從非典到新冠肺炎
From SARS to Novel Coronavirus (COVID-19) - English version is in the second half
新冠肺炎,Novel coronavirus (2019-nCoV) 新型冠状病毒肺炎,疫情越來越嚴重,被證實可以人傳人,也在武漢以外的許多地方發現病例,造成世界各國及世界衛生組織(WHO)高度關切,當然也讓很多住在中國大陸及附近區域的華人非常緊張,就好像當年的非典肺炎疫情即將再一次大爆發一樣。
目前,現代醫學還沒有找到治療新冠肺炎的方法,只能針對某些症狀來處理,疫苗的研發更是遙遙無期。怎麼辦?每次遇到這種情況,中醫就會被搬出來,這次也不例外。新冠肺炎爆發後,網上馬上有許多中醫對付新冠肺炎的文章。當然,除非哪位中醫師看過、治好過大量的新冠肺炎病例,所有的討論都是猜想、假設。然而,有些猜想及假設值得參考,有些猜想及假設卻明顯在誤導大眾。
我還沒有治療過新冠肺炎,不能大肆評論。不過,我治好過很多禽流感、豬流感、及每年流感導致的嚴重肺炎及其它病變的病人。其中許多病人是被美國大型西醫院證實為嚴重肺炎,被要求醫院或居家隔離,偷偷溜出來找中醫看診的。也因此許多病人及討論中醫的網站,希望我能針對新冠肺炎發表一些意見。
我們以前就討論過,這些彪悍的流感病毒,經過那麼多年、那麼多次的變種(mutation),每年都不一樣,東漢時期傳下來的經典中醫,根本沒有遇到過現在的病毒,怎麼可能治療如此嚴重的肺炎呢?
中醫從來就不認識病毒,也不從病毒種類的角度來思考。中醫是探討人體受到外界因素破壞,失去平衡後,身體會有哪些現象、哪些反應,根據那些現象、那些反應來調整身體狀況,期待身體能恢復到平衡狀態,把外界因素帶來的破壞減到最小。我打個半開玩笑的比方,警匪槍戰時,我們注意到壞人哪個方向來的火力強大,造成我們部署在哪個位置的警員傷亡,這時我們會趕緊重新部署人員,或者想辦法增派警力,我們大概無暇去管壞人是用哪個牌子的槍、哪個工廠做的子彈!
雖然幾百年幾千年下來,病毒變種等等的外界因素改變了非常多,人體演化的改變卻非常有限。人體的功能,無論是怎麼被破壞的,某項功能被破壞而導致的症狀、反應、後續演變,卻依然有明顯的脈絡可循。也因為如此,在很多情況下,中醫以專注人體本身平衡狀態的治療方式,反而比西醫專注在外來敵人的治療方式來得有效許多。
依據多年累積大量的臨床病例觀察,無論是禽流感、豬流感、還是每年的流感,人體敗壞的進程依然如同傷寒雜病論探討的一樣,非常簡化的說,從一般桂枝湯證、葛根湯證等的表寒,轉變到小青龍湯證等的裡寒,津液不足、水道運化失調而化熱,變成比較嚴重的大青龍湯證,或者更嚴重肺臟的寒熱夾雜,金匮要略肺痿肺癰咳嗽上氣病脈證治第七篇中的射干麻黃證、葶藶大棗瀉肺湯證、澤漆湯證、小青龍加石膏湯證等等混雜出現,搞得亂七八糟,也不再是什麼簡單方劑可以對應的。
然而,雖然進程很像,不同於一般外感的是,這些嚴重流感肺炎病情加重的改變速度快非常多,也來得猛烈頑強很多。一般的外感從桂枝湯證、葛根湯證等轉變到大青龍湯證或更複雜的病情,通常需要一兩週的時間。同時,還得病人自己非常不注意,或者醫生治療錯誤,一般感冒才會沒辦法自己好,反而變成嚴重的病症。這幾年的流感,從一開始覺得不太對勁,到嚴重複雜的病情,只需要三四天,而且有越來越快的趨勢。這大幅提高中醫師治療流感時,判斷功力及敏感度的要求,中醫師必須在許多症狀還沒有出現時,就得抓緊時間,趕緊行動,卻又不能預防過度,反而讓病情加重。換句話說,時機、劑量、藥材比例變得非常重要,稍有不慎,就無法反轉病情。
舉個例子,有些病人得了流感,咳嗽非常嚴重,痰非常多,呼吸困難。依照中醫的辨證,假如一致都是寒,舌苔白、小便清、怕冷等等,本來依照辨證論治,我們可能會開射干麻黃湯加減給病人。然而,因為流感的進程非常快速,中醫師得非常敏感,譬如看到舌苔白卻帶有一絲絲乾的感覺,就很可能得加上大寒的石膏來避免肺喪失津液,卻又不能加太多石膏,以免肺寒加重。又譬如聽到咳嗽聲音非常深沈,從肺的底部發出,又帶有膿痰的濁音,就很可能得加上瀉肺的葶藶來避免肺中水飲、痰飲大幅增加,卻又不能加太多葶藶,以免肺變得太虛弱。
