at: http://chp.gov.hk/en/data/1/10/641/697/3345.html [Accessed 22 Jul 2017].

Martens, E. and Demain, A. (2017). The antibiotic resistance crisis, with a focus on the United States. The Journal of Antibiotics, 70(5), pp.520-526.

World Health Organization. (2014). Antimicrobial resistance: global report on surveillance 2014. [online] Available at: http://apps.who.int/…/bitstream/10665/112642/1/978924156474… [Accessed 22 Jul 2017].

Centers for Disease Control and Prevention. (2016). Colistin-Resistant Enterobacteriaceae Carrying the mcr-1 Gene among Patients in Hong Kong. Available at: https://wwwnc.cdc.gov/eid/article/22/9/16-0091_article [Accessed 22 Jul 2017].

Butler, MS., Blaskovich, MAT. and Cooper MA. (2017). Antibiotics in the clinical pipeline at the end of 2015. The Journal of Antibiotics, 70, 3-24.

CenterWatch. (2017). Search Clinical Trials. [online] Available at: http://www.centerwatch.com/clinical-trials/listings/ [Accessed 22 Jul 2017].

Centre for Health Protection. (2017). Hong Kong Strategy and Action Plan on
Antimicrobial Resistance 2017-2022 [online] Available at: http://www.chp.gov.hk/files/pdf/amr_action_plan_eng.pdf [Accessed 22 Jul 2017].

Hong Kong Economic Journal. (2016). Most private doctors prescribing antibiotics too easily: expert. [online] Available at: http://www.ejinsight.com/20161103-most-private-doctors-pre…/ [Accessed 22 Jul 2017].

圖片來源：https://commons.wikimedia.org/…/File:Human_neutrophil_inges…

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一個平凡醫學生的日常。

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penicillin resistance 在 小小藥罐子 Facebook 的精選貼文

小小藥罐子 By 小小藥罐子

2016-12-19 07:50:50 有 39 人按讚
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〈ESBL = ？？？〉

最近，藥罐子相信，「雞」應該已經逃不掉，逐漸成為城中熱話，遺憾的是，主要的原因，並不是因為明年是雞年，而是……

唔……從前，說到雞，很多看倌，大多應該會聯想到「禽流感(Avian Flu)」；現在，除了禽流感外，還有四個英文字母，不知怎的，無緣無故，跟雞扯得上關係。

這四個英文字母，便是……ESBL。

實際上，ESBL，只是一組英文大階縮寫，全名其實是「Extended-Spectrum β-Lactamases」。

問題是，說到ESBL，不論什麼媒體，不管是網媒，還是紙媒，不管是電視新聞，還是報章雜誌，總是會跟「惡菌」扯上關係，同時鋪天蓋地，時時刻刻，提醒大家要關注隨之而來的抗藥性(Drug Resistance)問題嗎？

那麼，真的要說的話，兩者到底有什麼關係呢？

首先，在繼續討論前，藥罐子不妨在這裡，分享一下抗生素(Antibiotics)、抗藥性這場跨世紀的華麗對決！

在這場漫長的戰爭裡，一攻一守，雙方各有千秋，各有勝負，勝敗乃兵家常事，輸贏本是常態，沒有什麼好奇怪。

其中，針對一些抗生素，一些菌種已經能夠自行研發一種稱為「β-lactamase」的解藥，直接分解一類稱為「β-lactams」的抗生素，例如青霉素(Penicillin)，破壞這些抗生素的藥性，作為一種反制措施，抵禦抗生素的攻擊，讓抗生素不能發揮正常的功能，廢掉武功，導致失效。

當然，人類不是一盞省油的燈，面對這個情況，早有兩手準備，哼，你有解藥，難道我便沒有克制你這種解藥的解藥嗎？

對，無錯，現在，藥廠便已經成功研發一種稱為「β-lactamase Inhibitor」的抑制劑，作為附件，進行反擊，顧名思義，主要在抑制β-lactamase的活性，解除β-lactamase的功能，避免這類抗生素受到分解，從而保護這類抗生素，保存這類抗生素的活性，繼續發揮殺菌的藥效。

常言道：「你有張良計，我有過牆梯。」問題是，同一時間，在肉眼看不見的角落裡，既然稱為「惡菌」，那麼，不用問，菌種顯然不是善男信女，至少不是呆靶子，人爲刀俎，我爲魚肉，嗄，既然你有克制我這種解藥的解藥，那麼，難道我不會改良一下自己的解藥，破解你這種解藥嗎？