我們回頭來看這次的新冠肺炎。根據有限的資訊,我們知道感染後有大約兩週的潛伏期,這段時間沒有什麼症狀,病人可能只會感到有些疲憊。剛開始發病時,很像一般的感冒,病人會發熱、乏力,並不嚴重,沒有什麼流鼻涕等上呼吸道的症狀,有的甚至沒有發熱。約一半的病人一週多後恢復,另一半的病人卻在一週後出現呼吸困難,有些病人會快速進展為急性呼吸窘迫綜合征、膿毒症休克、代謝性酸中毒、凝血功能障礙等等嚴重的問題,可能導致死亡。
從上面的敘述,我們不難發現,一開始很像一般中醫外感的桂枝湯證、葛根湯證,一半的病人也就自己恢復了,另一半的病人卻出現快速的入裡化熱現象,肺津液迅速流失,非常濃稠的痰飲沈積在肺部下方。同時,中醫認為肺為人體調節津液的源頭,肺金生水,好比天空下雨一般,而當肺的功能及津液調節出現嚴重障礙,很快就會拖累三焦水道、腎臟等的功能,導致上面提到的幾種嚴重病情。換句話說,新冠肺炎可以讓輕微的太陽證外感,迅速發展成嚴重的肺痿肺癰,再進一步瓦解人體其它功能的運作。
怎麼治療?在沒有直接治療武漢肺炎病人的情況下,我們也只能根據有限的資訊來推論,不過,以前大量的流感肺炎治療病例,可以讓我們比較有信心的面對新冠肺炎。當病人已經出現明顯新冠肺炎症狀時,大多已經入裡化熱,嚴重的肺痿肺癰。這個時候,得用大劑量的石膏清肺熱、加強肺津液運作。也得靠葶藶、大戟等把肺下方濃稠的痰飲及胸腔可能的積液去掉,痰飲積液不去,是無法修復肺家津液運作的。同時,肺氣不宣,就好像吸管上頭堵住了,吸管內的水無法上下,我們還得使用麻黃等宣肺、發陽的中藥來配合。另外,肺已經受損了,除了大動作急救外,比較穩定後,還得靠一些潤肺的藥來收尾,讓肺完全恢復。如果我們列一個可能加入的中藥單,大致有石膏、葶藶子、大戟、生半夏、麻黃、射干、紫菀 、款冬花、 生薑、炙甘草、紅棗、麥門冬、杏仁等等。當然,如前面所言,用藥的時機、劑量、藥材比例非常重要,每一個病人的差異也很大,嚴格考驗中醫師的功力與膽識,一旦判斷錯誤,不但沒有效果,反而可能會加重病情。
網上有些中醫師,說新冠肺炎或其它流感肺炎可以用板藍根清熱解毒來治好。也有些中醫師說可以用麥門冬湯等等的輕劑治好嚴重的肺炎。甚至還有些中醫師說多喝綠豆湯可以預防新冠肺炎!其實,真的遇過、治好過禽流感、豬流感等嚴重流感肺炎的中醫師,一看這些文章,就幾乎可以確定這些人根本沒有治療過嚴重肺炎的經驗,充其量只是在西醫治療下,在旁邊幫幫病人一些小忙而已。這樣的情況下,難怪中國政府平時大力推展中醫,真的有如同新冠肺炎這樣重大疫情爆發時,卻看不到中國政府大量使用中醫方法來治療病人、控制疫情。醫學是實戰的學問,沒有大量臨床病例,講得再好聽都是沒有用的,如果希望中醫真的在主流醫學裡站立起來,希望中醫真的能面對大規模的疫情,回歸最基本的臨床療效,才是最重要的,其它都只像是武術表演,而非實際作戰。
From SARS to Novel Coronavirus (COVID-19)
Written in Chinese by Dr. Andy Lee, January 21, 2020
Translated to English by Dr. James Yeh and Dr. Andy Lee, March 28, 2020
The epidemic from Novel Coronavirus is becoming much more serious. Transmissivity among people has been proven. (Note: It's now named COVID–19. The term “Coronavirus” will be used here.) Cases were found in areas beyond Wuhan. It has caused serious attentions from the WHO (World Health Organization) and many countries around the world. The residents in China and the surrounding regions are quite worried and wonder whether it will break out like SARS (2003). (Note: The article was written on January 21, 2020, before Coronavirus became a global pandemic.)
So far, the modern medical field has not found a cure for Coronavirus, but resorts to treating patients’ symptoms only. Any vaccine to treat Coronavirus is still no way in the sight. What do we do? Every time such a situation happens, the topic of using Traditional Chinese Medicine (TCM) is raised (at least among the Chinese communities). There is no exception this time. Many articles related to using TCM on Coronavirus have been popping up on the web. However, unless some TCM doctors who have actually treated many Coronavirus cases, all the discussion would be hypotheses or assumptions. Some hypotheses are worth considering while many others could be quite misleading.
Personally I have not treated patients cases related to Coronavirus. (Note: Shortly after this writing, the author has directly and indirectly participated in treating patients of Coronavirus successfully, and has published other later blogs which included his involvement in treating those patients. Please refer to his medical blog http://www.DrLee.us.) However, I did treat and cure patients inflicted by other viruses in the past, such as the Bird Flu, Swine Flu, and other influenza. A good amount of those patients were diagnosed as severe pneumonia by large hospitals and were required for isolation or self-quarantine. Hence many of patients and online medical forums online are asking for my opinions about Coronavirus.
As we discussed before, all these viruses from the outbreaks are either newly found or mutated from previous strands. The strand can be different every year. Therefore, people always ask how one can say that the TCM knowledge developed in East Han Dynasty (25-220 AD) would be any useful for treating the modern diseases, let alone the severe ones.
It turns out that TCM does not recognize any virus and does not deal with the concept of which type of virus is microscopically at work. TCM looks at how human bodies would become out-of-balance and react to external stimuli. Once the body is out of balance, what symptoms will exhibit and what reactions will be to adjust the body conditions to regain the balance, hence to reduce the damage to the body to the minimum. Let me take an example to illustrate: when there is a gunfight between the police and bandits, we want to see which direction the shots are coming from, causing casualties of the police force, so that we are able to adjust or reinforce the police power. We have no time to think about which brand of the guns or bullets the bandits use.
Over thousands of years, the external viruses have changed and evolved quite a bit, but the evolution of human beings was quite limited. The human body function, no matter how it was damaged, the symptoms due to the damage of the function, the reactions, and the following progression of the disease still follow certain paths. For this very reason, TCM’s focus on the balance of the human body often surpasses the effectiveness of Western medicine, which focuses more on external treats and the microscopic aspect of how human body’s cells are impacted by the external treats.
From the accumulation of many years of clinical treatment and observations, no matter it is Bird Flu, Swine Flu or other influenza, the bodily ‘damage’ and its progression by the viral attack still follow the description of the classic TCM literature “Treatise on Cold Damage on Miscellaneous Disease” (傷寒雜病論). In short summary, the disease usually starts with “Exterior Deficiency or Weakness” (表虛) or “External Coldness” (表寒), for which is matched to one of the several syndromes named with the corresponding herbal remedies such as “Gui Zhi Tang” (桂枝湯) and “Ge Geng Tang” (葛根湯). Then, the disease moves onto the next stage “Interior Coldness” (裡寒) or “Lung Coldness” (肺寒), which shows the syndromes named as “Xiao Qing Long Tang” (小青龍湯), etc. When the respiratory system is “affected by the coldness”, the body fluid function of the respiratory system gets affected. The circulation function of the lung becomes “Dry and Overheated” (燥热). This would lead to a more serious stage “Heated Interior” (入裡化熱) and would often be matched to its herbal remedy “Da Qing Long Tang” (大青龍湯). Or, even worse, it becomes so-called “mixed coldness and heat” (寒熱夾雜) in the lung. Such a complex situation was extensively discussed in Chapter 7 of the classic literature “Synopsis of Prescriptions of the Golden Chamber” (金匮要略肺痿肺癰咳嗽上氣病脈證治第七篇). At this complex stage, the illness development varies significantly among patients of different preconditions and other variants. It is no longer the situation that a simple herbal remedy can be applied to all the situations. The TCM theory illustrates various treatments by those herbal remedies such as “She Gan Ma Hung Tang” (射干麻黃湯), “Ting Li Da Zao Xie Fei Tang” (葶藶大棗瀉肺湯), ”Ze Qi Tang” (澤漆湯), “Xiao Qing Long Jia Shi Gao Tang” (小青龍加石膏湯), and others.