對，說到這裡，姑且撇開其他不說，不難發現，在本質上，這根本是一場沒完沒了的軍備競賽。

至於，這種新解藥，其實便是ESBL。

ESBL，在藥性上，顧名思義，還是一種β-lactamase，所以，不用問，自然便能夠繼續分解「β-lactams」這類抗生素，導致這類抗生素進行分解、流失，破壞本來的藥性，抗衡抗生素的藥效，削弱抗生素的療效，甚至導致這類抗生素喪失功效，同時，不僅是β-lactamase，而且還是Extended-Spectrum這個新版本，簡單說，就是「擴充版」，強化功能，優化性能，提升相關的戰鬥力，擴大相關的抗藥性，涵蓋更廣的抗生素，反制更強的抗生素，便會讓更多抗生素束手無策，從而收窄相關的抗菌譜(Antibacterial Spectrum)，不能涵蓋這些菌種，不能殺滅這些菌種。

慶幸的是，所謂「天外有天，人外有人」，就算是「長八尺餘，力能扛鼎，才氣過人（《史記．項羽本紀》）」的項羽，「身七十餘戰，所當者破，所擊者服，未嘗敗北，遂霸有天下。（《史記．項羽本紀》）」，再怎麼所向披靡，遇人殺人，遇佛殺佛，還是會有棋逢敵手的時候。

在用藥上，這個對手，不是韓信，而是Carbapenems，主要是Ertapenem、Imipenem、Meropenem。

諷刺的是，Carbapenems，在藥理上，還是一種β-lactams，只是，跟其他β-lactams不同，就算是ESBL這種專門破解β-lactams的解藥，打遍天下無敵手，偏偏就是拿這種β-lactams沒辦法，弄來弄去，還是不能分解這種β-lactams，這樣的話，Carbapenems便能夠保護自己，保存自己的活性，無視ESBL的攻擊，繼續發揮殺菌的藥效，在用藥上，一般會留作備胎，減少這些藥出現抗藥性的風險，目的在讓這些抗生素作為最後的殺著，用來治療一些連其他抗生素都無法治療的菌種。

問題是，面對這個一時無兩的西楚霸王，想來想去，最後還是只有一個韓信，能夠跟項羽匹敵，爭一日之長短，所以，「國士無雙。（《史記．淮陰侯列傳》）」簡單說，就是「只此一家，別無分店。」這就是說，如果沒有韓信的話，楚漢相爭，誰勝誰負，真的猶未可知……

同時，請注意，不管是Carbapenems，還是韓信，兩者只是一種偶然遇上的驚喜，只是偶然，不是必然。

在用藥上，這就是說，如果連這類抗生素都宣告無效的話，新藥未至，新菌又起，ESBL便可以突破這道防線，過關斬將，長驅直進，如入無藥之境，這時候，便會產生「有病無藥」的問題，在治療上，便會舉步維艱。

這就是抗藥性所帶來的問題……

最後，扯遠一點：

其實，話是這樣說，無錯，但是，就算是韓信這位兵仙，面對項羽，還是拿對方沒辦法，四面楚歌，還是困不住項羽，十面埋伏，還是擋不住項羽，最後，還是讓項羽突破重圍，潰圍南出（《史記．項羽本紀》），所以，真的要說的話，韓信其實沒有贏，只是沒有輸，當然，逼的對手霸王別姬、烏江自刎，讓對手主動棄權，在相當程度上，還算是另一種勝利，這點倒是真……

最後的最後，姑且不論田父、烏江亭長這兩個人物是否真有其人，是真是假，總之，蕭何月下追韓信，韓信垓下追項羽，你追我趕，追著追著，趕著趕著，項羽「乃有二十八騎。漢騎追者數千人。（《史記．項羽本紀》）」在兵力上，雙方相差百倍，這方面，漢軍擁有壓倒性的數量優勢，在這個情況下，強弱懸殊，寡不敵眾，項羽「自度不得脫（《史記．項羽本紀》）」，與其他殺，倒不如自殺。

事情，應該就是這樣。

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本網誌旨在分享用藥知識，圖文僅供教育用途。 內容僅供參考，絕對不能用來自行診治。 本網誌致力確保內容準確，惟醫藥知識隨時更新，故對內容的準確性、完整性、及時性、適用性不會承擔任何責任。如有健康疑難，請盡快求醫，以免貽誤治療良機。部分內容涉及醫藥知識，可能會引起不安，敬請留意。
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長照是一個劇變的旋轉舞台 百年難得一見 沒有準備的人 被旋轉舞台甩出去 不是坐下就是躺下 而大象中醫是太極的推手 推動著旋轉舞台 讓 所有爬不起來的人 背後有一股推手力量 支撐再站起來
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長照是一個劇變的旋轉舞台 百年難得一見 沒有準備的人 被旋轉舞台甩出去 不是坐下就是躺下 而大象中醫是太極的推手 推動著旋轉舞台 讓 所有爬不起來的人 背後有一股推手力量 支撐再站起來
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