However, even the disease progressions are similar, the more serious viral attacks like Coronavirus can and often do progress much faster with more severe consequences than the common flu. As described in the previous paragraph, normally the disease progression of the “External Coldness” stage to the more serious “Heated Interior” stage usually takes one to two weeks. It is also often due to the ignorance of the patient or misdiagnosis and treatment of the doctor, which prevents the patient from recovering from this “catching a cold”. In the recent several years though, the time period between the time that the patient did not feel well and the time that the patient is in a serious and complex situation can be as short as 3 to 4 days. We also see the trend that this period gets shorter and shorter. In other words, the disease progression is getting much faster. This phenomenon poses a much higher demand on TCM doctors’ ability to make a quick and proper judgment and sensitivity to the subject matter. TCM doctors must intercept the disease progression before it reaches to a more serious stage, even without obvious symptoms of the next stage. TCM doctors have to timely prescribe the proper herbal remedy in terms of the type of herbs and relative dosages of herbs. Too weak a dosage could not stop the progression while too strong a dosage could worsen the condition also. A misjudgment would not be able the turn the conditions around, but hurt the patient more.
The above can be illustrated by a simple example. A patient caught flu and has symptoms such as heavy coughing, lots of sputum, and difficulty in breathing. From the TCM dialectics, with observations of white tongue coating, clear urine, and feeling chilly, etc., it is clearly caused by “Coldness”. Such a patient typically should be prescribed with “She Gan Ma Hung Tang” (射干麻黃湯) or its variations. However, due to the fast progression of the modern flu, the TCM doctor would need to pay attention to much subtle details such as the dryness of the tongue although it still shows the white coating. In this case, Sheng Shi Gao (Gypsum, 生石膏) might need to be added to the herbal remedy to make sure that the lung would not suffer dryness. Given that Sheng Shi Gao (Gypsum, 生石膏) itself is an ingredicient that is “very cold” in nature, the dosage could not be too strong to make the lung too chilly. At the opposite end of the spectrum, if the sound of the coughing is very ‘deep’, like dense sputum coming from the bottom of the lung, the herbal remedy might need to add Ting Li (Sisymbrium indicum, 葶藶) to clear up the lung to avoid too much mucus in the lung. And again, the dosage of葶藶 could not be too much to weaken the lung. (Note: Handling the proper timing and proper remedy can be a real test to the ability and experience of the TCM doctor.)
Let’s go back to the discussion on Coronavirus. From the limited information available so far, we know that there are about two weeks of incubation period after the infection. There are little symptoms during this period and the patient may just feel more tired than usual. More obvious symptoms will start like those of common flu with fever, fatigue but not too serious. Upper respiratory symptoms like running nose are less common. Some patients may not even exhibit fever. About half of the patients infected will recover over a week or so. The other half of the patients will experience difficulty in breathing, or rapid progression to acute respiratory distress syndrome, septic shock, metabolic acidosis, coagulopathy, etc. Some patients had died due to these severe conditions.
From the above description, this Coronavirus, in the beginning, is very much like the common flu and will stay in stages of “Exterior Deficiency or Weakness” (表虛) or “External Coldness” (表寒). Half of the patients infected will recover by themselves as in common cold. The other half of the patients may exhibit situations of rapid penetration into inner organs and excess ‘heat’, which causes loss of fluidity of respiratory system and accumulation of dense sputum at the lower part of the lung. In the TCM theory, the lung serves as the initial “gating factor” of body fluids. When the lung fails to serve the proper function, other organs like the kidney will be adversely affected also. In other words, Coronavirus can turn a light “External Coldness” to extremely severe “Lung Atrophy” (肺痿) and “Lung Abscess” (肺癰), which in turn will impair the function of other organs.
How to treat? Without direct experience of treating Coronavirus patients, we can only postulate from our limited information available in hand. (Note: Shortly after this writing, the author has directly and indirectly participated in treating patients of Coronavirus successfully. The treatments were exactly as outlined in this article.) From the ample experience of dealing pneumonia cases caused by flu, we are confident that we can also treat Coronavirus successfully. When patients are showing the obvious Coronavirus symptoms, most of them would have entered the stage of “Heated Interior” (入裡化熱) with “Lung Atrophy” (肺痿) or “Lung Abscess” (肺癰) to a certain degree. At this stage, we will need large dosages of Sheng Shi Gao (Gypsum, 生石膏) to clear the heat to ensure the proper fluidity function of the lung. Also, we will rely on Ting Li (Sisymbrium indicum, 葶藶), Da Ji (Euphorbia pekinensis Rupr., 大戟), etc. to clear up the dense mucus at the lower part of the lung and to remove the edema of the chest chamber. Without getting rid of the excess mucus and fluid, the lung cannot properly function. We need to use Ma Huang (Ephedra sinica Stapf., 麻黃), etc. to enhance the lung function (宣肺、發陽) and restore proper breathing. When the lung is damaged as in fibrosis, after the conditions stabilize, we need to “moisturize” the lung (润肺) to help the lung to recover fully. In other words, we will most likely use the herbal ingredients such as Sheng Shi Gao (Gypsum, 生石膏), Ting Li (Sisymbrium indicum, 葶藶), Da Ji (Euphorbia pekinensis Rupr., 大戟), Sheng Ban Xia (Pinellia ternate, 生半夏), Ma Huang (Ephedra sinica Stapf., 麻黃), She Gan (Belamcanda chinensis, 射干), Zi Wan (Aster tataricus, 紫菀), Kuan Dong Hua (Tussilago farfara flower, 款冬花), Sheng Jiang (Ginger, 生薑), Zhi Gan Cao (processed Glycyrrhiza uralensis Fisch., 炙甘草), Hong Zao (Ziziphus jujube, 紅棗), Mai Men Dong (Ophiopogon japonicas, 麥門冬), Xing Ren (Prunus armeniaca, 杏仁), and others. As we discussed in previous paragraphs, the timing, dosage, the relative ratios of different herbal ingredients are very critical. Given that there are quite some variations in patient conditions, the challenges on TCM doctors’ comprehensive knowledge, judgment and courage are unprecedented.
In those articles online, some TCM doctors claimed that Coronavirus can be cured by Ban Lan Gen (Isatis tinctoria root, 板藍根), which is believed to have natural antibiotic chemicals to “clear up the heat and toxics”. Some TCM doctors suggested using a simple mild herbal remedy “Mai Men Dong Tang” (麥門冬湯), which mainly relies on the ingredient Mai Men Dong (Ophiopogon japonicas, 麥門冬). Some people even suggested that having the green bean soup could prevent Coronavirus. In fact, those TCM doctors who have good experience of treating Bird Flu, Swine Flu, and pneumonia caused by other influenza would know that the people making those claims never had the real experience of treating severe pneumonia. They at most helped in a minor way the patients under Western medicine treatments. Under such conditions, it is not a surprise that the China government has not used TCM as the primary method of treating Coronavirus, despite its big promotion of TCM in the recent years. (Note: After this writing, Coronavirus epidemic became so severe in China that the China government changed its strategy and started to use TCM extensively in treating many mild Coronaviurs cases.)
Medicine is the science based on real treatment results. Without a good amount of successful cases in clinical treatments, it is useless to promote any fancy idea of treating patients. If we would like TCM to be respected in the mainstream medicine and to be meaningfully used in a severe epidemic like Coronavirus, it is critical to focus on the most fundamental. That’s the clinical results. Like the martial arts, unless you can fight off the bad guys, it’s just a show of fancy movements.
(http://andylee.pro/wp/?p=7169)
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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
antibiotic spectrum 在 一個平凡醫學生的日常。 Facebook 的最讚貼文
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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